Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

Otto Simonsson; Melissa Bradley; Joshua C Black; Karilynn M Rockhill; Andrew A Monte; Peter S Hendricks

doi:10.1001/jamanetworkopen.2026.36756

. 2026 Sep 29;9(9):e2636756. doi: 10.1001/jamanetworkopen.2026.36756

Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

Otto Simonsson ^1,^✉, Melissa Bradley ², Joshua C Black ³, Karilynn M Rockhill ³, Andrew A Monte ^3,⁴, Peter S Hendricks ²

¹Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden

²Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham

³Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, Denver, Colorado

⁴University of Colorado School of Medicine, Aurora

Accepted for Publication: July 31, 2026.

Published: September 29, 2026. doi:10.1001/jamanetworkopen.2026.36756

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. © 2026 Simonsson O et al. JAMA Network Open.

^✉

Corresponding Author: Otto Simonsson, PhD, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Tomtebodavägen 18A, 171 65 Solna, Sweden (otto.simonsson@ki.se).

Author Contributions: Ms Bradley and Dr Hendricks had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bradley, Rockhill, Monte, Hendricks.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Simonsson, Bradley, Monte, Hendricks.

Critical review of the manuscript for important intellectual content: Bradley, Black, Rockhill, Monte, Hendricks.

Statistical analysis: Bradley, Hendricks.

Obtained funding: Monte.

Administrative, technical, or material support: Black, Rockhill, Monte, Hendricks.

Supervision: Black, Monte, Hendricks.

Conflict of Interest Disclosures: Drs Black, Monte, and Rockhill reported being employees of Rocky Mountain Poison & Drug Safety (RMPDS), a division of nonprofit Denver Health and Hospital Authority, a subdivision of the State of Colorado. Outside of this work, RMPDS provides independent surveillance, research, and reporting services to government agencies, pharmaceutical manufacturers, and nongovernment organizations. No other organization or party besides the authors participated in the conception, analysis, drafting, or review of this manuscript. Dr Monte reported receiving grants from the Substance Abuse and Mental Health Services Administration (SAMHSA; grants HHSS283201700075I, 75S20321F42002, 75S20123P00004, and 75S20124P00003). Drs Monte and Black reported receiving support from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) under Award Number R01DA064612. Dr Hendricks reported receiving grants from Beckley Psytech, NIH, Reunion Neuroscience, and Usona Institute; personal fees from Bright Minds Biosciences, Journey Colab Corporation, Negev Labs, Otsuka Pharmaceutical Development and Commercialization, and Reunion Neuroscience; owning equity or stock options in AtaiBeckley, Inc, and Negev Labs; being cofounder of Equulus Therapeutics and Mycelial Health; and having a patent for 63/804,162 pending outside the submitted work. No other disclosures were reported.

Funding/Support: The National Survey Investigating Hallucinogenic Trends validation was funded through SAMHSA (grants 75S20123P00004 and 75S20124P00003) and ongoing data collection through NIDA and NIH (grant R01DA064612).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the SAMHSA or the NIH.

Data Sharing Statement: See Supplement 2.

^✉

Corresponding author.

PMCID: PMC13624878 PMID: 42809289

Abstract

This cross-sectional study describes health outcomes attributed to recent use of psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ibogaine, and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a nationally representative survey of US adults.

Introduction

Psychedelics such as psilocybin and lysergic acid diethylamide (LSD), as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA), have shown promise for psychiatric disorders in phase 3 trials.^1,2,3 Other psychoactive substances, such as ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), have also shown promise for psychiatric disorders in smaller trials.^4,5 These trial findings may not translate to general population settings, however, where dose and purity vary, co-use of other drugs can occur, and medical supervision is often absent, leaving public health messaging reliant on incomplete evidence⁶ as legislative reform accelerates.⁷ Here, we describe health outcomes attributed to recent use of these 5 substances in a nationally representative survey of US adults.

Methods

This cross-sectional study followed the STROBE reporting guidelines. Data were from the 2025 NSIHT (National Survey Investigating Hallucinogenic Trends),⁸ a double opt-in online panel survey of US adults in all 50 states. Responses were weighted to a nationally representative anchor survey through a data fusion and calibration process shown to be externally valid to US demographics, health, and drug use; 35 extreme weights were trimmed to the 99th percentile. The Colorado Multiple Institutional Review Board approved the NSIHT as expedited, nonexempt, human participants research. Respondents provided written informed consent. Race and ethnicity were self-reported through separate investigator-defined multiple-select items to characterize the populations reporting use.

