Psychedelic Research Recap July 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.

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

Recent Findings From Controlled Trials

Randomised controlled trials (RCTs) remain the gold standard for evaluating new treatments, and this month’s research delivered important findings across the psychedelic landscape.

Esketamine, already approved as an adjunct to oral antidepressants for treatment-resistant depression (TRD), took centre stage in a Phase IV trial testing it as a stand-alone therapy. In this large study (n=378), both 56mg and 84mg doses of esketamine nasal spray (Spravato) produced rapid and significant reductions in depression scores versus placebo. Side effects, mainly nausea, dissociation, and dizziness, were short-lived and mostly confined to dosing days. These results indicate esketamine monotherapy (which was approved at the start of 2025) could offer a lifeline for those who can’t tolerate or don’t respond to oral antidepressants.

Psilocybin therapy also continues to make waves. In France (where we rarely see psychedelic trials take place), a double-blind pilot trial examined psilocybin-assisted psychotherapy for individuals grappling with severe alcohol use disorder (AUD) and depression. Thirty recently detoxified patients received either two high (25mg) doses of psilocybin or a 1mg placebo. After 12 weeks, abstinence rates were dramatically higher in the psilocybin group (55% vs 11%), despite some placebo participants correctly guessing their assignment and dropping out. Even so, the data point to psilocybin as a promising intervention for this notoriously hard-to-treat dual diagnosis.

Visual perception under psilocybin got an objective look thanks to an eye-tracking study. Twenty-three participants, dosed with either a high or low amount of psilocybin mushrooms, viewed paintings while their gaze was monitored. High doses led to more focused, less scattered eye movements, with participants spending more time fixating on fine details. Interestingly, while emotional intensity went up, ratings of the artwork’s beauty did not shift. The takeaway: psilocybin appears to tune our attention to low-level visual elements (e.g. colour, texture) rather than altering our aesthetic judgments.

Drug development efforts are also moving forward with new compounds. RE104, a prodrug of 4-OH-DiPT engineered for a shorter duration than psilocybin, entered human testing in a Phase I trial. Forty-eight healthy adults with prior psychedelic experience received single doses from 5mg to 40mg. RE104 produced classic psilocybin-like effects lasting three to four hours, with dose-dependent increases in mystical-type experiences and good tolerability. The shorter time course makes RE104 a strong clinical candidate for situations where session length is a practical concern.

Meanwhile, sublingual 5-MeO-DMT is being explored in repeated, low-dose regimens. In a Phase I, double-blind, placebo-controlled study, 36 adults with moderate depression or anxiety symptoms received weekly 6–12mg doses (or placebo) over four weeks. The protocol aimed to test the safety and biological activity of microdoses without triggering a full psychedelic experience. The findings: no serious adverse events, fast absorption (blood peaks at 20 minutes), and EEG shifts without overt psychedelic effects. This supports the feasibility of low-dose 5-MeO-DMT regimens for future clinical investigation.

Zooming out, a new meta-analysis examined outcomes among control groups across 17 depression trials—psilocybin, SSRIs, and esketamine included. The key insight: control group improvement in psilocybin trials lagged significantly behind those in SSRI or esketamine studies, raising questions about whether psilocybin’s efficacy has been overestimated due to weak placebo responses (possibly related to unblinding and high participant expectations). Notably, dropout rates in psilocybin studies were much lower than in SSRI trials, hinting at better tolerability.

Early Findings From Open-Label Studies

Open-label and pilot studies play a crucial role at the early stages of research, offering a first look at safety, feasibility, and possible benefits in new populations or with new compounds. In these studies, both researchers and participants know which treatment is being given, so results are best viewed as preliminary signals rather than proof of efficacy. This month, new findings emerged around ibogaine for brain injury, MDMA for depression, and psilocybin for both bipolar disorder and obsessive-compulsive disorder (OCD).

A secondary analysis (see original paper here) involving combat veterans explored how magnesium-ibogaine therapy influences brain activity after traumatic brain injury (TBI). Using EEG, researchers tracked changes in the brainwaves of thirty veterans before and after treatment. They observed a shift towards slower oscillations, an increase in theta and alpha waves, and a decrease in faster beta and gamma waves. This distinct pattern was associated with improvements in PTSD and anxiety symptoms, as well as better cognitive functioning for up to a month post-treatment. Notably, these changes differed from the typical acute effects of classic psychedelics such as psilocybin.

Modern research has, for the first time, investigated MDMA-assisted therapy as a direct intervention for major depressive disorder (MDD). Previously, improvements in depression were mainly reported as secondary outcomes in PTSD trials. In this open-label pilot, twelve participants with moderate to severe depression underwent two MDMA sessions (each 80 to 120mg), supported by psychotherapy. The intervention proved safe and feasible, with marked reductions in depression scores and significant gains in daily functioning reported eight weeks after treatment.

Psilocybin therapy is now being trialled for bipolar II depression—a group usually left out of psychedelic research due to concerns about triggering mania. In a dose-escalation, open-label study, fourteen participants started with a 10mg dose, with an option to receive 25mg. Treatment was generally well tolerated, with only temporary side effects like mild anxiety or nausea. Crucially, no cases of mania or psychosis were reported. Depression scores improved significantly, with benefits sustained for up to ninety days, alongside clear gains in quality of life.

