Robin Carhart-Harris, Ph.D. (@RCarhart-Harris) is a distinguished professor of neurology and psychiatry at the University of California, San Francisco. He is one of the leading researchers in the study of how psychedelics such as psilocybin, LSD, and DMT can change the human brain and successfully treat various mental health challenges such as major depression, anorexia, obsessive-compulsive disorder (OCD), and addiction.
In this episode of Huberman Lab, Andrew Huberman sits down with Robin Carhart-Harris to break down the effects of psychedelic use on mental health. Dr. Carhart-Harris explains how psilocybin induces sustained changes in adaptive brain wiring and cognition, key components of safe and effective psychedelic journeys, the role of hallucinations, micro dosing vs. macro dosing, and much more.
Host: Andrew Huberman (@hubermanlab)
The term ‘psychedelics’ originally referred to drugs that mimic aspects of psychosis in their action
The Greek origin of the word psychedelic: psyche = soul; delic = make clear
Psychedelic pharmacology: compounds that work on serotonin 2A receptor in the brain
Psychedelics can reveal something about the mind that can’t be revealed otherwise – maybe because it’s masked, unconscious, or below the threshold of awareness
There are aspects of our minds and psyche not fully available to our conscious state
Psychedelics allow for increased communication across brain areas that wouldn’t engage under normal circumstances, possibly via serotonin 2A receptor
  • Increased consciousness and increased brain connection and communication happen in parallel but we don’t know causality, it’s more circular than linear
An increase in global and functional connectivity persists after the trip, with residual effects up to three weeks long
Microdose: dose of classic psychedelic like LSD or psilocybin that does not put you into a noticeable state of altered consciousness or hallucination
  • LSD microdose: around 10-12 micrograms (notice how small, LSD is particularly potent)
  • A true microdose should be sub-perceptual – you shouldn’t feel it
  • It’s hard to do studies with micro dosing and evidence of utility is thin
Studies on ‘healthy’ individuals on micro dose of psilocybin observed no changes in brain activity (as measured by imaging)
Dosing of mushroom vs psilocybin: 1000mg magic mushroom contains roughly 10mg psilocybin
Environment: intentional music to match journey, eye mask, 2 professionals + individual who ingested drug
All the published studies to date have music as a staple component of the environment – it would be interesting to see what happens if that was removed
There’s often some initial anxiety when a patient enters for the first time, ‘letting go’ is a huge component of the experience itself
Mantra of guided therapy: “trust, let go, be open”
  • Therapeutic rapport measured by the subjective scale on the morning of dosing has a very strong correlation to the quality of experience on the drug and therapeutic outcomes later
Phases of the journey: typically starts with some negative emotions and anxiety before the arc changes course
  • The psychedelics break down a sense of self and control and it can induce some fear and anxiety – you feel like you’re losing it
Sessions (usually 1-3) are typically spaced across a few weeks
Psychedelics make it easier to open up and do the hard work, diving into previous trauma – it’s critical to use in conjunction with psychotherapy and possibly meditative practice as well
Anorexia trial: 3 sessions spaced two weeks apart showed alleviation of obsessive thoughts about food and improvement in weight
  • As an aside, rates of anorexia have not increased despite what social media says
About 70% experience relief from depressive symptoms (as compared to citalopram)
  • Subjective pretrial expectancy about the efficacy of citalopram vs psilocybin did not predict the magnitude of response (suggesting the strength of psychedelic outcome is not a placebo response)
Study on healthy volunteers given either placebo or psychedelic: improvements in psychological well-being, increase in information complexity of brain activity, and even anatomical changes were seen with large dose (25mg) as recorded by brain activity and scanning
  • Anatomical changes are particularly interesting because the brain is fully developed at age 25 so this could have huge implications (of course, more studies need to be done)
Studies on fibromyalgia with 25mg psilocybin are ongoing
LSD is not used as much in trials because of the duration of the trip which lasts 8+ hours
There is potential that future studies will explore the use of both MDMA and psilocybin sequentially or in combination because they elicit different strengths (of course with psychotherapy as well)
DMT has a very short duration but powerful experience
DMT and 5-MeO-DMT are smoked
5-MeO-DMT is more of an ego dissolution experience and less visual hallucination
Ego dissolution: a sense that we are not as important as we think, which is not a helpful way to live your life but does allow you self-examine and feel interconnectedness with others
Ego dissolution from psychedelics is productive versus ego inflation effects seen with cocaine
The paradox of psychedelic therapy is that the ego dissolution doesn’t last – the ego can come back with a vengeance if the user hasn’t done the integration (talk therapy) work properly
In some California cities, you can purchase mushrooms over the counter at weed dispensaries
Federally, FDA is close to legalizing MDMA for therapeutic use (currently in Phase III trials) of PTSD
Psilocybin has also recently started Phase III trials for treatment-resistant depression
Laboratories and pharmaceutical companies are attempting to create drugs that can cure depression and other mental health disorders without the hallucinations
There would be much less stigma – people who would not be inclined to therapy and/or psychedelics would be drawn
Cons: it’s rare to create something that is beneficial for the system and the end user – creating something that is synthetic is always going to have a different effect
  • You’ll be able to get the pharmacology of psychedelics but would lose the ‘journey’ and experience of psychedelics and psychotherapy
Self-blinding citizen science to explore psychedelic microdosing (eLife)
Trial of Psilocybin versus Escitalopram for Depression (The New England Journal of Medicine)
Pivotal mental states (Journal of Psychopharmacology)
Increased global integration in the brain after psilocybin therapy for depression (Nature Medicine)
Structure-based discovery of nonhallucinogenic psychedelic analogs (Science)
Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research (Frontiers in Psychiatry)
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study (Nature Medicine)