Psychedelic Research Recap May 2025

Psychedelic Research Recap May 2025

Welcome back to our monthly update on psychedelic research!

Ketamine and psychedelic therapies are moving from experimental treatments to real-world clinical options, but questions about cost-effectiveness and safety remain central to their adoption. This month’s research tackles these practical concerns head-on, with economic studies suggesting ketamine could actually save healthcare systems money when replacing more expensive treatments like electroconvulsive therapy.

Safety data also offers encouraging news. Long-term follow-up of over 1,000 esketamine patients shows the treatment remains both effective and manageable over years of use, while new research reveals how different psychedelics can be safely administered through various routes and formulations.

Perhaps most intriguingly, studies of psilocybin and MDMA are uncovering how these therapies work at a deeper level. Unlike traditional antidepressants that can blunt emotions, psilocybin appears to preserve emotional responsiveness while still treating depression. Meanwhile, MDMA’s benefits for PTSD seem to flow directly through enhanced self-compassion, suggesting that explicitly targeting this mechanism could improve outcomes.

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.

Ketamine Health Economics in Depression Care

Ketamine is being studied not only for how well it eases stubborn depression but also for how it affects health budgets (health economics). The two papers below address the financial question from different angles. One embeds a cost study inside a clinical trial, while the other builds a large computer model to test what wider access might mean for the United States. Together, they give payers, clinics, and policy teams a clearer sense of whether ketamine is worth the outlay.

A cost-utility study tied to the KADS randomised trial followed 174 adults with treatment-resistant depression who received four weeks of subcutaneous ketamine or an active control (midazolam). When the control arm’s own drug and monitoring costs were factored in, ketamine both saved money and provided more quality-adjusted life years (QALYs; a measure that combines extra life and improved health into a single value). Under that “realistic” setup, it had a roughly 90% chance of beating Australia’s A$50,000 per QALY benchmark. If those control costs were stripped away, mimicking ketamine added on top of standard care, the drug became $A1,000 costlier over eight weeks and no longer met cost-effectiveness cut-offs. Broader “societal” figures that added travel, unpaid carer time, and lost work favoured ketamine even less.

Using published trial data, a U.S. Markov model projected what would happen if every eligible adult with non-psychotic, moderate-to-severe treatment-resistant depression could choose intravenous ketamine instead of electroconvulsive therapy (ECT). Starting with 350,000 patients and adding 11,296 each year, the model saw treatment uptake increase by 75,000 people in the first year and smaller rises in subsequent years. Across payers, patients, and society, the switch saved about $828 million per year, mainly fewer hospital costs and less time off work, while adding roughly $11 million in unpaid caregiver time. Savings stayed robust in sensitivity tests, but fell if insurers refused to cover ketamine or if maintenance relapse rates rose sharply. The work highlights that insurance policy, session logistics, and relapse control all shape the bottom line.

Psychedelic Therapies for Mental Health and Well-Being

Four studies this month explored psychedelic therapies in clinical trials. They covered well-being in religious leaders, self-compassion in MDMA-assisted therapy, emotional responsiveness in psilocybin (vs escitalopram), and traumatic memories in anorexia treatment with psilocybin.

Twenty-nine clergy from various faiths participated in a wait-list study with two supported psilocybin sessions, one month apart. Six months on, and still clear at 16 months, those dosed early showed stronger daily spiritual practice, greater openness to other traditions, better pastoral confidence, and higher life satisfaction. Ninety-six percent said at least one session ranked among their five most meaningful spiritual moments. No serious harms surfaced, though nearly half rated the experience as one of their five toughest psychological challenges. The data suggest psilocybin can safely deepen religious life without eroding doctrinal commitment.