Respondents reporting past 12-month use reported whether their physical or mental health had changed and whether they had used health care services during that period that they self-attributed to each substance. Respondents reporting past 3-month use were additionally asked, separately for each substance, which of 13 symptoms they had experienced during that period and attributed to that substance. These 13 items were selected a priori by the study team from the 32-item Swiss Psychedelic Side Effects Inventory,⁹ on the basis of clinical relevance, and adapted to a 3-month recall period. The shorter window limits recall bias. Respondents who used multiple substances answered the items for each substance they reported (see the eTable in Supplement 1 for exact wording of survey items). Analyses were descriptive; weighted percentages with 95% CIs were estimated in R statistical software version 4.4.1 (R Project for Statistical Computing).

Results

Of 1964 adults, past 12-month use was reported by 1151 respondents for psilocybin, 376 for LSD, 539 for MDMA, 74 for ibogaine, and 95 for 5-MeO-DMT. Weighted prevalence ranged from 0.2% (95% CI, 0.2%-0.3%) for ibogaine to 3.1% (95% CI, 2.9%-3.3%) for psilocybin; mean (SD) age ranged from 30.4 (8.9) to 37.2 (12.9) years; and male sex ranged from 62.4% (95% CI, 59.2%-65.6%) to 75.2% (95% CI, 65.2%-85.3%). Race was reported as American Indian or Alaska Native (range, 0.5% [95% CI, 0.0%-1.5%] to 3.4% [95% CI, 0.0%-7.6%]), Asian (range, 4.0% [95% CI, 2.7%-5.2%] to 7.6% [95% CI, 0.3%-14.9%]), Black or African American (range, 17.6% [95% CI, 15.0%-20.2%] to 31.9% [95% CI, 27.1%-36.7%]), Native Hawaiian or Pacific Islander (range, 0.0% to 2.6% [95% CI, 0.0%-6.2%]), White (range, 55.1% [95% CI, 41.9%-68.4%] to 74.8% [95% CI, 71.8%-77.7%]), or other (range, 5.2% [95% CI, 3.7%-6.6%] to 8.7% [95% CI, 1.0%-16.3%]) (other was offered as a checkbox without a write-in field, so the specific groups reported within this category were not captured by the survey), with 18.5% (95% CI, 15.9%-21.1%) to 33.0% (95% CI, 21.7%-44.3%) identifying as Hispanic or Latino ethnicity. The groups varied, for example, in lifetime psychiatric diagnoses (eg, schizophrenia diagnoses ranged from 2.3% [95% CI, 1.3%-3.3%] for psilocybin to 10.4% [95% CI, 2.3%-18.5%] for ibogaine), military service, therapeutic or clinical-setting use, substance co-use, and frequency of use. Notably, any worsening physical or mental health, as well as any use of health care services, attributed to the substance ranged from 6.2% (95% CI, 4.4%-7.9%), 4.7% (95% CI, 3.2%-6.2%), and 16.2% (95% CI, 13.6%-18.8%), respectively, for psilocybin to 45.1% (95% CI, 31.8%-58.4%), 34.5% (95% CI, 21.5%-47.5%), and 74.2% (95% CI, 63.1%-85.2%), respectively, for ibogaine. Physical health improvements were most frequently reported for 5-MeO-DMT (28.5%; 95% CI, 17.8%-39.2%), and mental health improvements were most frequently reported for psilocybin (51.2%; 95% CI, 47.8%-54.6%) (Table).

Table. Characteristics and Health Outcomes Self-Attributed to Use of Psilocybin, LSD, MDMA, Ibogaine, or 5-MeO-DMT.

