back to indexDr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab Podcast #38
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, I have the pleasure of introducing
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Dr. Matthew Johnson.
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Dr. Johnson is a professor of psychiatry
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at Johns Hopkins School of Medicine,
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where he also directs the Center for Psychedelic
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and Consciousness Research.
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As many of you know,
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there's extreme excitement about the use of psychedelics
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for the treatment of various disorders of the mind.
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Dr. Johnson's laboratory is among the premier laboratories
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in the world understanding how these compounds work,
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how things like psilocybin and LSD and related compounds
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allow neural circuitry in the brain to be shaped and change
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such that people can combat diseases like depression
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or trauma or other disorders of the mind
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that cause tremendous suffering.
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Dr. Johnson is also an expert in understanding
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how different types of drugs impact
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different types of human behaviors,
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such as sexual behavior, risk-taking, and crime.
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Dr. Johnson and his work have also been featured prominently
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in the popular press,
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such as articles in the New York Times
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and Michael Pollan's book, How to Change Your Mind,
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and in a feature in 60 Minutes about psychedelics
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and the new emerging science of psychedelic therapies
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for treating mental disorders.
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During the course of today's conversation,
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Dr. Johnson and I talk about psychedelics
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at the level of what's called microdosing,
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whether or not it is useful for the treatment
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of any mental disorders.
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We also talk about more typical macrodosing,
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what those macrodoses entail,
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and he walks us through what an experiment
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of a patient taking psychedelics
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for the treatment of depression looks like
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in his laboratory from start to finish.
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The conversation was an absolutely fascinating one
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for me to partake in.
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I learned so much about the past, present, and future
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of psychedelic treatments and compounds.
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And indeed, I hope to have Dr. Johnson
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on this podcast again in the not too distant future
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so that we can talk about other compounds
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that powerfully impact the mind and human behavior,
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and perhaps can also be used to treat various diseases.
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Before we begin, I'd like to emphasize
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that this podcast is separate
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from my teaching and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science-related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Athletic Greens.
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Athletic Greens is an all-in-one
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vitamin mineral probiotic drink.
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I've been taking Athletic Greens since 2012,
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and so I'm delighted that they're sponsoring the podcast.
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The reason I started taking Athletic Greens,
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and the reason I still take Athletic Greens
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once or twice a day, every day,
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is because it covers my foundational nutritional needs.
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It has the vitamins I need, the minerals I need,
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and the probiotics are important to me
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because there is now so much data
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about the importance of the so-called gut microbiome,
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maintaining healthy gut bacteria,
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and the ways in which those gut bacteria
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impact things like inflammation
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and keeping inflammation down in the brain and body,
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as well as supporting things like quality mood,
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endocrine function, metabolic function,
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just so many factors.
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The great thing about Athletic Greens
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is that it also tastes very good.
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I mix mine with water, a little bit of lemon juice,
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and as I mentioned, I drink that once or twice a day.
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If you'd like to try Athletic Greens,
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you can go to athleticgreens.com slash Huberman,
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and if you do that, you'll get the Athletic Greens,
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plus you'll get five free travel packs.
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The travel packs make it very easy
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to mix up Athletic Greens when you're on the road,
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and you'll get a year supply of vitamin D3, K2.
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There's now a lot of evidence that vitamin D3 and K2
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cardiac health, and so forth.
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So once again, that's athleticgreens.com slash Huberman
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and your year supply of vitamin D3 and K2.
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Today's podcast is also brought to us by Inside Tracker.
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Inside Tracker is a personalized nutrition platform
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that analyzes data from your blood and DNA
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to help you better understand your body
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and help you reach your health goals.
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I've long been a believer in getting regular blood work done
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and now with the advent of quality DNA tests,
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you can get a lot of information about your genetics
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and how that also impacts your immediate
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The reason I'm such a fan of getting blood work done
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is that it is really the only way to understand
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what's going on in your system at a level
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that can really inform your decisions
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about your immediate and long-term health.
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The problem with a lot of blood and DNA tests, however,
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but you don't know what to do with that information.
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that's best for you and for your health.
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If you'd like to try Inside Tracker,
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you can go to insidetracker.com slash Huberman
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to get 25% off any of Inside Tracker's plans.
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Just use the code Huberman at checkout.
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Today's podcast is also brought to us by Belcampo.
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Belcampo is a regenerative farm in Northern California
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that raises organic, grass-fed
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and finished certified humane meats.
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I eat meat about once a day.
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In general, my lunch or my breakfast
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consists of some meat
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and that meat has to be a very high quality.
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And generally I'll eat some vegetable as well.
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And then I tend to eat pastas and rice
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and things of that sort later in the day or in the evening
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in order to facilitate the transition to sleep.
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So I'm eating meat about once a day.
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And I always insist that the meat that I eat
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be of the very highest quality
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and that the animals were raised and maintained humanely.
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While conventionally raised animals
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are confined to feed lots
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and eat a diet of inflammatory grains,
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So you can feel good about what you're eating
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You can order Belcampo's sustainably raised meats
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to be delivered to you by using my code Huberman
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at belcampo.com slash Huberman
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and entering my code Huberman to get 20% off
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your first time order.
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I'm partial to the ribeyes or the New York steaks.
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So on one day I might have a ribeye,
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the next day I might have a New York steak.
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I also really like the meatballs.
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I'm a particular fan of the meatballs.
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So again, that's belcampo.com slash Huberman
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and enter the code Huberman at checkout
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to get 20% off your order.
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And now my conversation with Dr. Matthew Johnson.
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Well, Matthew, I've been looking forward
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to this for a long time.
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I'm a huge fan of your scientific work
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and I'm eager to learn from you.
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Likewise, big fan and happy to do this with you.
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Great, well, thank you.
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My first question is a very basic one,
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which is what is a psychedelic?
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We hear this term all the time,
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but what qualifies a substance as a psychedelic?
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Nomenclature is a real challenge
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in this area of psychedelics.
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So starting with the word psychedelic,
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it just, if you're a pharmacologist,
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it's not very satisfying
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because that term really spans
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different pharmacological classes.
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In other words, if you're really concerned
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about receptor effects and the basic effects of a compound,
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it spans several classes of compounds.
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But overall, so it's really more of a cultural term
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or it does have a relationship to drug effects,
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but it's at a very high level.
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So all of the so-called psychedelics
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across these distinct classes that I can talk more about,
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the way I put it is they all have the ability
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to profoundly alter one's sense of reality.
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And that can mean many things.
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Part of that is profoundly altering the sense of self
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acutely, so when someone's on the psychedelic.
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So the different classes that can be,
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the specific pharmacological classes
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that can be called a psychedelic
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are one, what are called the classic psychedelics.
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So in the literature, you'll see that term.
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And hallucinogen and psychedelic
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are all have traditionally been used synonymously.
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I think there was a little of a tendency
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to stay away from psychedelics as the baggage,
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but there's been a return to that in the last several years.
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But the classic psychedelics or classic hallucinogens
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are things like LSD, psilocybin,
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which is in so-called magic mushrooms.
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It's in over 200 species that we know of so far
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of mushrooms, dimethyltryptamine or DMT,
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which is in dozens and dozens of plants,
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mescaline, which is in the peyote cacti
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and some other cacti like San Pedro.
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And even amongst these classic psychedelics,
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there are two structural classes.
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So that's the chemistry.
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There's the tryptamine-based compounds
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like psilocybin and DMT.
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And then there's the phenethylamine-based compounds.
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So these are the two basic building blocks
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that you're starting from,
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either a tryptamine structure or a phenethylamine structure.
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But that's just the chemistry.
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All of the, what's more important,
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or at least to someone like me,
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are the receptor effects.
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And then ultimately that's going to have a relationship
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to the behavioral and subjective effects.
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So all of these classic psychedelics serve as agonists
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or partial agonists at the serotonin 2A receptor,
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so subtype of serotonin receptor.
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Then you have these other classes of compounds
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that you could call psychedelic.
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Another big one would be the NMDA antagonist.
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So this would include ketamine, PCP, and dextromethorphan,
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something I've done some research with,
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which folks might recognize from like robo-tripping,
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guzzling, like, you know, call syrup,
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which is something kind of like high school kids
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are known to do and they can't get ahold of real drugs,
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that type of thing.
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So a large overlap in the types of subjective effects
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that you get from those compounds
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compared to the 2A agonist classic psychedelics.
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But then you have, and by the way,
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this description, this framework I'm describing,
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not everyone will agree.
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Some people will say,
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no, psychedelic only means classic psychedelic.
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So there's different opinions here.
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But you have, gosh, salvinorin A,
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which is a kappa opioid agonist, which again-
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Where does that come from?
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It's a plant that became 20 years ago.
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It sort of popped onto the legal high scene.
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And there's a long history of this.
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Predating the internet, going back to like the stuff
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that went good or in the back of High Times Magazine.
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And most of this stuff like never worked, you know?
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It's like, smoke enough of anything,
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maybe you get a little bit lightheaded.
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But this is one of those things that popped around
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20 years ago when it quickly got the reputation of like,
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holy shit, this stuff actually works
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and works really strongly.
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And these smoked extracts particularly,
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people have these reality altering experiences
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on par with smoked DMT, the classic psychedelic.
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So often, and we did the first blinded,
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controlled human research with salvinorin A.
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So lots of entity contact.
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So feeling that you, in the experience of one,
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is actually interacting with autonomous beings,
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that type of thing.
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And then you have another big one,
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I probably should have mentioned even before the,
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you know, salvinorin A, but you have MDMA,
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which really stands in a class by itself.
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So it's been called an entactogen and-
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What does that mean?
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It means like, touching within.
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It sort of eludes the idea that it can really put someone
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in touch with their emotions.
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It's also been called an empathogen,
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meaning can it can afford empathy.
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But I think entactogen is probably,
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that's the term that I tend to focus on.
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And I know I'm not telling you anything you don't know,
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but for the viewers, the primary mechanism of MDMA
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is serotonin release.
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And to a degree, other monoamine release,
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dopamine, serotonin.
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And so structurally, that's also in the phenethylamine class
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which contains mescaline, the classic psychedelic,
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but also amphetamine.
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So just like Adderall is in that phenethylamine class.
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And so this is another example
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where chemistry doesn't dictate.
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I mean, you can tweak a molecule,
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it might have that same basic structure,
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but now you've profoundly changed the way
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it interacts with the receptor.
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So MDMA does not exert its actions
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by, I like to say, by mimicking the baseball,
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entering the postsynaptic receptor side,
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acting as an agonist.
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So mimicking the endogenous neurotransmitter serotonin,
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like the classic psychedelics do,
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MDMA works on the pitcher side
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of just basically throwing out more of the natural,
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Dumping more serotonin.
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Dumping more serotonin, flooding the synapse.
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So I get the impression that the psychedelic space
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is a enormous cloud of partially overlapping compounds.
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Meaning some are impacting the serotonin system
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more than the dopamine system.
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Others are impacting the dopamine system
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more than the serotonin system.
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Given that the definition of a psychedelic
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is that it profoundly alters sense of self,
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at least that's included as a partial definition.
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Can we break that down into a couple of subcategories?
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So for instance, hallucinating, either auditory or visual.
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Synesthesia, perceptual blending,
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the sense that you can hear colors and see sounds,
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for instance, a common report of people
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that take psychedelics in sufficiently high doses.
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So hallucinating, synesthesia,
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and then in terms of sense of self,
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you know, as a neuroscientist, I think,
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okay, what does it mean to alter a sense of reality?
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Really what the brain does in a very coarse way
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is to try and figure out what's happening in space,
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physical space, and that physical space could be within us
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or outside us, and what's happening in time.
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And as a vision scientist, the simplest explanation
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is when I move my hand from one location to another location,
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it's measuring the space,
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the location of my hand in space over time.
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And then you get a rate and a speed
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and all that kind of stuff, right?
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That gets more complicated
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as you get into the emotional realm.
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But is it fair to say that psychedelics
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are impacting the space time analysis
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that the brain is performing
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and thereby creating hallucinations
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and thereby altering, you know, the blending of senses?
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Is it fair to say that?
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I think it's fair to explore that area.
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And here's what I'm thinking.
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The clearly there is a changed relationship,
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certainly at the right dose of orientation and space time.
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I think as a, you know, I'm primarily a behaviorist
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and in terms of human behavioral pharmacology,
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I always go to comparative pharmacology.
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Okay, what can we say that is it truly unique
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about the classic psychedelic or psychedelics in general?
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So with that description, I'm thinking, okay,
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alcohol can really screw up your, you know,
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time-space orientation.
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And proprioception, your balance.
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Your vestibular, yeah.
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You know, and in many ways,
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and sort of in those gross motorways, like far worse,
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you know, of course everything's dose dependent,
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but in the classic psychedelics, you know,
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obviously the benzodiazepines being very similar alcohol,
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So, you know, I'd want to, you know,
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dig in a little more in terms of like,
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maybe there's something more specific we could say
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about that relationship to time and space
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that the psychedelics are tinkering with,
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It's an interesting hypothesis that the idea
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that that's a mediator, that that's something,
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that there's something fundamental about changing that,
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the representation in time and space.
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There might be something to that.
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I mean, I think of these as psychedelics
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as profoundly altering models, you know,
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we're all, you know, we're prediction machines
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and that's large, so much of that is top-down
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and psychedelics have a good way of, you know,
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loosely speaking, dissolving those models.
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And one of the reality-
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Can you give us an example of one of like a model,
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like I know that when I throw a ball in the air,
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it falls down, not up.
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That's a prediction that I learned as a child
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that I did not come into the world with a brain
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that knew that relationship between objects and gravity.
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But one of the first things that a child learns
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is the relationship between objects and gravity
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and their trajectories.
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Yeah, and with a four-year-old, I mean,
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I saw that at earlier ages,
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like that experimentation of like,
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oh yeah, that's what happens, you know?
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Right, so if he were to throw a ball,
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if your child were to throw a ball
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and it went up into the sky,
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that would be absolutely mind-blowing.
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It would be for an adult too.
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It'd be a pretty psychedelic experience probably.
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Right, and so there's a rule there, you're saying,
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there's a kind of a prediction,
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there's a rule that underlies a prediction
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that when that rule is violated,
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all of a sudden the circuit, presumably,
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for that prediction, it doesn't have a mind of its own,
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but somehow it creates a surprise element
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or a recognition element.
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And it's not filtered out, you know?
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And this might sound extreme, but there are these cases,
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it was overblown in sort of the propaganda
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of the late 60s, early 70s,
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but there are credible cases of people,
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I think it's very atypical,
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of sounds like they really thought they could fly.
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And jump out of a window.
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Now, far more people every year fall,
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I mean, who knows, they fall and die from height
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because they're drunk, so this is extremely rare.
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But there are some pretty convincing cases.
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There was one research volunteer in our studies
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that she looked like she was, in one of our studies,
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like she was trying to dive through a painting on the wall.
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She was fine, but she, reviewing the video,
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it looked like she really thought
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that she was going to go through that painting
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and who knows, enter the other dimension.
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Yeah, so they're violating these predictions.
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Yeah, the reason I ask it, the question the way I did,
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is because given the enormous cloud of different substances
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and given the range of previous experiences
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that people show up to a psychedelic experience with,
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I feel like the ability to extract
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some universal themes is useful,
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especially for people who haven't done them before, right?
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Who might not have an understanding
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of what their effects are like.
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Can we just briefly touch on the serotonin system
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and the dopamine system?
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I want to acknowledge it, as you already know,
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that there are many neuromodulator systems in the body.
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And, you know, the opioid systems, cannabinoid systems,
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but there's something so profound
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about the serotonin system and the dopamine system,
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because the way I define a neuromodulator is,
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it's a modulator, it changes the way
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that other circuits behave.
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And essentially it increases the probability
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that certain circuits will be active
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and decreases the probability
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that other circuits will be active, in a general sense.
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So, compounds like LSD,
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lysergic acid, diethylamide, and psilocybin,
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my understanding is that they primarily
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target the serotonin system.
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How do they do that at a kind of general level?
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And why would increasing the activity
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of a particular serotonin receptor
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or batch of serotonin receptors
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lead to these profoundly different experiences
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that we're calling model challenges,
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challenging pre-existing models and predictions?
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I mean, at the end of the day, it's a chemical
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and these receptors are scattered around the brain
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with billions of other receptors.
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What do we think is going on in a general sense?
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And this is really the area of active exploration
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and we don't have great answers.
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We know a good amount
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about the receptor level pharmacology,
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some things about post receptor signaling pathways.
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In other words, just fitting into the receptor,
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clearly serotonin itself is not psychedelic,
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or else we'd be tripping all of us all the time.
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Because when I eat a bagel,
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I get serotonin release, right?
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I mean, there's turkey, I mean, there's triptophan, right?
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My understanding of serotonin is that in very broad strokes,
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that it generally leads to a state of being fairly,
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it pushes the mind and body towards a state of contentment
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within the immediate experience.
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Whereas the dopamine system really places us
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into an external view of what's out there in the world
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and what's possible.
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Yeah, we need to do something.
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I mean, that's consistent with my understanding.
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And I'll certainly not, in terms of,
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I don't primarily identify as a neuroscientist,
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definitely tell the viewers
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that we're far more in your domain here than mine,
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but in terms of how psychedelics and other drugs
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interface at the neuroscience level.
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Well, feel free to explain it at the experiential level.
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I mean, it doesn't have,
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I think there probably are some audience members
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that are interested in, is it the 5-H2C?
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Is it the layer five neurons and cortex?
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That conversation we could hold,
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and that's an interesting conversation.
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But just in terms of the experience of serotonergic
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versus dopaminergic drugs,
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they do seem to create distinct classes of experience.
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So I think that's the appropriate level
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for us to discuss them.
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And in terms of how they, and I'd like to explore the biology
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a little bit here and tell you sort of what's known
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and what some of the ideas are.
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You have this path, as you know,
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these are levels of analysis,
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and it's not which one is going on.
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It's almost like, for the particular question,
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which level of analysis is most appropriate?
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Is a question best addressed by the biology,
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the chemistry, or the physics?
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That's how I think of receptor level,
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post-receptor signaling, downstream effects
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on other neurotransmitters,
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and then activation level effects,
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and then coordination of activation.
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So you've got the, clearly with the classic psychedelics,
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the 2A activation, we do know
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that there are downstream effects
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in terms of increasing glutamate transmission.
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So this is likely a commonality why ketamine
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is very psychedelic in a slightly different way.
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Do people hallucinate on ketamine?