A fMRI study of the much-analysed psilocybin-for-depression trial compared two high-dose psilocybin days plus six weeks of placebo against daily escitalopram plus inactive 1 mg psilocybin. Both arms got equal therapy time. At six weeks, the SSRI group showed lower BOLD responses to happy, fearful, and neutral faces across the cortex and amygdala, typical “emotional blunting”. The psilocybin group, despite larger clinical gains, showed no such dampening. We first covered this result as a pre-print in June 2023; many spin-off papers from the same parent RCT have since appeared. The message holds: psychedelics may relieve depression (though in this particular study, this was not found on the main depression measure) without flattening feelings.

A secondary look at the Phase III MDMA trial asked why symptoms fall. Three eight-hour MDMA sessions, each with careful prep and integration, produced large drops in harsh self-talk and equally large rises in kind self-regard across all Self-Compassion Scale sub-scores. Mediation analysis showed these changes fully accounted for the reductions in PTSD and depression seen versus placebo plus therapy. Alcohol and other drug use did not shift, hinting at different pathways there. Clinically, the work points to weaving explicit self-compassion practice into MDMA protocols to lock in gains.

In an open pilot with ten women (main results published here), two reported vivid return of long-blocked sexual assault memories during a single 25 mg psilocybin session. With therapist support, they processed the events, then saw sizeable weight gain and Eating Disorder Examination scores fall into remission by three months. While anecdotal, these cases show how psilocybin can loosen dissociative amnesia and let trauma work proceed, potentially breaking a core driver of eating-disorder pathology.

Safety Signals and Dosing Insights

In this third section, four papers look under the hood of different psychedelics, asking basic questions: How safe are they? How does the body handle them? What should clinics watch for over months or years? Taken together, they give regulators and prescribers firmer ground when deciding on dose, route, and patient follow-up.

A Phase I study in 29 healthy adults tested an unusual six-hour drip of the (normally) short-acting drug DMT. A small push dose was followed by a slow infusion set to keep blood levels below the point where strong visions occur. Even at the highest schedule, only mild colour swirls, light dizziness, slower tracking on a laptop task, and a short-lived jump in blood pressure were seen. No heart rhythm or lab problems cropped up, and the effects faded within hours. The finding that gentle, steady DMT is well-tolerated clears the first path for trying this approach alongside stroke rehab, where boosting brain plasticity without heavy mind-altering effects could aid recovery.

Researchers at the University of Basel compared three oral forms of LSD, an ethanol drink, a water drink, and a quick-dissolve tablet, to an intravenous shot in twenty volunteers. All formulations yielded near-identical blood levels and an unexpectedly high 80% oral bioavailability, indicating that most of the dose reaches the bloodstream. The IV route hit harder and faster, pushing up scores for both pleasant awe and anxious unease, plus extra nausea. For trials and future therapy, this result means that clinics can switch between base and tartrate salts or between liquid and tablet forms without recalculating the dose, but should expect a sharper ride with IV dosing.

Real-world alerts on esketamine nasal spray have been reported in 751 European safety reports logged since 2019. The two most common complaints were brief spikes in blood pressure (15%) and dissociation, a spaced-out feeling (15%). More concerning, the odds of reported suicidal thoughts or completed suicide were higher than for the older drugs fluoxetine and venlafaxine. Men made up most of the fatal cases, while women filed more non-fatal ideation. The authors stress that spontaneous reports cannot prove causation, yet the signal supports strict screening and follow-up for people with past suicidal crises.

Finally, a five-year open-label extension was conducted for 1,148 adults who had already completed an esketamine trial. Dosing stayed flexible, twice a week at first, then weekly, fortnightly, or every four weeks as needed, always paired with an oral antidepressant. Headache, mild nausea, and brief dissociation were the main side effects, which usually cleared up on the same day. Serious events were rare, and only one suicide occurred over roughly 1,000 patient-years (finding different results from the EU safety database reporting). On the benefit side, about half of the cohort remained in remission, and self-rated function kept pace. Cognitive tests showed no meaningful decline, even in older participants. These long-run data back the idea that with clinic oversight, extended esketamine treatment can stay both effective and manageable for many people whose depression had resisted other care.