CBD as New and Original Therapy for Alcohol Use Disorder

CBD treatment could help patients unable to reduce or stop alcohol consumption in preventing or reducing the effects of alcohol on the brain and the liver. It could be a new and original therapeutic option for people with alcohol use disorder, find the scientists in the latest preclinical review on the subject. CBD could decrease alcohol consumption, confirms a promising new human study.

Studies find that CBD reduces the overall level of alcohol drinking in alcohol use disorder (AUD) by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and inducing the death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties.

These are the conclusions of a review including 26 studies conducted between 1974 and 2018, published in Frontiers of Pharmacology in 2019. This review aims to offer a comprehensive overview of the current evidence about specific applications of CBD in subjects with AUD or animal models of AUD and to discuss what should be the next steps of research on these topics.

Alcohol Use Disorder

AUD is an addictive disorder characterized by a progressive loss of control upon alcohol use. According to the World Health Organization (WHO), AUD causes more than three million deaths a year, representing 5% of all deaths worldwide. People with AUD can be affected by the consequences of recurrent alcohol abuse, including alcohol-related liver disease (ARLD) and alcohol-related brain injury (ARBI).

ARLD is a progressive alcohol-induced liver injury, which starts with an increase in the amount of fat in the liver—steatosis—and continues into a progressive cell loss, fibrosis, and hepatic insufficiency—a process called cirrhosis. The injury can result in severe liver failure and represents a major risk factor for liver cancer. Liver damage caused by alcohol is responsible for 493,300 deaths every year, representing 0.9% of all global deaths. The major treatment goal in patients with ARLD is the prevention of the transition from steatosis to cirrhosis. This usually requires stopping or dramatically reducing the average amount of consumed alcohol in the long term. Through ARBI, AUD also affects the brain. Patients with AUD have reduced gray matter volumes and reduced cortical thickness and increased ventricular volumes. The most significant reductions in grey matter volumes are observed in the corticostriatal–limbic circuits, including the insula, superior temporal gyrus, dorsolateral prefrontal cortex, anterior cingulate cortex, striatum, and thalamus. Cognitive functions associated with these brain areas, like executive functions, working memory, emotion recognition, or long-term memory, are impaired in subjects with AUD. After alcohol withdrawal, cognitive dysfunctions start to improve quickly, but patients substantially recover only within the first weeks to months of alcohol abstinence and sometimes remain impaired. The recovery of structural brain alterations can be highly variable depending on brain areas and individual features. Both ARLD and ARBI involve alcohol-related inflammatory processes. Current medications for reducing alcohol drinking or supporting alcohol abstinence in AUD subjects are still insufficiently effective at a population level, and new therapeutic prospects are needed. Moreover, no drug for reducing alcohol-related harms, either on the brain or the liver, has ever been studied. All of this can pave the way for CBD as a new harm reduction drug, protecting the organs in patients with AUD.

Three specific applications of CBD

There are three specific applications of CBD in patients with AUD. First, CBD could help patients with AUD reduce their level of alcohol drinking. Second, by modulating the inflammatory processes in the liver, CBD could reduce alcohol-induced liver steatosis and fibrosis, thus constituting a novel harm reduction agent among subjects with AUD, particularly among those who still exhibit heavy drinking. Third, CBD could reduce ARBI.

Reducing Drinking Levels in Alcohol Use Disorder

In a mice study in 2018, CBD in a dosage of 30 mg/kg/day reduced activities needed to get alcohol by 40% and motivation to drink ethanol by about 50%. The relapse was about 30% lower with CBD in a dose of 120 mg/kg. When the scientists combined CBD and naltrexone, they found that the combination of both reduces ethanol consumption and motivation to drink ethanol more efficiently than either drug administered alone. In a study conducted on rats, where CBD was administered transdermally, the CBD effect was long-lasting, and the 50% reduction was still visible up to 138 days after the CBD treatment.

Preclinical evidence shows that CBD could significantly affect drinking levels in human subjects with AUD since it is effective on different aspects of the disease (intake, motivation, relapse, anxiety, and impulsivity). However, there are no available data on CBD efficacy in more relevant animal models of AUD, such as binge drinking models or in models that use more chronic exposure to ethanol and behaviors linked to addiction, such as a loss of control over intake, compulsive use of ethanol or increased motivation.

Reducing Alcohol-Related Liver Inflammation

Animal studies demonstrated that CBD could significantly reduce liver steatosis and fibrosis induced by chronic and binge ethanol administrations, based on its antioxidant, immunomodulatory, and lipid metabolic regulation properties.

A 2011 study found that CBD influences ethanol-fed rats and mice in a way that leads to the selective death of hepatic stellate cells (HSC), with the activation mechanism of this pathway independent from cannabinoid receptors.

Another mice study dating from 2014 demonstrated that CBD in doses of 5 mg/kg reduces binge-alcohol-induced liver damage. In 2017, a study found that injecting mice with 5 or 10 mg/kg of CBD modulated the ethanol-induced dysregulation of numerous genes and proteins involved in metabolism and liver steatosis. Furthermore, CBD attenuated hepatic neutrophils infiltration, oxidative and nitrative stress, decreased several markers of liver inflammation such as TNF-α, the expression of adhesion molecule E-selectin, proinflammatory chemokine, and cytokines, and thus, attenuated liver injury induced by chronic plus binge ethanol exposure.

CBD seems to have valuable therapeutic properties for ethanol-induced liver damage, through multiple mechanisms such as reduction of oxidative stress, modulation of inflammation, death of activated HSC responsible for fibrosis, stimulation of autophagy, and reduction of lipid accumulation responsible for steatosis.

Reducing Alcohol-Related Brain Damage

A 2005 study found that CBD, at dose range 40 mg/kg, significantly reduced ethanol-induced cell death for both hippocampal granular cells and entorhinal cortical pyramidal cells. Furthermore, CBD was demonstrated to have an antioxidant effect, which significantly decreased ethanol-induced neuronal death in the experiment.

A 2009 study that investigated CBD effects on cognitive and motor impairments caused by chronic liver disease found that CBD might improve cognitive and locomotor function, working through the A2a adenosine receptor.

A 2011 study of a hepatic encephalopathy model found that CBD restored neurological and cognitive functions and partially restored motor functions. CBD restored increased ammonia, bilirubin, and liver enzyme levels, as well as 5-HT levels in the brain.

The scientists conclude that, in preclinical studies, CBD significantly reduces alcohol-induced neuronal loss after a binge and chronic ethanol exposure, possibly through immunomodulatory properties involving regulation of the cerebral adenosine system, and antioxidant properties. Effects of CBD on ethanol-induced clinical impairments were also associated with significant improvement in cognitive functions.

Human study

Clinical studies are necessary to confirm these preclinical findings, but a human study published in March 2021 in the Journal of the Society of Psychologists in Addictive Behaviour suggests that CBD could decrease alcohol consumption in humans. In this naturalistic observational study, 120 cannabis and alcohol-using adults used one of three legal-market cannabis strains (predominantly THC, predominantly CBD, and CBD + THC) for five days. As a result, the CBD group drank fewer drinks per drinking day, had fewer alcohol use days, and fewer alcohol-cannabis co-use days compared with the other groups.

More studies are necessary to establish the benefits of CBD for people with alcohol use disorder. However, present evidence suggests it can become a powerful new agent in the battle against alcoholism and alcohol abuse.

Reviewed by Sasha Bajilo, founder of ILESOL Pharmaceuticals, an industrial scale producer of CBD products and formulations. Expert on Hemp/Cannabis policy, member of the Croatian Ministry of Health regulatory commission for medical cannabis.