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Yes, yes, and it's more dissociative,
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so someone is more likely to sort of
link |
be less behaviorally active.
link |
If they have a really high dose, they go into a K hole,
link |
and if they go in a really high dose,
link |
like you get into surgery, you're just unconscious.
link |
Not an A hole, but a K hole.
link |
A K hole, yeah, it's very different.
link |
The K hole, and ketamine's interesting
link |
because people can take kind of bumps
link |
and kind of dance on it
link |
with the sort of an alcohol level strength of effect,
link |
and that's sort of the classic kind of raving use of it.
link |
But then those folks want to titrate their dose
link |
because if they do more of like a line,
link |
you get up to like 75, 100 milligrams,
link |
then you're talking about, you know,
link |
if you're on the dance floor, you're on the floor,
link |
and your friends are trying to make sure
link |
people aren't stepping on you.
link |
Yeah, why would somebody want to take
link |
a dissociative anesthetic?
link |
Like to me, it's completely mysterious
link |
as to why someone would want to dissociate from their body.
link |
People claim that these NMDA antagonist psychedelics
link |
are extremely insightful, you know,
link |
in a very similar way to the experiences
link |
with the classic psychedelics.
link |
And ketamine is now legal for therapeutic use, right?
link |
Spravato, the intranasal form marketed by Janssen,
link |
which is S-ketamine, and it's one of the-
link |
Yeah, it's prescription, and-
link |
So people are taking in the nasal spray.
link |
And then are they undergoing talk therapy
link |
while they're doing this?
link |
So this is very interesting,
link |
and there's so much work that needs to be done.
link |
It's not treated as psychedelic therapy.
link |
And by that, psychedelic therapy, I mean,
link |
you tell the person they're going to have
link |
an altered experience.
link |
You tell them to pay attention to that experience,
link |
that they might learn something from that experience.
link |
And afterwards, you discuss that experience.
link |
With Spravato, the model is-
link |
That's the, yeah, the spray form of ketamine.
link |
It's been FDA approved for treatment-resistant depression,
link |
but you'll probably feel different.
link |
That's a side effect.
link |
That's an adverse effect.
link |
We don't think that has anything to do with the way it works,
link |
but just get this thing.
link |
It's a direct sort of chemotherapeutic effect in a sense.
link |
It's not facilitating a learning process.
link |
Now, there's older work.
link |
There was a guy, Krupitsky, in Russia
link |
that did extensive work with higher doses of ketamine.
link |
I should say Spravato at the prescribed doses
link |
isn't very, it's a pretty low dose.
link |
It's in the mild psychedelic range, but it's not very strong.
link |
But this older work that happened in the 90s
link |
and early 2000s in Russia,
link |
they were using very high doses
link |
and treating it like a psychedelic,
link |
treating it as if it was a psychedelic therapy.
link |
In other words, telling people,
link |
you're going to have this experience.
link |
It's going to, you know,
link |
we're hoping you learn something from it.
link |
We're going to help you through it.
link |
We're going to discuss it afterwards.
link |
And they found incredibly high rates of success
link |
in some pretty well-controlled trials
link |
for both heroin addiction and alcohol addiction.
link |
So I think a whole lot of work needs to be done now.
link |
And you see some of the ketamine clinics
link |
that are using ketamine off-label,
link |
a lot of them are treating it like psychedelic therapy.
link |
There's essentially no research at this point on that.
link |
Do you get better results?
link |
Straight abusive Spervado,
link |
there's some good variability,
link |
but its antidepressant effects last about a week.
link |
But they kick in immediately.
link |
Now, a week is a long time for like most psychiatric drugs.
link |
Like you take it every day.
link |
So that's amazing, but it's still just a week.
link |
We're seeing effects a year or more later
link |
with psilocybin and some of the classic psychedelics.
link |
That could be a pharmacological difference,
link |
or it could be that they get a lot more mileage
link |
out of ketamine if they treated it like psychedelic therapy.
link |
And so that's some-
link |
What would that look like?
link |
Really just like our psilocybin sessions,
link |
which I know I haven't described,
link |
but briefly you have anywhere from four to eight hours
link |
of preparation, getting to know the people
link |
who are going to be the guides
link |
or the therapists in the room.
link |
Yeah, maybe you could walk us through this.
link |
So let's say I were to come to one of your clinical trials,
link |
because these are clinical trials, right?
link |
At your lab at Hopkins.
link |
And would I need to be depressed
link |
or could I just be somebody
link |
who wanted to explore psychedelics?
link |
We've had studies for all of these
link |
and a number of other disorders.
link |
So healthy normal studies,
link |
the code for not a problem to fix,
link |
but we're all here.
link |
That's what's amazing about psychedelics though,
link |
because if you administer them under this model
link |
and you develop a relationship
link |
and give a high dose of psychedelic,
link |
you can be a healthy normal without a diagnosable issue.
link |
But man, we're all human
link |
and the issues seem to come to the surface.
link |
So, but we've done work with smoking cessation.
link |
So people trying to quit tobacco
link |
and haven't been successful.
link |
So a variety of reasons.
link |
So maybe I'll just ask some very simple questions
link |
that would kind of step us through the process.
link |
So let's say I were to sign up for one of these trials
link |
and I qualified for one of these trials.
link |
I'd show up, you said I would do several hours in advance
link |
of getting to know the team
link |
that would be present during this psychedelic journey.
link |
First there's screening.
link |
So it's kind of like a couple of days of both psychiatric,
link |
like structured psychiatric interviews
link |
about your whole, your past and symptoms
link |
across the DSM, the psychiatric Bible
link |
to see if you might have various disorders
link |
that could disqualify you.
link |
Like the main ones being the psychotic disorders,
link |
schizophrenia, and also including bipolar.
link |
So the manic side of bipolar.
link |
So after that, and also cardiovascular screening,
link |
heart disease, after that screening,
link |
then the preparation where you get,
link |
you're both, you develop a therapeutic rapport
link |
with the people who are going to be in the room with you,
link |
your guides, but you're also then didactically
link |
sort of explained about what the psychedelic could be like.
link |
And that's kind of a laundry list
link |
because they're more known by their variability
link |
than it's going to, it's not like cocaine.
link |
Like you're going to feel stimulated.
link |
You're going to feel like you can do any,
link |
it's like, or alcohol.
link |
You're probably going to feel more relaxed.
link |
It's like, I call them uppers, downers, and all-arounders,
link |
and the psychedelics are all-arounders.
link |
It's like, yeah, you could be,
link |
you could have the most beautiful experience of your life
link |
or the most terrifying experience of your life.
link |
So it's this kind of laundry list
link |
of like the things that could happen.
link |
So there's no surprises.
link |
I think it's so important for people to hear
link |
because the all-arounders, they,
link |
you really can't predict how somebody
link |
is going to react internally.
link |
I want to just briefly touch on something
link |
because we left that topic,
link |
but it occurred to me that a lot of these effects
link |
of psychedelics and how they function, et cetera,
link |
is still very mysterious.
link |
But then I recall to mind
link |
that how most prescription antidepressants work
link |
is also very mysterious.
link |
They increase serotonin or dopamine or epinephrine, et cetera,
link |
but why they take weeks on end,
link |
several weeks to kick in, et cetera, is also mysterious.
link |
But going back to the experience
link |
of coming to your laboratory.
link |
Okay, so let's say that somebody passes
link |
all the prerequisites and it's the day.
link |
Comes the day that they're going to have this experience.
link |
Are they eating mushrooms like you hear about
link |
or are they taking it in capsule form?
link |
And what sorts of doses are you prescribing?
link |
Is there a dose response curve?
link |
Yeah. And then secondary to that,
link |
I'd like to talk about microdose versus macrodose.
link |
So how do they get this stuff into,
link |
how do people receive it
link |
and how do they get it into their body?
link |
So they receive pure psilocybin.
link |
So the mushroom, and there are many species,
link |
the most private, people have taken mushrooms
link |
in the United States.
link |
It's most likely psilocybe cubensis.
link |
They're easy to grow.
link |
They grow in cow patties.
link |
It's easy for any body to grow them in their closet.
link |
It doesn't take a 1,000-watt light like cannabis.
link |
It takes like a little 10-watt light bulb
link |
and a Tupperware bin.
link |
So those are the types of mushrooms
link |
that people typically take.
link |
We're not administering those.
link |
Psilocybin is the compound.
link |
You could draw a molecule, psilocybin,
link |
again, based on the tryptamine structure.
link |
That's a single molecular entity.
link |
So it's a white powder.
link |
Does it look like serotonin molecularly?
link |
So if I were to show people
link |
the chemical structure of serotonin,
link |
the chemical structure of psilocybin,
link |
it would look quite similar.
link |
So they're basically taking serotonin.
link |
A modified version of serotonin, which makes sense.
link |
But then again, this repeated theme of the chemistry
link |
doesn't always neatly line up
link |
because like mescaline looks more like dopamine
link |
than it does like serotonin,
link |
but yet at the receptor activation level,
link |
the pharmacological effect,
link |
those are similar.
link |
But yeah, and what it does at the receptor
link |
is it's hitting the same switch,
link |
but then having an alternate response at the receptor level.
link |
So for people that don't necessarily understand
link |
the relationship between what we call ligand,
link |
the thing that parks in the receptor,
link |
and the receptor is the parking spot,
link |
one of the reasons that you can get such a variety
link |
of effects from different compounds is,
link |
for instance, serotonin might affect a certain pathway
link |
at a particular rate,
link |
and psilocybin might trigger activation
link |
of different components of that pathway at different rates,
link |
and so you can get vastly different experiences
link |
from two things that look chemically similar.
link |
This is also a good reason why people shouldn't just assume
link |
that they can cowboy their own chemistry, right?
link |
That what you see on paper and what you can mix up
link |
in a vial is often vastly different than what you predict.
link |
And there's a dose effect curve that's really interesting.
link |
Some of our early work with psilocybin in healthy normals
link |
looked at a true placebo plus four active doses,
link |
five, 10, 20, and 30 milligrams of psilocybin.
link |
Body weight adjusted,
link |
so those milligrams per 70 kilograms of body weight.
link |
We've recently published a paper in our newer trials
link |
where we're dropping the body weight adjustment
link |
because we're going across hundreds of volunteers.
link |
We've kind of figured out that you shouldn't really be,
link |
you don't need to be adjusting by body weight.
link |
Well, brain size doesn't vary that much between individuals.
link |
And, you know, at the end, this is a brain effect, mostly.
link |
Probably body as well.
link |
Okay, so the person ingests the powder or capsule?
link |
Yeah, and it doesn't take 30 milligrams as a small.
link |
You could fit it into a tiny little capsule,
link |
and it'll take about a half hour,
link |
but anywhere from 15 minutes to an hour to kick in.
link |
And you said the dose range was?
link |
Most of our studies are looking at
link |
where we want a psychedelic effect
link |
are in the 20 to 30 milligram range.
link |
Again, because we have adjusted by body weight
link |
and the average American is over 70 kilograms,
link |
Like people, and in fact, have gotten more like 40, 45
link |
in a lot of cases.
link |
But it's still a small pill.
link |
The session day itself is not full of,
link |
for most of our studies, is not full of tasks.
link |
We really want to look at the therapeutic response.
link |
Obviously, if it's a therapeutic study,
link |
we want it to be a meaningful experience.
link |
And research has found, not surprisingly,
link |
that you get a less meaningful experience
link |
when you're in an FMRI
link |
or when you're doing a lot of cognitive tasks.
link |
We've done some research of that type, for sure,
link |
and plenty of colleagues have.
link |
But when you're in a therapeutic study,
link |
or if you're trying to understand the therapeutic effects,
link |
you have to recognize there's this trade-off
link |
of what you can do.
link |
So our typical therapeutic model,
link |
which again, isn't just limited necessarily
link |
to the therapeutic studies
link |
where we're trying to treat a specific disorder,
link |
is to have that preparation
link |
so the person feels very comfortable with their guides.
link |
I mean, ultimately, what I tell people is like,
link |
any emotional response, it's all welcome.
link |
I mean, you could be crying like a baby hysterically.
link |
Like, that's what you should be doing
link |
if that's what you feel like.
link |
And so in a lot of ways,
link |
sometimes people with psychedelic experience on their own,
link |
it can be harder to train them in this model
link |
because in the real world,
link |
people with psychedelic experience,
link |
a lot of times the rule is, you know, hold your shit.
link |
So several friends go to a party,
link |
they split a bag of mushrooms.
link |
It's like, you know, there's a social pressure
link |
for good reason not to be the guy, you know,
link |
in the corner of the room
link |
where everyone's trying to just have a good time, relax,
link |
like crying about your mother.
link |
Your other friends are, they're having an experience too,
link |
and you're being a drama king and blah, blah, blah.
link |
And so like, yeah, compose yourself, hold your-
link |
You're doing, I mean, you're doing therapy for people.
link |
It's not just about the experience.
link |
Right, and the experience itself is very much shaped
link |
by that container, by the environment,
link |
and the degree to which one allows it to happen.
link |
Like one should let go of control.
link |
Yeah, let's talk about the letting go of control.
link |
And then as we march through this hypothetical experience
link |
that does take place in your lab,
link |
so we're using a sort of generic case example, if you will.
link |
The letting go of control is an interesting feature,
link |
actually, because one of the common themes
link |
of good psychoanalysis or psychotherapy of any kind
link |
is that there's a trust built between the patient
link |
and the analyst, and that relationship becomes a template
link |
for trust more generally and trust in oneself.
link |
It's actually the end goal of good psychoanalysis
link |
is that the patient actually, one of the end goals
link |
is that they develop an empathy for themselves,
link |
which almost sounds like an oxymoron,
link |
but if you spend a little time with that statement,
link |
it actually pans out.
link |
So the psychedelic experience is one in which chemically
link |
you're under a new set of conditions, right?
link |
Coarsely, space and time are altered in some way,
link |
For instance, I might be going to a strongly
link |
interoceptive mode where I'm focusing on everything
link |
within the confines of my skin,
link |
whereas normally we're sort of interacting in space
link |
and pens and conversation, and I'm sort of,
link |
if I had, occasionally I'll pay attention to my breathing,
link |
but I'm sort of dilating and contracting my focus
link |
for different things all the time.
link |
The letting go of control, it seems to me,
link |
could be sort of the expansion of one perceptual bubble
link |
to the point where you're not actually worried
link |
that that perceptual bubble is going to pop or that,
link |
meaning you're not worried about what people think of you.
link |
You're not worried whether or not your brain
link |
is going to explode,
link |
even though a thought could feel enormous.
link |
If I keep going like this, it almost sounds psychedelic,
link |
but that's the idea here.
link |
Or if I'm paying attention, for instance,
link |
to some somatic experience,
link |
like the coursing of waves of heat through my body,
link |
that I'm not suddenly saying, you know, is that weird?
link |
I'm actually just going deeper and deeper into it.
link |
So it's essentially expanding our perceptual phenomenon.
link |
How do you convince people to go further
link |
and further down that path?
link |
What do you think allows them to do that?
link |
Because I think that, to me,
link |
is one of the more unusual aspects to psychedelics
link |
is that normally the social pressure,
link |
but also just our internal pressure from our own brain
link |
is pay attention to many things at once, not just one.
link |
Especially these days.
link |
Multitask, and the more that we focus on one thing,
link |
the more bizarre that thing actually can appear to us, right?
link |
I mean, even if it's the tip of your finger
link |
and you're not taking any psychedelics,
link |
you spend a long enough looking at the tip of your finger,
link |
you will notice some very weird things, right?
link |
I think of that as the classic psychedelic effect
link |
or one classic effect,
link |
and one I've used many times of this example
link |
of why people shouldn't necessarily, you know,
link |
one should be judicious
link |
in putting themselves in these circumstances.
link |
Someone could be, you know,
link |
having a very strong psilocybin experience
link |
and they're trying to navigate their way in Manhattan,
link |
crossing the street,
link |
and they might be staring into the hand and realize,
link |
like that's, their hand is the most amazing miracle.
link |
Like the entire universe has essentially conspired
link |
to come to this one point
link |
to make this absolutely breathtaking.
link |
It's almost like, I think of the simplest form of,
link |
well, we know that the simplest form of learning
link |
Simply keep applying stimuli
link |
and there's less response.
link |
Like, this is what organisms do.
link |
This is what we have to do.
link |
And it's like, there's this dishabituation component
link |
Yes, like we wouldn't be able to get through life
link |
if we wouldn't be able to cross that street
link |
if we were like, oh, like this is a miracle.
link |
Well, I'm so glad you,
link |
no, I'm so glad you brought this up.
link |
I mean, here I'm reflecting my bias as a vision scientist,
link |
but most people don't realize this,
link |
but if you look at something long enough,
link |
it eventually disappears.
link |
It doesn't actually disappear,
link |
but perceptually it disappears.
link |
You have these little microsaccades that ensure
link |
But most of us don't look at any one thing for very long.
link |
The brain's default is to perceptually jump around
link |
like crazy with the visual system,
link |
with the auditory system.
link |
We all, ADD, people talk about ADD a lot,
link |
is sort of baked into our underlying networks at some level.
link |
And then we can force attention.
link |
But it sounds like in psychedelics,
link |
one of the primary goals therapeutically
link |
is to really drill into one of these perceptual bubbles
link |
and expand that bubble.
link |
And the safety it seems is the safety,
link |
it's sort of like a permission to do that
link |
without worrying that something's going to happen.
link |
Right, because I've had people there on the couch.
link |
Yeah, I remember one lady said,
link |
this is probably 13, 14 years ago,
link |
said, Matt, tell me again, I can't die.
link |
I feel like my heart is going to rip through my chest.
link |
I mean, she was feeling her.
link |
And I should say, typically,
link |
cardiovascular response is modest.
link |
The pulse and blood pressure go up somewhat.
link |
It can be dangerous for people
link |
if they're at severe heart risk,
link |
and we do monitor.
link |
Are you monitoring this the whole time?
link |
So they're plugged into a variety of devices.
link |
Yeah, so every half hour or so,
link |
we take their own protocol,
link |
and we space it out a little further,
link |
further into the time course.
link |
But we take their blood pressure and their pulse.
link |
And if it goes over a certain level, we have a protocol.
link |
And we've had to do this only a few times.
link |
But the physician comes in,
link |
gives them a little nitroglycerin under the tongue,
link |
and knocks the blood pressure down a little bit,
link |
doesn't affect the experience.
link |
So we have it all in place,
link |
even though they'd probably be fine
link |
out of an abundance of caution.
link |
But yeah, but someone can feel that,
link |
my God, I'm going to die.
link |
Like, I have never felt my heart beat like this before.
link |
And the experience of the breath
link |
can be just absolutely fantastic.
link |
This sort of, and the breath is obviously interesting
link |
because it's this automatic control,
link |
but it can also be voluntary.
link |
So people can get into a sense of like,
link |
my God, what if I forget, what if I forget?
link |
like a stoner movie. What if I forget to breathe?
link |
But people, that can be so compelling.
link |
And so one of the reasons,
link |
and get back to one of your questions,
link |
it's like, what do we do to kind of allow them
link |
to go further into these bubbles?
link |
It's like, one is wearing the eye shades.
link |
We don't call them blindfolds
link |
because that has a negative connotation like being kidnapped.
link |
And they're probably seeing a lot in there anyway.
link |
So blind isn't the appropriate word.
link |
I've never thought of it.
link |
These should be like inner sight shades.
link |
But when you close the eyes,
link |
the levels of activity in the retina actually are maintained.
link |
It's just spontaneous activity.
link |
and I'd be curious about your thoughts on this.
link |
But the way I describe it is that the mind's eye,
link |
meaning this kind of loose term we use,
link |
can be on rocket boosters.
