A single dose in depression

Depression · Phase 2 · RCT · 2023

Randomised trial, 104 people with depression, a single 25-mg dose versus an active placebo over six weeks.

-12,3 points greater drop on the depression scale than the active placebo

In short: A single guided dose reduced symptoms markedly more than an active placebo across six weeks, in one of the larger trials of its kind. No serious adverse events occurred.

Context: Six weeks of follow-up. How long the effect carries beyond that is not yet shown by this trial.

Raison et al. (Usona Institute), 2023. JAMA. DOI: 10.1001/jama.2023.14530

Treatment-resistant depression

Depression · Phase 2b · RCT · 2022

Phase 2b trial, 233 people with treatment-resistant depression, a single dose at three strengths.

233 participants, the largest trial of its kind

In short: Even in people for whom standard antidepressants had already failed, a single higher dose reduced symptoms markedly. A second option when the first one does not hold.

Context: The effect is documented over three weeks. How long it lasts beyond that is being tested in ongoing Phase 3 trials.

Goodwin et al. (COMPASS), 2022. New England Journal of Medicine. DOI: 10.1056/NEJMoa2206443

Alcohol dependence

Addiction · Phase 2 · RCT · 2022

Double-blind trial, 93 people with alcohol dependence, two doses versus an active placebo.

9,7% / 23,6% heavy drinking days, psilocybin versus placebo

In short: In alcohol dependence, heavy drinking days fell to less than half compared with a placebo. With entrenched patterns, this opens room that willpower alone rarely reaches.

Context: More than nine in ten could tell whether they received psilocybin or placebo. That weakens the blinding and tempers the numbers.

Bogenschutz et al., 2022. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2022.2096

Psilocybin versus an antidepressant

Depression · Phase 2 · RCT · 2021

Phase 2 trial, 59 people with depression, psilocybin versus escitalopram over six weeks.

57% in remission, versus 28% on the SSRI

In short: In a head-to-head comparison, psilocybin came out ahead of a common antidepressant on several measures. For people with persistent depression, that is a result to take seriously.

Context: The primary measure was statistically inconclusive and the group was small. A strong signal that needs further confirmation.

Carhart-Harris et al., 2021. New England Journal of Medicine. DOI: 10.1056/NEJMoa2032994

Anxiety in life-threatening illness

Anxiety, Meaning & End of Life · RCT · 2016

Randomised trial, 51 people with life-threatening cancer, one high dose.

6 months of relief from anxiety and depression

In short: People in an existentially heavy situation had markedly less anxiety and more calm for months after a single session. Precisely around the big questions of life and death, this work can move something.

Context: Participants had life-threatening cancer. An important finding, specific to that context.

Griffiths et al. (Johns Hopkins), 2016. Journal of Psychopharmacology. DOI: 10.1177/0269881116675513

Cancer, anxiety and the final questions

Anxiety, Meaning & End of Life · RCT · 2016

Randomised trial, 29 people with life-threatening cancer, one dose versus a placebo.

60-80% still had markedly less anxiety or depression after 6.5 months

In short: The sister trial to the Johns Hopkins work, here at NYU. A large share of people had less anxiety and more peace with the existential questions for over half a year. At the end of life especially, this work can move a great deal.

Context: Small group, specific to people with life-threatening cancer. An important, context-bound finding.

Ross et al. (NYU), 2016. Journal of Psychopharmacology. DOI: 10.1177/0269881116675512

The founding paper

Meaning & End of Life · RCT · double-blind · 2006

Double-blind study, 36 healthy adults, high dose versus a comparator.

2 von 3 named the experience among the most meaningful of their lives months later

In short: The study that re-founded modern psychedelic research. A large share of participants counted the experience among the most meaningful of their lives months later. Serious science of this field begins here.

Context: Healthy volunteers, not patients. Foundational for understanding the experience, not for a particular treatment.

Griffiths et al. (Johns Hopkins), 2006. Psychopharmacology. DOI: 10.1007/s00213-006-0457-5

The German trial (EPIsoDE)

Depression · Phase 2b · RCT · Germany · 2026

Government-funded trial, 144 people with treatment-resistant depression, at Charité Berlin and the Central Institute Mannheim.

144 participants, the largest German trial of its kind

In short: The first large, government-funded psilocybin trial in Germany. The planned primary measure was missed, yet further measures showed a clinically meaningful reduction. Important for the legal and research picture in the German-speaking region.

