Psychedelic Research Recap June 2025

Psychedelic Research Recap June 2025

Welcome back to our monthly update on psychedelic research!

Psychedelic science reached a milestone this month: the first Phase III data for psilocybin (COMP360) in treatment-resistant depression. The single 25 mg dose produced a 3.6 point MADRS drop at week 6 (over placebo), clinically meaningful yet smaller than many expected. Our recap adds six more depression papers that round out the picture, covering high-dose LSD, oncology psilocybin, veteran follow-ups, cost-per-remitter economics, and a meta-analysis that adjusts for unblinding. A Phase II study of inhaled 5-MeO-DMT showed an even larger effect, and a confirmatory Phase III trial is already planned.

Mechanistic work also advanced. Simultaneous PET-MRI under LSD linked receptor occupancy, blood flow, and rising network entropy; two fMRI papers tied local signal drops to receptor density profiles. Precision mapping showed psilocybin reliably flattens network boundaries months apart, and a salivary oxytocin pilot suggests a quick biomarker for LSD therapy.

Mind-state research stayed busy. Controlled and naturalistic studies found that psilocybin, a DMT-harmine mix, and retreat settings all boost mindfulness, compassion, and the “presence of meaning,” while a three-item Peak Experience Scale proved useful for real-time dosing of 5-MeO-DMT.

Safety data remained central. A review of 93 psychedelic-induced psychosis cases showed most resolve in under two weeks with modern atypical antipsychotics. The first randomised trial of vaporised DMT reported only brief, mild vital-sign spikes. Finally, an international Delphi panel delivered the 30-item ReSPCT checklist for reporting set and setting, giving future trials a common safety framework.

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.

Psychedelic Therapies for Depression

In June, six papers all look at treatments that aim to beat major depression faster or more completely than current drugs. The set ranges from long-term follow-ups after a single psilocybin dose to an economic model for esketamine and a meta-analysis that examines the common “everybody knows who got the trip” problem.

A two-year follow-up (of this study) of 30 people with cancer and major depression found that one 25 mg psilocybin session plus brief therapy still halved depression scores in 54% of participants and cut anxiety in 46%. Half were in full remission, and a quarter reached that point without any further antidepressant treatment.

Ten U.S. veterans with severe treatment-resistant depression took the same 25 mg dose in another small study. At six months 80% still met response and 50% remission, but by twelve months, those rates slipped to 40% and 30%. The drop suggests redosing or added therapy may be beneficial after half a year in high-burden cases.

In a Swiss randomised trial, 61 patients got either two “full” LSD sessions (100µg then 200µg) or two 25 µg sessions meant to act as an active placebo. Two weeks after the second dose, the high-dose arm cut clinician-rated depression by about 13 points versus 4 in the low-dose arm, and the gap held through week 12. Acute effects were stronger, but side effects were similar, making a Phase III study the logical next step.

Modelling work using ESCAPE-TRD data found that esketamine nasal spray plus an oral antidepressant brought 50% of patients to remission at 32 weeks versus 33% for quetiapine augmentation. After factoring drug, visit, and productivity costs, the spray ended up about $3k cheaper per remitter for commercial insurers and $456 cheaper for Medicaid, with bigger savings if all non-responders moved straight to rTMS.

A secondary look at a 59-person head-to-head trial showed that two high-dose psilocybin sessions rewired thinking styles better than daily escitalopram. Psilocybin lifted optimism and dismantled rigid “dysfunctional attitudes” across three domains, whereas the SSRI mostly tamped down pessimism. The data backs the idea that psychedelics act by loosening entrenched belief networks rather than flattening mood.

A pre-print pre-registered meta-analysis pooled eight psychedelic trials and sixteen open-label SSRI/SNRI studies. When both sides were equally “unblinded,” average symptom improvement on the HAMD-17 was the same (difference ≈0.3 points). Open-label antidepressants did slightly better than blinded ones, showing that expectancy lifts scores, while psychedelic outcomes barely changed with blinding. The finding cools claims of clear-cut superiority and underlines the need for large, fully controlled head-to-head trials (of which there are near-zero; besides the oft-cited 59-person trial we just discussed).

Imagining the Mind on Psychedelics

Five studies looked under the hood of LSD, psilocybin and MDMA. Using scans that show blood flow and network traffic, plus simple saliva and blood tests, they map how these drugs act in real time. The results matter for dose setting, safety and the hunt for easy-to-measure signals that tell us when a trip is helping.

