The Science of Psychedelics for Mental Health | Dr. Robin Carhart-Harris

KEYPOINTS

• 01

  Classic psychedelics are 'psyche-revealing'

  Carhart-Harris, a pioneer of psychedelic clinical research, notes that 'psychedelic' means mind- or psyche-revealing. He argues that what makes LSD and psilocybin uniquely interesting, compared with psychedelic-like drugs such as ketamine, MDMA or cannabis, is how they bring previously unconscious material into awareness. Explaining that biologically is, he says, a major gap to fill.

• 02

  Microdosing evidence is thin so far

  Definitions vary. A microdose of LSD is around the perceptual threshold of 10–12 micrograms, often taken on a schedule such as one day on and one or two days off. Popularizers like Jim Fadiman argue a true microdose should be sub-perceptible. Claims of better well-being and creativity lack compelling evidence, partly because placebo-controlled take-home dosing over weeks is hard and costly. A New Zealand study he thinks was well designed showed promising mood effects in presentations but was unpublished at the time.

• 03

  Don't calibrate mushroom doses from clinical milligrams

  Trials use 25 mg of synthetic psilocybin. Carhart-Harris estimates mushrooms contain roughly 1% psilocybin (plus psilocin), 'maybe a little higher,' but stresses this is guesswork. Proper potency studies hadn't been done, and he warns people not to use his answer to dose themselves.

• 04

  Psychedelic therapy is very different from taking a psychedelic

  Sessions use an eye mask, music throughout, settled conditions and ideally two mental-health professionals, at least one of them a psychiatrist, clinical psychologist, psychotherapist or psychiatric nurse. Protocols are similar across sites. Two dosing sessions spaced one to three weeks apart are the default at Hopkins, Imperial and NYU. His anorexia trial uses three.

• 05

  'Trust, let go, be open' predicts outcomes

  Mentored by Johns Hopkins guides Bill Richards and Mary Cosimano, his team adopted this mantra, which he attributes to Richards. Trust in the therapist, measured even by a single rating on dosing morning, predicts the quality of the experience and outcomes weeks or months later. Readiness to surrender and to be open also predict response, but openness can be terrifying for people carrying significant trauma.

• 06

  Psilocybin reduces brain modularity, and this tracks recovery

  During a trip, communication across brain networks increases. In two separate depression cohorts this decrease in modularity was still present the next day in one and three weeks later in the other. The size of the change correlated with symptom improvement. He cautions not to over-read it, since sharper analytical cognition is associated with more modularity. Depression, he suggests, is like a rut in a landscape: easy to fall into, hard to climb out of.

• 07

  The 'entropic brain' effect scales with trip intensity

  EEG shows brain activity becomes more complex, harder to predict and more informationally rich on psilocybin. The effect reliably tracks the strength of the subjective experience: the bigger the trip, the bigger the effect.

• 08

  Placebo doesn't explain psilocybin's antidepressant effect

  In the psilocybin-versus-escitalopram trial, participants generally expected more from psilocybin. Yet pre-trial expectancy predicted response to escitalopram on virtually every one of about 12 scales and predicted response to psilocybin on none. He calls it 'a smash on the head' for the placebo critique, while granting skeptics have a point.

• 09

  Psychedelics dissolve the ego; cocaine inflates it

  In one of his studies, dose-dependent measures cleanly separated drugs: cocaine increased ego inflation without touching dissolution, while psychedelics did the opposite. His hypothesis is that 2A receptors are densely expressed in evolutionarily recent brain regions.

• 10

  MDMA therapy is more interpersonal, and suggestion plays a role

  MDMA sessions involve more talking and less use of eye shades. People often feel love for those around them, making the work closer to talk therapy. MDMA teams encourage patients to listen to their 'inner healer,' language Carhart-Harris notes has been criticized as suggestive. He concedes suggestion is probably one of the vehicles of the therapy, and that honesty about this matters.

• 11

  Combining psilocybin and MDMA is an open question

  Underground therapists already combine the two. Carhart-Harris is interested because traditions often learn by trial and error, and in some patients sequencing the drugs might help. Psilocybin can reach 'the kernel of your suffering' but sometimes aggressively, which can overwhelm people with PTSD, while MDMA softens the emotional edge. Huberman stresses that such use is illegal and that the science should come first.