Context: The primary endpoint was not statistically significant. The positive effect comes from secondary measures and should be read with corresponding caution.

Mertens, Gründer et al. (CIMH Mannheim · Charité Berlin), 2026. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2026.0132

Depression, from Zurich

Depression · RCT · Zurich · 2023

Double-blind trial, 52 people with depression, a moderate dose versus a placebo.

54% in remission two weeks after a single dose

In short: One of the few European trials, run at the University of Zurich. A single moderate dose reduced symptoms markedly more than a placebo over two weeks. Close to our own region.

Context: Follow-up of only two weeks, small group. A solid European result that needs longer trials.

von Rotz et al. (Universität Zürich), 2023. EClinicalMedicine. DOI: 10.1016/j.eclinm.2022.101809

Follow-up after twelve months

Depression · Follow-up · 2022

Follow-up of the same group, twelve months after therapy.

12 months on, still stable for most

In short: A year later, the effect was still present for most participants. What opens up in the session can carry a long way when the integration afterwards is sound.

Context: Follow-up of the same small group. One of the few genuine long-term measurements, with the same limits.

Gukasyan et al. (Johns Hopkins), 2022. Journal of Psychopharmacology. DOI: 10.1177/02698811211073759

Effect over twelve months

Depression · Phase 2 · RCT · 2021

Randomised trial, 24 people with depression, two guided psilocybin sessions.

12 months of sustained effect

In short: Two guided sessions worked quickly and stayed measurable for most participants across a full year. The question is less whether it works and more how long it lasts.

Context: Very small group of 24 people. Meaningful for the duration of the effect, limited in transferability.

Davis et al. (Johns Hopkins), 2021. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2020.3285

Microdosing, honestly tested

Microdosing · RCT · self-blinding · 2021

Large placebo-controlled study, 191 people who blinded themselves, microdose versus placebo.

= Placebo the microdose worked no better than the placebo

In short: The key study against the microdosing hype. Participants felt better, but so did the placebo group. The benefit of microdosing is largely explained by expectation. Important for an honest framing.

Context: Participants dosed themselves, not a clinical setting. That is exactly what makes it close to real life and its message robust.

Szigeti et al. (Imperial College), 2021. eLife. DOI: 10.7554/eLife.62878

New connections in the nervous system

Brain & Mechanism · Lab · preclinical · 2018

Laboratory study in nerve cells and animal models on how psychedelics affect connectivity.

↑ more branching and contact points between nerve cells

In short: The study that showed a physical mechanism. Psychedelics led nerve cells to form new branches and connections. This may explain why a window for change opens after a session.

Context: Laboratory work in cells and animals, not in humans. Explains a possible mechanism, not a clinical effect.

Ly et al. (UC Davis), 2018. Cell Reports. DOI: 10.1016/j.celrep.2018.05.022

What happens in the brain

Brain & Mechanism · Neuroimaging · 2012

Imaging study, 15 healthy volunteers, brain activity under psilocybin in the scanner.

fMRT showed reduced activity in the brain's central hubs

In short: The foundational imaging study. Psilocybin dampened activity in the hubs that hold our habitual sense of self together. A possible reason why rigid patterns can loosen under the effect.

Context: Healthy volunteers, very small group. Explains mechanisms, not the effect in an illness.

Carhart-Harris et al. (Imperial College), 2012. PNAS. DOI: 10.1073/pnas.1119598109

The safety guidelines

Safety · Guidelines · 2008

Foundational professional guidelines on screening, preparation, support and safety in psilocybin sessions.

Standard the safety framework behind almost every later trial

In short: The foundation of safe work. These guidelines set out how screening, preparation, set and setting and support must look. Almost every later trial rests on them, and so does our practice.

Johnson et al. (Johns Hopkins), 2008. Journal of Psychopharmacology. DOI: 10.1177/0269881108093587

The key in the brain

Brain & Mechanism · Mechanism · 1998

Controlled human study identifying where psilocybin acts in the brain.

5-HT2A the receptor through which psilocybin works

In short: The study that pinned down the biological target. Block a particular receptor and the effect disappeared. That established what psilocybin actually works through in the brain.

Context: Basic study of the mechanism, not a treatment trial. Important for understanding, not for application.

Vollenweider et al. (Universität Zürich), 1998. NeuroReport. DOI: 10.1097/00001756-199812010-00024

Anorexia, a first step

Eating Disorders · Phase 1 · open-label · 2023

Open-label feasibility study, 10 women with anorexia, a single 25-mg dose.

