Your Genes May Determine How Your Body Processes Cannabis—and Most People Have Atypical Variants

Retrospective chart review of 71 patients with prior pharmacogenomic testing who reported oral cannabis use. Average age 68.5, primarily white women. Genotyping of CYP2C9, CYP2C19, CYP3A4, and CYP3A5. Medication review for CYP450 interactions with THC and CBD.

RTHC-00186 emphasized the importance of 'start low, go slow' CBD dosing for epilepsy, partly because of drug interactions. This study reveals that even without drug interactions, the majority of patients have genetic variants that alter cannabinoid metabolism. This means the same dose produces different blood levels in different people—which could explain why clinical trials show inconsistent results and why individual patients have such variable experiences.

This provides a pharmacogenomic lens for understanding variable cannabis response. RTHC-00214's geriatric cannabis clinic included medication review—this study shows why genetic review should be added. The variable drug response also helps explain mixed results in clinical trials: RTHC-00182 found CBD didn't help knee OA, and RTHC-00158 found no overall symptom benefit in cancer—but in both cases, individual patients may have had very different drug exposures despite identical doses.

Retrospective, small sample (71 patients). Primarily white older women—allele frequencies vary across ethnic groups. No outcome data (were atypical metabolizers actually more or less responsive to cannabis?). Self-reported oral cannabis use. The study generates hypotheses about how genetic variants affect cannabis response but doesn't test those hypotheses clinically. Chart review can't capture all relevant medications or supplements.