Characteristic	Participants, No. (%) [95% CI]^a
Characteristic	Psilocybin (n = 1151)	LSD (n = 376)	MDMA (n = 539)	Ibogaine (n = 74)	5-MeO-DMT (n = 95)
Estimated US adults, No. in millions (95% CI)^b	8.12 (7.58-8.66)	2.58 (2.27-2.89)	3.93 (3.54-4.33)	0.56 (0.42-0.71)	0.74 (0.57-0.91)
Weighted past-year prevalence, % (95% CI)	3.1 (2.9-3.3)	1.0 (0.9-1.1)	1.5 (1.3-1.6)	0.2 (0.2-0.3)	0.3 (0.2-0.3)
Age, mean (SD) [95% CI], y	37.2 (12.9) [36.3-38.0]	33.2 (12.0) [31.9-34.6]	31.7 (9.5) [30.8-32.7]	30.4 (8.9) [27.9-32.9]	31.6 (11.1) [29.2-34.1]
Sex
Female	502 (37.6) [34.4-40.8]	137 (33.1) [27.5-38.6]	211 (34.9) [30.1-39.6]	26 (26.1) [15.4-36.8]	27 (24.8) [14.7-34.8]
Male	649 (62.4) [59.2-65.6]	239 (66.9) [61.4-72.5]	328 (65.1) [60.4-69.9]	48 (73.9) [63.2-84.6]	68 (75.2) [65.2-85.3]
Race
American Indian or Alaska Native	51 (3.1) [2.1-4.1]	11 (2.3) [0.8-3.8]	14 (1.9) [0.8-3.1]	1 (0.5) [0.0-1.5]	3 (3.4) [0.0-7.6]
Asian	46 (4.0) [2.7-5.2]	19 (4.7) [2.5-6.9]	24 (4.7) [2.5-6.9]	6 (7.6) [0.3-14.9]	5 (5.1) [0.0-10.6]
Black or African American	206 (17.6) [15.0-20.2]	85 (22.8) [17.7-28.0]	172 (31.9) [27.1-36.7]	26 (29.7) [18.0-41.3]	24 (25.3) [14.9-35.8]
Native Hawaiian or Pacific Islander	9 (0.7) [0.1-1.3]	2 (0.5) [0.0-1.2]	1 (0.1) [0.0-0.2]	0	2 (2.6) [0.0-6.2]
White	861 (74.8) [71.8-77.7]	257 (67.8) [62.2-73.4]	318 (58.3) [53.3-63.3]	38 (55.1) [41.9-68.4]	59 (61.4) [49.8-73.0]
Other^c	68 (5.2) [3.7-6.6]	22 (5.2) [2.7-7.7]	44 (6.4) [4.2-8.6]	6 (8.7) [1.0-16.3]	8 (6.6) [1.6-11.6]
Hispanic or Latino ethnicity	211 (18.5) [15.9-21.1]	82 (23.1) [18.0-28.3]	115 (21.9) [17.7-26.2]	20 (27.6) [15.8-39.4]	29 (33.0) [21.7-44.3]
Bachelor’s degree or higher	429 (41.5) [38.2-44.9]	135 (38.3) [32.5-44.2]	205 (41.7) [36.7-46.7]	38 (57.0) [43.9-70.0]	47 (55.0) [43.3-66.7]
Never served in military	1059 (92.2) [90.4-94.0]	338 (88.5) [84.6-92.3]	490 (90.7) [87.9-93.5]	53 (71.6) [59.8-83.3]	69 (68.3) [57.1-79.5]
Not a first responder	1107 (95.8) [94.4-97.3]	352 (92.3) [89.1-95.5]	503 (92.9) [90.4-95.4]	56 (75.2) [63.4-87.0]	69 (66.9) [55.3-78.5]
Annual household income, $
<49 999	465 (36.6) [33.4-39.9]	167 (38.5) [32.7-44.3]	206 (35.2) [30.4-40.0]	24 (32.2) [19.7-44.8]	31 (32.2) [21.1-43.3]
50 000-99 999	418 (37.0) [33.7-40.2]	127 (35.3) [29.6-41.1]	198 (36.8) [32.0-41.7]	33 (37.3) [25.0-49.7]	32 (33.2) [22.2-44.2]
≥100 000	268 (26.4) [23.3-29.4]	82 (26.2) [20.7-31.6]	135 (28.0) [23.4-32.6]	17 (30.4) [17.0-43.8]	32 (34.6) [23.2-46.0]
Mental health diagnoses (lifetime)
Bipolar disorder	160 (12.3) [10.2-14.4]	51 (12.9) [8.8-16.9]	82 (13.6) [10.2-17.0]	11 (16.4) [5.9-27.0]	14 (16.3) [7.0-25.5]
Schizophrenia	26 (2.3) [1.3-3.3]	11 (2.7) [0.9-4.5]	16 (2.9) [1.3-4.5]	7 (10.4) [2.3-18.5]	6 (7.8) [1.4-14.2]
Psychosis or psychotic episode	39 (3.4) [2.2-4.6]	17 (4.5) [2.1-6.8]	15 (2.2) [0.9-3.6]	6 (8.3) [1.5-15.1]	7 (6.5) [1.4-11.6]
Use characteristics
Medical symptom treatment	394 (33.1) [30.0-36.3]	93 (25.0) [19.7-30.4]	108 (20.6) [16.5-24.8]	38 (52.0) [38.5-65.4]	47 (54.0) [42.3-65.8]
Medical office or clinic	88 (8.4) [6.4-10.3]	56 (19.3) [14.1-24.5]	76 (16.3) [12.4-20.2]	30 (43.4) [30.0-56.7]	34 (40.6) [28.8-52.4]
Monthly use or more	182 (16.4) [13.8-18.9]	70 (20.7) [15.5-25.9]	109 (18.8) [14.9-22.6]	38 (47.8) [34.4-61.2]	30 (32.7) [21.4-43.9]
Any substance co-use	775 (66.2) [63.0-69.5]	259 (67.3) [61.6-73.0]	393 (72.0) [67.5-76.6]	60 (78.3) [66.6-90.0]	69 (73.2) [63.0-83.4]
Any preparation before use	581 (52.4) [49.1-55.8]	234 (66.1) [60.6-71.7]	317 (61.4) [56.5-66.2]	65 (91.4) [85.3-97.5]	72 (81.4) [73.3-89.6]
Any supervision during use	599 (52.9) [49.5-56.2]	228 (62.2) [56.5-68.0]	338 (63.0) [58.1-67.9]	60 (85.0) [76.8-93.3]	71 (79.9) [71.4-88.4]
Any integration after use	566 (51.3) [47.9-54.6]	230 (63.3) [57.6-69.1]	291 (56.8) [51.8-61.7]	61 (86.3) [78.4-94.3]	66 (74.4) [64.8-84.0]
Physical health change (past 12 mo)
Any worsening	58 (6.2) [4.4-7.9]	50 (13.5) [9.4-17.6]	64 (11.9) [8.7-15.2]	34 (45.1) [31.8-58.4]	38 (42.7) [30.9-54.5]
Any improvement	264 (24.0) [21.1-27.0]	95 (27.8) [22.3-33.4]	110 (22.3) [18.0-26.6]	20 (26.3) [14.5-38.2]	28 (28.5) [17.8-39.2]
Mental health change (past 12 mo)
Any worsening	48 (4.7) [3.2-6.2]	37 (10.8) [6.9-14.6]	61 (11.4) [8.1-14.7]	22 (34.5) [21.5-47.5]	28 (30.1) [19.3-40.8]
Any improvement	579 (51.2) [47.8-54.6]	161 (43.7) [37.7-49.6]	186 (36.6) [31.7-41.5]	27 (37.2) [24.1-50.2]	33 (37.0) [25.3-48.8]
Any health care services (past 12 mo)	168 (16.2) [13.6-18.8]	93 (27.3) [21.9-32.8]	129 (27.1) [22.5-31.7]	51 (74.2) [63.1-85.2]	55 (63.8) [52.7-74.8]

