Unusual experiences and early-onset psychosis associated to hallucinogen use in adolescents: a systematic review and meta-analysis.

Abstract

Background: Hallucinogen use among adolescents is increasing worldwide. In this context, in recent years, hallucinogens have re-emerged in scientific and public discourse. However, whether there is an association between hallucinogens use in adolescents and the impact of such use in individuals with Early-Onset Psychosis (EOP), remains unclear. This systematic review and meta-analysis evaluated the prevalence and impact of hallucinogen use in adolescents with EOP, and the association between hallucinogen exposure and psychotic symptoms in community samples.

Methods: We carried out a PRISMA-compliant systematic search (PubMed, Web of Science, Cochrane Library, PsycINFO; last search in July 2025). We included observational studies enrolling individuals under 18 years. Independent reviewers performed study selection, data extraction, and risk-of-bias assessment (using the Newcastle-Ottawa Scale). We conducted a random-effects meta-analysis to estimate the prevalence of hallucinogen use in adolescents with EOP. Other clinical and functional outcomes, as well as evidence from community-based samples, were synthesized narratively. This was due to heterogeneity in design and reporting, which precluded the meta-analysis.

Results: Twelve articles met our inclusion criteria. 39.9% included individuals were female and the mean age was 16.1 years. In EOP, pooled prevalence of any hallucinogen use was 14.3% (k = 6; N = 713; 95% CI: 3.9%-40.9%). LSD use in the included studies ranged from 1.8 to 12.5%. MDMA use ranged from 3.5 to 42.9%. Hallucinogen use in EOP was consistently associated with polysubstance use and indicators of clinical complexity, including suicidality, conduct disorder, reduced educational attainment, and depot antipsychotic treatment. In the general population, hallucinogen use showed weak and inconsistent associations with psychotic symptoms and manic symptoms, but which largely attenuated after adjustment for other drugs and genetic vulnerability. Newcastle-Ottawa Scale (NOS) scores ranged from 4 to 9, with a mean score of 6.4.

Conclusions: Hallucinogen use is common in adolescents with EOP and seems to be associated with more complex clinical trajectories, particularly higher rates of suicidality. Although not an isolated causal trigger, hallucinogens may contribute to symptom exacerbation in neurodevelopmentally or genetically predisposed youth. Future research should prioritise longitudinal, large-scale studies and introduce clinical trials in the field.