Psychedelic Research Recap August 2025
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.
Papers Published in August 2025
15 studies from the Blossom database published this month.
Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial
In a Phase 2, non-randomised open-label trial of 22 adults with PTSD, a single 25 mg dose of psilocybin administered with psychological support was generally well tolerated with no serious adverse events and mostly transient side-effects, and was associated with large, clinically meaningful reductions in PTSD symptoms and improvements in functioning and quality of life sustained to 12 weeks. These results indicate single-dose psilocybin may be safe and potentially efficacious for PTSD, warranting further controlled investigation.
Psilocybin-assisted therapy for treatment-resistant depression in the US: a model-based cost-effectiveness analysis
This cost-effectiveness analysis found that psilocybin-assisted therapy (PAT) for treatment-resistant depression (TRD) may offer economic value at $5,000 or less per treatment course, yielding an incremental cost-effectiveness ratio of $117,517 per QALY gained over 12 months, with cost-effectiveness highly sensitive to treatment price (95% probability at $3,000 vs 1% at $10,000).
Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
This pre-clinical mouse study tested chronic administration of serotonin, d-fenfluramine, or subhallucinogenic doses of LSD on cardiovascular health. Serotonin and d-fenfluramine caused ventricular thickening and valve regurgitation, respectively, while LSD produced no significant ventricular or valvular changes. Receptor binding assays showed LSD, psilocybin, and norfenfluramine had similar affinity for 5-HT2B, but LSD’s activation was short-lived, providing no evidence of heart remodeling with prolonged low-dose LSD.
The Potential Economic and Public Health Impact of MDMA-Assisted Group Therapy for PTSD in Ukraine
Using a decision-analysis model for 1,000 Ukrainian PTSD patients, the study estimates MDMA-assisted group therapy with supplemental individual sessions would cost US$1.1m, avert 19.2 deaths, gain 717 QALYs, have an ICER of US$1,537/QALY and produce net societal savings of US$2.6m, with scaled 50% coverage over 10 years potentially saving ~48,000 lives, 1.5 million QALYs and US$5.6bn. These results indicate MAT is likely to be cost‑effective or cost‑saving and could substantially improve population health, supporting its inclusion in Ukraine’s PTSD treatment strategy.
Resilience and Brain Changes in Long-Term Ayahuasca Users: Insights From Psychometric and fMRI Pattern Recognition
Long-term ayahuasca users exhibited higher psychological resilience and distinct patterns of emotional brain reactivity on fMRI, with a machine-learning classifier separating users from controls at 75% accuracy and a regression model predicting individual resilience (r = 0.69). These findings suggest long-term ayahuasca use is associated with neural adaptations in emotional processing detectable by multivariate pattern analysis.
Ayahuasca-inspired DMT/harmine formulation alters creative thinking dynamics during artistic creation
In a double‑blind, placebo‑controlled within‑subject study using an ecologically valid painting task, an ayahuasca‑inspired DMT/harmine formulation impaired convergent thinking (particularly in participants with higher baseline reasoning) and showed trend‑level reductions in divergent fluency and elaboration. At the process level both DMT/HAR and harmine reduced incubation‑related transitions, while DMT/HAR uniquely decreased transitions from incubation to illumination, indicating psychedelics alter the dynamic pathways to creative insight and that subjective altered meaning and insightfulness selectively predict divergent but not convergent outcomes.
DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers
In this open-label exploratory crossover study of nine experienced ayahuasca users, three Acacia‑derived oral formulations delivering DMT plus harmala alkaloids were well tolerated, produced no clinically significant physiological changes, and elicited psychedelic effects rated comparable to (and for ACL‑010 sometimes more beneficial than) traditional ayahuasca. These findings suggest Acacia‑based DMT/harmala formulations are a feasible alternative for future clinical trials, although generalisability is limited by the small sample size and open‑label design.
Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat
In a preliminary uncontrolled study of 21 veterans with traumatic brain injury, participation in two psilocybin retreat ceremonies was associated with large reductions in PTSD, depression and anxiety symptoms and with EEG changes (reduced frontal/temporal delta–theta power and increased alpha–beta coherence) consistent with improved emotional regulation and neural communication. These findings suggest psilocybin retreats may improve psychological wellbeing and brain connectivity in veterans with TBI and warrant larger, controlled trials.
The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation
This rodent study found that the nonhallucinogenic psychoplastogen tabernanthalog (TBG) promotes cortical neuroplasticity and sustained antidepressant effects through the same 5-HT2A, TrkB, mTOR, and AMPA receptor pathway as psychedelics, but without inducing the immediate glutamate burst or immediate early gene activation previously thought necessary for psychedelic-induced neuroplasticity.
Complex slow waves in the human brain under 5-MeO-DMT
This naturalistic EEG study (n=29) examines the effects of inhaled synthetic 5-MeO-DMT (12mg) on brain activity in healthy individuals. It finds that 5-MeO-DMT radically reorganises low-frequency neural activity flows, making them incoherent, heterogeneous, and nonrecurring. It also causes broadband activity to exhibit slower, more stable, low-dimensional behaviour with increased energy barriers to rapid global shifts.
Efficacy and safety of esketamine for smoking cessation among patients diagnosed with lung cancer and major depression disorder: A randomized, placebo-controlled clinical trial
This multicenter, randomised, placebo-controlled clinical trial (n=236) investigates the efficacy and safety of esketamine (ESK) (8x35mg) for smoking cessation in patients with lung cancer and major depressive disorder (MDD). Eight weekly intranasal ESK sessions significantly improved both self-reported (44.1%) and biologically verified (28.8%) smoking abstinence at 6-month follow-up, alongside reductions in depression, anxiety, nicotine dependence, and respiratory symptoms.
Health-related behavioral changes following the use of psychedelics in naturalistic settings
This cross-sectional study (n=2,510) of US adults with psychedelic experience found that participants retrospectively reported widespread improvements in health behaviours including reduced alcohol (66%) and tobacco (49%) use, better dietary habits (49%), and decreased impulsivity (48-72%), with microdosers and frequent users showing greater positive changes.
Implementing psychedelic-assisted therapy: History and characteristics of the Swiss limited medical use program
This review (2025) of the Swiss limited access scheme describes how approximately 100 physicians treated 723 patients with MDMA, LSD, or psilocybin in 2024, with patients typically receiving 2-4 psychedelic-assisted therapy sessions within 12 months for treatment-resistant conditions.
Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects
This secondary of a single-blind, randomised study (n=16) using DMT (0-120mg) with harmine (0-180mg) in an ayahuasca-inspired (‘pharmahuasca’) formulation found that harmine significantly enhanced DMT bioavailability and prolonged absorption, resulting in higher sustained plasma concentrations and increased subjective psychedelic effects, with population pharmacokinetic/pharmacodynamic modeling revealing substantial interindividual variability in clearance, bioavailability, and sensitivity to psychedelic effects.
The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial
This secondary analysis of an RCT comparing psilocybin therapy to escitalopram in MDD patients (n=59) found that psilocybin produced superior improvements in cognitive biases. Psilocybin significantly increased self-reported optimism (d=1.1) and optimistic beliefs about desirable life events (d=1.1), while improving all three domains of dysfunctional attitudes (achievement, dependency, and self-control). Escitalopram showed more modest effects, reducing pessimism about negative events and improving only the achievement domain of dysfunctional attitudes.