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Abbreviations: 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine; LSD, lysergic acid diethylamide; MDMA, 3,4-methylenedioxymethamphetamine.

^{^a}

No. of respondents represents the unweighted sample size.

^{^b}

Estimated US adults refers to the total projected population size based on the applied survey weights.

^{^c}

Other was offered as a checkbox without a write-in field, so the specific groups reported within this category were not captured by the survey.

Past 3-month use was reported by 667 respondents for psilocybin, 218 for LSD, 335 for MDMA, 59 for ibogaine, and 72 for 5-MeO-DMT. Endorsing at least 1 of the 13 adverse effects attributed to the substance was reported by 75.6% (95% CI, 71.8%-79.3%) for psilocybin, 83.6% (95% CI, 77.8%-89.4%) for LSD, 81.4% (95% CI, 76.5%-86.4%) for MDMA, 94.8% (95% CI, 90.0%-99.7%) for ibogaine, and 92.8% (95% CI, 86.4%-99.1%) for 5-MeO-DMT. For each of the 13 adverse effects, the highest percentages were observed among respondents reporting ibogaine or 5-MeO-DMT use (range, 31.3% [95% CI, 18.1%-44.6%] to 64.6% [95% CI, 50.9%-78.3%]) (Figure). For instance, heart palpitations or chest pain or pressure was attributed to ibogaine and 5-MeO-DMT use by 44.2% (95% CI, 29.2%-59.2%) and 51.3% (95% CI, 37.7%-64.9%), respectively, whereas thoughts of death or suicide were attributed by 59.3% (95% CI, 45.0%-73.7%) and 36.6% (95% CI, 23.2%-49.9%), respectively.

