Psychedelic Research Recap September 2025

Welcome back to our monthly update on psychedelic research!

September 2025 saw clear advances in psychedelic research, especially in anxiety, depression, and addiction treatments. A major trial showed that a single dose of lysergide (MM120) significantly reduced anxiety in generalised anxiety disorder without additional psychotherapy. Another study found that combining psilocybin with mindfulness-based therapy improved depressive symptoms among healthcare workers more than mindfulness alone. Early-stage trials also suggested promising outcomes for psilocybin in treating methamphetamine addiction and for ayahuasca-assisted therapy in alleviating severe grief.

Human lab studies further defined MDMA’s unique effects, showing enhanced feelings of community-level trust not observed with methamphetamine, and demonstrating that its close relative, MDA, produces longer-lasting and stronger subjective experiences. Mechanistic research provided fresh insights by linking brain activity changes directly with subjective experiences under DMT, aligning closely with earlier studies of other psychedelics. However, LSD microdosing trials found minimal evidence for pain relief, highlighting questions about dosing thresholds and tolerance.

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.

MDMA and MDA in controlled trials

MDMA and MDA sit in the same family, but do not feel the same. Here we cover two human studies: a within-person lab comparison of MDMA, MDA, and lysine “prodrugs,” and a social study that sets MDMA against methamphetamine.

In a five-arm crossover study with healthy volunteers (n=23), equimolar MDMA (100 mg) and MDA (92 mg) were compared alongside lysine-MDA and lysine-MDMA. MDA produced stronger and longer effects than MDMA (about 6.1 vs 4.1 hours), with more stimulation, more visual changes, and more “bad drug effects.” Lys-MDA behaved like a slow-release MDA, delaying onset and peak but not softening peak intensity. Lys-MDMA failed to release MDMA and was essentially inactive. All active arms raised vital signs as expected; MDMA and MDA also increased oxytocin, a hormone linked to social bonding. Taken together, the signal is clear: MDA has a punchier, more psychedelic-leaning profile and a tighter tolerability window than MDMA.

Two small, placebo-controlled studies tested social attitudes after a structured chat. On 100 mg MDMA (n=15), people reported higher “global trust” in their community and society shortly after the session; the matched placebo session did not show this shift. A separate study with 20 mg methamphetamine (n=20) found no change in trust or other social-well-being scores versus placebo. The contrast supports a distinct prosocial effect with MDMA that does not generalise to a standard stimulant comparator. How long this trust effect lasts beyond the acute window remains to be shown.

Tryptamines and How They May Help

Psilocybin and ayahuasca sit in the same broad family (tryptamines). This section groups two psilocybin trials, one ayahuasca therapy study, and one DMT brain-imaging reanalysis. Together, they touch clinical signals (depression, burnout, substance use, grief) and mechanisms (how the brain changes during a DMT state).

A randomised trial tested psilocybin plus mindfulness-based stress reduction (MBSR) for frontline clinicians with depression and burnout. The combo arm (group psilocybin-assisted therapy with a 25mg dose inside an 8-week MBSR course) beat MBSR alone on depression at two weeks, with no serious adverse events. Gains on burnout, demoralisation, and connectedness also leaned toward the combo, though most secondary effects did not hold after multiple-testing correction.

An open-label pilot in methamphetamine use disorder delivered one 25 mg psilocybin session with brief prep and integration built on motivational enhancement and ACT. It was feasible and safe in an outpatient clinic. Meth use days dropped to zero at day-28 and rose modestly by day-90; craving and distress fell, and well-being rose. With no control group and small N, these are signals, not proof.

A three-arm, non-randomised study of ayahuasca-assisted meaning reconstruction therapy for recent bereavement reported larger drops in severe grief than therapy alone or no treatment. The ayahuasca group also showed gains in post-traumatic growth and quality of life. No serious adverse events were reported. Because allocation was sequential and open-label, expectancy and selection effects are possible. Still, the effect sizes are large enough to justify a randomised trial of early grief care.

A reanalysis of two DMT datasets used connectome harmonic decomposition to map how brain activity plays out over the brain’s wiring. Under DMT, the brain shifted toward higher-frequency “harmonics,” and the diversity of patterns (entropy) rose, in line with prior reports for psilocybin, LSD, and ketamine. Crucially, these metrics tracked the moment-to-moment intensity people reported during the dose. This links subjective experience to measurable changes in brain dynamics and supports a shared signature across classic psychedelics.

Two LSD Studies

Lysergamides (LSD family) act mainly at the 5-HT2A receptor. This final section covers a Phase IIb trial in generalised anxiety disorder (GAD) using MM120 without psychotherapy, and a microdose study in healthy people testing pain tolerance.

In a Phase IIb trial of MM120 for GAD, a single session with 100 µg or 200 µg MM120 reduced anxiety significantly at week 4 compared to placebo, and these benefits persisted through week 8. Lower doses (25 µg and 50 µg) showed no meaningful difference from placebo. Visual changes, nausea, and headache were common but generally brief side effects. Crucially, the trial did not involve any accompanying psychotherapy, meaning the improvements seen were purely from the drug. Based on efficacy and tolerability, 100 µg appears most suitable for further testing in Phase III trials.

A LSD microdosing study for pain found that over four sessions, LSD microdoses (15 µg) failed to improve pain tolerance or reduce pain ratings compared to placebo, as assessed by the Cold Pressor Task. LSD did modestly increase blood pressure, which correlated with better pain tolerance, but subjective experiences of drug effects did not relate to pain outcomes. A secondary analysis excluding individuals who hit the maximum pain-tolerance threshold found marginal improvements after just the first dose, indicating 15 µg may be too low or repeated dosing might lead to rapid tolerance.

What you can find on Blossom

Last month, we added eight studies to the database of over 2250 research publications. Our link overview provides links to 166 psychedelic studies published in September 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.