Associations between psychedelic use and migraine history in Swedish twins
Is lifetime psychedelic use (primarily psilocybin or LSD) associated with a lower incidence of migraines?
This study used data from the Swedish Twin Registry to examine whether lifetime psychedelic use (primarily psilocybin or LSD) is associated with a history of migraine. The twin design is important because it helps account for shared genetic and family environmental factors that can confound observational studies
Psychedelic use was associated with lower odds of migraine. Compared with participants who had never used psychedelics, those who had used psychedelics had: 24% lower odds of reporting a history of migraine after adjusting for demographic characteristics and other substance use.
The association remained after controlling for genetics and family environment
Among identical (monozygotic) twin pairs discordant for psychedelic use, the twin who had used psychedelics had 62% lower odds of reporting migraine than their genetically identical co-twin who had not (aOR 0.38, 95% CI 0.19–0.76).
In the between-pair analysis, twin pairs in which at least one twin had used psychedelics showed 50% lower odds of migraine than pairs in which neither twin had used psychedelics (aOR 0.50, 95% CI 0.26–0.96).
The findings are consistent with growing interest in psychedelics as potential treatments for headache disorders. The authors discuss several possible mechanisms, including:
Modulation of serotonin (5-HT2A and related) receptors, which play a role in migraine pathophysiology.
Effects on neural circuits involved in pain processing.
Possible anti-inflammatory and neuroplasticity-related effects.
However, the study was not designed to test these mechanisms directly.
Abstract
Background:
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.
Methods:
This cross-sectional study included three cohorts of twins from the Swedish Twin Registry and evaluated associations between psychedelic use and migraine history.
Results:
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, p = 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, p = 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.
Conclusions:
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.
Simonsson O, Sun S, Wesseldijk LW, Ullén F, Osika W, Mosing MA. Associations between psychedelic use and migraine history in Swedish twins. Journal of Psychopharmacology. 2026;40(5):831-836. Read Paper
For more psychedelic news and research, visit the psychedelic health professional network homepage.
