Associations between psychedelic use and migraine history in Swedish twins.

While psychedelics have shown initial promise in the treatment of migraine, experimental studies have relied on small and homogenous samples, which limit the reliability and generalizability of findings. These limitations underscore the complementary value of other research designs that leverage larger and more representative samples. This cross-sectional study included three cohorts of twins from the Swedish Twin Registry and evaluated associations between psychedelic use and migraine history. In this study, 50,726 twins answered questions related to the use of psychedelics. There were 1287 twins who reported psychedelic use, of whom 420 were monozygotic twins. While 271 twin pairs were discordant on psychedelic use, 40 twin pairs (16 male, 24 female) were discordant on both psychedelic use and migraine history. When restricting the analyses to monozygotic twins in the between-within logistic regression model, the between-pair association was significant, with pairs in which at least one twin reported psychedelic use showing lower odds of migraine history (adjusted odds ratio (aOR) = 0.50, = 0.041). The within-pair association was also significant, with twins who reported psychedelic use showing lower odds of migraine history compared to their co-twin (aOR = 0.38, = 0.008). Notably, subgroup analyses showed that these results were broadly the same when only males were included in the models, but no significant associations were observed in female-only models. The findings from this twin study suggest that psychedelics may be linked to a lower likelihood of migraine, with potential differences by sex. This warrants further investigation and highlights the importance of sex-specific analyses in future studies.