The effect of CBD on alcohol use disorders
In this review, the researchers reveal details supporting proponents of CBD and its effectiveness on alcohol use disorders. However, the paper's authors also call for human clinical trials, none of which have been published to date, to "pave the way for testing new harm reduction approaches in AUD (alcohol use disorders)."
Other studies have found that mice regularly dosed with the non-intoxicating marijuana compound were also less likely to relapse after weaning from alcohol, even when stressed.
Given its effects on different aspects of the disease, including, motivation, consumption, anxiety or relapse, CBD may have an important effect on alcohol consumption levels in human subjects with alcohol use disorders. However, the scientists add that it would be useful to have data using models of heavy drinking and models focusing on long-term alcohol exposure.
What you need to know about alcohol use disorder
Alcohol use disorder is an addictive disorder characterised by a progressive loss of control when drinking alcohol. AUD (Alcohol Use Disorder) consists of several clinical criteria that include alcohol tolerance, withdrawal symptoms, craving, and medical and psychosocial consequences. AUD is responsible for a high burden of disease.
The number of people with AUD is increasing.
In the world, AUD causes more than 3 million deaths each year, accounting for 5% of all deaths (World Health Organization, 2018). Specifically, subjects with AUD may be affected by the consequences of recurrent alcohol abuse on the body, including alcohol-related liver disease (ARLD) and alcohol-related brain injury (ARBI).
What you need to know about CBD
Cannabidiol (CBD) is a natural constituent of Cannabis sativa. Unlike tetrahydrocannabinol (THC), CBD does not have psychotomimetic properties. However, CBD has several important effects on the central nervous system, including anxiolytic, antipsychotic, analgesic and antiepileptic effects. In this regard, a mouth spray with CBD and THC in a 1:1 ratio has been approved in Canada as a treatment for spasticity in multiple sclerosis since 2005, and is now approved in 22 countries worldwide.
Because of its diverse effects on the brain and on systemic inflammation, CBD implies a wide potential range of complementary therapeutic applications in AUD.
- First, CBD could help AUD patients reduce their alcohol consumption.
- Second, by modulating inflammatory processes in the liver, CBD could reduce alcohol-induced hepatic steatosis and fibrosis, thus constituting a novel harm reduction agent in AUD subjects, especially in those who still consume alcohol heavily.
- Third, CBD could reduce ARBI.
The aim of this narrative review is to provide a comprehensive overview of the current body of evidence on these three specific applications of CBD in subjects with AUD or animal models of AUD, and to discuss the next steps in research on these topics.
CBD to reduce alcohol consumption levels
The effects of CBD on alcohol consumption have been tested in preclinical studies using several procedures to investigate AUD, including the propensity to drink ethanol with the choice of two bottles or the operant self-administration procedure, and behavioural sensitisation.
Four main studies have been published to date, and they provide comprehensive and congruent evidence that, in rodents, CBD can reduce ethanol consumption, motivation for ethanol, relapse, reinstatement after extinction, and levels of anxiety and impulsivity correlated with ethanol consumption.
Studies conducted in mice
An initial study in male C57BL/6J mice, an ethanol-preferring strain, demonstrated that CBD administration reduced the reinforcing properties, motivation and relapse of ethanol (Viudez-Martínez et al., 2018). Increasing doses of CBD (30, 60 and 120 mg/kg) administered intraperitoneally (ip) progressively decreased both ethanol preference (from 75% to 55%) and intake (from approximately 6 g pure ethanol/kg body weight/day to 3.5 g/kg/day) in a two-vial choice paradigm (water versus 8% ethanol solution).
The results were confirmed in an operant paradigm in which mice had to press a lever to access 36 ml of an 8% ethanol solution. In the operant paradigm, animals had to work (press a lever) to access ethanol; this is useful for assessing motivation to drink ethanol, as the price to be paid (effort) can be increased by the experimenter.
In the context of this operant paradigm, which includes a saccharin decolourisation phase, administration of the subcutaneous (sc) formulation of controlled-release CBD microparticles (30 mg/kg/day, sc) significantly reduced the number of active lever presses by approximately 40% in a fixed-ratio programme (one press is required to obtain ethanol) as well as in a more demanding three-ratio programme (three presses required to obtain ethanol).
It also reduced motivation to drink ethanol by about 50% in a graded ratio programme, and relapse by about 30% after a quenching session with an i.p. dose of 120 mg/kg the dose. This had no effect on water reinforcement or motivation. In addition, CBD reduced ethanol-induced hypothermia by 3.0 g/kg and ethanol-induced convulsions by 4.0 g/kg, but had no effect on blood ethanol concentration. CBD treatment was associated with changes in gene expression of key targets closely related to AUD.
CBD reduced alcohol consumption
A single administration of CBD (30 mg/kg/day, s.c.) during oral ethanol self-administration decreased the expression of Oprm1, GPR55 and CB1 receptor genes in the nucleus accumbens (NAc), while CB2 receptor expression increased; it also decreased gene expression of the gene coding for tyrosine hydroxylase (TH) in the ventral tegmental area (VTA).
In a second study, the same authors tested the effect of CBD (20 mg/kg sc), naltrexone (0.7 mg/kg, oral) and their combination in male C57BL/6J mice using the same operating paradigm (Viudez- Martínez et al., 2018). They found that the combination of CBD and naltrexone reduced ethanol consumption and motivation to drink ethanol more effectively than either drug alone. 5-HT1A receptor gene expression was reduced in the dorsal raphe nucleus after CBD treatment.