link |
So a lot of times, for some people,
link |
like a compound like psilocybin,
link |
for some people, there's no perceptual effect.
link |
Like if they're looking at this room,
link |
it would pretty much look the same.
link |
Sometimes folks say,
link |
yeah, things seem a little bit brighter.
link |
Now, some people will say,
link |
oh my God, there's waves.
link |
That wall is waving and these curtains are, you know.
link |
On these compounds,
link |
people don't typically see pink elephants.
link |
You do actually get that in another class.
link |
I didn't mention the anticholinergics,
link |
sort of like atropine and scopolamine, those drugs.
link |
Those are the true hallucinations
link |
where you thought you were having a conversation
link |
with someone who was never there.
link |
We will definitely get to those.
link |
But the reason I kind of cringe and say,
link |
oh my, when you talked about those,
link |
is that knowing a little bit
link |
about the pharmacology of acetylcholine,
link |
the idea of manipulating that system,
link |
to me, sounds very uncomfortable.
link |
Because like the whole idea of, well, witches and flying,
link |
there was a whole history there, you know,
link |
hundreds of years ago, so-called witches,
link |
taking these agents and then thinking
link |
they were flying around on broomsticks
link |
and things of that sort.
link |
And there's a lot of mythology around the broomsticks.
link |
It's complicated, but that sounds very unpleasant.
link |
One thing about the serotonergic,
link |
let's just, with psilocybin.
link |
So there's an expansion
link |
of a particular fairly narrow percept.
link |
It could be sound, could be an emotion, could be sadness,
link |
could be a historical event or a fear of the future.
link |
And you've mentioned before that there's something
link |
to be learned in that experience.
link |
There's something about going into that experience
link |
in an undeterred way that allows somebody
link |
to bring something back into more standard reality.
link |
Given the huge variety of experiences
link |
that people have on psychedelics,
link |
given the huge variety of humans that are out there,
link |
but what are now very clear therapeutic effects
link |
in the realm of depression,
link |
what do you think is the value of going into this
link |
fairly restricted perceptual bubble,
link |
what we are calling letting go or giving up control?
link |
Because if the experiences are many,
link |
but the value of what one exports from that experience
link |
is kind of similar across individuals,
link |
that raises all sorts of interesting questions.
link |
And this is not a philosophy discussion.
link |
We're talking about biology and psychology here.
link |
So let's say I decide I'm going to focus on the tip
link |
I mean, in a psychedelic state,
link |
I could fall in love with this pen.
link |
I do happen to like these Pilot V5s and V7s very much,
link |
but I could feel real love for the pen, right?
link |
That's not an unreasonable thing to expect
link |
in a psychedelic journey.
link |
And in the context of your laboratory model,
link |
which I think is a great one,
link |
that experience would be just as valid
link |
as me going into the experience of some of the deep friction
link |
that I might have with a family member
link |
over my entire lifespan.
link |
And yet the export from that,
link |
those two vastly different experiences
link |
is one of feeling a better relationship
link |
to the world and to oneself.
link |
So what does this tell us about-
link |
Like how can the pen and the processing
link |
your childhood trauma both lead to?
link |
So what does this, I mean, at that level,
link |
it raises this question like, first of all, how, why,
link |
I mean, or just what are your thoughts on that?
link |
So this is definitely in the,
link |
this is in the terrain we're figuring out, you know?
link |
So there's no, educated speculation
link |
is the best I can provide.
link |
But I think the best, the most,
link |
I think the common denominator
link |
are persisting changes in self-representation.
link |
Okay, tell me more about self-representation.
link |
That's the way one holds the sense of self,
link |
the fundamental relationship of a person in the world.
link |
I mentioned earlier that these experience
link |
seems to alter the models we hold of reality.
link |
And I think that the self is the biggest model,
link |
that I am a thing that's separate from other things.
link |
And that's, I am defined by certain,
link |
I have a certain personality and I'm a smoker
link |
that's having a hard time quitting,
link |
or I'm a depressed person that, you know,
link |
views myself as a failure and all of these things.
link |
Those are models too.
link |
And I think, I think that change in self-representation
link |
may be an end point for these different experiences.
link |
I mean, maybe the falling in love with the pen,
link |
the whole idea that you're,
link |
especially in contemplation afterwards,
link |
and obviously I'm speculating here,
link |
but the whole idea that you could
link |
have such a deep connection with this random,
link |
obviously random aspect of the universe
link |
could potentially lead to this, you know,
link |
transformed understanding of the self and like,
link |
the pen may be a proxy for the miracle of reality,
link |
in a way that relies nothing on,
link |
on no supernatural thinking, you know,
link |
you can be a hard atheist and take this,
link |
ultimately, oh my God, like that,
link |
just like the pen, this is, you know,
link |
this is amazing, the fact that we exist.
link |
And so there could be an extrapolation chair
link |
and you use the pen, but I think it sounds so similar
link |
to Aldous Huxley's classic description
link |
on the doors of perception of the chair and the drapes.
link |
Like he took 500 milligrams of mescaline.
link |
Is that a high dose of mescaline?
link |
And that's, you know, that's a heroic dose for sure.
link |
And he just going off on the chairiness of the chair,
link |
like this chair is exuding the quality of being a chair.
link |
So this is this expansion of the perceptual bubble,
link |
a narrow, a narrow percept that then grows
link |
within the confines of that narrow percept.
link |
So sense of self is a very interesting phenomenon.
link |
And if we could dissect it a little bit,
link |
there's the somatic sense of self.
link |
So the ability to literally feel the self
link |
into this process we call interoception.
link |
And then there's the title of the self, the I am blank.
link |
And I noticed you said that several times.
link |
It's intriguing to me, I have a good friend.
link |
I don't think I can or should mention his name,
link |
but he had a very long and successful career
link |
within one of the more elite teams
link |
and within the SEAL teams.
link |
And he's a fairly philosophical guy,
link |
also very practical guy,
link |
but he has said many times to me
link |
that the most powerful words in any language are I am,
link |
because whatever follows that,
link |
tends, if you repeat it enough,
link |
tends to have this kind of feedback effect
link |
on how you are in the world.
link |
And the first pass, it sounded to me a little bit
link |
like kind of like internet psychology type thing,
link |
like the secret or something to say,
link |
which frankly I'm just not particularly.
link |
Yeah, so if you kind of like the whole fake it
link |
like I don't actually subscribe to any of that.
link |
But in dissecting that a little bit further with him,
link |
I came to realize that these words I am are very powerful.
link |
I don't think you reprogram your brain just by saying them,
link |
but how one defines themselves internally,
link |
not just to other people,
link |
but how one psychologically and by default
link |
defines themselves, I think is a very powerful,
link |
like and depressed people,
link |
as well as happy people seem to define themselves
link |
in terms of these categories of emotional states.
link |
So I think it's so interesting that letting go
link |
and going into this perceptual bubble,
link |
which is facilitated by obviously a really wonderful team
link |
of therapists, but also the serotonergic agent
link |
allows us to potentially reshape the perception of self.
link |
That's a tremendous feat of neuroplasticity.
link |
Right, and I think certainly more work needs to be done.
link |
This is the horizon.
link |
And I should credit Chris Lethaby, a philosopher
link |
in Australia who has a forthcoming book.
link |
It might be out right about now or soon,
link |
within the coming months, Psychedelics and Philosophy.
link |
That's the title of the book.
link |
It might be Psychedelic Philosophy.
link |
It's really close.
link |
Chris Lethaby, we'll put a link to it.
link |
Right, and so his conclusion in this,
link |
it's a really great book and he really plays with the idea.
link |
It's like psychedelic experiences come along
link |
with a lot of supernatural stuff, experience.
link |
It can certainly go along with that,
link |
but the idea is like, can these experiences
link |
and including those therapeutic effects
link |
be explained from a naturalist point of view?
link |
And his conclusion is that the changes
link |
in self-representation may be the commonality.
link |
Now that could go along with plant spirits
link |
and the Buddha and chakras and whatever your model,
link |
you know, system in Jesus, all of that,
link |
but it could also be completely devoid
link |
of any supernatural, any religious.
link |
And we do, in fact, see all of these varieties.
link |
So I think there's something about this change
link |
There seems to be something on the identity level,
link |
both with, I think, of the work we did
link |
with cancer patients who had substantial depression
link |
and anxiety because of their cancer,
link |
and also our work with people
link |
trying to quit cigarette smoking.
link |
I mean, there's this real,
link |
there seems to be, when it really works,
link |
this change in how people view themselves,
link |
like with smoking, like really stepping out of this model,
link |
like I'm a smoker, it's tough to quit smoking cigarettes,
link |
I can't do it, I failed a bunch of times.
link |
I remember one participant during the session,
link |
but he held onto this afterwards, said,
link |
my God, it's like, I can really just decide,
link |
like flicking off a bucket, I can decide not to smoke.
link |
And it's, I call these duh experiences with psychedelics
link |
because people often, like in the cancer study,
link |
they say, I'm causing most of my own suffering.
link |
Like I can follow my appointments, I can do everything,
link |
but I can still plan for the vacation,
link |
I'm not getting outside in the sunshine,
link |
I'm not playing with my grandkids, I'm choosing to do that.
link |
And it's like, they told themselves that before,
link |
and the smoker has told themselves a million times,
link |
I can, so it sounds, when it comes out of their mouths,
link |
and folks will say, this is part of the ineffability
link |
of a psychedelic experience, folks say,
link |
I know this sounds like bullshit, and this sounds like,
link |
but my God, I could just decide.
link |
Like, they're feeling this gravity of agency,
link |
which I think is interesting,
link |
because regardless of the debates
link |
on the reality of free will,
link |
I think the philosophy of that,
link |
whether it's ultimately free will, like pure agency,
link |
if that exists, which I'm skeptical of,
link |
or just the idea that clearly we have a sense of agency,
link |
there's something there,
link |
whether it's the sense of agency even,
link |
that is the human being has,
link |
and that seems to be at times fundamentally like supercharged
link |
from a psychedelic experience, this idea like,
link |
I'm just going to make a decision.
link |
Like normally, like you tell a depressed person,
link |
like, don't think of yourself that way,
link |
you're not a failure, look at all the, it's just, yeah,
link |
it's like, and you can actually, in one of these states,
link |
have an experience where you realize like, my God,
link |
just like using MDMA to treat PTSD,
link |
and we're going to be starting work with psilocybin
link |
someone could really reprocess their trauma
link |
in a way that like has lasting effects,
link |
and clearly there's probably something, you know,
link |
reconsolidation of those memories,
link |
they are altered, you know,
link |
very consistent with our understanding
link |
of the way memory works.
link |
So the whole idea, people can actually, in a few hours,
link |
have such a profound experience
link |
that they decide to make these changes in who they are,
link |
There seems to be something like that.
link |
And that's profound.
link |
I mean, I think a few moments ago,
link |
I made some semi-disparaging statements
link |
about things like the secret and affirmations,
link |
and the reason I do that with a nod to the fact
link |
that the people who are putting those ideas forward
link |
are well-intentioned people
link |
is that the neural networks of the brain put language last.
link |
We tell stories, you know, and stories are very powerful,
link |
but I think one of the most cruel aspects
link |
of the whole self-help literature in popular psychology
link |
is this idea that everything you say,
link |
your brain and body hear it.
link |
That's actually a very unkind or even cruel thing
link |
for people who are depressed or anxious to hear,
link |
because if they hear that and believe that,
link |
and I want to be clear, I don't think it's true,
link |
that they think that it's very hard to control thoughts.
link |
Is it very hard to control thoughts?
link |
So if somebody says, you know, I can't,
link |
and then somebody says, well, no,
link |
every time you say you can't,
link |
your brain hears that and it reinforces it,
link |
that's a very treacherous place to live.
link |
And language is powerful, but neural networks, the brain,
link |
and the networks that underlie emotionality and perception
link |
and sense of self, they don't change in response to language.
link |
They change in response to experience.
link |
And it just fundamentally, you need,
link |
there are some prerequisites.
link |
You need certain neuromodulators present,
link |
like serotonin or dopamine.
link |
You need them to be at sufficient levels.
link |
You don't need a drug necessarily to do it.
link |
You could, you know, you give a kid a kitten or a puppy,
link |
their first kitten or puppy,
link |
and the levels of dopamine and serotonin,
link |
I've never measured them,
link |
but we can be pretty sure that they are higher
link |
than baseline and that experience will reshape them, right?
link |
Likewise with an adult in certain circumstances.
link |
So I think I'm fascinated by this idea
link |
that a somatic and a perceptual experience,
link |
but a real experience of the sort that you're describing
link |
is what allows us to reshape our neural circuitry
link |
and to feel differently about ourselves.
link |
And I know there's been really tremendous success
link |
in many individuals of alleviating depression,
link |
of treating trauma with these different compounds.
link |
I want to step from the experience
link |
under the effects of the psychedelic.
link |
So the person there with your team,
link |
they go into this expanded perceptual bubble.
link |
If things go well,
link |
they're able to do that to a really deep degree.
link |
Maybe it's the relive trauma.
link |
Maybe it's the beauty of their ability
link |
to connect to things in the world.
link |
And I want to talk about the transition out of that state
link |
and then the export into life,
link |
because this is really where the power of psychedelics
link |
seems to be in the therapeutic sense
link |
is the ability to learn, truly learn from that experience
link |
so that the learning becomes the default,
link |
that one doesn't have to remind themselves,
link |
oh, I am, you know, they don't have to do an affirmation.
link |
I am a happy person.
link |
I am a happy, you know, I always think of Bart Simpson
link |
like writing on the chalkboard, right?
link |
Didn't work for him.
link |
Doesn't work for this other stuff too.
link |
But so as they transition out of this state,
link |
I know that there's a kind of a heightened,
link |
there's a so-called peak
link |
where everything seems to be kind of cascading in
link |
at such a level that the person just,
link |
they can't really turn it off at that point.
link |
It would be challenging.
link |
And then they start to exit the effects of the drug.
link |
Are those transition zones, are those valuable,
link |
much like is the transition
link |
between a dream and the waking state valuable?
link |
Because you're in a sort of mishmash of altered reality
link |
What do you do to guide people through the,
link |
out the tunnel as they exit the tunnel?
link |
And I have to say,
link |
like this is where we need more experimentation.
link |
Really the clinical model goes back
link |
to literally the late 1950s.
link |
And there's been virtually no experimentation on,
link |
let's say, you know, randomize people to,
link |
we're going to talk more during the latter half
link |
of the session versus not,
link |
versus we have them write an essay
link |
after their session versus not,
link |
versus we have this amount of integration.
link |
What's the discussion?
link |
In your studies, are they writing or talking
link |
as they're doing it?
link |
And it's called very loosey-goosey term integration,
link |
but for us means as they're coming back from the experience
link |
to sort of five, six hours in,
link |
so this is the afternoon,
link |
they've been dosed around nine o'clock,
link |
so this is like four o'clock or so.
link |
Just some initial,
link |
tell us about the experience.
link |
Do you want to not unpacking it totally,
link |
but kind of initially just have a little bit discussion
link |
before they go home.
link |
So there's a little bit of that,
link |
but then that night their homework is to write something.
link |
So it could be, you know, a few bullet points.
link |
It could be, you know, 20 pages
link |
and we get everything, you know, in that range,
link |
but, you know, try not to be self-critical.
link |
It's not great at like, this is just to process.
link |
And for a point of discussion the next day.
link |
So they write something, they come in the next day
link |
for a one to two hour,
link |
depending on the study, integration session.
link |
Basically, let's discuss your experience
link |
and depending on what study it's in,
link |
like what might that mean for your dealing with cancer?
link |
What might that mean for your smoking?
link |
Or becoming a non-smoker?
link |
So you encourage them to simply take it seriously.
link |
And I think this is, again,
link |
is sort of one of the points
link |
that could be the antithesis
link |
of what some just kind of social users use.
link |
I mean, this was written about by Houston Smith,
link |
the scholar of religion,
link |
in terms of these mystical experiences
link |
that can happen from psychedelics
link |
and how a lot of times the attribution
link |
to a drug effect is dismissed.
link |
Like even if one has this, you know,
link |
this sense of being one with the universe
link |
and it totally like shakes their soul, so to speak,
link |
you know, but the next day their friends are like,
link |
ah, dude, you were screwed up.
link |
Too much acid for you, woo.
link |
You know, like, man, next time
link |
you needed to have a few more beers to like bring that down.
link |
You know, like this sort of like, you know,
link |
social, you know, reinforcement
link |
for dismissing the experience.
link |
Oh God, you're talking out of your head, man.
link |
Like, you know, even if it's, you know, good natured,
link |
but it's this dismissal, it's not like, you know,
link |
what you want to do, you know,
link |
is like, tell me more about that.
link |
You know, you were crying at one point,
link |
like in talking about your mom, let's talk about that.
link |
What was that like?
link |
Do you remember that?
link |
Are you doing that follow-up
link |
or they're encouraged to do that in their own life
link |
with the various people in their life?
link |
Both, so we do that explicitly in the follow-up
link |
where we have these discussions.
link |
And I, depending on what the situation is,
link |
you might encourage the person to kind of follow up.
link |
It's really, the basics of it is supportive therapy.
link |
It's non-structured.
link |
It's, you know, use all the, you know, reflective listening
link |
and the sort of the humanistic psychology thing,
link |
you know, unconditional positive regard for the person.
link |
But, you know, I think if, you know,
link |
if someone feels inclined to, you know,
link |
apologize to their sibling about something,
link |
it's like, yeah, go ahead and call them up.
link |
When it, with something big, like a relationship change,
link |
I'd be like, sit on that two weeks.
link |
Don't make any big, don't end any relationship.
link |
Don't quit your job.
link |
Don't make any big-
link |
Do you also tell them not to start any relationships?
link |
I don't remember that ever coming up.
link |
I was just wondering, you know, but it makes sense
link |
Like if they're dating and they're thinking like,
link |
ah, it might be time to take it to the next level.
link |
Should I ask this girl to marry me?
link |
If it did come up, I would say there too.
link |
Why don't you sit on that a week or two
link |
and let your sober mind-
link |
Don't get a puppy.
link |
Certainly don't get four puppies until you're-
link |
I have a question about flashbacks.
link |
You know, one of the kind of things you hear is,
link |
you know, flashbacks and that people,
link |
do people get flashbacks?
link |
And if so, what is the basis of flashbacks?
link |
The on the street lore about this
link |
is that somehow some of the compound gets stored
link |
in body fat tissues and then released later.
link |
Like is that complete nonsense?
link |
No evidence for that.
link |
So probably complete nonsense.
link |
Flashbacks are nonsense or the storage in body fat
link |
is complete nonsense?
link |
The storage in body fat.
link |
So to answer whether flashbacks are complete nonsense,
link |
we have to define it.
link |
So I really think these are multiple constructs
link |
that are going on.
link |
It's not the same thing that fall under that term.
link |
There is a phenomenon that appears real
link |
that's called hallucinogen persisting perceptual disorder.
link |
A certain number of people,
link |
very small number of people percentage wise
link |
who have used psychedelics
link |
will have these persisting perceptual disorders.
