Yang KH, Heifets BD, Krystal A, et al. — JAMA Psychiatry, Sep 16, 2026
Correct guessing of treatment assignment now exceeds 90% in high-dose psilocybin trials, versus roughly 60% in ordinary antidepressant trials. UCSF's Josh Woolley and co-authors propose UMBRAA — Unidentifiable Multidrug Blinding with Reduced, Authorized Awareness — pairing carefully selected, already-approved drugs with limited disclosure to participants about which drugs they're getting, instead of a single inert or low-dose placebo. No trial has tested it yet; this is a proposed framework, not a result.
Orsini CA, Wong J, Di Luch M, et al. — JAMA Psychiatry, 2026
Reviewed 112 randomized psychedelic trials and found only 29.5% even assessed whether blinding held — but 57.1% cited it as a limitation anyway. Among the trials that did check: psilocybin, LSD, and ayahuasca trials reported blinding-failure rates above 90%; inert-placebo MDMA trials exceeded 85%. No control strategy — active placebo or otherwise — consistently preserved blinding across the trials reviewed.
Cherian KN, Keynan JN, Anker L, et al. — Nature Medicine, Jan 2024
30 special-operations veterans with mild traumatic brain injury from repeated blast exposure received oral ibogaine with magnesium (to mitigate cardiac risk) at a clinic in Mexico. One month out, average self-reported reductions were 88% for PTSD, 87% for depression, and 81% for anxiety symptoms — single-arm and uncontrolled, but a striking signal that drove Stanford's continued ibogaine research.
Mitchell JM, Ot'alora G. M, van der Kolk B, et al. — Nature Medicine, Sep 2023
The confirmatory "MAPP2" Phase 3 trial — 104 patients with moderate-to-severe PTSD, broader and more diverse than the first Phase 3 study. Met both primary and secondary endpoints, confirming the earlier 2021 trial's results; safety profile was consistent with prior MDMA-assisted therapy studies.
Holze F, Gasser P, Müller F, Dolder PC, Liechti ME — Biological Psychiatry, Feb 2023
42 patients received 200µg LSD-assisted therapy in an investigator-initiated trial. STAI-G anxiety scores dropped significantly more than placebo at 16 weeks; one serious adverse event (acute transient anxiety) was reported. A 2024 follow-up found remission held at roughly a third of participants through week 102.
Goodwin GM, Aaronson ST, Alvarez O, et al. — New England Journal of Medicine, Nov 2022
233 patients with treatment-resistant depression across 22 sites in 10 countries received a single 25mg, 10mg, or 1mg (control) dose of COMPASS Pathways' synthetic psilocybin, COMP360. The 25mg group showed significantly greater MADRS reduction than the 1mg group at week 3; about 30% of the 25mg group were in remission.
Bogenschutz MP, Ross S, Bhatt S, et al. — JAMA Psychiatry, Oct 2022
93 adults with alcohol use disorder received psilocybin or diphenhydramine (active placebo) alongside 12 weeks of manualized therapy. The psilocybin group's heavy-drinking days dropped to 9.7% vs. 23.6% in the placebo group — a 13.9-point gap — with no serious adverse events in the psilocybin arm.
Mitchell JM, Bogenschutz M, Lilienstein A, et al. — Nature Medicine, Jun 2021
90 participants with severe PTSD were randomized to MDMA-assisted therapy or placebo with therapy. CAPS-5 scores dropped by 24.4 points in the MDMA group vs. 13.9 in placebo, with no reported adverse events of abuse potential, suicidality, or QT prolongation.
Davis AK, Barrett FS, May DG, et al. — JAMA Psychiatry, May 2021
27 participants with major depressive disorder were randomized to immediate vs. delayed (waitlist) psilocybin-assisted therapy. 71% showed a clinically significant response at both week 1 and week 4; effects were rapid and sustained for at least a month.
Carhart-Harris R, Giribaldi B, Watts R, et al. — New England Journal of Medicine, Apr 2021
59 patients with moderate-to-severe depression received two 25mg psilocybin doses with placebo pills, or two 1mg psilocybin doses with daily escitalopram. The primary outcome (QIDS-SR-16 at week 6) showed no statistically significant difference between arms; most secondary outcomes favored psilocybin but weren't corrected for multiple comparisons.
Szigeti B, Kartner L, Blemings A, et al. — eLife, Mar 2021
191 people who already microdosed ran a self-blinding protocol at home, mixing placebo capsules into their own supply without knowing which was which. Both groups improved over 4 weeks, with no meaningful difference between microdose and placebo — the largest placebo-controlled microdosing dataset to date, and the strongest evidence that microdosing's reported benefits are substantially a placebo effect.
Yang J, Ren C, Zhang Y, Chen L — Neurourology and Urodynamics, Mar 2020
A systematic review of 75 papers on ketamine-induced bladder damage. Proposes that ketamine or its metabolites, concentrated in urine, directly damage the urothelium's barrier function and trigger inflammation and apoptosis — the mechanism behind the bladder damage documented in cases like the one covered in our BBC "Down the K Hole" review.
Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR — The American Journal of Drug and Alcohol Abuse, 2019
Observational survey of people who used vaporized 5-MeO-DMT ("toad medicine") in naturalistic group settings. Users reported unintended but significant improvements in self-reported depression and anxiety symptoms — not a controlled trial, but among the earliest data on the compound's effects in humans outside the lab.
Palhano-Fontes F, Barreto D, Onias H, et al. — Psychological Medicine, Jun 2018
29 patients with treatment-resistant depression received a single dose of ayahuasca or placebo. 64% of the ayahuasca group responded by day 7 vs. 27% on placebo; remission trended toward significance (36% vs. 7%, p=0.054). A real placebo response showed up too, but ayahuasca's effect was larger and held longer.
Daly EJ, Singh JB, Fedgchin M, et al. — JAMA Psychiatry, Feb 2018
67 adults with treatment-resistant depression received placebo or one of three intranasal esketamine doses (28/56/84mg) twice weekly for two weeks, alongside their existing antidepressant. Dose-dependent MADRS improvement appeared within a week and held through an 8-week follow-up — pivotal data behind what became Spravato.
Noller GE, Frampton CM, Yazar-Klosinski B — The American Journal of Drug and Alcohol Abuse, 2018
A 12-month follow-up of patients treated with ibogaine for opioid dependence at a New Zealand clinic — one of the longest-running observational datasets on real-world ibogaine addiction treatment, tracking outcomes well past the acute detox window most other studies stop at.
Griffiths RR, Johnson MW, Carducci MA, et al. — Journal of Psychopharmacology, Dec 2016
51 cancer patients with life-threatening diagnoses received a high dose (22 or 30 mg/70kg) and a low dose of psilocybin in a crossover design. High-dose sessions produced large decreases in depression and anxiety; at 6-month follow-up, roughly 80% still showed clinically significant improvement.
A 90-page, widely-cited review of psychedelic pharmacology, history, and clinical potential, covering mechanism of action, structure-activity relationships, and safety across the classic psychedelic compounds — closer to a textbook chapter than a typical paper, and still one of the most-cited references in the field a decade later.
Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR — Journal of Psychopharmacology, Sep 2014
An open-label pilot in 15 smokers combining psilocybin sessions with cognitive behavioral therapy for smoking cessation. 12 of 15 (80%) were biologically verified abstinent at 6-month follow-up — a notably high rate for any smoking-cessation intervention, though the open-label design means it can't isolate psilocybin's specific contribution.
Carhart-Harris RL, Erritzoe D, Williams T, et al. — Proceedings of the National Academy of Sciences, Jan 2012
One of the first modern neuroimaging studies of psilocybin — 30 volunteers scanned with task-free fMRI after IV psilocybin or placebo. Counterintuitively, psilocybin decreased blood flow and activity in brain hub regions (thalamus, cingulate cortex) rather than increasing it, reshaping how researchers think about what a psychedelic actually does to the brain.
Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R — Psychopharmacology, Dec 2011
18 volunteers received five ascending psilocybin doses (0 to 30mg/70kg) a month apart. Effects scaled consistently with dose; at the two highest doses, participants' self-rated mystical-type experiences held up at 14-month follow-up, consistent with how outside observers rated the same participants' behavior change.
MacLean KA, Johnson MW, Griffiths RR — Journal of Psychopharmacology, Nov 2011
The first study to show measurable personality change in healthy adults following a single, discrete event. Participants who had a mystical-type experience during a high-dose psilocybin session showed significantly higher Openness scores more than a year later — personality traits are normally considered stable in adulthood, which is what made this result notable.
Nutt DJ, King LA, Phillips LD — The Lancet, Nov 2010
A committee scored 20 drugs across 16 harm criteria (9 to the user, 7 to others). Alcohol ranked most harmful overall (72/100), ahead of heroin (55) and crack cocaine (54); classic psychedelics and MDMA scored near the bottom of the list. The ranking correlated poorly with the UK's actual legal drug classification — a mismatch this paper is most often cited for.
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH — Biological Psychiatry, Feb 2000
The first placebo-controlled, double-blind trial of an NMDA receptor antagonist for depression. 7 patients received a single IV dose of ketamine (0.5mg/kg) or saline in a crossover design; Hamilton Depression scores dropped 14 points on ketamine vs. 0 on placebo within three days — the foundational result behind every ketamine-for-depression program that followed, including Spravato.
Strassman RJ, Qualls CR — Archives of General Psychiatry, Feb 1994
11 experienced hallucinogen users received four IV doses of DMT in a double-blind, placebo- controlled design — the first modern controlled human DMT study. Peak blood levels and subjective effects appeared within 2 minutes and were largely gone by 30 minutes.
Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R — Archives of General Psychiatry, Feb 1994
Companion paper to Strassman & Qualls Part I — describes subjective effects across the same graded IV DMT doses and introduces the Hallucinogen Rating Scale, still in wide use in psychedelic research today.
