Pharmacogenetic association study of cannabis use in chronic pain

Background: Pain is one of the leading causes of disability worldwide. Despite the various pharmacological treatments available, patients with chronic pain often remain with significant disabilities and unsatisfactory pain control. Cannabis and cannabinoids are sometimes used in the treatment of chronic pain as they have been shown to be useful in a subset of patients. Some of the adverse effects associated with cannabis use, such as cannabis use disorder (CUD) and cannabis-induced psychosis, have been associated with several genetic variants. Despite this, the paucity of the data or the contradictory results for reported variants limits our ability to use them as genetic markers to personalize cannabis treatment tailored to patients’ genetic background. The aim of this genetic association study was to investigate the link between previously reported genes and cannabinoid response in terms of pain response, CUD and risk of psychotic adverse events in patients with chronic pain.

Methods: Phone or in person interviews were conducted to document participants’ characteristics, cannabis use and effects, concurrent pharmacotherapy and comorbid conditions. Screening for CUD was performed using the Cannabis Use Disorders Identification Test – Revised. Blood or saliva samples were collected for the genotyping of 18 variants in 11 genes (BDNF, CNR1, CNR2, COMT, CYP2C9, FAAH, GABRA2, HES7, KAT2B, NRG1 and OPMR1).

Results: One hundred participants were recruited, with blood or saliva samples collected from 77 of them. Two single-nucleotide polymorphisms (SNP) in cannabinoid receptor 1 (CNR1) were associated, before multiple testing correction, with psychotic adverse events. Namely, T allele carriage of the CNR1 rs1049353 C > T variant increased the odds of having psychotic adverse events (OR = 6.1, 95% CI 1.7 – 27.9, p-value = 0,009) and C allele carriage of the CNR1 rs2023239 T > C intronic variant also increased these odds (OR = 3.5, 95% CI 1.5 – 9.4, p-value = 0,033). These findings were not significant after adjustment for multiple SNPs testing and none of the variants were associated with CUD or pain response.

Conclusions: These results suggest alternative allele carriers of rs1049353 and rs2023239 could be at an increased risk of psychotic adverse events related to cannabis use, although additional investigation is required to replicate and confirm these findings.