Jason Luoma, Ph.D.

That's an oversimplification but might capture sole of the core pathways. After all, neuroplasticity is just the underlying substrate for more rapid learning. Anywhere in life where we see more rapid learning, we will see more neuroplasticity by definition.

The longer term potential for positive affect changes may have to do with transcendent emotions and experiences setting off new ways of seeing the world and patterns of living that then get reinforced and sustained over time. That reinforcement process would feature dopamine centrally.

The lack of addiction potential may have to do with lack of reliability of the euphoric effects and often slow onset as well as rapid tolerance in classics.

That's a great question I don't know the answer to. I'm a psychologist so my speculation would come more thru understanding the experience versus the neurochemistry.

There were a lot of weaknesses in this small study, so we shouldn't get too excited from this one trial, but it adds to the body of research on psychedelics' impacts on positive motivational circuits. #psychedelicscience

Read more here: doi.org/10.1016/j.ja...

The theory: anhedonia may stem from impaired neuroplasticity in brain reward circuits. Psilocybin's ability to promote neuroplasticity and rewire dysfunctional circuits could help restore the capacity for pleasure and motivation.

Intriguingly, a mediation analysis suggested the anti-anhedonia effect may be at least partially independent of general antidepressant effects.

The study: 30 participants with treatment-resistant depression received 25mg psilocybin with psychotherapy. Significant reduction in anhedonia at the 2-week primary endpoint, with clinically meaningful improvements persisting at 3 and 6 months.

Here's a new study on the role of psilocybin in reducing anhedonia in depression. Maybe 70% of people with depression experience anhedonia — and it's one of the hardest symptoms to treat.

SSRIs frequently leave it untouched or even make it worse ("emotional blunting").

There seem to be a number of sources of data suggest that psychedelics may exert their effects through heightening positive affect and motivational systems (e.g., reward responding), not solely through dampening or reducing negative affect, which is more characteristic of antidepressants.

A thread.

This is a topic of high debate right now. Probably the best current solution is a lower does of the same substance. Downside of that is larger sample sizes are probably needed = more expensive.

Read the paper here: doi.org/10.1556/2054... #psychedelicscience

Results: 19/20 participants completed treatment. Depression scores dropped significantly (Cohen's d = 1.89). High satisfaction ratings. Zero severe adverse events.

Without a control group, we can't separate psilocybin from expectancy, placebo, or concurrent therapy. Still, an excellent start.

Non-profit funders wouldn't cover mushroom costs (risking 501c3 status), so the licensed grower donated them. Even in a legal state program, the point-of-sale remains a federal crime. Welcome to psychedelic research in 2026.

Why? Oregon rules prohibit facilitators from handling or administering psilocybin. Mushrooms must be sold to clients by service center staff. The DEA viewed facilitation as "observational rather than medical intervention" - allowing them to avoid Schedule I research waivers.

The lead researcher is both a licensed naturopathic doctor AND psilocybin facilitator. For screening visits, he acted as a doctor. For treatment sessions, he could ONLY act as a facilitator - no diagnosis, no medical scope. This had to be explicitly stated to avoid "role conflation."

Despite being legal in Oregon, researchers had to navigate federal Schedule I restrictions:

DEA refused to provide ANY determinations in writing - only verbal phone calls
Facilitators couldn't "administer" psilocybin under their medical licenses
Participants had to purchase mushrooms on-site

🧵 First clinical trial ever conducted in a state-regulated psychedelic program just published. Oregon's psilocybin program has served 20,000+ people but the majority are wealthy out-of-state travelers. This study targeted low-income participants to test feasibility. #psychedelicscience

Legislation, Industry, and the Future of Psilocybin for PTSD - Lucid News The FDA acceptance of Compass Pathway’s Investigational New Drug Application for their COMP360 compound as a possible therapy for PTSD introduces a new area of possible therapies using psilocybin.

approval to study psilocybin/COMP360 assisted therapy for PTSD

we shall see if it is more effective than MDMA

www.lucid.news/legislation-...

Good point. I think there's lots of confusion out there about those two concepts. Also several models out there on each of those concepts, so lots of potential for confusion.

All this covered in more detail in a valuable new paper by Marcus Hughes: doi: 10.1176/appi.ps.20250169 #psychededelicscience

Bottom line: We need intentional recruitment, retention of diverse populations, culturally competent providers, and protection of researchers working on health disparities - especially now.

The situation is cruel: Psychedelics have been made illegal and through that harmed Black communities through discriminatory law enforcement - but are now being fast-tracked as breakthrough therapies primarily accessible to White, affluent, educated individuals.

This creates a crisis: How do we address the 85% White participant problem when we can't even NAME the problem in grant applications? The very language needed to describe and fix inequity is being systematically erased from research vocabulary.

And now, a new threat: Recent federal policy changes restrict terms like "diversity," "equity," "disparity," and "racism" in grant proposals. Researchers risk losing funding if their work is deemed noncompliant with executive directives.

Historical context amplifies this dissonance: erroneous beliefs about biological differences in drug susceptibility between racial groups, the War on Drugs' disproportionate impact on Black communities, and continued underrepresentation in contemporary trials.

For Black individuals considering PAT, there's a unique cognitive dissonance: balancing potential therapeutic benefits against the legacy of unethical experimentation on Black populations, disproportionate drug criminalization, and ongoing systemic racism in healthcare.

This matters beyond just fairness. Group-level sociocultural differences critically shape both "set" (mindset, expectations) and "setting" (environment) in psychedelic-assisted therapy. Without diverse participants, we can't generalize safety and efficacy data to all populations.

The numbers are stark: In US clinical trials of psilocybin, MDMA, LSD, and other psychedelics, minoritized racial-ethnic groups are severely underrepresented - despite often experiencing the greatest burden of mental health conditions and systemic trauma.

Psychedelics are FDA "breakthrough therapies" - but breakthrough for whom? New analysis reveals 85% of US psychedelic trial participants are non-Hispanic White, raising urgent questions about who actually benefits from this "revolution" in mental health. 🧵 #psychedelicscience