link |
Like they'll see halos around things.
link |
They'll see some trails, like, you know,
link |
like the after images following an object in motion.
link |
They'll see distortions in color.
link |
And it'll be like anything else
link |
that's a disorder in the DSM.
link |
It has to be clinically distressing
link |
and it has to be persisting over some number of months.
link |
And so very rare, very mysterious.
link |
Some of the keys to that are amazingly,
link |
it's never been seen in the thousands of participants
link |
either from the older era,
link |
from the late fifties to the early seventies,
link |
people in psychedelic studies with LSD, psilocybin, masculine
link |
and it's never been seen in the modern era.
link |
Again, now with thousands of participants
link |
at a number of centers like ours throughout the world.
link |
So it seems to be something that is
link |
for some reason happening in illicit use.
link |
So that brings in, okay, is there polypharmacology?
link |
You know, like, cause you're drinking during it.
link |
Did you take what you thought you'd do?
link |
Yeah, what's the dose, what's the purity?
link |
But then also what I think is actually even more so
link |
than that what's likely going on
link |
is some sort of very rare neurological susceptibility.
link |
There is one paper that is a case series
link |
of individuals reporting these symptoms
link |
and they didn't limit it to just people
link |
who had had hallucinogen history.
link |
And the amazing thing about this is that
link |
a number of people seem to have straight up HPPD diagnosis.
link |
Hallucinogen persisting perceptual disorder
link |
who have never taken a psychedelic.
link |
So it's often prompted by alcohol,
link |
benzodiazepines, cannabis, even tobacco.
link |
And I believe in one individual,
link |
no lifetime history of any,
link |
it wasn't preceded by any of those substance use.
link |
So I think of it like the precipitation exacerbation
link |
of psychotic disorders.
link |
It seems pretty clear through observation
link |
that some people with either predisposition
link |
or active psychotic disease
link |
that this can destabilize them.
link |
The same way that a life experience
link |
can destabilize those person more easily,
link |
I think of it like that there's probably
link |
some pretty rare neurological susceptibility.
link |
We have tended, going this goes back to the 80s,
link |
clinical practice, it ended up in the DSM
link |
focused on hallucinogen because I relate it
link |
to the psychology of xenophobia.
link |
It's always the weird other thing that gets the attribution.
link |
You don't attribute to the thing like,
link |
oh yeah, did you smoke cigarettes?
link |
It's like, well, yeah, but I see lots of people drinking
link |
and not ending up with this.
link |
Like you take a crazy like drug
link |
and you can get people to believe all sorts of crazy stuff.
link |
The biggest example of that is the cathinone derivatives,
link |
so-called bath salts.
link |
And if you remember several years back,
link |
the guy in Florida that ate the other guy's face,
link |
there was a homeless guy that like literally
link |
ate part of someone's face off, like yeah.
link |
It's one of the crazies.
link |
While the person was alive.
link |
While the person was alive.
link |
And all it took was one sheriff's deputy to say,
link |
well, I don't know, but I bet it was
link |
some of that bath salts stuff that's been going on.
link |
The only thing in his system-
link |
Maybe we can set the record straight for people.
link |
What was the, why would he say bath salts?
link |
And was it bath salts?
link |
And so the only thing in his talks was cannabis,
link |
which we all know,
link |
typically people don't eat people's faces off
link |
after they get stuff-
link |
Makes you hungrier, but not that hungry.
link |
So it's just an example of the xenophobia.
link |
Like today, if you get on Google Images
link |
and look up bath salts,
link |
one of the most common images you'll see
link |
is this poor guy's face being eaten off.
link |
So we're just so ready to latch on,
link |
just like the people of another culture
link |
that we don't know of.
link |
It's very easy to assign attribution to a class
link |
that you're very unfamiliar with.
link |
So I think the psychedelics got that attribution
link |
with this very rare neurological susceptibility,
link |
the way that alcohol didn't.
link |
So I think it's not specific to psychedelics,
link |
but we don't really know.
link |
But we look at it,
link |
and our research have never seen an example of it.
link |
But flashbacks can mean a number of other things.
link |
I think the most common thing people experience
link |
is what we call state-dependent learning.
link |
It's returning yourself to a similar context
link |
can bring back the same thoughts
link |
and emotions as the experience.
link |
So someone used mushrooms a week ago.
link |
Now they do something like they smoke some cannabis,
link |
or they take a warm bath,
link |
or they're simply relaxed
link |
and it seems to come out of the blue,
link |
and all of a sudden these,
link |
or they follow a thought trail
link |
that reminds them of their,
link |
and they find themselves in that same experience again.
link |
I think that's more state-dependent learning.
link |
It's not the distressing component that is in,
link |
and it's typically not perceptual.
link |
And then another class
link |
are just sort of perceptual anomalies
link |
within a day or two following the experience,
link |
which is not HPPD.
link |
Most people have joked that this is a free trip.
link |
Like you might see a few trails or halos the day afterwards.
link |
It doesn't last longer than that.
link |
And it doesn't screw you up.
link |
Like, oh yeah, I'm still seeing some trails.
link |
Most people will say.
link |
So it could mean any of those things.
link |
Flashback is, yeah.
link |
No, I appreciate you clarifying that.
link |
I mean, one very common misconception
link |
about neuroplasticity is that it's an event
link |
and it's not an event, it's a process.
link |
And we have no understanding
link |
of the duration of that process.
link |
However, the experience of any drug
link |
or any life experience, right,
link |
even if it's a trauma or a wonderful experience
link |
or a psychedelic experience, doesn't matter,
link |
sets in motion a series of dominoes that fall.
link |
And it's the falling of those dominoes
link |
that we call neuroplasticity.
link |
I mean, the reshaping of neural circuits could take years.
link |
It's the trigger and then there's the actual change.
link |
And so I think that some of what you described
link |
could be literally the reordering of circuitry,
link |
that in some individuals might extend longer than others.
link |
And there is one phenomenon
link |
that I've been told people experience.
link |
And I'm wondering whether or not
link |
any of the patients you've worked with
link |
or people in your trials have reported this.
link |
I've never done ayahuasca,
link |
which I'm assuming has some overlap
link |
with the serotonin system.
link |
Probably hits a variety of systems.
link |
So it's DMT, the active, yeah, it's orally active.
link |
MAO inhibitors that allow the DMT
link |
Right, I should have recalled that, absolutely.
link |
Well, I've never done it,
link |
but a number of people I know that have done ayahuasca
link |
as well as people I know who have done MDMA
link |
report an increased sense of what are sometimes called ASMR,
link |
or these autonomic sensory meridian reflexes, which is,
link |
and it's interesting,
link |
a lot of people have these naturally and they hide these.
link |
It's actually something
link |
that many people keep hidden to themselves.
link |
I'll just ask you if you can do it.
link |
So some people are able to pass a,
link |
like a shiver down their spine
link |
or up their spine consciously.
link |
You know, like you can kind of,
link |
like I'm able to actually pass a shiver up my spine.
link |
I actually learned how to do this when I was a kid
link |
I was standing on a field in sports camp
link |
and I was like, it's really hot here.
link |
And I could actually create like a cooling,
link |
cooled perception.
link |
Some people, I told someone this once
link |
and then this led to a discussion of, oh, I can do it.
link |
But I always hid that from people
link |
because it's actually somewhat pleasurable.
link |
And this is a well-known phenomenon, ASMR.
link |
And some people I know who have taken MDMA therapeutically
link |
or ayahuasca will report that they feel great relief
link |
They can generate these autonomic reflexes
link |
through their body more readily.
link |
Probably, I'm guessing,
link |
because they were able to tune into a kind of deeper sense
link |
Now on the internet, ASMR, if you look it up,
link |
it's a little bit like the bath salt thing,
link |
but in the other direction.
link |
Like there were people that pay,
link |
let's just say there are accounts on YouTube
link |
that have many, many millions of viewers
link |
of people that will whisper to them about,
link |
like for instance, there's people that will go listen to,
link |
it seems to be women in particular,
link |
whispering about like car mechanics or something
link |
or about, or scratching.
link |
So there are certain sounds will do this,
link |
whispering, tapping, finger tapping,
link |
and people experience immense pleasure from it.
link |
It's not really sexual pleasure,
link |
but it's this kind of deep core of the body.
link |
It's the autonomic nervous system
link |
down the corner of the spine.
link |
Probably what a certain number of people
link |
would call Kundalini,
link |
which is another one scientifically who, yeah.
link |
People who do long duration Kundalini breathing sessions,
link |
many of them will report later feeling
link |
as if their perception of self is outside of their head,
link |
that they're literally walking.
link |
It's very uncomfortable for them
link |
that they feel like they're walking around
link |
with their sense of self extended beyond the body.
link |
And this is a clinically described neurologic phenomenon.
link |
Have any studies been done?
link |
I would imagine that person might actually like,
link |
Like that would be an interesting experiment.
link |
That would be the kind of thing my lab
link |
would want to get into.
link |
Yeah, their body could clear,
link |
but their projection wouldn't.
link |
Yeah, the sense of self.
link |
I mean, there's a well-known phenomenon.
link |
It's very, in a few individuals,
link |
very sad where people actually avidly seek out
link |
amputation of their limbs
link |
because their limbs they feel don't belong to their body.
link |
This is a very sad and fortunately very rare,
link |
but also very sad condition.
link |
Anyway, I think that the core of this conversation
link |
that we're drilling into is this notion
link |
of reordering the self.
link |
And it's a relief to me to know that flashbacks
link |
are not something that is kind of, forgive the term,
link |
baked in to the psychedelic experience.
link |
And I suppose that's a good segue
link |
to ask about other sorts of drugs.
link |
Having said baked in,
link |
the temptation is to go to marijuana or cannabis,
link |
but if we could, I'd like to just ask about
link |
some of the more dopaminergic compounds,
link |
in particular MDMA.
link |
My understanding is that MDMA
link |
is a purely synthetic compound,
link |
that you're not going to find MDMA in nature.
link |
DMT was first synthesized in the lab
link |
and then we thought it didn't exist in nature
link |
and then like Richard Schultes
link |
found it like everywhere in South America.
link |
A plan out there might be making MDMA,
link |
but as far as we know now, no.
link |
And we'll talk about DMT and its sources within the body,
link |
but MDMA could exist elsewhere,
link |
but has been synthesized.
link |
And my understanding is that MDMA
link |
leads to very robust increases
link |
in both dopamine and serotonin simultaneously,
link |
which from a neural network's perspective
link |
is a very unusual situation, right?
link |
Normally, because dopamine puts us in this exteroceptive,
link |
looking outside ourselves,
link |
seeking things in the world beyond the skin, our own skin,
link |
and dopamine, excuse me, serotonin tends to focus us inward.
link |
Those are almost mutually exclusive
link |
kind of neurochemical states,
link |
although they're always at different levels.
link |
So why would it be that having this increased dopamine
link |
and increased serotonin would provide an experience
link |
that is beneficial?
link |
And how do you, to the extent that you can describe it,
link |
how do you think that experience differs
link |
from the sorts of experiences that people have on psilocybin
link |
or more serotonergic agents?
link |
Just broadly speaking.
link |
In terms of that balance,
link |
in terms of the effects generally on serotonin and dopamine,
link |
I can only speculate,
link |
like sort of is that dopaminergic component necessary
link |
for, let's say we know that the amygdala
link |
is less reactive under acute effects,
link |
and that may play a role in,
link |
there's less sort of control from the amygdala
link |
in terms of like one's experience of memory.
link |
So it may be part of this sort of reprocessing,
link |
this reconsolidation of these memories in a different way
link |
where the amygdala is not like going crazy,
link |
saying freak out, like fight or flight.
link |
Well, I should have said,
link |
it seems like MDMA is being used clinically anyway,
link |
mainly for trauma, not just for depression.
link |
Although part of that, we really don't know,
link |
and maybe that MDMA is great for depression
link |
and some of these other, and it may be that,
link |
and I'm going to be looking at this soon,
link |
that psilocybin is great for treating PTSD.
link |
A lot of underground therapists say that,
link |
underground psychedelic therapists.
link |
So we don't really know yet which people doing illegal,
link |
but more like a professional therapist would,
link |
it's just illegal.
link |
And this is a kind of a growing thing.
link |
So we don't really know which,
link |
it's speculating, but it may be that MDMA
link |
for a broader number of people is better for trauma
link |
because the chances of having
link |
an extremely challenging experience,
link |
what I call the bad trip, like really freaking out,
link |
is much lower with MDMA.
link |
People can have bad trips,
link |
but they're of a different nature.
link |
It's not sort of like freaking out
link |
because all of reality is sort of shattering
link |
and it's less of this,
link |
it can take so many forms with the classic psychedelics,
link |
but typically you'll hear something like,
link |
I didn't know it was going to be like this,
link |
no matter how hard you tried to prepare them,
link |
that like, this is like, get me off this drive.
link |
You're talking about LSD or psilocybin.
link |
LSD, psilocybin, IY, yeah, yeah.
link |
And just the sense of like, I'm going insane.
link |
This is so far beyond anything I've ever experienced
link |
and it's scaring the shit out of me.
link |
How often does that happen?
link |
I don't have a toe hold on anything,
link |
even that I exist as an entity.
link |
And that can be really, I think, frankly, experientially,
link |
that's kind of the gateway
link |
to both the transcendental mystical experiences,
link |
the sense of unity with all things,
link |
which we know our data suggests
link |
is related to long-term positive outcomes.
link |
Wait, I want to make sure I understand.
link |
So you're saying the bad trip
link |
can be related to the transcendental experience?
link |
Right, I think those are both speculating,
link |
but you have to pass through this sort of like,
link |
reality shattering, including your sense of self.
link |
And one can handle that in one of two ways.
link |
You can either completely surrender to it
link |
or you can try to hang on.
link |
And if you try to hang on,
link |
it's going to be more like a bad trip.
link |
So again, I wish there was more
link |
and hopefully there will be more experimentation.
link |
There's a lot going on here in the black box
link |
in terms of the operant behavior
link |
of how you are within yourself,
link |
choosing to handle, like letting go.
link |
And eventually we'll be able to see this in real time
link |
with brain imaging.
link |
Ah, there they are surrendering to the psychedelic experience.
link |
Here they are trying to hold on, but we're not there yet.
link |
But I think through clinical observation,
link |
it seems pretty clear that something like that is going on.
link |
And certain drugs like DMT, smoke DMT, can be so strong.
link |
The reason I think that can be so extraordinary,
link |
you can compare to the others,
link |
because it like forces people.
link |
Like there is no choice to hang out in it.
link |
I've never done it.
link |
I was told that DMT is like a high-speed locomotive
link |
into the psychedelic experience
link |
and out of the psychedelic experience.
link |
And there's no ability to hold on to the self
link |
while you're in the kind of peak phase.
link |
A lot of people say that,
link |
but Terrence McKenna,
link |
who is kind of the classic bard on DMT effects,
link |
he would say the sense of self was intact,
link |
but everything else, the sensorium and what you navigated,
link |
what you oriented towards,
link |
everything else changed basically.
link |
But it's hard to, when everything's changing,
link |
it's hard to say like, what is the self that's changing?
link |
What is the rest of the world?
link |
Well, and language is totally deficient
link |
to describe experience anyway, much less on a psychedelic.
link |
What is McKenna's background?
link |
Like what is his qualification for being this,
link |
as you referred, this bard of DMT?
link |
And we're talking about Terrence
link |
and there's also the brother Dennis,
link |
whom I know who's-
link |
Can only imagine what Thanksgiving dinner is like
link |
at their house. Terrence passed away
link |
years, a couple of decades ago now,
link |
but he's sort of the one who's known as being a bard
link |
and you can find hundreds, if not thousands of hours of him
link |
on the lecture circuit in the eighties and nineties
link |
But his background was really, oh gosh,
link |
I don't recall what his college degree was in,
link |
but he basically, when he was like 19,
link |
he traveled to South America
link |
and actually on the initial trip with his brother
link |
who was even younger than him, with some other friends
link |
and just in search for a DMT snuff
link |
that they had read about in the Harvard archives
link |
from the work of Schultes from a generation before,
link |
but they had discovered all of these mushrooms growing
link |
that down there, the psilocybin mushrooms,
link |
what they recognized and just took a lot of mushrooms and-
link |
And talked about it.
link |
And Terrence was basically a very intelligent,
link |
very well-read and literature and culture person
link |
that could be, he was sort of the next generation's
link |
Tim Leary, someone who could really speak,
link |
get a little closer to the magnitude
link |
of what the psychedelic experience was like for people.
link |
And he served, like Leary, somewhat of an advocate.
link |
I mean, he would tell people, folks,
link |
you could see the equivalent of a UFO landing
link |
on the White House lawn.
link |
Like it's right there.
link |
It'll take five minutes.
link |
It'll shake everything in your reality.
link |
He would sort of goad people into doing it.
link |
Well, certainly science and clinical medicine
link |
are just but two lenses with which to explore
link |
these things in life.
link |
But part of the reason I ask is I feel like, you know,
link |
in the world of health and fitness,
link |
you have this very extreme condition
link |
of like Arnold Schwarzenegger's and bodybuilders
link |
who have like 2% body fat and they look like,
link |
to most people, they look kind of freakish,
link |
especially now, right?
link |
Oh, especially now.
link |
Made Arnold look like regular.
link |
Back in his day, yeah.
link |
And you have contortionists who can put themselves
link |
into a small box and wrap themselves into a pretzel.
link |
But from those two very extreme subculture practices
link |
that, I don't know anything about contortionism really,
link |
but except that they get really bendy,
link |
but it was a community that included lifestyle practices
link |
and nutritional practices and then drug practices.
link |
From those very extreme subcultures,
link |
there's been an export, which is that, you know,
link |
weight training is healthy, right?
link |
The general public has done that.
link |
Or that yoga is healthy.
link |
So contortionism to yoga, et cetera.
link |
And I feel like a similar thing is happening
link |
in the realm of psychedelics where it was Leary
link |
I mean, like I'm from the Bay Area.
link |
I'm not far from the Menlo Park VA
link |
where One Flew Over the Cuckoos is basically based on, right?
link |
Ken Kesey and those guys.
link |
And you know, there has been an attempt
link |
at creating this movement toward openness about psychedelics
link |
and their positive effects.
link |
This has happened before.
link |
The difference is that now there are people like you
link |
inside the walls of the university
link |
or publishing peer reviewed studies and things of that sort.
link |
The reason I asked about McKenna was, you know,
link |
it seems like McKenna and his brother are,
link |
but you know, just two of many people,
link |
Michael Pollan, et cetera,
link |
who have no real formal training in biology or psychology.
link |
The other guys who were at universities lost their jobs.
link |
They were actually removed from places like Harvard
link |
and other universities for their kind
link |
of cavalier explorations, right?
link |
And now things are kind of returning.
link |
So in the same way that bodybuilding led to weight training
link |
in every corner gym, you know, men, women, and children,
link |
and contortionism is one extreme,
link |
but people generally think that yoga is a pretty
link |
healthy practice, right?
