Long-term exposure to Δ<sup>9</sup>-THC shifts control of the NAc shell from cortical to limbic input, likely contributing to cognitive and psychiatric dysfunction that is associated with cannabis use.
The effects of trans-del-ta-9-tetrahydrocannabinol (Δ9-THC) in marijuana and other preparations of cannabis are mediated by the endocannabinoid system, which is also briefly introduced.Much variation exists in the current literature regarding the functional changes associated with chronic cannabis use.
Potential drivers for a rising prevalence of cannabis use disorders comprise changes in consumption patterns and increasing levels of THC in available cannabis products.
These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.
Neither cannabis smoke nor THC exposure during adolescence produced robust alterations in adult behavior after a period of abstinence, suggesting that adverse effects associated with adolescent cannabis use might be due to non-cannabinoid concomitants of cannabis use.
Overall, there is a need for regulated cannabis markets to develop more effective packaging and labelling standards to allow consumers to effectively titrate their THC intake, with the goal of promoting lower-risk cannabis use.
Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.
Studies from preclinical animal models indicate that sustained activation of CB1 receptor signaling is a major contributing factor for the onset of cognitive deficits associated to chronic cannabis use, in particular within the working memory and decision-making domains.
These results demonstrate dose-dependent separation in the subjective response to oral Δ<sup>9</sup>-THC administration by sex, which might contribute to the differential development of problematic cannabis use.
Using latent growth curve modeling of 10 waves of longitudinal data spanning mean ages 18.4-23.8 years in a sample of non-Hispanic White individuals (n = 334), we tested if genotype at each CNR1 SNP was associated with both level and growth of cannabis use over time.
Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users.
In either case, greater CB1R receptor availability may contribute to the increased susceptibility of schizophrenia subjects to the deleterious effects of cannabis use.
These data replicate previous findings of reduced hippocampal and amygdalar volume among heavy cannabis users, and suggest that CNR1rs2023239 variation may predispose smaller hippocampal volume after heavy cannabis use.
Our findings suggest that heavy cannabis use in the context of specific CNR1 genotypes may contribute to greater WM volume deficits and cognitive impairment, which could in turn increase schizophrenia risk.
Genes such as ELTD1 on chromosome 1, in addition to genes on chromosomes 4 (eg, GABRA2) and 6 (eg, CNR1), may be associated with the genetic risk for cannabis use disorders.
There was no evidence of association between schizophrenia and CNR1 (OR=0.97, 95% CI 0.82-1.13) or CHRNA7 (OR=1.07, 95% CI 0.77-1.49) genotypes, or of interactions between tobacco use and CHRNA7, or cannabis use and CNR1or COMT genotypes.
An example of replicable gene-environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use.