10 women for whom the treatment proved safe and feasible

In short: A cautious first step in a hard-to-treat condition. The study mainly tested safety and feasibility, not efficacy. A beginning, not evidence of effectiveness.

Context: Very small open-label study, explicitly about feasibility. It says nothing yet about effectiveness.

Peck et al. (UC San Diego), 2023. Nature Medicine. DOI: 10.1038/s41591-023-02455-9

Cluster headache

Pain & Headache · Pilot · RCT · 2022

Exploratory double-blind pilot RCT, 16 people with cluster headache, low-dose regimen.

16 participants in a first controlled investigation

In short: A first controlled look at one of the most tormenting headaches there is. The study was small and exploratory, yet hinted at possible relief. A beginning for a barely researched field.

Context: Very small exploratory study. The finding is preliminary and needs larger confirmation.

Schindler et al. (Yale), 2022. Headache. DOI: 10.1111/head.14420

Creativity

Creativity · Experiment · RCT · 2021

Double-blind placebo-controlled study, psilocybin and tests of creative thinking.

7 days later, more new ideas than the comparison group

In short: During the session, people felt more creative yet scored lower on the tests. A week later, they generated more new ideas than the comparison group. The effect shows up in the weeks that follow rather than in the moment itself.

Context: During the effect, measurable performance dropped even as people felt more creative. The picture is mixed and calls for a careful reading.

Mason et al., 2021. Translational Psychiatry. DOI: 10.1038/s41398-021-01335-5

The first modern depression trial

Depression · Pilot · open-label · 2016

Open-label feasibility study, 12 people with treatment-resistant depression, two doses with psychological support.

12 von 12 showed reduced symptoms after one week

In short: The trial that reopened the field. All twelve participants had reduced symptoms, and for most the effect held for months. A first, clear signal that larger trials went on to take up.

Context: Small open-label pilot without a control group, only twelve people. Groundbreaking, but not conclusive on its own.

Carhart-Harris et al. (Imperial College), 2016. The Lancet Psychiatry. DOI: 10.1016/S2215-0366(16)30065-7

Alcohol, the first evidence

Addiction · Pilot · open-label · 2015

Open-label proof-of-concept, 10 people with alcohol dependence, psilocybin with therapy.

10 participants whose drinking dropped markedly after the session

In short: The small precursor that made the later large alcohol trial possible. After the sessions, participants drank markedly less. A first signal that the 2022 randomised trial went on to confirm.

Context: Open-label study without a control group, only ten people. Valuable as a precursor, not conclusive on its own.

Bogenschutz et al., 2015. Journal of Psychopharmacology. DOI: 10.1177/0269881114565144

Smoking cessation

Addiction · Pilot · open-label · 2014

Open-label pilot, 15 long-term smokers, psilocybin with behavioural therapy.

80% smoke-free after 6 months (12 of 15)

In short: In a small pilot group, four in five long-term smokers were smoke-free after six months, well above usual methods. A strong early signal that larger trials still need to confirm.

Context: Open-label pilot without a control group, only fifteen people. An impressive signal that larger trials must first confirm.

Johnson et al. (Johns Hopkins), 2014. Journal of Psychopharmacology. DOI: 10.1177/0269881114548296

The first cancer pilot

Anxiety, Meaning & End of Life · Pilot · RCT · 2011

Early pilot study, 12 people with advanced cancer, a low-moderate dose versus a placebo.

6 months on, still measurably improved mood

In short: The first modern trial on psilocybin for cancer anxiety at all. Cautiously dosed, small group, yet mood improved over months. The starting point for the later larger trials.

Context: Very small pilot with a low dose. Historically significant, limited in what it can show.

Grob et al. (UCLA), 2011. Archives of General Psychiatry. DOI: 10.1001/archgenpsychiatry.2010.116

Obsessive-compulsive disorder

OCD · Pilot · open-label · 2006

Open-label pilot, 9 people with OCD, several doses under observation.

9 participants with temporarily much reduced obsessive-compulsive symptoms

In short: For nearly two decades the only trial on OCD. In all nine participants, symptoms dropped markedly during the session. An early, isolated signal that needs larger trials.

Context: Tiny open-label study without a control group, the effect was temporary. A first signal, no more.

Moreno et al., 2006. Journal of Clinical Psychiatry. DOI: 10.4088/jcp.v67n1110