The strongest evidence for the benefits of psychedelics and MDMA comes from clinical trials: screened participants, supervised sessions, measured doses. This magazine has covered that efficacy story at length, for psilocybin in depression, MDMA in PTSD and LSD in anxiety. A new research letter in JAMA Network Open looks at the other side: what people report in general-population settings, where dose, purity, supervision and reasons for use vary widely.[1] It provides federally funded survey data on psychedelic adverse effects in an online US sample weighted to produce nationally representative estimates, filling a gap that controlled trials cannot address.
What the Survey Did
Researchers from the Karolinska Institute, the University of Alabama at Birmingham, Rocky Mountain Poison and Drug Safety and the University of Colorado analysed the 2025 National Survey Investigating Hallucinogenic Trends, which reached 1,964 adults through an online panel and weighted their responses to a nationally representative anchor survey. Past-year users reported health changes and health-care use they attributed to each substance: 1,151 for psilocybin, 376 for LSD, 539 for MDMA, 74 for ibogaine and 95 for 5-MeO-DMT. Because some respondents used more than one substance, the substance-specific groups overlap. Not all of this use was unsupervised: 43.4% of ibogaine users and 40.6% of 5-MeO-DMT users reported using in a medical office or clinic. Those who had used in the past three months were also asked about 13 specific adverse effects, adapted from the Swiss Psychedelic Side Effects Inventory.[1]
What People Reported
At least one of the 13 listed effects was commonly reported for every substance: 75.6% of psilocybin users, 83.6% for LSD, 81.4% for MDMA, 94.8% for ibogaine and 92.8% for 5-MeO-DMT. These rates count any of 13 listed effects, so they say more about how common some adverse experience is than about severity. The past-year outcomes are more telling:
| Past 12 months (weighted %) | Psilocybin | LSD | MDMA | Ibogaine | 5-MeO-DMT |
|---|---|---|---|---|---|
| Mental health improved | 51.2 | 43.7 | 36.6 | 37.2 | 37.0 |
| Mental health worsened | 4.7 | 10.8 | 11.4 | 34.5 | 30.1 |
| Physical health worsened | 6.2 | 13.5 | 11.9 | 45.1 | 42.7 |
| Any substance-attributed health-care service use | 16.2 | 27.3 | 27.1 | 74.2 | 63.8 |
For psilocybin, reported improvement outnumbered reported worsening by roughly ten to one. For ibogaine and 5-MeO-DMT, users were about as likely to report worse mental health as better, and most reported health-care service use they attributed to the drug. That broad category does not reveal what kind of care people received or how much involved emergencies or physical injury.
The other half of the finding is scale. The survey estimates about 8.1 million past-year psilocybin users in the US, against roughly 0.56 million for ibogaine. So, as the authors put it, the estimated number of adults reporting adverse outcomes “was nevertheless greatest for psilocybin, LSD, and MDMA.”[1]
The Ibogaine and 5-MeO-DMT Signal
Heart palpitations or chest pain in the past three months were reported by 44.2% of ibogaine users (95% CI 29.2–59.2) and 51.3% of 5-MeO-DMT users (37.7–64.9). The authors note that the ibogaine finding is consistent with its known association with QTc prolongation, a change in the heart’s electrical rhythm, and arrhythmia.[1]
Thoughts of death or suicide in the past three months were reported by 59.3% of ibogaine users (95% CI 45.0–73.7) and 36.6% of 5-MeO-DMT users (23.2–49.9). These figures rest on 59 and 72 respondents, hence the wide intervals. The survey recorded selected lifetime psychiatric diagnoses, but the analysis did not adjust for those differences or establish whether thoughts of death or suicide began before or after use. Reported schizophrenia, for example, ranged from 2.3% of psilocybin users to 10.4% of ibogaine users.
If you are struggling or having thoughts of suicide, help is available now. In the US, call or text 988 or chat at 988lifeline.org to reach the 988 Suicide & Crisis Lifeline.[2] Elsewhere, findahelpline.com lists free crisis lines by country. In an emergency, call your local emergency number.
What the Survey Cannot Tell Us
The authors list the limits themselves. The design is cross-sectional, so it cannot establish cause. Pre-existing differences such as psychiatric history, and the use of other drugs alongside these, may explain some patterns; the analysis was descriptive and did not adjust for them. Self-attribution may vary by substance: in the authors’ words, the “prolonged, somatically demanding experience produced by ibogaine” and the “overwhelming phenomenology” of 5-MeO-DMT may increase attribution of pre-existing or coincidental symptoms. The ibogaine and 5-MeO-DMT samples were small, and recall bias may have played a part.[1]
Readers should also know the disclosures. The survey was funded by SAMHSA and the National Institute on Drug Abuse, which had no role in the study. Senior author Peter Hendricks reports grants or fees from several psychedelic companies, including Beckley Psytech, Usona Institute and Reunion Neuroscience, and equity in AtaiBeckley. Three authors are employees of Rocky Mountain Poison and Drug Safety, which provides surveillance and research services to government agencies, drug manufacturers and nonprofits.[1] None of this invalidates the data.
Why It Matters Now
In September, Definium announced topline results, not yet published in a peer-reviewed journal, from a second positive Phase 3 trial of its LSD tablet in generalized anxiety disorder: 245 participants, with a 5.1-point placebo-adjusted improvement on the HAM-A anxiety scale at week 12 for the 100 µg dose.[3] In April the FDA agreed to a rolling submission and review process for Compass Pathways’ planned COMP360 new drug application for psilocybin in treatment-resistant depression.[4] Ketamine, the one fast-acting option already in clinical use for depression, was not part of this survey; its risks are covered in our ketamine overdose guide.
The authors conclude that the findings support safety surveillance, targeted harm reduction and balanced communication about risks and benefits.[1]
Clinical trials and population surveys answer different questions. Trials estimate benefits and risks under controlled conditions; this survey captures what users attribute to these drugs in much less controlled settings. Neither cancels out the other.
This article is for information only and is not medical advice.
References
- Simonsson O, Bradley M, Black JC, Rockhill KM, Monte AA, Hendricks PS. Adverse health outcomes of psilocybin, LSD, MDMA, ibogaine, and 5-MeO-DMT. JAMA Netw Open. 2026;9(9):e2636756. doi:10.1001/jamanetworkopen.2026.36756
- Substance Abuse and Mental Health Services Administration. 988 Suicide & Crisis Lifeline fact sheet.
- Definium Therapeutics. Definium Therapeutics announces positive topline results from Phase 3 Panorama study of DT120 ODT in generalized anxiety disorder. Press release, September 2026.
- Compass Pathways. Compass Pathways announces FDA granted NDA rolling review request and awarded Commissioner’s National Priority Voucher. Press release, April 24, 2026.
