Studies suggest that THC increases dopamine firing release in several parts of the brain. Van der Stelt and Di Marzo [95] discuss several mechanisms that may inter-link the endocannabinoid and dopaminergic pathways. The possibility exists that cannabinoids indirectly activate mesolimbic dopaminergic pathways [96-100]. This makes a variety of dopaminergic receptor genes, such as DRD2, (which have been shown to be associated with alcoholism and drug addiction [101,102]) important candidate genes for earlier stages of cannabis involvement. A more intriguing, and controversial, hypothesis that links dopaminergic genes and cannabis posits that cannabinoids may increase dopamine system hyperactivity and thereby contribute to the link between cannabis use and psychotic symptoms [103-112]. Some forms of psychosis are attributed, in part, to excessive dopamine production in the nucleus accumbens, making the gene encoding the dopamine transporter (DAT1, SLC6A3), which is responsible for dopamine re-uptake, a good candidate. Genes that encode enzymes assisting in the production and metabolism of dopamine, such as TH (tyrosine hydroxylase, converting tyrosine to dopamine) and DBH (dopamine beta-hydroxylase, converting dopamine to norepinephrine) may also contribute to the etiology of cannabis-mediated reward.
