Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants.
In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.
In addition, AG and GG genotypes of OPRM1 rs1799971 were correlated with migraine episodes, AG and GG of OPRM1 rs1799971, and CT and CC of CNR1rs806368 with a family history of migraines (second degree relatives), and CT and CC of CNR1rs2023239 with a positive response to therapy.