A first-of-its-kind PET-MRI study gave healthy volunteers LSD and tracked both receptor binding and brain function at once. LSD clamped onto about half the brain’s serotonin-2A sites at modest plasma levels, pushed blood faster through the brain without widening big arteries, cut chatter between networks (especially vision) and made signal patterns more chaotic. Feelings peaked later than blood levels, hinting at slow receptor release. The picture differs from psilocybin and calls for fresh ideas on how LSD works.

A separate fMRI re-analysis of 15 people who got intravenous LSD found local brain activity and local synchrony both dipped in touch and sight regions and in the default-mode hub. The strongest drops sat in areas packed with dopamine-D2 and serotonin-1A receptors, showing that more than one receptor family shapes the LSD state.

In a small clinical pilot, ten patients with stubborn depression gave saliva during an LSD-assisted therapy session. Oxytocin, the “bonding” hormone, climbed sharply about 90 minutes after dosing (the same window when the trip felt strongest) and then fell. The rise was clear despite patients staying on their usual meds, hinting that a quick spit test could one day confirm when the drug is doing its job.

A precision imaging trial scanned seven experienced volunteers dozens of times. On psilocybin, their brain networks lost some of their usual modular borders, a change that reversed after the session yet reappeared six months later when four returned for a second dose. Each person kept a unique but reliable brain “fingerprint,” and psilocybin brought far richer mystical ratings than the active placebo methylphenidate.

Finally, a crossover study with 15 healthy adults showed that 100 mg MDMA fired up the stress axis: ACTH tripled, and cortisol jumped nearly 70% within two hours, while the thyroid, growth, and sex-hormone axes barely moved. Prolactin nudged upward but not quite above the noise. The clear, swift hormone surge supports testing MDMA as a dual challenge for both oxytocin and adrenal function in clinical research.

How Psychedelics Shape Lasting Meaning

In this third section, four papers focus on what people feel and keep after a psychedelic session, and on quick ways to measure those shifts. Together, they show that deep experiences can lift mood, grow kindness, and add purpose, while new tools make it easier to track and fine-tune those effects in the clinic.

A double-blind crossover study gave 40 healthy adults two moderate psilocybin doses about fifteen months apart. No matter their sex, past trips, or whether the session happened in an EEG lab or an MRI scanner, volunteers reported lasting gains in mood, self-understanding, and spirituality four weeks later. Even sessions that included some fear ended well and did not predict harm, backing the safety of repeated dosing in controlled settings.

In a new analysis of a 31-person placebo-controlled trial, an intranasal DMT plus sublingual harmine mix (modelled on ayahuasca; also named pharmahuasca) boosted mindfulness and both self- and other-directed compassion one day after dosing. The jump was clearest in “high-sensitivity” participants who felt the drug effects most strongly, hinting that personal traits modulate psychological pay-offs.

A pooled analysis of 973 people across a psilocybin depression trial, a healthy-volunteer lab study, and retreat goers found a solid rise in the “presence of meaning” score after psychedelic use, with only a mild drop in the “search for meaning.” Bigger meaning gains went hand-in-hand with better well-being and lower depression, and were tied to stronger mystical, ego-blurring, and emotional-breakthrough moments.

Finally, data from three 5-MeO-DMT studies (84 participants) showed that a three-question Peak Experience Scale works well for rapid dosing feedback. The scale had high internal consistency (α=0.896) and lined up closely with longer surveys such as the Mystical Experience Questionnaire and Ego Dissolution Inventory, making it a handy tool to judge whether an inhaled dose has reached the desired depth or if an extra puff is needed.

Safe Practice for Psychedelic Sessions

The final three papers tackle safety from three angles: what to do when a rare psychotic episode follows use, whether inhaled DMT is physically safe, and how to document extra-drug factors so future trials run smoothly and comparably.

A systematic review pulled together 93 published cases of psychedelic-induced psychosis (mostly after LSD or MDMA) in users averaging 24 years old. Symptoms typically cleared in about two weeks. Modern “atypical” antipsychotics such as olanzapine or risperidone worked in 91% of cases, while older drugs like haloperidol helped only 27%. About one-third later received a schizophrenia-spectrum diagnosis, showing the need for follow-up even after recovery.

The first randomised trial of vaporised DMT gave 25 healthy volunteers a single 60 mg inhalation in a cross-over design. The trip was intense but brief; blood pressure and heart rate rose for under ten minutes, then normalised. Lab tests stayed within normal limits; most side effects were mild throat irritation or brief nausea. The data support inhaled DMT as a fast, manageable option for future therapy studies.

An international Delphi panel of 89 experts agreed on 30 must-report “set and setting” items, now called the ReSPCT checklist. It covers room design, music, staff roles, preparation, integration plans and how safe and supported participants feel. Using this common template should make it easier to compare results across studies and spot which context elements matter most for both benefit and risk.