Genetic Analysis Suggests Cannabis Use May Increase Risk of Parkinson's Disease and ADHD in Women

Using two-sample Mendelian randomization with GWAS data, the study found genetically predicted lifetime cannabis use was associated with increased risk of Parkinson's disease (OR=1.78, 95% CI: 1.03-3.08) and ADHD in women (OR=1.65, 95% CI: 1.05-2.59). No significant causal associations were found with Alzheimer's, ALS, epilepsy, migraine, schizophrenia, anorexia, or autism.

Two-sample Mendelian randomization using publicly available GWAS summary statistics. Genetic instruments for lifetime cannabis use tested against 10 neuropsychiatric disorders. Inverse variance weighted (IVW) method as primary analysis.

Traditional observational studies cannot easily separate whether cannabis use causes neuropsychiatric conditions or whether people predisposed to those conditions are more likely to use cannabis. Mendelian randomization uses genetic variation to approximate a natural experiment, providing stronger evidence about causal direction.

The Parkinson's finding is unexpected given that some cannabis compounds have been explored as neuroprotective agents. If confirmed, it would complicate the narrative around cannabis and neurodegeneration. The sex-specific ADHD finding adds to growing evidence that cannabis affects men and women differently.

Mendelian randomization assumes genetic variants affect the outcome only through cannabis use (no pleiotropy). Moderate p-values that would not survive strict multiple comparison correction. Cannot assess dose-response, timing, or type of cannabis. European-ancestry GWAS limits generalizability.