Among adolescents with early-onset psychosis, about 14% have used hallucinogens, and such use is linked to more complex clinical trajectories including higher rates of suicidality, conduct disorder, reduced educational attainment, and need for depot antipsychotic treatment. In the general adolescent population, hallucinogen use shows only weak and inconsistent associations with psychotic or manic symptoms, which largely disappear after accounting for other drug use and genetic vulnerability. The findings suggest hallucinogens are not an isolated causal trigger for psychosis but may worsen symptoms in youth with neurodevelopmental or genetic predispositions.
A systematic review of 23 studies examined whether serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA can trigger manic or hypomanic symptoms. Rates of such symptoms ranged from 5.8% in controlled trials of psilocybin-assisted therapy for depression to 30% in naturalistic studies of people with bipolar disorder. When manic symptoms occurred, they were typically acute and self-limited. Higher risks were seen in individuals with bipolar I disorder, family vulnerability, polysubstance use, or unsupervised use. Registry data showed a 4% prevalence of later transition to bipolar disorder, with little evidence for a hallucinogen-specific signal. The authors conclude that these substances pose a low but clinically meaningful relative risk of transient mood symptoms in susceptible individuals while remaining relatively safe in controlled settings.