A separate analysis examined whether the intensity of mystical experiences during psilocybin therapy predicted outcomes for people with treatment-resistant depression. Among thirty-one participants with either major depressive disorder or bipolar II, those who reported stronger mystical experiences during their first 25mg psilocybin session saw greater reductions in depressive symptoms two weeks later. This correlation was not observed for subsequent sessions, but far fewer participants received additional doses, making these findings less certain.

OCD also featured in this month’s research highlights, with an open-label study testing a single, low dose of psilocybin (10mg) in nineteen adults with the disorder. One week after treatment, there was a substantial drop in OCD symptoms, particularly in compulsive behaviours. While the effect was moderate to large initially, it faded over the following weeks. Side effects were minimal, indicating that lower doses of psilocybin could be a promising avenue for future, larger-scale OCD trials.

A Look at Psychedelics in the Real World

Moving beyond the strict protocols of clinical trials, observational studies explore how psychedelics are actually used in real-world settings. Rather than assigning treatments, these studies monitor natural patterns of use, offering valuable insights into both the benefits and risks that can emerge outside a controlled, therapeutic environment.

A large, longitudinal study of over twelve thousand US residents delivered a nuanced warning about unsupervised psychedelic use. Participants were followed over time, and the data showed that, on average, those using psychedelics without supervision experienced a slight rise in depressive symptoms. This increase was most pronounced among individuals using psychedelics in so-called “risk contexts”—for instance, starting with a negative mindset or without psychological support. In these cases, challenging experiences were more common and often linked to worsening symptoms. This stands in contrast to other recent findings, such as a cross-sectional survey of 2,510 users who retrospectively reported broad improvements in health and reductions in alcohol and tobacco consumption. The discrepancy likely stems from study design; this new research tracked outcomes as they happened, while retrospective surveys are shaped by memory and subjective interpretation. The key message is that, outside of supervised settings, the context in which psychedelics are used is critically important.

In contrast, another observational study focused on veterans attending psychedelic retreats, where structured support and community were central features. Fifty-eight veterans participated in retreats centred on either psilocybin or ayahuasca, each including group activities and therapeutic guidance. Four weeks later, the results pointed to marked improvements: symptoms of depression dropped by 29%, PTSD by 26%, and both sleep and quality of life improved substantially. Psilocybin retreats produced slightly greater overall gains, while ayahuasca retreats were somewhat more effective for PTSD. The data also showed that men benefited more than women on most measures, and those starting with the most severe symptoms made the largest strides.

Foundational and Preclinical Psychedelic Research

This final group of studies shifts the spotlight to the underlying science of psychedelics, going beyond clinical outcomes to reveal how these compounds affect the brain and body at a fundamental level. Through computational modelling, extensive pharmacological screening, and preclinical research, these investigations build the foundation for interpreting human trials and shaping future directions.

A computational modelling study compared the effects of psilocybin and the antidepressant escitalopram on the brains of people with depression. The findings revealed a striking contrast: psilocybin increased the brain’s susceptibility to change, promoting greater flexibility or plasticity, while escitalopram made the brain’s activity more stable and resistant to change. Despite these opposing actions, both compounds nudged brain dynamics towards healthier patterns. These results support the idea that psilocybin opens a temporary “window of plasticity,” offering a mechanistic explanation for its therapeutic promise.

Expanding the focus, a large receptor profiling project systematically mapped the pharmacology of forty-one psychedelic compounds. While the centrality of the 5-HT2A receptor was reaffirmed, the study also highlighted the broad “promiscuity” of these substances, interacting with most serotonin, dopamine, and adrenergic receptors. This polypharmacology likely accounts for the wide spectrum of therapeutic and adverse effects, including cardiac risks related to the 5-HT2B receptor. The findings serve as a detailed reference point for developing next-generation psychedelics with improved safety and specificity.

Oral mescaline’s pharmacology received its most comprehensive examination yet in a modern analysis pooling data from two Phase I studies. The results confirmed that mescaline’s effects scale directly with dose and identified a half-life of approximately three and a half hours. At a lower dose of 100mg, effects were brief (under three hours), whereas 800mg produced up to fifteen hours of psychoactivity. At least 53% of the oral dose reached the bloodstream, offering a clear picture of mescaline’s absorption and how this relates to the user’s experience.

Another secondary study revisited data from a trial using “pharmahuasca,” a combination of DMT and harmine designed to mimic ayahuasca. Using advanced modelling techniques, researchers showed that harmine substantially increases DMT’s bioavailability and prolongs its effects. The analysis also uncovered substantial individual variability in both drug metabolism and sensitivity, underscoring the need for personalised dosing strategies in future clinical applications.

Finally, early preclinical evidence has pointed towards a possible anti-ageing effect of psilocybin. Laboratory experiments found that psilocin (the active metabolite of psilocybin) extended the lifespan of human cells in vitro. In parallel, aged mice given monthly doses of psilocybin exhibited a much higher survival rate than those given a placebo. While translating results from animal studies to humans must be done with extreme caution, these findings raise intriguing new questions about psilocybin’s potential as a geroprotective agent.

What you can find on Blossom

Last month, we added 18 studies to the database of over 2250 research publications. Our link overview provides links to 181 psychedelic studies published in July 2025.

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