TOPLINE

Users of psychoactive substances ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) reported higher rates of adverse health effects, including cardiac symptoms and suicidal thoughts, than users of psilocybin, lysergic acid diethylamide (LSD), or MDMA, a cross-sectional study showed. Psilocybin, LSD, and MDMA were estimated to affect a larger proportion of US adults than ibogaine or 5-MeO-DMT.

METHODOLOGY

• Investigators conducted a cross-sectional study using data from the 2025 National Survey Investigating Hallucinogenic Trends, a verified online panel survey of adults across the US.
• A total of 1964 adults were included, and the responses were weighted to a nationally representative survey.
• Participants who reported using one or more substances during the past year were asked whether they noticed changes in their physical or mental health and whether they used healthcare services that they attributed to the substance.
• Participants who used one or more substances in the past 3 months were asked whether they experienced any of 13 specific symptoms chosen from the Swiss Psychedelic Side Effects Inventory and attributed to the substance.

TAKEAWAY

• Past-year use was most common for psilocybin (n = 1151), followed by MDMA (n = 539), LSD (n = 376), 5-MeO-DMT (n = 95), and ibogaine (n = 74). Past 3-month use followed a similar pattern, reported for psilocybin (n = 667), MDMA (n = 335), LSD (n = 218), 5-MeO-DMT (n = 72), and ibogaine (n = 59). Estimated past-year users were highest for psilocybin (8.12 million), followed by MDMA (3.93 million), LSD (2.58 million), 5-MeO-DMT (0.74 million), and ibogaine (0.56 million).
• Among past-year substance users, self-attributed worsening of physical health, worsening mental health, and healthcare use were lowest for psilocybin (6.2%, 4.7%, and 16.2%, respectively) and highest for ibogaine (45.1%, 34.5%, and 74.2%, respectively). Physical health improvements were reported by 22.3%-28.5% of users across substances (highest for 5-MeO-DMT), and mental health improvements ranged from 36.6%-51.2% (highest for psilocybin).
• Among those reporting use in the past 3 months, adverse effects were most common among users of ibogaine (94.8%) and 5-MeO-DMT (92.8%) and relatively less common among users of psilocybin (75.6%), MDMA (81.4%), and LSD (83.6%).Adverse effects varied by substance; heart palpitations or chest pain/pressure was reported by 44.2% of ibogaine users and 51.3% of 5-MeO-DMT users, and thoughts of death or suicide were reported by 59.3% and 36.6%, respectively.

IN PRACTICE

"[T]hese 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," the authors wrote.

SOURCE

The study was led by Otto Simonsson, PhD, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden. It was published online on September 29 as a Research Letter in JAMA Network Open.

LIMITATIONS

The study was limited by its cross-sectional design, preexisting differences between groups, small subgroup sizes of users of ibogaine and 5-MeO-DMT, reliance on self-reported data, and a potential recall bias.

DISCLOSURES

The National Survey Investigating Hallucinogenic Trends validation was funded by the Substance Abuse and Mental Health Services Administration and ongoing data collection by the National Institute on Drug Abuse and the National Institutes of Health. Disclosure information for the study investigators is available in the original study publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.