Psychedelics for Treating Mental Disorders

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

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

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

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

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

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

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

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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