CHRNA2 encodes the neuronal acetylcholine receptor (nAChR) alpha-2 subunit, and there is no reported functional link between cannabis use and alpha-2 subunit containing nAChRs. We hypothesize three potential ways of the involvement of CHRNA2 in CUD: 1) Substances in cannabis might interact directly with the alpha-2 subunit containing nAChRs as studies have found cannabidiol, a non-psychoactive component of cannabis, to inhibit the alpha-7 containing nAChRs37. 2) Cannabis could indirectly affect the alpha-2 subunit containing nAChRs. After binding of an agonist (e.g. acetylcholine), the nAChR responds by opening of an ion-conducting channel across the plasma membrane. This causes depolarization of the membrane and can result in presynaptic neurotransmitter release including dopamine38. Since the psychoactive active compound of cannabis THC has been found to affect the release of acetylcholine in various brain regions39 it could be speculated that this, through alpha-2 subunit containing nAChRs, could affect dopamine release, a known neurotransmitter involved in addiction. 3) There could be a strong biological link between expression of CHRNA2 and the cannabinoid receptor 1 gene (CNR1). This hypothesis is based on evaluation of gene-expression correlations