Two-panel dot plots of adverse effects by substance, with percent and millions axes. Two stacked panels labeled A and B, each a horizontal dot plot with colored circular markers and horizontal 95 percent confidence interval lines. A title at upper left reads Proportion of each substance’s users affected. Panel A left column header reads Adverse effect, followed by 13 row labels from top to bottom: Desire to take the substance again; Changes in vision; Sleep difficulties; Excessive elation or impulsivity; Fatigue or tiredness; Headache; Anxiety, fear, or panic; Heart palpitations or chest pain or pressure; Nausea or vomiting; Memory problems or blackouts; Paranoia; Return of substance effects; Thoughts of death or suicide. Panel A horizontal axis label reads Proportional frequency of users, percent (95 percent C I), with tick labels at 0, 20, 40, 60, and 80. Each adverse-effect row contains five colored point estimates with matching horizontal confidence intervals. A legend at lower right maps colors to substances: Psilocybin in dark blue-gray, L S D in teal, M D M A in magenta, Ibogaine in orange, and 5-M e O-D M T in tan. Panel B title at left reads Estimated total number of US adults affected. Panel B repeats the same adverse-effect rows and color scheme. Panel B horizontal axis label reads Estimated number of adults affected, millions (95 percent C I), with tick labels at 0, 0.5, 1.0, 1.5, 2.0, and 2.5. In Panel B, points and confidence intervals for Psilocybin extend farthest right in several rows, including the top row near about 2.2 million, while other substances cluster mostly between about 0.1 and 1.0 million depending on the adverse-effect row. — A, Proportion of respondents reporting a given adverse effect for each substance, shown as point estimates with 95% CIs. B, Estimated total number of US adults affected by each adverse effect for each substance, shown in millions with 95% CIs. Adverse effects are ordered by prevalence pooled across substances. Some labels do not correspond exactly to the questionnaire wording; exact wording of all survey items is provided in the eTable in Supplement 1. All estimates refer to respondents reporting past 3-month use of the given substance and to adverse effects experienced in that period.

Discussion

In this nationally representative cross-sectional survey of US adults, self-attributed adverse outcomes were most frequent among respondents reporting ibogaine or 5-MeO-DMT use. The estimated number of adults reporting such outcomes was nevertheless greatest for psilocybin, LSD, and MDMA. Although these descriptive patterns should be interpreted cautiously, many findings may indicate comparative pharmacological risk, such as the cardiac adverse effects attributed to ibogaine, for instance, which are consistent with its known association with QTc prolongation and arrhythmia.¹⁰

There were several limitations. First, the cross-sectional design precludes conclusions about causality. Second, preexisting differences across groups (eg, psychiatric history), as well as potential substance co-use, may partly explain observed patterns and preclude attribution to pharmacology alone. Third, self-attribution may vary by substance (eg, the prolonged, somatically demanding experience produced by ibogaine and the overwhelming phenomenology of 5-MeO-DMT may increase attribution of preexisting or coincidental symptoms). Fourth, small ibogaine and 5-MeO-DMT samples yielded wide 95% CIs. Other limitations, including recall bias, may have further influenced findings. Taken together, these findings support safety surveillance in the general population, targeted harm reduction where warranted, and balanced public health communication about potential risks and benefits of these substances.

Supplement 1.

eTable. Exact Wording of Survey Items Corresponding to the Figure

jamanetwopen-e2636756-s001.pdf^{(259.1KB, pdf)}

Supplement 2.

Data Sharing Statement

jamanetwopen-e2636756-s002.pdf^{(13.6KB, pdf)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eTable. Exact Wording of Survey Items Corresponding to the Figure

jamanetwopen-e2636756-s001.pdf^{(259.1KB, pdf)}

Supplement 2.

Data Sharing Statement

jamanetwopen-e2636756-s002.pdf^{(13.6KB, pdf)}

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Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

Otto Simonsson, PhD

Melissa Bradley, MPH

Joshua C Black, PhD

Karilynn M Rockhill, PhD

Andrew A Monte, MD, PhD

Peter S Hendricks, PhD

Abstract

Introduction

Methods

Results

Table. Characteristics and Health Outcomes Self-Attributed to Use of Psilocybin, LSD, MDMA, Ibogaine, or 5-MeO-DMT.

Figure. Dot Plot of Adverse Effects Self-Attributed to Use of Psilocybin, Lysergic Acid Diethylamide (LSD), 3,4-Methylenedioxymethamphetamine (MDMA), Ibogaine, or 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT).

Discussion

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

Otto Simonsson, PhD

Melissa Bradley, MPH

Joshua C Black, PhD

Karilynn M Rockhill, PhD

Andrew A Monte, MD, PhD

Peter S Hendricks, PhD

Abstract

Introduction

Methods

Results

Table. Characteristics and Health Outcomes Self-Attributed to Use of Psilocybin, LSD, MDMA, Ibogaine, or 5-MeO-DMT.

Figure. Dot Plot of Adverse Effects Self-Attributed to Use of Psilocybin, Lysergic Acid Diethylamide (LSD), 3,4-Methylenedioxymethamphetamine (MDMA), Ibogaine, or 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT).

Discussion

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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