About 4% of individuals with a neuropsychiatric disorder had a serious adverse event—including worsening depression, suicidal behavior, psychosis, or convulsions—after being given a “classic” psychedelic as part of a research study, according to a meta-analysis that spanned some 75 years issued by JAMA Psychiatry. The meta-analysis identified no such adverse events among healthy participants; at the same time, tracking of such events should be improved, the study researchers wrote.
“Recording aversive experiences as adverse events is pragmatic and necessary. In particular, the presence and absence of any [adverse events] … such as precipitation of an affective or psychotic illness, persisting perceptual disturbances, and cardiac toxicity, should be clearly reported,” wrote Jared T. Hinkle, M.D., Ph.D., of Johns Hopkins University School of Medicine, and colleagues. “…Our results broadly indicate that while medically or psychiatrically significant adverse events, for example, psychosis [or] suicidality, are relatively rare, these events are often serious when they occur."
Hinkle and colleagues examined 214 clinical or research studies going back to 1951, for which 53% (114 studies) reported analyzable adverse event data. These studies included 1,726 healthy participants, 934 participants receiving outpatient psychiatric care, and 844 participants receiving inpatient psychiatric care; all participants received high doses of one of the four most actively studied psychedelics: LSD (lysergic acid diethylamide), psilocybin, DMT (dimethyltryptamine), or 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine). All studies involving inpatients were done prior to 1970, researchers noted.
Results were as follows:
- In contemporary research studies (since 2005), there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders.
- Of 584 outpatient participants administered high-dose psilocybin, three exhibited delayed suicidal behaviors; all three individuals had treatment-resistant depression.
- Reports of other adverse events requiring medical intervention, such as paranoia or headache, were rare.
- Just two serious acute events (within 48 hours of psychedelic effect) were identified in outpatient participants: One person given LSD in a study of anxiety experienced “acute transient anxiety and delusions” refractory to lorazepam, which required olanzapine and overnight observation, and one participant with depression and a history suggestive of orthostasis given DMT experienced a substantial blood pressure drop.
The researchers cautioned that only 29% of contemporary studies with adverse event data reported all adverse events, as opposed to only listing adverse drug reactions. This could explain the lower-than-expected reported rate of certain adverse events—for example, visual hallucinations—among participants. The researchers also noted that individuals with psychotic or manic disorders are typically excluded from contemporary research studies.
“Although psychedelic treatments were initially very well tolerated in participants with psychiatric conditions, the rate of potentially life-threatening delayed adverse events was higher in participants with psychiatric conditions than those without. The reasons for this remain undetermined,” Hinkle, a PGY-2 psychiatry resident at Johns Hopkins Hospital, told Psychiatric News Alert via e-mail. “Also, these data do not generalize to psychedelic use outside of a clinical or research context, so psychiatrists should advise their patients accordingly.”
For more information, see the Psychiatric News article “Psychedelic Use in Psychiatry Demands New Informed Consent Process, Bioethicists Say.”
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