Cannabidiol reduces ethanol consumption, motivation and relapse in mice

Abstract

This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self-administration experiment was carried out to evaluate the effects of CBD [a single s.c. administration of a microparticle formulation providing CBD continuous controlled release (30 mg/kg/day)] on the reinforcement and motivation for ethanol. The effects of CBD (60 and 120 mg/kg/day, i.p.) on ethanol-induced relapse were also evaluated. Gene expression analyses of tyrosine hydroxylase in ventral tegmental area and μ-opioid (Oprm1), cannabinoid (CB 1 r and CB 2 r) and GPR55 receptors in nucleus accumbens (NAcc) were carried out by real-time polymerase chain reaction. Cannabidiol reduced the ethanol-induced hypothermia and handling-induced convulsion but failed to modify blood ethanol concentration. CBD reduced ethanol consumption and preference in the two-bottle choice, significantly decreased ethanol intake and the number of effective responses in the oral ethanol self-administration, and reduced ethanol-induced relapse. Furthermore, the administration of CBD significantly reduced relative gene expression of tyrosine hydroxylase in the ventral tegmental area, Oprm1, CB 1 r and GPR55 in the NAcc and significantly increased CB 2 r in the NAcc. Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

“…There is mounting evidence that the endogenous cannabinoid (eCB) system is involved in motivation for rewards, including modulating the rewarding effects of drugs . In relation to nicotine dependence, cannabinoid receptor 1 (CB1R) antagonists, such as rimonabant, decrease nicotine conditioned place preference and self‐administration in pre‐clinical models of addiction .…”

Cannabidiol modulates the expression of neuroinflammatory factors in stress‐ and drug‐induced reinstatement of methamphetamine in extinguished rats

“…Effective pharmacological targets for the treatment of drug abuse must diminish drug craving while leaving cognitive functions intact. Cannabidiol (CBD) is a compound of the herb Cannabis sativa that lacks the psychotomimetic and reinforcing properties . In the CNS, CBD has neuroprotective, antioxidative, and anti‐inflammatory properties .…”

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

“…In this previous study, we showed that animals treated with CBD (20 mg/kg) during the acquisition phase of cocaine operant taking extinguished seeking behavior in a similar extent than control mice. Similarly, CBD (60 mg/kg) did not facilitate extinction learning of ethanol taking behavior in rats (Viudez-Martínez et al, 2018). Another study using heroin also described that CBD (10, 20 mg/kg) did not affect lever pressing during extinction training (Ren et al, 2009).…”

“…Other works hinted at a possible participation of CB1 receptors in the protective effects of CBD in drug selfadministration studies. Striatal CB1 mRNA expression was found reduced following a CBD treatment with drug seeking attenuating effects (Ren et al, 2009;Viudez-Martínez et al, 2018). The effects of AM4113 on CBD-induced changes during extinction learning indicates that the expression of these effects are modulated by CB1 cannabinoids receptors on reinstatement conditions.…”

“…Such 'extinction bursting' behavior is often considered as a measure of the urge to consume the drug (craving) that is not 18 affected by the acute pharmacological effects of the drug or the development of a previous extinction learning and thus, is viewed as a predictor of relapse behavior (Wee et al, 2012). Such an effect was not reported in the previous studies evaluating the effects of CBD treatment on extinction learning (Ren et al, 2009;Viudez-Martínez et al, 2018). Similarly, Mahmud et al (2017) did not find that CBD (5, 10 mg/kg) reduced cocaine seeking in the first withdrawal session.…”