link |
These are matter of degrees, right?
link |
And now here you are inside the walls
link |
of a very highly respected university, Johns Hopkins.
link |
You're on the medical school side of the undergrad.
link |
So in the med school, which is, you know,
link |
a serious health institution.
link |
You know, the question is to me, you know,
link |
what are the valuable exports, right?
link |
And where does the extreme lie?
link |
I mean, clearly there's a problem
link |
with tinkering with reality through pharmacology.
link |
And there's a benefit, it sounds like,
link |
to tinkering with reality through pharmacology.
link |
And what's so striking to me is this,
link |
is the elements of atypical experience,
link |
atypical representation of the self.
link |
So for the average person, right?
link |
Or for kids that are hearing this,
link |
kids that are in their teens, right?
link |
What are the, I want to talk about,
link |
what are the dangers of psychedelics?
link |
This is something you don't hear a lot about these days,
link |
and it's not because I'm anti-psychedelic at all,
link |
but what are the dangers, right?
link |
If a kid or adult has a predisposition toward,
link |
let's say psychotic thinking, right?
link |
Or auditory hallucinations,
link |
or is on the Asperger's side of the autism spectrum,
link |
is there an increased risk of bringing the mind
link |
into these states?
link |
Because it sounds like a very labile situation.
link |
So could we talk a little bit about that?
link |
And are there classes of these different drugs,
link |
whether or not it be MDMA, LSD, or DMT,
link |
that you think are particularly sharp blades
link |
and therefore need to be wielded particularly carefully?
link |
Yeah, so these can be profoundly destabilizing experiences
link |
and ones that ideally are had in a safe container,
link |
sort of where someone, what are the relevant dangers
link |
and what can we do to mitigate those?
link |
So there's two biggies.
link |
One, and I've already mentioned,
link |
it's people with very severe psychiatric illness,
link |
not depression, not anxiety.
link |
I'm talking about psychotic disorders like schizophrenia
link |
or mania as part of bipolar disorder.
link |
So, and diagnostically, this has shifted.
link |
So it's a little hard to say how many people today
link |
with bipolar would have been labeled as schizophrenia
link |
back in the 60s when some of this early research
link |
or just clinical observation was done.
link |
So it seems very clear that folks with a predisposition
link |
or active disease, they could be destabilized.
link |
And so some of the cases that we know of,
link |
I always think of Sid Barrett,
link |
the first singer of Pink Floyd, seems pretty clear,
link |
although I think the family-
link |
I don't know what happened there.
link |
I should be, sorry, Pink Floyd fans.
link |
I've never, the songs are just really long.
link |
Yeah, you're more of a punk guy, right?
link |
So I've got my foot in a lot of worlds,
link |
definitely in part in the Floyd world,
link |
but he basically went crazy early on.
link |
He, it seemed, I don't think his family ever admitted it,
link |
but he developed schizophrenia, classic pattern.
link |
And he was doing a lot of LSD.
link |
But like a lot of these cases,
link |
it looked like he was showing all of the signs
link |
of some hints that he had that susceptibility before.
link |
And often this is hard to disentangle what causes what,
link |
because when do people typically, not always, but develop,
link |
when's the modal period for first break?
link |
It's adolescence, early adulthood, yeah.
link |
And when do people start playing with drugs?
link |
Same exact time period.
link |
So it can be hard to disentangle, but it seems pretty clear.
link |
Now I should also say, there are cases of folks
link |
with schizophrenia that say psychedelics have helped them.
link |
There's anecdotes for everything.
link |
Do the people around those schizophrenics
link |
say it's helped them?
link |
Because when schizophrenics say things, you have to,
link |
I mean, with all due compassion and respect
link |
for schizophrenia, it's a disorder of thinking.
link |
So if they're saying it helped them.
link |
Yeah, can you trust them?
link |
I wouldn't be surprised if there was some kernel of truth
link |
in some cases, but they're just so,
link |
it seems very clear that the other side is there too.
link |
And that there ever is a therapeutic potential there
link |
for those disorders,
link |
that shouldn't be the first thing on our list.
link |
We need to learn a lot more because of the level of risk
link |
before we start doing research to see if,
link |
you know, psilocybin can help with schizophrenia.
link |
Like, I don't think that that may never be the case,
link |
but even if it is, you'd have to be even more cautious
link |
and figure some more things out first
link |
with some of these other disorders.
link |
What about bipolar disorder?
link |
Can it be exacerbated by these compounds?
link |
Yeah, and it may be that sort of the manifestation
link |
of people having prolonged psychiatric issues
link |
after a psychedelic experience, as atypical as that is,
link |
when that happens, it may be that might be more
link |
like a manic episode than a psychotic episode,
link |
and that can be a blurry line.
link |
And it's, the folklore is that, you know,
link |
people go on a trip and they never come back.
link |
That's clearly not the case because, you know,
link |
the drug is metabolized like for anyone else,
link |
and the next day there's not, you know,
link |
it's virtually nothing in the system.
link |
But it reshapes circuitry, I mean.
link |
Right, and there's still, and I really do think, you know,
link |
much like the positive, you know, long-term effects that,
link |
you know, this class of problems is related to like the,
link |
to the experience and the destabilization
link |
that can happen from that experience,
link |
if it's not in the right container.
link |
And again, like these people are susceptible to, you know,
link |
some people with that psychotic predisposition,
link |
they lucky to be born to a great family, stable environment.
link |
They maybe never have a full break or the one that they have
link |
is not nearly as bad as what, you know,
link |
someone who's homeless and is coming from all kinds
link |
of early childhood trauma.
link |
Like the disease is probably going to be far worse, you know.
link |
So, you know, having a psychedelic experience
link |
is like one of those destabilizing experiences, you know.
link |
So, now fortunately it's really easy
link |
to identify those people.
link |
And we even err on the side of extreme caution
link |
by eliminating people with like, say,
link |
a first degree relative.
link |
In some studies, even a second degree relative.
link |
Given the heritability, there's some increased chance
link |
if your brother or your...
link |
So, in an abundance of caution, even eliminating that.
link |
I think eventually if it's approved for use,
link |
FDA use, that we could dial back on that as we learn more.
link |
I think it's, again, overly cautious, which is-
link |
But you're doing an early stage clinical trial.
link |
Yeah, it's the appropriate place
link |
to start at this point in time.
link |
But, you know, if you give a skid
link |
or another structured psychiatric interview
link |
with a clinician sitting down with this person
link |
for a few hours to delve into their history.
link |
And like, you can very reliably determine
link |
if this person has either, you know,
link |
a psychotic disorder or bipolar disorder
link |
or a strong predisposition.
link |
So, that's, you know, that you can screen for that.
link |
And that's how you address that.
link |
The far more likely danger is the bad trip.
link |
Anyone can have this.
link |
The most psychologically healthy person
link |
in the world, probably.
link |
You jack the dose high enough,
link |
and especially in a less than an ideal environment,
link |
you can have a bad trip.
link |
You even get it in an ideal environment like ours,
link |
at a high dose of around 30 milligrams of psilocybin.
link |
After, you know, the best preparation we can provide,
link |
about a third of people will say,
link |
essentially, at some point they have a bad trip, you know.
link |
At some point within the entire journey.
link |
Right, now they could have
link |
one of the most beautiful experiences of their life,
link |
sometimes, like a couple minutes later.
link |
But at some point, they had a sense of strong anxiety,
link |
fear, losing their mind, feeling trapped,
link |
something like that.
link |
Now, typically when people have that in the, you know,
link |
when they're just taking on their own,
link |
like a lot of things, they're fine.
link |
They get through it.
link |
You know, they're more likely to be better off
link |
if they're not having to navigate the streets of Manhattan.
link |
That, you know, or, and if they're with, you know,
link |
other people with friends,
link |
better that those friends aren't also dealing
link |
with their own psychedelic experience,
link |
but probably having some friend of any type,
link |
but whether they're on there is better than having nothing.
link |
So very dependent on context.
link |
And so the tough thing here that,
link |
that in conveying to the public is that
link |
a lot of folks will say,
link |
man, I've taken psychedelics hundreds of times,
link |
and this is like your fear-mongering,
link |
and, you know, there's no, you know,
link |
you're exaggerating the danger there.
link |
So I want to say it is atypical,
link |
but sometimes, and I have a file folder
link |
that grows larger every year of these cases,
link |
either in the medical literature or from the news
link |
of people that freak out on a psychedelic
link |
and they get hurt or they die.
link |
They run into traffic.
link |
They fall from a height,
link |
whether they thought they could fly
link |
or whether they just fell like they,
link |
you can do when you're drunk
link |
or you're intoxicated on any substance.
link |
Sometimes that's unclear.
link |
Or gosh, one of the craziest cases was a kid,
link |
like an 18 year old or so in Oregon several years back
link |
that just, he even wrote about,
link |
I want to take the biggest, he had done mushrooms before.
link |
I want to take a heroic dose,
link |
the biggest dose I've ever taken.
link |
He ended up just totally out of it,
link |
ended up in a neighbor's house.
link |
He was just totally disoriented,
link |
disconnected from reality,
link |
and the cops ended up killing him.
link |
And it was just tragic,
link |
obviously an overuse of force in that case,
link |
because he was actually naked at the time,
link |
this naked like 120 pound, I think,
link |
as a recalled kid that ended up dying.
link |
Well, it's analogous to the reason I use the examples
link |
of like bodybuilding culture.
link |
I mean, people there have taken excessive amounts
link |
of antibiotics and diuretics and died.
link |
Then the contortionist culture,
link |
people have put themselves in a little plexiglass boxes
link |
to do, at the extremes, you're going to get deaths.
link |
And at the extremes,
link |
and one of the extremes is the sheer number of people
link |
with different biological makeups taking the same drug.
link |
And so you can create extremes through numbers.
link |
You can take extreme,
link |
you create extremes through dosage, right?
link |
Well, this is why I'm such a fan of the fact
link |
that people like yourself are doing clinical trials
link |
inside the walls of universities.
link |
Not because I think that psychedelics only have utility
link |
in those environments,
link |
but because it's so important toward creating
link |
their transition to legality
link |
and to understand what legality means
link |
for a compound like this, right?
link |
Right, I mean, again,
link |
we'll stay with the anabolic steroids.
link |
There's now testosterone and estrogen replacement therapy.
link |
Hormone replacement therapy is a common
link |
medically approved practice,
link |
but that's vastly different
link |
than people taking their own stuff or diet
link |
or deciding how much they need to take, right?
link |
Like we said, there's yoga and there's contortionism
link |
in a plexiglass box and thinking of Houdini or something.
link |
So these are a matter of degrees.
link |
Speaking of dosage,
link |
I definitely want to ask you about microdose
link |
versus standard or macrodose.
link |
Tell me that I'm wrong,
link |
but I'm always a little bit,
link |
I sort of, a little,
link |
I'm micro cynical, if you will,
link |
about this term microdose.
link |
And the reason is that many people that I know
link |
who talk about microdosing
link |
are taking dosages of compounds that work at,
link |
that are very powerful at microgram levels.
link |
So the word micro,
link |
I think can be a little bit confusing to people
link |
because microdose implies less than something.
link |
It's a mini dose, right?
link |
And yet some of these compounds
link |
are tremendously powerful at microgram concentrations.
link |
So what it constitutes a microdose
link |
and what is the value of so-called microdosing, if any,
link |
and how does it differ from standard
link |
or what I can only assume is called macrodosing?
link |
And so LSD would be the prototypical example
link |
of that super potent compound.
link |
What size dosage of LSD will lead to hallucinations
link |
and kind of standard?
link |
So sort of the entry point for psychedelic type effects,
link |
which may not involve hallucination.
link |
Actually, most classic psychedelics
link |
don't lead to true hallucinations
link |
as defined in psychiatry.
link |
You know, thinking you're talking to the person
link |
that's not there, seeing the pink elephant.
link |
No, it's more like tracers and things like that.
link |
Right, and some people never get that
link |
even at a very high dose.
link |
So I think more broadly in terms of the psychedelic effects,
link |
which isn't just perceptual,
link |
unless we get into the level of,
link |
as you were alluding to earlier,
link |
a broader definition of perception,
link |
like one's models of the world, the model of the self,
link |
you can consider all of that perception
link |
in terms of truly not sensation, but perception,
link |
the construction of putting together reality.
link |
So yeah, yeah, yeah.
link |
So the psychedelic effects are typically considered
link |
to start for LSD around 100 micrograms.
link |
So a 10th of a milligram is 100 micrograms.
link |
So someone taking 100 micrograms of LSD,
link |
nowadays people might mistakenly refer to that
link |
as a microdose because it's micrograms,
link |
but that's actually a macrodose of LSD.
link |
Right, and that's one of the most common mistakes
link |
or situations that people get into with microdosing
link |
is they intend it to be a microdose,
link |
but it ends up being a full-blown dose.
link |
Now, people do, when they're working with LSD
link |
and they're microdosing, they'll shoot for something
link |
like say 10 milligrams, something in that range,
link |
10, 20 milligrams of LSD.
link |
So a 10th, a fifth, something of kind of
link |
your entry-level psychedelic dose.
link |
People's ability on the street to do this,
link |
say the street as if they're on the corner,
link |
but anyway, like outside of the medical profession
link |
to do this, it varies as you can imagine.
link |
And they're not measuring purity and molarity
link |
or things like that, typically.
link |
And there's ways to do it.
link |
So even if you don't ultimately know the dose
link |
that's in like the blotter paper of acid,
link |
one could at least get a sense of like,
link |
yeah, having one of those tabs is one of those hits
link |
is a psychedelic experience.
link |
They could do something like put it in water,
link |
it's 100% aqueous soluble.
link |
You could make sure it all gets into solution
link |
and then volumetrically measure.
link |
It's gonna be homogeneously distributed
link |
so you can take 1 10th of that volume of water
link |
after it's fully dissolved.
link |
That whatever you started with,
link |
you're gonna have a 10th of that dose.
link |
So the people that are more sophisticated
link |
will do things like that.
link |
And when they're working with mushrooms,
link |
they'll grow a bunch of mushrooms
link |
and then they'll say, put it in a coffee grinder.
link |
I'm not telling people to do this, by the way,
link |
I'm just describing, so don't do this at home,
link |
but like grind it all up so it's homogenous.
link |
Because you can have like,
link |
sort of taking two caps and a stem,
link |
hey, this two caps and a stem that this buddy takes
link |
has a different potency than this two caps and a stem
link |
that the other buddy takes.
link |
So people that are kind of in the know
link |
will grind it all up into a homogenous powder
link |
and they'll pack it into whatever size capsule
link |
and they'll know that.
link |
And again, even if they don't have,
link |
sometimes they might have a buddy
link |
that'll sneak it into the HPLC at their job or whatever,
link |
Not my lab, that's never happened.
link |
Yeah, seriously, never happened.
link |
But they'll at least know that,
link |
hey, I've got a sense of what two capsules do.
link |
I've got a sense of what five capsules do.
link |
But in reality, like that's not what people do.
link |
They'll take a piece of blotter paper
link |
and they get a tiny little pair of scissors,
link |
a Swiss army knife pair of scissors,
link |
and they'll cut up the tab of acid,
link |
which is like a quarter inch square or something.
link |
And they'll cut it up in 10 little pieces.
link |
And it's like, you have no idea
link |
like if it's equally distributed in that media.
link |
Yeah, and we can chuckle about it.
link |
And, but to me, one of the reasons
link |
why this experiment around psychedelics,
link |
this cultural experiment and this legal experiment,
link |
we're seeing this now,
link |
but this was all attempted once before in the 60s and 70s.
link |
The difference was it was all out in the street.
link |
The people in universities who were dabbling with this stuff,
link |
most of them lost their jobs
link |
or were asked to leave through-
link |
They lost their funding for this research minimally
link |
and they had to move on to other topics.
link |
So these are precarious times.
link |
I mean, we're at a key moment where everyone assumes
link |
that this is all going to be legal in a few years.
link |
But I think that that's a premature assumption, frankly.
link |
But, and let's touch on the legality
link |
and some of the things that are happening now.
link |
But what is microdosing psilocybin
link |
versus the sorts of dosages that you described before
link |
in the 10 to 40 milligram range?
link |
I've heard of people taking one or two milligrams
link |
of psilocybin every day as a way to quote, unquote,
link |
and for those listening,
link |
I'm just making air quotes with my fingers,
link |
increase plasticity,
link |
which is a term that I personally loathe
link |
because what does that mean?
link |
I mean, you don't really want your brain to be plastic
link |
because you need to maintain your ability
link |
to make predictions.
link |
Ordering chaos, like prediction.
link |
You need models of the world.
link |
You need heuristics.
link |
Plasticity is never the goal or be it plasticity
link |
is never the goal.
link |
The goal-directed plasticity is the goal, right?
link |
Learning a language, reshaping your experience to a trauma,
link |
altering the perception of self.
link |
But plasticity is a process like-
link |
Yeah, schizophrenia is a lot of plasticity.
link |
Exactly, right, right.
link |
It might even be, there's one theory
link |
that it's extreme ongoing plasticity
link |
and that's why people never create
link |
stable representations of anything.
link |
That's kind of a minority view out there,
link |
but so what's the business with microdosing
link |
and is there any clinical evidence
link |
or peer-reviewed published evidence
link |
that it works, quote unquote,
link |
to make people feel better about anything?
link |
So microdosing is the aim of taking,
link |
again, something around a 10th of what would be
link |
sort of an entry-level psychedelic dose
link |
for whatever compound.
link |
So like, yeah, with psilocybin,
link |
usually people, almost never do people have
link |
like pure psilocybin.
link |
Like one milligram of psilocybin
link |
would be in the range of a microdose.
link |
More likely people are going to have mushrooms.
link |
So like something like a half of a gram of mushroom.
link |
I know people that are doing this every day.
link |
They're doing these every day.
link |
It's like in their, like the same way that I take,
link |
like I'm personally,
link |
I'm not recommending other people do this,
link |
but I take some, I'm a fan of LCL carnitine lately.
link |
I've been kind of experimenting with that a little bit,
link |
which is not a psychedelic compound.
link |
I take it every day.
link |
And they're taking their psilocybin every day.
link |
That's their supplement.
link |
So yeah, the claims are, and there are a number of them,
link |
there's two general ones.
link |
One is sort of acting in place of the ADHD treating drugs.
link |
So the psychomotor stimulants.
link |
So like a better version of Adderall.
link |
The other claims are essentially a better version
link |
of the traditional antidepressants,
link |
a better version of Prozac.
link |
So people are taking both for attention deficit
link |
and for depression.
link |
Yeah, and the aspects of those disorders
link |
that we all have a degree of,
link |
just like amphetamine is going to increase the focus
link |
at the right dose of anyone who takes amphetamine,
link |
pretty much, whether you're ADHD diagnosed or not,
link |
the idea is that there may not be necessarily a clear divide
link |
between the therapeutic need and positive psychology,
link |
even improving mood and focus.
link |
So it's not necessarily correcting ADHD,
link |
but improving focus to supercharge your life.
link |
And so those are the claims.
