cannabidiol and Alcoholism

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota-gut-brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm-reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions.

Topics: Alcoholism; Animals; Brain; Cannabidiol; Cannabinoids; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcohol-induced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

Topics: Alcoholism; Animals; Behavior, Animal; Cannabidiol; Humans

Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses.. As socially stressful events pose particular challenges at developmental stages, this research applied the resident-intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms.. Binge-like alcohol exposed intruder rats displayed a compromised defensive behaviour against the resident and a blunted response of the stress system, in addition to indexes of abnormal dopamine (DA)/glutamate plasticity and dysfunctional spine dynamics in the NAc. CBD administration (60 mg/kg) was able to: (1) increase social exploration in the binge-like alcohol exposed intruder rats, at the expenses of freezing time, and in control rats, which received less aggressive attacks from the resident; (2) reduce corticosterone levels independently on alcohol previous exposure; (3) restore DA transmission and (4) facilitate excitatory postsynaptic strength and remodelling.. Overall, the maladaptive behavioural and synaptic plasticity promoted by the intersection between binge-like alcohol withdrawal and exposure to adverse social stress can be rescued by a CBD

Topics: Alcoholism; Animals; Cannabidiol; Dopamine; Ethanol; Humans; Nucleus Accumbens; Rats; Substance Withdrawal Syndrome

The cannabinoid cannabidiol (CBD) is currently under investigation as a pharmacotherapy for alcohol use disorder. The aim of the present study was to examine whether acute and chronic treatment with pure CBD would decrease alcohol seeking and consumption behaviors or alter drinking patterns in male baboons with extensive histories of daily alcohol intake (1 g/kg/day).. Seven male baboons self-administered oral alcohol (4% w/v) in a validated chained schedule of reinforcement (CSR) procedure that modeled periods of anticipation, seeking, and consumption. In Experiment 1, CBD (5-40 mg/kg) or vehicle (peanut oil, USP) was administered orally 15- or 90-minutes prior to the start of the session. In Experiment 2, oral doses of CBD (10-40 mg/kg) or vehicle were administered for 5 consecutive days during ongoing alcohol access under the CSR. In addition, behavioral observations were conducted to assess potential drug side effects (e.g., sedation, motor incoordination) following chronic CBD treatment immediately after the session and 24-hours after drug administration.. Across both experiments, baboons self-administered an average of 1 g/kg/day of alcohol under baseline conditions. Administration of acute or chronic CBD (150-1200 mg total CBD dose/day) that encompassed the purported therapeutic dose range did not significantly reduce alcohol seeking, self-administration or intake (g/kg). Drinking patterns (i.e., number of drinks/bouts, bout duration, nor interdrink interval) also were not altered. There were no observable behavioral disruptions following CBD treatment.. In sum, the current data do not support use of pure CBD as an effective pharmacotherapy to reduce ongoing excessive drinking.

Topics: Alcohol Drinking; Alcoholism; Animals; Cannabidiol; Ethanol; Humans; Male; Papio

Cannabidiol (CBD) is found in the cannabis plant and has garnered attention as a potential treatment for alcohol use disorder (AUD). CBD reduces alcohol consumption and other markers of alcohol dependence in rodents, but human research on CBD and alcohol is limited. It is unknown whether CBD reduces drinking in humans, and mechanisms through which CBD could impact behavioral AUD phenotypes are unknown.. This study explores effects of oral CBD on breath alcohol level (BrAC), and subjective effects of alcohol in human participants who report heavy drinking.. In this placebo-controlled, crossover study, participants consumed 30 mg CBD, 200 mg CBD, or placebo CBD before receiving a standardized alcohol dose. Participants were blind to which CBD dose they received at each session and completed sessions in random order. Thirty-six individuals completed at least one session and were included in analyses.. Differences in outcomes across the three conditions and by sex were explored using multilevel structural equation models. BrAC fell fastest in the placebo condition, followed by 30 mg and 200 mg CBD. Stimulation decreased more slowly in the 200 mg CBD condition than in placebo (b =  - 2.38, BCI [- 4.46, - .03]). Sedation decreased more slowly in the 30 mg CBD condition than in placebo (b =  - 2.41, BCI [- 4.61, - .09]). However, the magnitude of condition differences in BrAC and subjective effects was trivial.. CBD has minimal influence on BrAC and subjective effects of alcohol. Further research is needed to test whether CBD impacts alcohol consumption in humans, and if so, what mechanism(s) may explain this effect.

