Psychedelic exposure in pregnancy: a scoping review to inform perinatal drug safety and clinical counseling.

Abstract

Psychedelic and psychedelic-adjacent substances, including 3,4-methylenedioxymethamphetamine (MDMA) and classic serotonergic hallucinogens, are undergoing renewed therapeutic investigation and remain in non-medical use. Inadvertent exposure during early, unrecognized pregnancy is clinically plausible, yet pregnancy-specific safety evidence is limited. To map and synthesize the extent, characteristics, and limitations of primary human evidence on prenatal exposure to MDMA, psilocybin, and classic hallucinogens (lysergic acid diethylamide (LSD), mescaline/peyote, and N,N-dimethyltryptamine (DMT)/ayahuasca), and to identify clinically relevant evidence gaps for perinatal counseling and pharmacovigilance. Peer-reviewed primary human studies (cohort, case-control, cross-sectional, case series, case reports, and brief reports) describing prenatal exposure with reported maternal, obstetric, neonatal, congenital anomaly, or child neurodevelopmental outcomes were included. Animal and preconception-only studies were excluded. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were searched from inception to March 2025. Supplementary methods included Google Scholar screening and citation tracking. Data were charted in duplicate using a standardized form and synthesized descriptively by substance and outcome domain. Consistent with scoping methodology, no formal risk-of-bias assessment or meta-analysis was undertaken. Twenty-three primary human sources (1968-2020) met inclusion criteria: MDMA (n = 11), LSD (n = 11), and mescaline/peyote (n = 1). No eligible primary human pregnancy outcome studies were identified for psilocybin or DMT/ayahuasca. The evidence base was heterogeneous and predominantly comprised small cohorts, teratology service follow-up reports, and case-based publications, frequently limited by self-reported exposure, polysubstance confounding, and inconsistent outcome definitions. Human evidence on prenatal psychedelic exposure remains sparse and methodologically constrained. Absence of data for several substances should not be interpreted as evidence of safety. Clinicians should counsel with explicit acknowledgment of uncertainty while supporting harm reduction and appropriate follow-up. Structured perinatal pharmacovigilance and ethically designed evidence-generation strategies are needed as therapeutic psychedelic research expands.