link |
So none of the peer reviewed studies
link |
that have much credibility,
link |
none of them have shown a benefit.
link |
And they've tried.
link |
Now there's only at this point four or five studies that,
link |
and I think for things like this,
link |
you really need double-blind research because the effects,
link |
I mean, there was one study done in Amsterdam
link |
where people knew they were taking psilocybin truffles,
link |
basically same as mushrooms,
link |
more like the roots of the mycelia.
link |
Well, taking what would be considered a microdose
link |
and then doing some cognitive measures before and after.
link |
And the types of things that,
link |
like a lot of cognitive measures
link |
are measured on the order of reaction time
link |
I mean, and the types of effects you get,
link |
as you could imagine,
link |
are ones that you would totally expect could be there
link |
from either a practice effect or an expectancy effect,
link |
So for something like these claimed,
link |
you can imagine a sort of an increased focus,
link |
enhancement of cognition.
link |
These are gonna be more subtle effects
link |
that you really need a good placebo control for.
link |
The handful of studies that have done that have shown,
link |
they've ranged from finding no effect whatsoever
link |
to just a little bit of impairment,
link |
like impairing someone's ability to do time estimation
link |
and production tasks.
link |
So you want an accurate sense of time,
link |
at least if you're navigating in the real world.
link |
It's different if you're on the couch on a heroic dose
link |
for therapeutic reasons where you're safe,
link |
but if you're crossing the street,
link |
if you're in your work life,
link |
which is the way people are claiming to use it,
link |
it helps them be a better CEO.
link |
Like you want an accurate sense of time.
link |
So if anything, the data suggests
link |
that it makes it a little bit less accurate.
link |
And there's evidence that someone feels a little bit
link |
impaired and they feel a little bit high.
link |
So in terms of, you call that abuse liability in research,
link |
not surprising, you take a little bit of a drug
link |
that can result in some type of a high
link |
and you take a little tiny bit of it,
link |
you'll feel a little bit high.
link |
So, you know, none of the,
link |
so far, no studies have shown any increase in creativity,
link |
enhancement of any form of cognition
link |
or a sustained improvement in mood.
link |
Now, no studies have actually looked
link |
at the system of microdosing
link |
that the aficionados are claiming.
link |
And there's a couple of models out there,
link |
but folks like Paul Stamets and others,
link |
they'll have particular formulas.
link |
They're like, you need to take it one day
link |
and then take so many days off and take it every four days.
link |
And I don't want to get into whose model is what,
link |
but it's always something like that.
link |
Some pattern of use, usually not every day.
link |
And the claim is that it's not just, you know,
link |
sometimes people get benefit that first time
link |
when they take it, but they really say,
link |
you need to be on it for a while.
link |
Like a few weeks in, you may start to notice
link |
through this pattern of using it.
link |
And you're feeling the benefits on those off days,
link |
like the three or two days in between your active doses.
link |
So those are the claims.
link |
Again, we don't know that there's any truth to that working,
link |
but studies have not been done to model that.
link |
So that's a big caveat.
link |
We as a field, I say we as the scientific field,
link |
have not done the studies to really model, you know,
link |
what the real aficionados are claiming, you know,
link |
where the therapeutic benefits come from.
link |
That said, it's almost assuredly
link |
there's a good amount of placebo there.
link |
But the caveat to that is like almost everything
link |
in medicine or therapeutics,
link |
there's, it's going to have some degree of placebo there.
link |
Belief effects are, I have a colleague at Stanford,
link |
Aaliyah Crum, who has published really beautiful work
link |
on belief effects that show that essentially
link |
you give the same milkshake to two people,
link |
you, or two groups of people,
link |
you tell them that one contains a lot of nutrients,
link |
the other is a low calorie shake.
link |
They're, the insulin response.
link |
Varies dramatically between the two or two groups
link |
rather doing equivalent amounts of physical movement.
link |
And you tell one group that it's going to be good for them
link |
and help them lose weight.
link |
And they lose on average eight to 12 pounds more
link |
doing the exact same patterns of movement.
link |
So, and I think that these belief effects boil down
link |
to all sorts of kind of network-wide neuromodulation,
link |
things of that sort.
link |
And then the work at Harvard suggesting
link |
that even if you don't have deception,
link |
you give a placebo and say, this is a sugar pill.
link |
You know, tell them that.
link |
And they could still treat things.
link |
I think irritable bowel was the first thing they looked at.
link |
And so there's a huge, so there's a reality there.
link |
There's a necessity in developing drugs
link |
to make sure it's not only that,
link |
but in the actual practice of medicine,
link |
hopefully what you're always getting
link |
is some underlying direct efficacy
link |
plus the placebo that it enhances at.
link |
Now, it could be that this is, the real question is,
link |
is the microdosing, are those claims 100% placebo
link |
or are they only part placebo and part real,
link |
you know, quote unquote effect.
link |
My bet is, and this is totally based on anecdotes
link |
that I think there is probably a reality
link |
to the antidepressant effects.
link |
I find that more intriguing
link |
because of the suffering with depression.
link |
Even if it's, it wouldn't be as interesting
link |
as I think what we're doing with high dose psilocybin
link |
or psychedelics to treat depression.
link |
It would be, if this is developed and there's a reality,
link |
it would be more like a better, you know,
link |
perhaps a better SSRI, a better Prozac.
link |
Which are similar.
link |
That being said, we need more tools
link |
than fewer tools in the toolbox.
link |
And it shouldn't be that surprise.
link |
Like even before, going back to the tricyclics
link |
and the MAO inhibitors, going back to the fifties,
link |
like augmenting extracellular serotonin
link |
in one way or another, for many people,
link |
leads to a reduction in depressive symptoms.
link |
It wouldn't be that crazy for chronically stimulating
link |
a subtype of serotonin receptor
link |
that you have an antidepressant effect.
link |
So I think if I had put my bets on it,
link |
that if there's anything real, it is in that category.
link |
Although I'm very open to like, maybe there is something
link |
to the creativity, to the, you know, improved cognition,
link |
which covers many domains in and of itself.
link |
But my greatest hopes are on the antidepressant effects.
link |
That said, in the big picture,
link |
I think all of the most interesting thing
link |
about psychedelics are the heroic doses.
link |
I mean, the idea that you can give something
link |
one, two, three times, and you see improvements
link |
in depression months later and in addiction,
link |
you know, over a year later and with these, you know,
link |
people dealing with potentially terminal illness.
link |
I mean, it's, I mean, I'm interested in big effects
link |
and I don't think you're ever going to get
link |
the really big effects.
link |
There's also some concern that almost all of these
link |
common, the more common psychedelics, even counting MDMA,
link |
they have serotonin 2B agonist effects.
link |
And agonizing serotonin 2B has been shown to lead
link |
to heart valve formation problems, morphology issues.
link |
And so this is why Fen-Phen was pulled from the market.
link |
Very effective diet drug.
link |
And it was the portion of that combination
link |
that had the serotonin 2B activity that was the problem.
link |
And so we don't know.
link |
So all of the toxicologists I've ever spoken to about this
link |
would, you know, say, and cardiologists say like,
link |
look, hey, if there was some concern there,
link |
it's not applicable to the whole idea
link |
of you taking something a few times therapeutically
link |
within a lifetime.
link |
But the idea of taking something like, you know,
link |
twice a week for years.
link |
I mean, even the hippies back in the sixties
link |
weren't doing that, right?
link |
Like there's not even these natural,
link |
and even if there was some heart valve disease problem
link |
that stemmed from psychedelic use,
link |
who's connecting those dots?
link |
That's not showing up in the clinical charts
link |
for anyone to figure out.
link |
So there is, and just theoretically,
link |
there is more of a concern.
link |
If something's going to happen with heart valves,
link |
it's more likely that those issues would arise
link |
when someone's taking these things like, yeah,
link |
let's say twice a week for the next five years.
link |
And so I do want to throw that out to people
link |
to really consider.
link |
Right, yeah, it's something I hadn't heard before
link |
that in micro sounds safer,
link |
micro dosing as opposed to heroic or macro dosing.
link |
And yet, unless, and in the context of your lab
link |
and other labs doing similar work,
link |
you've got this people checking blood pressure,
link |
you've got people that are really monitoring
link |
your psychological and physical safety.
link |
When people are out there micro dosing,
link |
it sounds like there's the potential,
link |
either through this serotonin 5-H2B receptor
link |
or other mechanism that maybe there could be
link |
some kind of cumulative negative effects.
link |
And I think that's a really important consideration.
link |
So I'm glad you brought it up.
link |
So the brain is very plastic early in life.
link |
It becomes less plastic as we age,
link |
although it maintains some degree of plasticity
link |
throughout the lifespan.
link |
The year 25, not the year 25,
link |
but rather the age 25 years is sort of an inflection point
link |
where the rigidity of the nervous system
link |
seems to really take off.
link |
Of course, people don't wake up on their 25th birthday
link |
and find they have no neuroplasticity,
link |
whereas the day before they had a lot,
link |
these are, it's plus or minus, whatever it is,
link |
a year or two, but depends on the individual.
link |
However, the young brain is very plastic.
link |
And I could imagine there could be great risks,
link |
who knows, maybe even benefits,
link |
but I'm certainly not thinking about those.
link |
I'm mainly thinking about the risks
link |
for young people taking psychedelics.
link |
Are there any trials looking at people in clinical trials
link |
this would be under the age of 18?
link |
Has anyone explored this in a rigorous way?
link |
Given the potential to exacerbate psychotic symptoms
link |
and bipolar symptoms in some people,
link |
is there heightened risk of that?
link |
What's the story with age of use and psychedelics
link |
for therapeutic purposes?
link |
There's no formal research,
link |
although there's a very high chance that there will be.
link |
And so this is one of the very interesting things
link |
folks may not realize or appreciate
link |
about the FDA approval process.
link |
So the FDA already in multiple instances
link |
has signaled that they want to see those studies before.
link |
Well, not before it's approved necessarily for adults,
link |
but they're going to eventually want to see it.
link |
In fact, so the MAPS group that's developing MDMA for PTSD,
link |
they've already signaled
link |
that that's kind of on the list of interest.
link |
And there's even some incentives in the FDA pathways
link |
for incentivizing folks to explore
link |
that use in young people.
link |
I know in some of the work that I helped with
link |
in pushing psilocybin into phase 2B clinical research,
link |
the FDA said, well, why can't you give this to kids?
link |
It's like, are you aware that depression
link |
is a problem with adolescents?
link |
And it's really interesting
link |
because this FDA is very concerned about pseudospecificity.
link |
The idea that you put out a drug and say,
link |
oh, this is good for men, but not women.
link |
This is good for black folks, but not white folks.
link |
And now sometimes there's a very good rationale for that.
link |
Like when we're talking about hormones
link |
and for a specific, for men versus women.
link |
And there's certain issues,
link |
certain disease say it's like maybe sickle cell anemia
link |
that's more relevant to-
link |
It tastes excellent.
link |
But absent of something that they're very concerned
link |
about saying, oh, this is for this type of person,
link |
but not that type of person.
link |
So age is one of those things.
link |
And also this recognition,
link |
much like the emphasis at NIH with rodent studies
link |
and human studies that like,
link |
you can't just say you're studying men
link |
or just you need a rationale if you're only-
link |
Yeah, to be clear to people, it's a recent switch,
link |
but there's a stipulation in every federally funded grant
link |
that both sexes, we don't refer to gender
link |
in scientific studies, unless it's a study of gender per se.
link |
We refer to sex, meaning biological sex.
link |
So that there's a stipulation that in order to receive
link |
and continue to receive funding,
link |
you have to do studies on both males and females
link |
of that species, including humans.
link |
And at least, even if you're not powered for it,
link |
at least looking at that in exploratory analysis,
link |
like as a grant reviewer, I'm charged with looking at,
link |
did they address like sex
link |
as a biologically relevant variable?
link |
Right, does the same drug have different effects
link |
in males versus females?
link |
Right, and you can at least look at the trends,
link |
even again, if you're underpowered
link |
to look at those between subject type effects.
link |
Which is a great shift that didn't exist
link |
in 10 years ago, sounds like we're both on grants panels.
link |
As study section members, you didn't have to do that.
link |
Now it's an important biological variable.
link |
If you don't look at that,
link |
you essentially won't get your funding.
link |
And age is a similar thing.
link |
So it's the whole idea like,
link |
man, if something could help kids, like what's the rationale?
link |
So I think there's going to be,
link |
now obviously you're going to have in those studies
link |
at least just as much, probably more,
link |
it should be more of a cautionary approach.
link |
It's probably going to be,
link |
would certainly whatever disease states are looked at
link |
are going to have to be probably treatment resistant,
link |
at least as a first step.
link |
Suicidal depression.
link |
Yeah, yeah, and so all of that in the mix,
link |
but hey, you know, if this stuff really helps people,
link |
you know, that are 25 or 30,
link |
like what's the rationale that it won't help a younger person?
link |
You know, and there's these generic kind of concerns
link |
about the developing nervous system
link |
is more susceptible to problem.
link |
I mean, it cuts both ways
link |
because it's also more plastic generally and adaptable
link |
and maybe resilient to injury in certain ways.
link |
But, you know, you hear the rhetoric
link |
about kids, their brains and drugs,
link |
and it's like the developing brain is a special concern.
link |
So yeah, but I think we're going to be
link |
seeing research eventually.
link |
That's interesting.
link |
I went to the high school that is infamous, sadly,
link |
Gunn High School, for having the highest degree,
link |
at least at one point, of suicide rate.
link |
And a very large number of suicides.
link |
This was written up in the Times and elsewhere.
link |
Is it a very academically successful school?
link |
It's a very academically-
link |
So there's a lot of high pressure.
link |
Yeah, very academically demanding school
link |
to the point where they've restricted,
link |
the kids will meet often at 6.30 a.m. or 6 a.m. before school
link |
for study groups and things of that sort.
link |
So some of it may relate to that.
link |
But I have to say that even prior
link |
to all that academic pressure,
link |
when I went there, the pressure wasn't like that.
link |
You know, we had an unusual number of suicides
link |
for whatever reason.
link |
And, you know, and so the idea of kids being prescribed,
link |
and I want to emphasize prescribed, not just using,
link |
but prescribed psychedelics for therapeutic purposes,
link |
I think might make some people balk.
link |
But the idea of kids killing themselves
link |
should also make people balk.
link |
And so I'm relieved to hear that there's going to be
link |
a rational, scientific, safe,
link |
clinical trial-based exploration of this.
link |
I want to ask you about the current status
link |
of these drugs and compounds.
link |
I'm pretty active on social media,
link |
more so on Instagram than on Twitter.
link |
But as I have been on Twitter a little bit more recently,
link |
I've noticed that there's a lot of dialogue
link |
around your account and other people's accounts
link |
around a couple of themes related to psychedelics.
link |
First of all, what is the status of the transition
link |
to legality for prescription purposes?
link |
So medical doctors, MDs,
link |
prescribing it legally for therapeutic purposes.
link |
That's the first question.
link |
The second question is what is the status
link |
as it relates to possession and criminal charges?
link |
So for a long time, I lived in Oakland,
link |
where we were one day told not too long ago,
link |
it is now quote-unquote decriminalized is what I was told.
link |
I double-check people.
link |
But what does that mean?
link |
And then the other issue and the third question,
link |
and we can parse these one by one,
link |
is this issue of, let's just say I'm aware
link |
of a lot of investor dollars going into companies
link |
that are essentially companies focused on psychedelics
link |
as therapeutics or psychedelics generally.
link |
I have to assume that they are investing in anticipation
link |
of a shift in the legal status.
link |
And there's a lot of interest now,
link |
like will psilocybin become a taxable thing
link |
just like marijuana?
link |
So let's start with the question of like,
link |
what is going on in the US legally?
link |
Is it illegal to possess and sell and use these compounds?
link |
My understanding is you can still go to jail
link |
for having these compounds in your possession
link |
Right, so even though the legal landscape
link |
is very different than with cannabis,
link |
there are some similarities.
link |
So one of the similarities is that regardless
link |
of what local municipal, whether city or state
link |
is decriminalized, and that word itself can mean many things.
link |
So the devil, some forms of decriminalization
link |
is close to what folks would call legalization
link |
and others are like pretty weak,
link |
just saying we suggest that the police
link |
make it their lowest law enforcement priority,
link |
that type of thing.
link |
So they can choose.
link |
Turn the other kind of thing.
link |
Right, but even the cops can still choose to.
link |
But someone could get pulled over for one thing searched
link |
and then by definition, if it's illegal and they find it,
link |
then they have to do something about it.
link |
And that'll probably be determined
link |
by both judicial precedent.
link |
Is it going to be thrown out?
link |
And just the local prosecutor,
link |
even before, are they going to choose,
link |
even at post arrest are going to pursue
link |
to really go after those charges,
link |
make those charges stick.
link |
So I think that's still in play
link |
and is going to depend on the municipality.
link |
But like cannabis, federally,
link |
these are all schedule one compounds.
link |
Which means they're illegal.
link |
Which means they're illegal.
link |
The caveat to that, just as has always been the case
link |
since Prop 215 in California with cannabis in 96,
link |
is that, hey, 99% of drug enforcement
link |
is done at the local and state level.
link |
The DEA, which is the federal level of law enforcement,
link |
is a tiny fraction of the arrests.
link |
I mean, most people that are arrested for any drug
link |
are done by local or state level authorities.
link |
But it's still technically illegal.
link |
And so you can, and they could potentially,
link |
and depending on the ambiguity of local law,
link |
even those local officials could charge you
link |
with a federal crime.
link |
And theoretically, the feds could always come in.
link |
Now, although you'll, again, a similar case
link |
with the whole cannabis history,
link |
it was the feds came in in the early days,
link |
but the folks that were basically highly visible.
link |
They went after Tommy Chong for selling bongs.
link |
But I remember him being on The Tonight Show one time,
link |
and I think it was back in the Jay Leno days,
link |
he says, but oh, along the Santa Monica boardwalk,
link |
like every shop sells bongs.
link |
How did you go to prison for a half year for bongs?
link |
It's because he was, and they're-
link |
Because he was famous.
link |
Because he was Tommy Chong.
link |
And there was some high profile cannabis groups
link |
that were distributing it and they were very vocal.
link |
Those were the ones rated by the DEA in the early days,
link |
not the ones kind of keeping to themselves,
link |
keeping it quiet and just doing their thing.
link |
So there's always the potential for selective enforcement.
link |
And so, and like this initiative in Oregon,
link |
which is a state level legalization of psilocybin therapy,
link |
which is really interesting.
link |
Part of their plan for two years is to figure out
link |
how to integrate with the federal level.
link |
And I don't know how that's going to go
link |
because unless you rewrite the Controlled Substances Act,
link |
it seems like the best you're going to get
link |
is a tolerance from the federal government.
link |
And that could be very, hey, you change administrations.
link |
And this is psilocybin by a prescription
link |
from a medical doctor, or you're talking about therapists
link |
who have master's degrees or PhDs or self-appointed coaches
link |
or something like that, administering psilocybin,
link |
but without any oversight.
link |
So this is all getting figured out in the Oregon case.