Topics: Alcohol Drinking; Alcoholism; Cannabidiol; Cross-Over Studies; Double-Blind Method; Ethanol; Humans

The main goal of this study was to evaluate if the administration of cannabidiol (CBD) regulates behavioral and gene expression alterations induced by spontaneous alcohol withdrawal (SAW) in mice. Increasing doses of ethanol were administered to C57BL/6J male mice for 15 days (2.5, 3 and 3.5 g/kg/12 h, p. o.), and SAW was studied at 6, 12, 24, and 72 h after the last ethanol administration. The efficacy of acute CBD (10, 20, and 40 mg/kg, i. p.) to regulate behavioral changes induced by SAW was explored at 6 h. Gene expression analyses of cannabinoid receptors 1 (Cnr1) and 2 (Cnr2), mu-opioid receptor (Opmr1), and proopiomelanocortin (Pomc) in the nucleus accumbens (NAcc), and Pomc and tyrosine hydroxylase (Th) in the ventral tegmental area (VTA), were carried out by real time-PCR. Pearson correlation was used to identify potential associations between the gene expression data and the anxiety-like behaviors. Biostatistical studies suggest associations between gene expression data and the anxiogenic behaviors in mice exposed to the SAW model and treated with VEH and 40 mg/kg of CBD. Mice exposed to the SAW model showed significant somatic withdrawal signs, anxiety-like behaviors, and remarkable changes in the gene expression of all brain targets at 6 h. CBD dose-dependently normalized the behavioral, somatic withdrawal signs and anxiety-like behaviors and modulated gene expression changes in the NAcc, but not in the VTA. The results of this study suggest that CBD may regulate specific alcohol withdrawal-associated alterations. However, further studies are required to explore the possible mechanisms involved.

Topics: Alcoholism; Animals; Brain; Cannabidiol; Ethanol; Male; Mice; Mice, Inbred C57BL; Pro-Opiomelanocortin; Substance Withdrawal Syndrome; Ventral Tegmental Area

Among individuals with alcohol use disorder (AUD), it is estimated that the majority suffer from persistent sleep disturbances for which few candidate medications are available. Our aim wass to critically review the potential for cannabidiol (CBD) as a treatment for AUD-induced sleep disturbance. As context, notable side effects and abuse liability for existing medications for AUD-induced sleep disturbance reduce their clinical utility. CBD modulation of the endocannabinoid system and favorable safety profile have generated substantial interest in its potential therapeutic use for various medical conditions. A number of preclinical and clinical studies suggest promise for CBD in restoring the normal sleep-wake cycle and in enhancing sleep quality in patients diagnosed with AUD. Based on its pharmacology and the existing literature, albeit primarily preclinical and indirect, CBD is a credible candidate to address alcohol-induced sleep disturbance. Well-designed RCTs will be necessary to test its potential in managing this challenging feature of AUD.

Topics: Alcohol Drinking; Alcoholism; Cannabidiol; Ethanol; Humans; Sleep

Topics: Alcoholism; Animals; Biomedical Research; Brazil; Cannabidiol; Cannabis; Dronabinol; Epilepsy; Freedom; Humans; Medical Marijuana; Police; Psychopharmacology; Research Personnel

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.

Topics: Administration, Cutaneous; Alcoholism; Animals; Anxiety; Brain; Cannabidiol; Cocaine-Related Disorders; Drug-Seeking Behavior; Impulsive Behavior; Male; Motor Activity; Rats; Rats, Wistar; Recurrence; Stress, Psychological; Substance-Related Disorders