As evidence continues to accumulate, neutral CB1R antagonists (such as AM4113), CB2R agonists (JWH133, Xie2-64), and nonselective phytocannabinoids (cannabidiol, β-caryophyllene, ∆<sup>9</sup>-tetrahydrocannabivarin) have shown great therapeutic potential for SUDs, as shown in experimental animals.
Cellular signaling mediated by CB1R is involved in numerous physiological processes, and pharmacological CB1R modulation is considered a tenable therapeutic approach for diseases ranging from substance-use disorders and glaucoma to metabolic syndrome.
The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression--and probably also for co-morbid psychiatric conditions such as substance use disorders--through a high neuroticism and low agreeableness phenotype.