link |
And again, there's that two-year period of like,
link |
basically we're going to figure this out.
link |
What is it with Oregon?
link |
They're ahead with a lot of, you know, euthanasia.
link |
I love the state of Oregon.
link |
But it's interesting how you have these pockets.
link |
Oregon, Vermont seems to be one.
link |
You know, you've got these kind of pockets
link |
where people are experimental with plant compounds.
link |
They seem to be green, woodsy areas for,
link |
at least in my mind, but there's sort of a culture
link |
around plants and the use of plants as therapeutics.
link |
And combine that with the West,
link |
just more geographically of more of the anti-federalism,
link |
the anti, I mean, the Oregon ranchers from several years ago
link |
that held up the, you know, the whatever wildlife place,
link |
you know, and that was a big showdown with the feds,
link |
you know, and the, you know, just kind of the West
link |
is kind of known for, you know, more of those issues.
link |
So you combine the two,
link |
the hippie dippie, California, Oregon vibe,
link |
with the kind of anti-
link |
Although I would argue it's becoming less hippie dippie
link |
than, although it was,
link |
that there's always been a tradition,
link |
not just in the culture around drugs,
link |
but certainly in academia and in tech, et cetera,
link |
that the West has been a place
link |
where people have tried to throw off traditionalism
link |
and kind of lineage and like who your parents are,
link |
what school you went to, and the past
link |
as a determinant of what's next
link |
and exciting about the future.
link |
Whereas, and here we are an East Coast institution guy
link |
and a West Coast institution guy.
link |
I think that it's this idea of kind of innovation
link |
and the future versus do we stay grounded
link |
in history and tradition.
link |
And of course there are great institutions on both sides.
link |
What's interesting is that Hopkins,
link |
Johns Hopkins Medical School,
link |
I think of as a real like East Coast academic institution.
link |
It is on the East Coast, but here you are
link |
doing these very pioneering and important
link |
and exploratory studies in a,
link |
certainly not a hippie dippie environment.
link |
Very conservative psychiatry department,
link |
even amongst psychiatry departments.
link |
And as a psychologist in a psychiatry department,
link |
psychiatry is certainly more conservative than psychology,
link |
even within academics.
link |
But even amongst psychiatry departments,
link |
it's a very conservative department.
link |
So we've got the law at the federal level.
link |
We've got the law at the state and local level.
link |
And then we've got this question
link |
of whether or not it's going to be physicians.
link |
So MDs, people with PhDs or master's degrees,
link |
or whether or not it will be kind of a free-for-all
link |
And the life coaches.
link |
The life coaches and the general public.
link |
I mean, cannabis, I'm not a pot smoker.
link |
It's never appealed to me.
link |
That's just me and my pharmacology.
link |
But you can buy cannabis most places in the U.S.
link |
without a ton of risk, it seems, right?
link |
Are we going to see a time in which
link |
you can essentially go into a shop
link |
on Abbot Kinney Boulevard in Venice, California?
link |
And right now you can go buy marijuana
link |
if you have a marijuana carta.
link |
That's my understanding.
link |
I see a lot of people going in and out of these stores.
link |
The police certainly have no problem with it.
link |
Is there going to come a time
link |
where people can just go buy psilocybin?
link |
Like they do in Amsterdam and have for a long time.
link |
Do you think that time is coming?
link |
I think so at a certain point.
link |
And I don't know how long.
link |
It's hard to imagine our current level
link |
of drug criminalization holding up for,
link |
and I'm thinking like large spans of time,
link |
like really in a hundred years
link |
are we going to be doing this 500 years?
link |
Like how could that?
link |
It's not going to be sustainable.
link |
But in five years, for instance.
link |
So I don't think so in the United States.
link |
I do think eventually you're going to see something like that
link |
because there's going to be no way.
link |
And I think we're going to,
link |
I hope that we're going to eventually come so strongly.
link |
We're going to move on from this model of criminalizing drugs
link |
that we're really going to focus on regulating drugs
link |
at the right level for that drug.
link |
And I like the word regulation better than legalization.
link |
So, I mean, I could imagine what one day regulation,
link |
smart regulation might mean for psychedelics.
link |
Maybe it could mean that there will be,
link |
whether or not you have a diagnosis of a problem,
link |
it may be that even for personal exploration,
link |
you can do this legally,
link |
but you first have to maybe take a court, get a drive.
link |
And this has been, I'm not the first to say this,
link |
but get equivalent of a driver's license.
link |
You have to go to get some sort of training.
link |
Maybe your first number of experiences
link |
need to be with trained guides who can facilitate it.
link |
And then the public health information
link |
for anyone using this that this is what riskier use is.
link |
All use is going to have risk.
link |
This is what riskier use is.
link |
This is less risky use.
link |
These are the factors.
link |
So I think eventually we're going to be getting for any,
link |
but I would say the same thing for like methamphetamine
link |
and heroin and cocaine, like all of these drugs,
link |
it's hard to imagine the current approach
link |
of just feeding a black market
link |
and really exacerbating a lot of the harms from drugs.
link |
You know, that happens under the current model.
link |
It's hard to imagine that maintaining.
link |
That isn't to say, I think it should be
link |
in all of the 7-Elevens, you know,
link |
sold to kids at the other extreme.
link |
But I do think it's probably not going to be soon
link |
in the United States.
link |
I do want to make the major point that
link |
even if psychedelics had never been made illegal,
link |
I think the trajectory of the medical research right now
link |
would still need to happen.
link |
If it's effective as an antidepressant,
link |
like we need it to be, you know,
link |
there's all the evidence suggesting that
link |
whatever disorder we're talking about,
link |
the efficacy is going to be increased
link |
and the risks are going to be mitigated drastically
link |
in the types of models we're talking about
link |
with the screening, with the preparation,
link |
with the integration of cognitive behavioral therapy
link |
depending on the disorder you're treating,
link |
with the integration afterwards with the professionals.
link |
So we would be doing it anyway.
link |
So it's not like this versus that.
link |
So I don't see it as a race between the decriminalization
link |
or legalization of these compounds
link |
versus their medical development.
link |
Some people who are psychedelic fans
link |
get all into a bunch about the medical development.
link |
They say, you guys want to like, you want to keep it only
link |
for your medical research and I retire
link |
and you want to be in control of it as academics.
link |
And my take is I didn't make it illegal for anyone.
link |
We're only moving the needle in one direction.
link |
And again, even if it was already illegal,
link |
and I've done plenty of survey research of people reporting,
link |
they took mushrooms for fun or for personal exploration.
link |
And they said, my God, why am I smoking?
link |
And they quit smoking 20 years because of it,
link |
or it's helped with their depression,
link |
or it's helped with them overcoming alcoholism
link |
or these different.
link |
Sometimes that happens out of the blue
link |
when people use psychedelics.
link |
Nonetheless, obviously the efficacy rates
link |
are going to be higher when you bring it
link |
into these medical models and it's going to be safer.
link |
So we need to be pushing that.
link |
And my best guess is that MDMA is going to be approved
link |
within the next three years.
link |
And for prescription by a physician.
link |
Yes, and not just take two and call me in the morning,
link |
but in the clinics,
link |
the way that those PTSD trials are being run.
link |
So the MDMA would be approved for PTSD
link |
and every disorder needs to be looked at separately.
link |
And it's going to only be approved for those things.
link |
Now, there's going to be questions about-
link |
Right, because approved and legalized and regulated are,
link |
you know, now we're getting into the nuance.
link |
I think when people hear it's going to be approved
link |
in two years, they think that they'll be able to buy
link |
and sell and use MDMA without legal consequences.
link |
And I do not think that's going to be the situation.
link |
It's not the way it is.
link |
And I will say that I think the quote unquote,
link |
psychedelic community, I mean,
link |
they've been doing what they want to
link |
and will carry on doing what they want to anyway, right?
link |
It's not like the legal status has prevented them
link |
from doing what they're doing.
link |
In fact, unlike Lee Erie and Timothy Leary and Huxley
link |
and, you know, and some of the others that were very vocal
link |
and lost their jobs and some of them even went to jail,
link |
I mean, you've got a lot of public figures now
link |
like McKenna and others who are just basically out there
link |
talking about psychedelics.
link |
Michael Pollan, who is more of a writer,
link |
foodie guy gone psychedelic dabbler, writer guy.
link |
I know he's kind of a polymath,
link |
but you know, the legal status didn't seem to hinder their,
link |
at least online career.
link |
So I don't know, I haven't looked at their bank accounts,
link |
but I'm imagining they're doing just fine, right?
link |
So the fact that the work is happening inside
link |
of big institutions, I think it's important
link |
that you point out, and I'm just trying to underscore
link |
that that's in no way antagonistic
link |
to what people are doing.
link |
It's in support of a different sort of mission,
link |
which is to explore the validity in different contexts
link |
in a really controlled way,
link |
which I really, you know,
link |
I think it's a really important mission.
link |
I want to make sure that I ask you
link |
about the other really important mission
link |
that you're involved in with respect to psychedelics,
link |
which is not about depression per se,
link |
but is about a neurologic injury or head injury.
link |
I realize it's early days for this,
link |
but I think there's a lot of concussion out there, sadly.
link |
There's a lot of TBI, traumatic brain injury,
link |
not just from sports.
link |
I think people sometimes forget that it's not,
link |
the major source of traumatic head injury is not football,
link |
it's not hockey, it's not boxing,
link |
it's not any of that stuff.
link |
It's construction workers and it's people,
link |
I mean, if you've ever seen the helmets
link |
that construction workers wear, I mean-
link |
The jackhammer, oh my God.
link |
The jackhammer that- How could that not be just like-
link |
Yeah, I have a colleague that works on this
link |
in bioengineering and when you look at the,
link |
you know, we always think sports,
link |
but there are many people who make a living
link |
in a way that is over time is detrimental to their brain
link |
and they don't have the option
link |
of just not being a professional athlete
link |
or something of that sort.
link |
And if they're not doing the construction,
link |
someone else needs to do it.
link |
Someone else has to do it, right.
link |
And we forget, for some reason,
link |
and I too, it didn't occur to me until I heard it,
link |
like the people who are doing construction
link |
and then of course with bike accidents
link |
and falls and things like that as well.
link |
Military, you know?
link |
Military, absolutely.
link |
So what do you think is the potential for these compounds,
link |
particularly psilocybin, but other compounds as well
link |
for the treatment and possible even reversal
link |
of neurological injuries and what sorts of things
link |
are you excited to do in that realm?
link |
Yeah, so this is definitely on the more exploratory end.
link |
So it's based upon, so, you know,
link |
this is sort of beyond the improvement
link |
of psychiatric disorders like depression
link |
or depression and anxiety associated
link |
with a terminal illness or a substance use disorder,
link |
So those are sort of psychiatric disorders.
link |
So this is, you know, there are anecdotes of people saying
link |
that psychedelics have helped heal their brain.
link |
You know, they've been in one of these situations
link |
like in sports, a sport where there's repetitive head impact
link |
and they're claiming that using psychedelics
link |
has actually improved their cognitive function,
link |
for example, improved their memory,
link |
including it improved their mood,
link |
but it's kind of more of the cognitive function,
link |
things like memory are...
link |
Now, the caveat is if you've successfully improved
link |
someone's depression,
link |
you can get some cognitive improvement too,
link |
but that's a more of a weaker, more indirect effect.
link |
But if you take these anecdotes and you combine it
link |
way across orders of analysis to the rodent research
link |
from several labs like David Olson, Brian Roth,
link |
these folks that have shown different forms
link |
of neuroplasticity unfolding after,
link |
like sort of post acutely.
link |
So after in the days following the administration
link |
of psychedelic compounds,
link |
a variety of psychedelic compounds
link |
and even some non psychedelic structural analogs
link |
that you see these different forms of neuroplasticity.
link |
So the growth of dendrites and new connections
link |
being formed with different neurons.
link |
So those effects may be at play
link |
and they improve in the psychiatric treatments
link |
that we're dealing with.
link |
We don't know that, it seems like a decent guess,
link |
and we're going to be figuring out whether that's the case.
link |
But another potential that that sets up
link |
is that maybe that's what's going on
link |
with these claims of improvements
link |
from neurological issues,
link |
that there's actually a repair of the brain
link |
from injuries underlying things that,
link |
situations where there's repetitive head impact,
link |
perhaps there's a potential for helping folks recover
link |
from stroke and disorders like that.
link |
There's a wide variety of disorders.
link |
Now it's a bit of magic and a bit of like,
link |
it's something that the enthusiasts
link |
kind of can do some hand waving
link |
and claim that this is already known.
link |
It is more exploratory.
link |
But what I'm hoping to do is some work with retired athletes
link |
who have been exposed by the nature of their sport,
link |
for example, NNA athletes in the UFC
link |
who have been exposed to repetitive head impacts
link |
like a lot of sports, a lot of sports expose people to,
link |
and who are retired from the sport
link |
and are suffering from say depression,
link |
which can impart result from those types
link |
of that history of head impact.
link |
See if we can fix the depression,
link |
but then also as a cherry on top
link |
and a more exploratory aim,
link |
see if we can have evidence of improvement
link |
in cognitive function and associate like using MRI,
link |
see if it affects gray matter over time,
link |
these types of things to see if they're actually
link |
some evidence of this improved,
link |
like this more direct repair of the brain.
link |
But again, it is very sort of like,
link |
we've got some rodent data,
link |
we've got some human anecdotes.
link |
We will acknowledge it's early days
link |
and we look forward to seeing the data.
link |
I appreciate how cautious you are,
link |
and tentative you are, you're not drawing any conclusions.
link |
I think from a purely logical
link |
and somewhat mechanistic perspective,
link |
I mean, if we assume that lack of ability to focus
link |
or degradation and mood is the reflection of neurons
link |
in the brain, I think we can agree on that.
link |
Some dialogue between neurons of the brain
link |
and that what needs to be changed
link |
is the nature of that dialogue, aka neuroplasticity.
link |
We know that reordering of neural circuitry require,
link |
in the adult, requires these things like intense focus
link |
followed by rest, et cetera.
link |
But the basis for that, like beneath focus is the mechanism,
link |
is a mechanism rather,
link |
beneath the bin that we call deep rest is a mechanism
link |
and those mechanisms are neuromodulator driven.
link |
So to me, I'm not reviewing your grant,
link |
but from a rational perspective,
link |
it seems that drugs that increase certain neuromodulators,
link |
like serotonin or dopamine in a controlled way,
link |
and then coupling that with learning of some sort,
link |
sensory input of some sort,
link |
it makes sense that that would lead to,
link |
could, I should say, lead to reordering of circuitry
link |
that would allow for better thinking, better mood,
link |
many of the same things that you've observed
link |
in the clinical trials for depression.
link |
So the rationale is really strong.
link |
I think that's a very exciting area.
link |
I get asked all the time about TBI and traumatic brain injury
link |
and right now, it's kind of,
link |
there isn't a whole lot that people can do
link |
and people are dabbling in the space of hyperbaric chambers
link |
and people will do sauna and breath work
link |
and people are kind of clipping at the margins
link |
of what really is a problem that resides deep to the skull.
link |
So I think I just want to applaud the exploration.
link |
I think it's great provided that exploration
link |
is being done in a controlled way.
link |
It sounds like that's what you're doing with the UFC.
link |
Yeah, so that's, they were really gracious
link |
and had myself and a few of my colleagues
link |
out to their headquarters in Vegas.
link |
Impressive place, right?
link |
There's a dialogue going on there.
link |
I'm hopeful that there's going to be some work with them,
link |
but it's in process now in terms of exploring it.
link |
There's a real interest and I'm just really impressed
link |
by the organization and their commitment to athlete health
link |
We have a colleague out there,
link |
we're doing a little bit of work with them, Duncan French,
link |
who's a serious academic in his own right.
link |
And I think when people hear UFC,
link |
they just think about the octagon and fighting
link |
and pay-per-view fights and things,
link |
but in talking with them,
link |
and I'm sure you've had these discussions as well,
link |
they are very much interested in the health
link |
and longevity of their fighters.
link |
They are also interested in the health and longevity
link |
of their fighters being a template
link |
for how to treat traumatic brain injury
link |
and improve human performance in other sports
link |
and in the general public.
link |
And I think it's not an image of the UFC
link |
that commonly comes to mind
link |
because they haven't been particularly verbal
link |
about it in the press,
link |
but I think it's great they're bringing in academics.
link |
I mean, geeks like us going out
link |
to the UFC Performance Center.
link |
I mean, you do MMA,
link |
but I'm basically just a geek walking through the place.
link |
But the fact that they're interested in talking
link |
to scientists is really,
link |
but a point in their favor.
link |
Along the lines of other groups and individuals
link |
that have impacted the space that you're working in
link |
in this pioneering of the psychedelic space,
link |
I think if someone submitted a grant saying,
link |
I want to study how psilocybin impacts human depression,
link |
I'm guessing having worked on these panels before
link |
that the response might've been closer to,
link |
well, we need to do a lot of studies in rodents
link |
and a lot of studies in primates.
link |
And then maybe, just maybe we could explore these drugs
link |
because the National Institutes of Health
link |
actually has a whole institute devoted to addiction, right?
link |
Of exploring compounds only
link |
in terms of their negative effects, right?
link |
Which is where I've gotten all of my NIH funding.
link |
Which is so interesting, right?
link |
And it's a super important institute.
link |
I want to be clear.
link |
There are amazing people there.
link |
But philanthropy and foundations have been very important
link |
in supporting pioneering research.
link |
And so maybe we just talk a little bit about that.
link |
So your lab receives funding from taxpayer dollars
link |
through the National Institutes of Health.
link |
Is that mainly where your funding comes from?
link |
So our group has gotten some funding
link |
from like say the National Institute on Drug Abuse, NIDA.
link |
For some, a small subset of the psychedelic work,
link |
but only for some work geared towards understanding
link |
these things as drugs of abuse.
link |
Of course, when you do a study though,
link |
Show us how they're, explore how they're bad.
link |
Right, but when you're doing that,
link |
you can explore like the good stuff too, you know?
link |
But the large majority of the work
link |
and the most interesting work
link |
has been funded by philanthropy.
link |
Private philanthropy.
link |
So I still have some grant support from NIDA
link |
outside of psychedelics.
link |
I'm shifting more and more of my time
link |
towards focusing only on psychedelics.
link |
And in fact, us getting the center level funding
link |
from some really big picture philanthropists
link |
like helped me to start to make that transition.
link |
But groups like the Hefta Research Organization,
link |
Dennis McKenna, which is one of the founding members,
link |
brother of Terrence McKenna,
link |
who's by the way, an ethnobotanist,
link |
that's what his PhD is in.
link |
What does that mean, ethnobotanist?
link |
Studying the, essentially the anthropology
link |
of psychoactive plant use.
link |
You can get a degree in that?
link |
You know, hanging out with cultures
link |
and studying their use of these compounds
link |
in the traditional ways.
link |
There's, that degree exists at Johns Hopkins?
