A rat G protein-coupled receptor (rTAR1) stimulates cAMP production when exposed to trace amines such as p-tyramine, beta-phenethylamine, tryptamine, and octopamine. Psychostimulant and hallucinogenic amphetamines, ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of catecholamine neurotransmitters also act as potent agonists at this receptor. These findings indicate that trace amines and catecholamine metabolites may be endogenous ligands for a novel intercellular signaling system in the vertebrate brain and periphery. The potency of amphetamines, including MDMA (ecstasy), as rTAR1 agonists suggests that some effects of these drugs may be mediated through this receptor in addition to neurotransmitter transporter proteins.
A genetic variant of ABCB1, which encodes a protein that pumps substances out of cells, may influence how the body processes THC from smoked cannabis. In 48 young adults who used cannabis 1–4 days per week, those carrying a C allele at the rs2235048 polymorphism had higher blood levels of THC metabolites after smoking a single cannabis cigarette than those with the TT genotype. C-allele carriers also reported using cannabis more frequently each week and greater drug liking. No other subjective drug effects differed between groups. The findings are preliminary and suggest that ABCB1 could affect cannabis-related traits and risk for cannabis use disorder, but larger studies are needed.