Episode 38: Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders | Huberman Lab

Key Takeaways

  • LSD, psilocybin, ayahuasca generally afford less controllable experiences than MDMA which has a relatively low chance of a “bad trip” with MDMA
  • MDMA is unique and has a potential clinical indication for trauma specifically because it leads to an increase in dopamine and serotonin simultaneously
  • The theory is that the more you try to hold on and control the experience, the worse your trip will be
  • A psychedelic experience is shaped by the environment: psychedelic experiences can be destabilizing if not done in the proper setting
  • Psychedelics are contraindicated if someone has bipolar disorder, schizophrenia, psychotic thinking, hallucinations – or – any first or second degree relative with any of the above
  • The greatest improvements in therapeutic psychedelic use are in macro or “heroic” doses – not microdosing
  • Microdosing holds promise as an anti-depressant but more research needs to be done on the efficacy
  • Two psychedelics have been designated as breakthrough therapies by FDA: (1) Psilocybin for depression; (2) MDMA for trauma


Dr. Matthew Johnson (@Drug_Researcher) is a Professor of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine. He is one of the most published scientists on the human effects of psychedelics and has conducted pivotal research on the behavioral economics of drug use, addiction, and risk behavior.   

In this episode of Huberman Lab, Dr. Huberman hosts Dr. Johnson to discuss all things past, present, and future of psychedelics. They review the biology and medical clinical-trial uses of psilocybin, MDMA, ayahuasca, DMT, and LSD as well as discuss what the clinical trials are revealing about the potential these compounds hold for the treatment of depression, addiction, trauma, eating disorders, ADHD, and other disorders of the mind.

Host: Andrew Huberman (@hubermanlab)

What Is A Psychedelic?

  • The definition of a psychedelic can vary depending on the field of study or who is describing
  • Psychedelics span classes of compounds but have underlying commonalities
  • Psychedelic: compounds that have the ability to acutely alter the sense of self and sense of reality
  • Examples of “classic psychedelics” include LSD, psilocybin, DMT, mescaline
  • Classic psychedelics downstream effects of increasing glutamine transmission
  • Chemical structures can be tryptamine based compounds or phenethylamine compounds
  • NMDA antagonists are also considered a separate class of psychedelics
  • Psychedelics lead to persisting changes in self-representation

Classes Of Drugs

  • Anti-cholinergics are true hallucinations – i.e., talking to someone who isn’t there
  • MDMA is unique because it leads to robust increases in dopamine and serotonin simultaneously  
  • MDMA is considered an “empathogen” – puts people in touch with their emotions
  • MDMA is clinically used more for trauma than depression because chances of having a “bad trip” is relatively low
  • Serotonergic drugs: LSD and psilocybin target the serotonin system
  • Psilocybin looks structurally like serotonin

Steps To Guided Psychedelic Experience

  • Step one: screening, semi-structured interview to learn about past, disqualifying disorders (e.g., schizophrenia)
  • Step two: physical and medical screening to rule out adverse conditions  
  • Step three: 4-8 hours preparation getting to know guide or therapist leading
  • You can’t predict how someone is going to react: could be the best or worse experience depending on
  • Patients are administered pure psilocybin pill (usually 20-30mg range, adjusting for bodyweight) which takes about 15-60 minutes to kick in
  • Session day is not full of tasks, primarily focused on therapeutic effect
  • Patients are invited to let go of control: all emotional responses are welcome – the goal is to release any emotion that comes to them (e.g., cry, laugh, breathe heavy, etc.)
  • Letting go allows participants to reshape the definition of self
  • Depressed and non-depressed people define themselves into categories of emotional states
  • The experience is shaped by the environment
  • Follow up & care after experience: patients receive supportive, non-structured therapy and are encouraged to discuss and confront (if appropriate) things that come up

Dangers Of Psychedelics

  • There’s a risk assessment that needs to be taken into consideration when tinkering with reality through pharmacologics
  • Psychedelics are contraindicated if: someone has a predisposition to psychotic thinking, hallucinations, Asperger’s side of autism, a manic portion of bipolar, schizophrenia, first or second degree relative with any of the above
  • “Psychedelics can be profoundly destabilizing experiences.” – Dr. Matthew Johnson
  • At some point throughout the trip, there’s often a period of time with a sense of high anxiety, wanting it to end
  • It is atypical, but there are cases of people that freak out and die on psychedelics – examples: run into traffic, jump from a building, break into someone’s house, and get shot or injured


  • General definition of microdose: taking approximately 1/10th of entry-level psychedelic dose
  • Microdosing can be a misleading term because some of the compounds are extremely potent in tiny doses
  • One of the biggest errors in micro-dosing is being unaware of potency and accidentally taking too much
  • General LSD microdose: 10-40 milligram range
  • General psilocybin microdose: 1-2 milligrams
  • Greatest hopes of microdosing are in anti-depressant effects: so far, no microdosing studies have shown an increase in creativity, sustained improvement in mood
  • The greatest effects have been in “heroic” doses where you see improvements in things like addiction months later after the first dose

Treatment And Reversal Of Traumatic Neurological Injury

  • Exploratory research being done beyond the improvement of psychiatric disorder
  • Anecdotally, people say psychedelics helped heal their brain (memory, mood) after traumatic brain injury
  • There are claims of repair of the brain from injuries underlying head trauma
  • Future studies: see if psychedelic use can not only fix depression but also improve mood, cognition, and grey matter over time
  • Drugs that increase certain neuromodulators in a controlled way could lead to reordering of circuitry
  • UFC is bringing in scientists and researchers to study traumatic brain injury for the health and longevity of their fighters, and create a model for future athletes in other sports
  • New research is in small part NIH funding and mostly private money

Legality Of Psychedelic Use And Possession

  • Federally, all psychedelics are schedule 1 compounds– but 90% of drug enforcement happens at the local level
  • Oregon has a state-level legalization effort for psilocybin therapy with a plan to integrate federal government
  • It’s hard to imagine our current model of criminalizing drugs lasting for the long term – but there should be regulation of use e.g., maybe you need a license, requirement to meet with a “guide” or therapist, etc.
  • Prediction: MDMA will likely be approved for prescription by a physician, with a guide, for PTSD within 3 years

Kids & Psychedelics

  • Brains of people under 25 are very plastic and could be more susceptible to risk
  • There is no formal research yet but highly likely there will be
  • The FDA has signaled they’d like to see studies in youth
Huberman Lab : , , , ,
Notes By Maryann

More Notes on these topics

Top Insights and Tactics From

31 Best Podcasts of All Time

FREE when you join over 35,000 subscribers to the
Podcast Notes newsletter

No Thanks