Psychedelic Research Recap October 2025
Psychedelic Research Recap October 2025
Welcome back to our monthly update on psychedelic research!
October 2025 was a calm month for psychedelic research. Whilst we saw record investments, there was a significant dip in research that was published. In our recap, we look back at an fMRI study on emotional reactivity in psychedelic users, another null result for microdosing for cognitive enhancement, and the importance of set and setting in psychedelic treatments.
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.
October’s Randomised Trials
We start with highlights of the latest randomised, placebo-controlled trials testing psychedelic compounds in people. The studies look at both new drugs and well-known ones, using careful methods to measure safety, mental effects, and biology.
The first pair of trials tested whether microdosing psilocybin truffles could sharpen thinking, boost mood, or improve social functioning in healthy people. Over several weeks, volunteers took tiny doses, or a placebo, then completed a mix of tasks and surveys. No clear cognitive or emotional benefits turned up for microdosing, apart from some physical sensations like alertness or mild nausea in those who took the active truffles. Both groups reported mostly positive experiences, suggesting that expectation or context played a big role. These results challenge the idea that microdosing psilocybin leads to real-world gains in a healthy population.
Another trial introduced GM-2505, a new short-acting psychedelic meant for supervised use in therapy. Like the psilocybin studies, it used a double-blind, placebo-controlled setup with healthy volunteers. GM-2505 produced the expected psychedelic effects and brainwave changes, but with a time window shorter than psilocybin and longer than DMT. Side effects were mild and faded quickly. This kind of profile may be helpful for therapy sessions that need a predictable start and finish.
The next RCT study focused on psilocybin’s effects on the brain’s synaptic density, a marker for neuroplasticity. Again, a placebo-controlled design was used, but the researchers split participants into two groups: one received psilocybin in a supportive room, the other in an MRI scanner. The setting made a clear difference. Only those dosed in the calm, supportive room showed bigger increases in synaptic density and stronger, more positive experiences. This matches findings from the earlier studies—context matters, not just the drug or the dose. It also hints that the environment could shape long-term brain changes after psychedelics.
A final study compared two stimulants: methamphetamine and MDMA. In a crossover trial, volunteers received each drug and a placebo on different days. Methamphetamine, but not MDMA, lowered blood levels of a key endocannabinoid (2-AG), a chemical linked to stress and reward. Both drugs raised heart rate and stress hormones, but the differences in endocannabinoid response suggest unique biological effects for each drug, despite some similarities in how people feel on them. Just like the earlier studies, this trial shows that close design and direct comparison can reveal where drugs overlap and where they differ.
Therapeutic Context and Lasting Impact of Psychedelics
This section looks at how psychedelics affect emotional processing, what makes therapy work, and which factors might lead to better outcomes. The studies use brain imaging, interviews, and clinical follow-up to understand not just the drugs themselves, but the people and settings involved.
The first (pre-print) study used brain scans to compare people with at least ten psychedelic experiences to non-users. Experienced users were faster and more accurate at spotting angry faces and showed less activity in brain regions tied to threat. They also had stronger responses to happiness and less rigid separation between different emotions in self-focused brain regions. These effects might reflect longer-lasting changes in emotional processing that appear after repeated psychedelic use.
A second study interviewed people who received psilocybin therapy for cancer-related depression (see this earlier study). Those who were able to accept and let go during intense moments, and who felt safe and supported, were more likely to benefit. Preparation, therapist presence, music, and even small ritual touches all mattered. The hardest moments often led to the greatest healing, but only when people trusted the environment and those around them.
The final study gave psilocybin therapy to people with depression who had not improved with other treatments. Most participants saw their symptoms improve in the weeks after two sessions, though some relapsed or did not respond. People who went in with a better mindset or had spiritual or meaningful experiences were more likely to get better. Expectations alone did not predict who improved. A few participants needed extra support, highlighting the need for strong preparation and careful follow-up.
Taken together, these studies suggest that psychedelics can shape emotional processing and offer help for depression, but outcomes rely on much more than the drug alone. Preparation, support, and a safe setting are key to real change.
Papers Published in October 2025
10 studies from the Blossom database published this month.
Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial
In a multicentre phase 2b randomised placebo‑controlled trial of 198 adults with moderate to severe GAD, a single dose of MM120 (lysergide D‑tartrate) produced a dose‑dependent reduction in HAM‑A scores at 4 weeks, with 100 µg and 200 µg showing significant improvements versus placebo (least‑squares mean differences −5.0 and −6.0 points, respectively). Adverse events were dose‑related—most commonly visual perceptual changes and nausea—supporting the efficacy and informing dose selection for phase 3 trials.
A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer
In a randomized, placebo‑controlled ascending‑dose study in 48 healthy volunteers, single IV doses of GM‑2505 up to 20 mg were well tolerated and showed dose‑proportional pharmacokinetics (t1/2 40–50 min) with dose‑dependent neuroendocrine, neurophysiological and subjective psychedelic effects, including decreased theta/alpha and increased gamma EEG power. The duration of cardiovascular and subjective effects was intermediate between psilocybin and DMT, indicating a practical 10–15 mg IV dose range for supervised clinical use.
Investigating Emotional Reactivity in Experienced Users of Psychedelics: a cross-sectional fMRI study
In a preregistered cross-sectional fMRI study comparing experienced naturalistic psychedelic users (≥10 lifetime uses; N = 33) with matched non‑users (N = 34), users were faster and more accurate at recognising angry faces, suggesting reduced interference from threat-related stimuli. Neuroimaging showed diminished limbic and salience‑network responses to anger, enhanced parietal and sensorimotor responses to happiness, increased precuneus activation to fear, and reduced emotional‑category differentiation in the frontal medial cortex and parahippocampal gyrus, indicating sustained neurofunctional alterations in emotional processing associated with naturalistic psychedelic use.
Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics
This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.
Psilocybin’s effect on human brain synaptic plasticity
A single psilocybin dose increased frontal and hippocampal synaptic density in healthy participants one week after dosing, measured with [11C]UCB-J PET targeting synaptic vesicle glycoprotein 2A (SV2A). Participants dosed in a therapeutic-like room showed stronger mystical-type experiences, longer-lasting psychological benefits and greater synaptic increases than those dosed inside an MRI scanner, indicating that psilocybin’s neuroplastic effects are modulated by environmental context.
The effect of methamphetamine and 3,4-methylenedioxymethamphetamine on peripheral endocannabinoid concentrations: a study in healthy adults
This within-subject, double-blind study (n=22) found that acute administration of methamphetamine (14 mg/70 kg) significantly lowered plasma 2-arachidonoylglycerol concentrations compared to placebo at 150-180 minutes post-administration, whilst MDMA (100 mg) did not affect endocannabinoid levels, and higher anandamide concentrations during the placebo condition correlated with disliking the 'drug effects'.
Psilocybin with psychotherapeutic support for treatment-resistant depression: a pilot clinical trial
An open‑label pilot trial of two 25 mg psilocybin sessions with preparatory and integration psychotherapy for treatment‑resistant depression produced a clinically meaningful reduction in self‑rated depressive symptoms at three weeks (Hedges’ g = −1.27) that was maintained at 20 weeks, although individual responses varied (two sustained responders, three relapses, two non‑responders). Exploratory analyses linked pre‑dosing mindset, spiritual experiences and perceptual shifts to outcome trajectories, with adverse events consistent with prior studies and no serious adverse events.
Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study
This cost-utility analysis, alongside a randomised controlled trial (n=174), compared subcutaneous ketamine (twice-weekly for 4 weeks) with midazolam in treatment-resistant depression. Including midazolam costs, ketamine raised QALYs (0.435 vs 0.352) and was dominant with an 89-91 % chance of costing < $50 000/QALY, but once these comparator costs were excluded ketamine was no longer cost-effective (ICER ≈ $108 500-$251 250/QALY, ≤ 5 % probability).
Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval
This real-world safety analysis of esketamine in the United States (n=58,483 patients, 1,486,213 treatment sessions over 58 months) found that sedation, dissociation, and increased blood pressure occurred in 34.7%, 41.0%, and 0.9% of sessions respectively, with serious adverse events in <0.1-0.18% of sessions, suicide rates lower than background rates, and 210 cases of abuse/misuse reported, confirming the established safety profile with no new safety signals identified.
Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study
This open-label study (n=19) found that 10mg oral psilocybin produced a significant reduction in OCD symptoms compared to 1mg, with a large effect size (Cohen's d = 0.82) one week after dosing, particularly for compulsions rather than obsessions, though effects diminished over subsequent weeks.