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Psychedelics for Treating Mental Disorders

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

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


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