link |
I don't think that degree exists at Hopkins,
link |
but I mean, the kind of the most,
link |
and you know, as you'll, as you know from academia,
link |
I'm not, you know, sometimes folks,
link |
I'm not sure how many people's PhD
link |
is actually in ethnobotany
link |
or is actually in something else.
link |
But the real focus is like,
link |
my degree is general experimental psychology.
link |
10,000 kids out there just decided
link |
they're going to major in ethnobotany.
link |
I mean, one of the pioneers of the psychedelic area
link |
before Leary and before,
link |
and actually he was late even for the human researchers,
link |
like folks like Humphrey Osmond and Abraham Hoffer
link |
and Sidney Cohen were earlier.
link |
But even before those folks,
link |
Richard Schultes at Harvard,
link |
he was, I mentioned him earlier in the conversation,
link |
discovered all of this,
link |
these various tribes using ayahuasca or yage,
link |
a different name for the same thing,
link |
throughout South America
link |
and these DMT containing snuffs and all of this.
link |
So, you know, that was, you know, ethnobotany,
link |
this kind of intersection of anthropology
link |
and these psychoactive plant compounds.
link |
So the Hefta Research Institute,
link |
which Dennis is a founding and active member of,
link |
they have funded a lot of our early work.
link |
There's also an organization called the Beckley Institute
link |
based in England that Lady Amanda Fielding
link |
has been the head of that has,
link |
they provided the first funding for our psilocybin
link |
smoking cessation research and the Hefta came in
link |
and provided subsequent funding.
link |
But it's, and then there are other groups,
link |
a Council on Spiritual Practices,
link |
a great guy named Bob Jesse,
link |
funded some of the original work at Hopkins,
link |
looking at the nature of mystical experience
link |
outside of treating disease states or disorders,
link |
but just understanding these,
link |
like people take these compounds
link |
and astonishingly, you know, frequently,
link |
we'll say that was the most important
link |
everything I've ever experienced.
link |
It's like, what the hell is that?
link |
Yeah, I had someone mention recently,
link |
I think this might surprise people a little bit,
link |
certainly surprised me.
link |
I had a friend who adores his children.
link |
He's got three children.
link |
He adores his children.
link |
Happy marriage and great, great father.
link |
They're both great parents.
link |
And he told me that as part of a clinical trial,
link |
he had a DMT experience,
link |
that he claims, he said,
link |
I'd love to tell you that the birth of my children
link |
was as profound, but that was a more profound experience
link |
than the birth of my children.
link |
Any one of them and all of them combined.
link |
And I was like, wow, now I've never done DMT,
link |
but I was like, wow, that's a pretty strong statement.
link |
Now he did it in the context of one of these,
link |
you know, clinical explorations.
link |
I assume that was part of a legal clinical trial,
link |
but the, I mean, that's saying something.
link |
It's saying something.
link |
I mean, he's a very rational, very grounded guy, otherwise.
link |
But so philanthropy, foundations, and then-
link |
Most recently, and so I just, I can't,
link |
cause I can't skip it.
link |
Our center level funding-
link |
Oh yeah, you can't skip magic.
link |
Which changed a year and a half.
link |
That's like, we, I mean, the Hefner group,
link |
the Beckley group, I mean, these are wonderful.
link |
I mean, these are people that have been holding
link |
the flame alive during the darkest hours, like the,
link |
same thing with MD, with the MAPS organization
link |
more on the MDMA side,
link |
like holding that candle during the darkest years.
link |
That, you know, so we've, but, you know,
link |
smaller organizations connected to smaller,
link |
but growing over time, you know, pockets of wealth.
link |
But, you know, we basically limped on,
link |
limped along on a wing and a prayer until recently,
link |
when we got the $17 million gift
link |
so that we could create a nominal center.
link |
And as you know, basically to the university,
link |
that means you get a certain number of dollars,
link |
and a lot of them, you can call yourself a center.
link |
You know, it's a capital investment, you know,
link |
staff, you know, equipment, salary support,
link |
which has always been the huge thing for us.
link |
But the $17 million gift,
link |
which was split between the Cohen Foundation,
link |
so Steven and Alexandra Cohen,
link |
they covered half of it.
link |
And the other half, the Tim Ferriss collaborative,
link |
basically Tim and a few friends,
link |
ponied up that the, you know,
link |
divided the rest of that half of that $17 million gift
link |
and came together to just, I mean,
link |
it just, it's completely transformed our,
link |
the work that we've done and our ability to,
link |
like to fully delve into this area and not worry that like,
link |
oh, if I focus on this,
link |
rather than putting another three NIDA grants
link |
on some other topic that may or may not get funded,
link |
like if I focus too much on the psychedelics,
link |
am I putting my career at jeopardy?
link |
So you're now not only a tenured professor,
link |
you're also a full endowed-
link |
Right, so that came-
link |
By the way, when you say somebody
link |
is a fully endowed professor,
link |
I want to be very clear what that means.
link |
That means that there's funding-
link |
Well, it might mean all of the above,
link |
but no, I'm just kidding.
link |
I have no knowledge of your particular situation,
link |
but you probably do.
link |
But sure, what we're essentially saying is that funding,
link |
which does not change somebody's salary level,
link |
I just want to be clear,
link |
because I think the general public isn't,
link |
there's no reason why they would understand
link |
all the nuts and bolts of how this works.
link |
Academia is weird.
link |
Yeah, academia is weird
link |
because we're not talking about increasing,
link |
we're not talking about an endowment
link |
or philanthropy that went to increase Matt's salary.
link |
That's something that's set at the university level.
link |
It's always been said,
link |
and it at least is still true now,
link |
which is that nobody goes into science for the money,
link |
at least not at the academic level.
link |
but allows people to devote more of their time and energy
link |
to these exploratory realms like psychedelic research
link |
or in the case of my lab,
link |
the work that we're doing with David Spiegel's lab
link |
on respiration, breath work,
link |
and hypnosis for modulating brain states.
link |
These are not typically areas
link |
that the National Institutes of Health
link |
and other major organizations
link |
have institutions set up to support.
link |
Now there is an exciting initiative,
link |
which is the NCCIH, which is Complementary Health.
link |
And now we're not just throwing out acronyms
link |
just to bat back and forth acronyms,
link |
but I think what we're seeing now
link |
is a movement toward science and scientists and clinicians
link |
and the general public and philanthropy
link |
being engaged in this dialogue,
link |
which says, okay, there are problems in the world,
link |
depression, head trauma, psychological trauma, PTSD, ADHD.
link |
These problems clearly exist.
link |
The solutions are going to involve behaviors
link |
that are going to involve nutrition,
link |
supplementation, social connection.
link |
However, there are drugs,
link |
there are compounds that can change the brain
link |
and allow the brain to change its circuitry
link |
through experience
link |
and psychedelics are one of several others,
link |
but one of the powerful levers, it sounds like.
link |
And I just want to say that I think
link |
the reason I reached out to you
link |
and I'm so excited to sit down and chat with you
link |
is because I see very few people
link |
inside the halls of academia
link |
who have thrown their arms
link |
around this issue of psychedelics in a way
link |
and gone through the trouble
link |
of trying to find the funding to get it done,
link |
gone through the trouble of trying to set up clinical trials.
link |
I know what's involved in doing this.
link |
It's so complicated.
link |
It's so time-consuming and painstaking
link |
and you've made real progress.
link |
I mean, you guys are publishing papers.
link |
There's a new dialogue emerging
link |
that isn't just books on bookshelves
link |
and psychonaut gurus on the internet
link |
who also play an important role,
link |
but you're really moving this field forward.
link |
And I know there are others as well.
link |
There are colleagues in England and others as well.
link |
We acknowledge them, but I just want to say personally
link |
that I'm inspired and impressed
link |
by the way that you've gone about this
link |
and the level of rigor.
link |
I mean, when I ask you a question about serotonin,
link |
most people will just kind of kick back to me.
link |
Well, yeah, you got receptors and you got a ligand,
link |
but I mean, it's clear to me that you care about the details
link |
and that you care about the future of this area
link |
and you also really care about these patients
link |
and these individuals.
link |
So I know I'm speaking on behalf of a ton of people now
link |
and in the future that don't even know
link |
what they're going to receive as a consequence of this.
link |
I just want to voice a real sincere thank you
link |
It's like your lab and your work matters
link |
and that's a really special and unique thing.
link |
I appreciate that.
link |
I had a good colleague, in fact,
link |
shared some grant support under the multi-PI system
link |
years ago and she actually took a job at NIH
link |
as a review officer and I remember her telling me,
link |
and she actually left when she had multiple RO1s,
link |
so it's like she didn't move to it.
link |
The RO1s are kind of the bread and butter,
link |
big grants that every card carrying,
link |
it's a mark of respect in our community
link |
to have one or several of these, yeah.
link |
Yeah, yeah, and it's like you eat what you kill in academia,
link |
it gets to what we're talking about later.
link |
It's like you don't make more money by pulling more grants,
link |
but you're able to pay the salary that,
link |
like the university doesn't pay you your salary,
link |
it goes through them.
link |
You're just able to do more work.
link |
Yeah, and you're able to,
link |
and if you don't pull in the grants to cover your salary,
link |
your job can come to an end.
link |
Even if you're tenured at a place like Hopkins,
link |
they can do tricks like slowly lower your salary over these.
link |
Or they just take away your space.
link |
Yeah, they put you in a closet and give you no support
link |
for trainees and basically make life hell for you.
link |
So you can drive a cab in Baltimore
link |
and call yourself a full professor at Hopkins,
link |
truthfully, but you may have no ability
link |
to get anything done.
link |
But yeah, I remember one of the things
link |
this colleague said, who is successful,
link |
but left on top said,
link |
I really don't know that I'm making a difference
link |
in the world, and she did some great memory research
link |
and connected to drugs, also connected to aging,
link |
but she said, I don't feel the impact
link |
of what I'm doing in the real world.
link |
And it's unfortunately there for a lot of academia.
link |
What we do, it stays in the ivory tower.
link |
The world is a beautiful but messed up place,
link |
and a lot of this doesn't disseminate
link |
and because of the various structures,
link |
the way the world is set up,
link |
and thankfully, because the work that our group,
link |
as well as a few others around the world
link |
over the last 20 years,
link |
you do have an emerging psychedelic startup industry
link |
now with billions of dollars of investment.
link |
And yeah, that's gonna turn into both good and bad,
link |
like it's upping the ante.
link |
There's gonna be a lot of good and bad
link |
that comes from that,
link |
but any new technology is gonna result in that.
link |
But we've got psilocybin designated
link |
for two separate entities as a breakthrough therapy
link |
by the FDA, and people may not realize,
link |
and MDMA is designated as a breakthrough therapy for PTSD.
link |
This is a really big deal.
link |
That's a very high, I mean,
link |
pharma companies would pay millions of dollars
link |
to get their new drug a designation like that.
link |
And what it means is early research is showing,
link |
saying it shows a high potential for treating disorders
link |
that don't have very good treatments.
link |
So we're, and we're probably,
link |
again, a few years away from both MDMA
link |
and probably a year or two after that psilocybin
link |
being treated for PTSD and depression respectively.
link |
This is, you know,
link |
we have to wait for the phase three studies,
link |
but if the results hold up,
link |
even if the effect size is like halved
link |
of what we're seeing now,
link |
it's still gonna be a lot larger
link |
than what you're seeing with the traditional medications.
link |
And so it's gonna be approved if the data hold up,
link |
and it probably will from my judgment.
link |
So I feel like what I'm doing
link |
is actually having a positive impact
link |
in the world in a way that,
link |
and I feel lucky that I got interested in an area
link |
that happens to plug into a place in the world
link |
where there is that opportunity,
link |
where some great colleagues and friends
link |
are focused on areas where I wish they had the opportunity
link |
for their work to be disseminated.
link |
I wish that, I mean,
link |
I was lucky to be interviewed on 60 Minutes
link |
because of this work.
link |
And I was like, oh my God, I know so many,
link |
there's a bit of a, you know, imposter syndrome.
link |
Like, oh my God, I know so many scientists
link |
that deserve, you know, more so than me
link |
to have that level of exposure.
link |
But if you happen to be in that place
link |
where you gotta do your best to make it work,
link |
to take advantage of that luck
link |
and that intersection of the world and to push it.
link |
And, you know, I've been lucky,
link |
but also did take a bit of a leap of faith early on.
link |
I did have some advisors that told me like,
link |
you've got a really promising pedigree early on.
link |
Like, are you sure you want to focus
link |
much time on this psychedelic stuff?
link |
You've embraced risk.
link |
I mean, I think that, I mean,
link |
the world's changed since in 2020, certainly,
link |
but, you know, channels like social media, podcasts
link |
and things of that sort, you know,
link |
your exposure is because people are interested
link |
And that's why people like myself
link |
are interested in talking to you.
link |
I mean, you know, at Stanford,
link |
there are now a few labs starting to explore psychedelics
link |
more at the mechanistic level,
link |
but so in animal models, excellent labs,
link |
but also I can imagine,
link |
and because of the pioneering work
link |
that you've done at Hopkins,
link |
it'll start to become more common.
link |
I'm certain that people are going to have questions
link |
about how to get in contact with you and learn more.
link |
If people have trauma, PTSD, depression,
link |
you know, it's likely that they're going to start
link |
seeking ways in which they can potentially
link |
participate in clinical trials.
link |
You're very active on Twitter, active, I should say,
link |
you've got other obligations,
link |
but where you are active on social media,
link |
you're active on Twitter.
link |
It's drug, it's at drug downscore researcher.
link |
Drug underscore researcher.
link |
That's how to find me.
link |
Great account, by the way.
link |
Matthew and I recently got into a dialogue there
link |
about some of the deeper effects of psychedelics
link |
in the literature versus how they're being discussed
link |
in the general public, and I follow his account,
link |
and it's a really wonderful account
link |
for whether or not you have a science background or not.
link |
If people are, and I'm going to try and persuade you
link |
to be more active on Instagram,
link |
but I don't know if I'll succeed in that.
link |
I'll try to get my Instagram name going on.
link |
You're a busy guy, and I get it.
link |
I'm running a lab too, I get it, you're busy,
link |
but drug downscore researcher there as well.
link |
Your lab at Hopkins is pretty straightforward
link |
to find through a Google search of your name,
link |
Matthew Johnson, Johns Hopkins University.
link |
Are there portals for people to explore clinical trials,
link |
participation in clinical trials of various kinds?
link |
Yeah, and so in our group,
link |
so you go to hopkinspsychedelic.org.
link |
That's the website, and if you can't remember that,
link |
just Johns Hopkins Psychedelic.
link |
Yeah, we will provide it.
link |
Yeah, and you're going to find us.
link |
It'll be the first thing that pops up, and we have,
link |
trust me, if we have a study on something,
link |
it's going to be on that website.
link |
That means they're being very polite,
link |
so I will be a little bit more aggressive and say,
link |
don't email him directly.
link |
He won't see that email.
link |
Wait until there's a posting for a study,
link |
and then sign up through the correct portal.
link |
And I try to get back to those emails,
link |
but frankly, and it's because, you know,
link |
I'm lucky the area has taken off so much,
link |
but there are many days where I simply get so many requests
link |
that I can't get through my day.
link |
Yeah, if I answer all the, so yeah, trust me.
link |
And something that a lot of folks don't get
link |
and being in academia like we are,
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it's easy to forget how people don't,
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understandably don't realize this.
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This is experimental research.
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It's FDA approved as an experiment, you know,
link |
so we're working towards formal FDA approval
link |
for straight up clinical use.
link |
But right now, someone can't bring me a case
link |
of some idiosyncratic thing and say,
link |
I'm suffering from this complex constellation
link |
of depression. You're not a clinician.
link |
And yeah, I'm not a clinician, and even if I was,
link |
I wouldn't be able to treat them with psilocybin
link |
or to send them anywhere that was legal to take it.
link |
You know, so if we're going to be treating you,
link |
it has to be, or anyone else in the United States
link |
or most other countries for that matter,
link |
it's going to have to be under the guise
link |
of a very specific protocol.
link |
This number of milligrams to treat PTSD,
link |
to treat major depressive disorder,
link |
to treat treatment resistant tobacco use disorder,
link |
so nicotine addiction, very specific studies.
link |
This is not one-off treatment.
link |
And folks say like, oh, I can pay to go out to Baltimore.
link |
If you see my, oh, my son has this, you know, complex,
link |
like in their tragic cases, but you,
link |
so if you're interested in a study, go to our website.
link |
If it's not on their website, you know,
link |
we don't have a study on it.
link |
There are going to be forthcoming studies,
link |
so I'm going to be starting studies on opioid addiction
link |
and PTSD and an LSD study for chronic pain.
link |
The day that those are open for recruitment,
link |
they're going to be up on our website.
link |
So that's where you look to see everything.
link |
And in fact, I would just recently, a couple of days ago,
link |
put up a couple of survey studies,
link |
also where we post links to our survey studies.
link |
So if you've had psychedelics and you've taken them
link |
for therapeutic intent for PTSD or for depression
link |
or anxiety, you can find a link.
link |
And also if you've done breath work for those reasons,
link |
we have a link for a study of that type up there now,
link |
which is a holotropic style breath,
link |
very psychedelic type of breathing technique
link |
that can lead to some of these similar experiences.
link |
More broadly outside of our group,
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because there's a growing number of groups in the US
link |
doing this and in Europe doing this research,
link |
but you can go to clinicaltrials.gov.
link |
And if you look in for the main search term of psilocybin
link |
or MDMA or psychedelic plugin, those terms,
link |
you can get a list of the growing number.
link |
I mean, I think there's over 40, maybe it's been a while.
link |
There might be over 50 now, I don't know,
link |
but studies with just psilocybin going on right now
link |
on clinicaltrials.gov.
link |
So check out clinicaltrials.gov to see what's going on,
link |
but it's going to be, if you're going to do anything legal,
link |
it's going to be in the context of a very specific study.
link |
It's not going to be one-off treatment.
link |
Right, and I should say just, and not just legal,
link |
but also supported in the right framework
link |
that you described of having a team, et cetera.
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Obviously people will do what they will do.
link |
Oh yeah, go ahead.
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I will say, if people,
link |
I never encourage people to take drugs of any,
link |
I don't encourage caffeine use.
link |
Every drug has its risk.
link |
I encourage my own caffeine use, but nobody else's.
link |
I'm drinking up right now.
link |
Yeah, this is a very strong mate is what we're drinking.
link |
It does not lead to a alteration in my perception of self
link |
to the extent that we talked about earlier.
link |
However, this conversation wasn't a good example
link |
of how we can enter a perceptual bubble.
link |
I learned so much about psychedelics
link |
and the future of this for sake of mental health
link |
and other aspects of health.
link |
Matt, thank you so much for your time, for your knowledge.
link |
And I think you put it best earlier
link |
for holding the candle in a very dark time.
link |
And then now there's light.
link |
Well, thanks for helping to spread that light.
link |
And I really appreciate what you've been doing.
link |
This is a great, great medium that you have going on.
link |
So thank you for doing it.
link |
Thank you for joining me for my conversation
link |
with Dr. Matthew Johnson.
link |
If you're enjoying this podcast and learning from it,
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