Psychedelic Research Recap August 2025

Welcome back to our (belated) monthly update on psychedelic research!

August highlighted both the clinical potential and the societal relevance of psychedelic therapies. Psilocybin remained at the forefront, with trials showing safety and tolerability in PTSD patients, significant antidepressant and anxiolytic effects in those with life-threatening illness, and robust symptom improvements among veterans with traumatic brain injuries following retreat-based use. Economic evaluations underscored the feasibility of implementation, with psilocybin for treatment-resistant depression modelled as cost-effective at lower price points, and MDMA group therapy for PTSD in Ukraine projected to deliver major public health gains and cost savings.

Beyond psilocybin and MDMA, the field expanded in scope. Preclinical work demonstrated that chronic low-dose LSD may not carry the same cardiovascular risks as fenfluramine or serotonin, while the psychoplastogen tabernanthalog (TBG) induced neuroplasticity and sustained antidepressant-like effects without immediate early gene activation. Research on ayahuasca and related formulations revealed altered brain-emotion patterns in long-term users, alongside disruptions in creative cognition during artistic tasks.

This month’s recap is made possible by our supporting members.

Check out the research link overview for all the studies we didn’t add to the database.

Psilocybin and Ayahuasca Studies in Humans

The thread across the five published studies is simple: defined doses, measured outcomes, and careful follow-up. Two trials used randomisation and blinding (so neither participant nor staff knew the allocation). Others were open-label or case-control. Together, they show symptom change in serious illness and trauma, signals in brain activity, and a more mixed picture when it comes to creativity.

One controlled trial in people with life-threatening illness compared a single 25 mg psilocybin session plus therapy with an active placebo (100 mg niacin) plus the same therapy. By 6–7 weeks, the psilocybin group showed larger drops in depression and state anxiety and gains in quality of life and spiritual well-being. After the blind, everyone was offered psilocybin; those who started on placebo caught up, and one versus two sessions looked similar by 26 weeks. Effects on the day (brief blood-pressure rise, nausea, transient anxiety) were expected and short-lived, with no serious events.

Safety and signal in PTSD point in the same direction. In a multicentre, open-label Phase II trial, a single 25 mg psilocybin dose with psychological support was well-tolerated: no serious adverse events, and most side effects were gone by the next day. Symptoms on clinician-rated PTSD scales fell fast and stayed lower through weeks 4 and 12, with better function and quality of life. Not having a control arm means we can’t rule out expectancy, but the pattern matches prior mood work and supports a controlled RCT next.

Field data in veterans with traumatic brain injury gives a complementary view. In a coached retreat with two mushroom ceremonies over six days, PTSD dropped ~50%, depression ~65%, and anxiety ~28% at four weeks. EEG (a brainwave test) shifted toward lower delta/theta power and higher alpha/beta coherence, signals often linked to better emotion control and thinking.

Brain markers also show up in long-term ayahuasca users. A case-control fMRI study in males found higher psychological resilience in regular users than in matched non-users. During an emotion task, multivariate models distinguished users from controls with 75% accuracy and even predicted individual resilience scores from brain patterns. This cannot prove cause and effect, but it suggests lasting differences in circuits for emotion control (amygdala, medial frontal) that fit with the psychometric data.

Finally, creativity is not a simple “more is better” story. In a new analysis of a within-subject, double-blind study, a DMT/harmine mix (“pharmahuasca”) impaired convergent thinking (picking the best answer) and showed trend-level dips in divergent thinking (idea fluency). During a real painting task, both harmine and the mix reduced “incubation” steps, and the mix uniquely cut transitions from incubation to “illumination” (the insight moment). In short, stage-specific effects can help idea generation in some contexts while making it harder to shape output on the spot.

Cost, Coverage, and Real-World Access

This section links three angles on the same question: is psychedelic care worth paying for, and how do you run it at scale? A U.S. model for psilocybin in treatment-resistant depression (TRD) stresses price as the main lever. A Ukrainian model for MDMA shows how group formats can stretch scarce staff and still return strong value. Switzerland then offers a live program that turns policy into day-to-day care.

In the U.S. TRD model, psilocybin-assisted therapy is near the cost-effectiveness line only if the total program cost stays low. At $5,000 all-in, the incremental cost-effectiveness ratio (ICER) is $117,517/QALY (quality-adjusted life year) over 12 months and is often acceptable under common U.S. thresholds; at $10,000, it is rarely acceptable; at $3,000, it is usually acceptable. Gains are modest per person, so price dominates the result, with remission and relapse assumptions as secondary drivers. The practical levers are program design choices that cut therapist time without hurting outcomes (e.g., group prep/integration, shared monitoring on dose day, task-sharing), which now need prospective validation.

For Ukraine, the MDMA model leans into group care from the start. A cohort of 1,000 PTSD patients over 3 years costs about $1.1M, adds 717 QALYs, and averts ~19 deaths, giving an ICER near $1,537/QALY for payers and net savings once productivity and caregiver time are counted (~$2.6M). Scale that delivery model to 50% of eligible civilians over 10 years, and the projection is ~48,000 lives saved, ~1.5M QALYs gained, and ~$5.6B in societal savings.

Switzerland shows how early regulated access happens in practice. Under the limited medical use scheme, ~100 physicians treated 723 patients in 2024 (MDMA 245, LSD 130, psilocybin 348), typically 2–4 sessions within 12 months. Routine consults are sometimes reimbursed; dose days are often out-of-pocket or foundation-funded; medicine costs are a small share compared with therapist time. Basic guardrails, such as case-by-case authorisations, training via societies, supervision, and registries, create a light quality system and produce real-world data that payers and regulators can use while formal coverage pathways catch up.

Pre-Clinical Work in Rodents

This final section looks at pre-clinical work, where researchers test psychedelics in animals or at the receptor level. These studies do not measure patient outcomes but help flag possible safety issues and clarify how brain changes arise. Two recent papers illustrate both sides: one on the long-term safety of LSD microdosing, and one on how a nonhallucinogenic ibogaine analogue drives plasticity.

In mice, chronic low-dose LSD did not show the same heart risks that appear with other serotonergic drugs like fenfluramine. Serotonin caused ventricular thickening, and fenfluramine led to valve regurgitation, but repeated LSD exposure produced no measurable structural or functional heart changes over eight weeks. Receptor tests confirmed that LSD binds strongly to 5-HT2B receptors, which are implicated in cardiac problems, but only weakly and briefly activates them. This likely explains why pathology did not emerge. While the translation to humans is uncertain and people with existing heart problems could still face risks, the data suggest prolonged LSD microdosing is less likely to cause the kind of heart damage linked to other drugs.

A separate rodent study focused on tabernanthalog, a synthetic ibogaine analogue designed to avoid hallucinogenic effects. The compound increased dendritic spines in the prefrontal cortex and produced sustained antidepressant-like behaviours. These benefits depended on the same pathways as psychedelics (serotonin 2A, TrkB, mTOR, and AMPA receptors) but without the glutamate bursts or immediate early gene activation long thought to be essential. This shows that brain growth and behavioural effects can be separated from hallucinogenic activity, opening the door to safer compounds that may be easier to scale as medicines.

What you can find on Blossom

Last month, we added 10 studies to the database of over 2250 research publications. Our link overview provides links to 162 psychedelic studies published in August 2025.

If you enjoy Blossom, please subscribe to our weekly psychedelic research newsletter.

You can also join us at any level of membership to browse the website without limits.