Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes

Abstract

Aim To examine whether withdrawal after abstinence and cue-elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH). Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers. Participants Participants were 105 students at the University of Colorado, Boulder between the ages of 18 and 25 years who reported smoking marijuana daily. Measurements Participants were assessed once at baseline and again after 5 days of abstinence, during which they were exposed to a cue-elicited craving paradigm. Outcome measures were withdrawal and craving collected using self-reported questionnaires. In addition, urine samples were collected at baseline and on day 5 for the purposes of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC–COOH) metabolite analysis. Findings Between the two sessions, THC–COOH metabolite levels decreased significantly, while measures of withdrawal and craving increased significantly. The CNR1 SNP displayed a significant abstinence × genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence × genotype interaction on craving. Conclusions These genetic findings may have both etiological and treatment implications. However, longitudinal studies will be needed to clarify whether these genetic variations influence the trajectory of marijuana use/dependence. The identification of underlying genetic differences in phenotypes such as craving and withdrawal may aid genetically targeted approaches to the treatment of cannabis dependence.

Associations between Cannabinoid Receptor-1 (CNR1) Variation and Hippocampus and Amygdala Volumes in Heavy Cannabis Users

“…In addition to our previous findings of association between rs202329 variance and cannabis withdrawal, craving, and cue-elicited brain activation (Filbey et al, 2010;Haughey et al, 2008), this SNP has been associated with other SUD intermediate phenotypes, including greater alcohol cue-elicited brain activation and greater subjective reward after consuming alcohol , greater alcohol craving at higher levels of alcohol consumption (van den Wildenberg et al, 2007), greater trait impulsivity (Ehlers et al, 2007), and, as part of a haplotype block with other CNR1 SNPs, greater severity of nicotine dependence (Chen et al, 2008). Although these other studies did not report participants' cannabis use, it is highly comorbid with alcohol and nicotine use.…”

Marijuana craving in the brain

“…For example, auditory-presented imagery scripts induce craving in marijuana smokers, and the magnitude of this craving varies as a function of the amount of marijuana-related content presented in the script (43). Craving also increases when abstinent frequent marijuana users are exposed to an auditory script that is paired with a tactile cue, such as a used marijuana pipe or bong (41,42). Importantly, in this paradigm, cue presentation increases craving beyond the effects induced by abstinence.…”

Brain structural and clinical changes after first episode psychosis: Focus on cannabinoid receptor 1 polymorphisms

“…Nevertheless, other studies have shown that CNR1 variants are associated with depression remission after only 12 weeks (Mitjans et al, 2013). Previous association studies which have investigated CNR1 rs2023239 polymorphisms have tested the relationship of these variants to cannabis withdrawal (Haughey et al, 2008), impulsivity (Ehlers et al, 2007) and metabolic syndrome in patients with schizophrenia (Yu et al, 2013) as well as in the general population (Milewicz et al, 2011;Lenarcik-Kabza et al, 2014). On the other hand, the significant interaction in patients homozygous for the G allele in rs1049353, the at-risk allele T for rs1535255 and the T/C for rs20233239 polymorphism yielded significantly higher SAPS scores after 3 years compared with SAPS scores in the other patients.…”