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The Role of CBD and the Endocannabinoid System in Addiction


Drug and alcohol addiction are chronic disorders that have both biological and environmental contributing factors. Addiction is incredibly difficult to treat because there are few effective medications, high rates of relapse and because addiction itself is a multifaceted condition. New and innovative approaches to treating addiction like CBD for addiction are of great interest but are also quite controversial.

CBD is derived from cannabis, and while CBD does not appear to have any addictive qualities, THC can. Since cannabis use disorder is an addiction condition itself, many are hesitant to consider integrating CBD and hemp into addiction recovery programs. However, research has suggested that the endocannabinoid system plays a considerable role in the pathology of addiction. Using non-psychoactive cannabinoids like CBD to balance the endocannabinoid system could be supportive in addiction treatment programs.

Can CBD help people in addiction recovery?

CBD for Addiction Table of Contents

CBD & Addiction Recovery

When it comes to using a “drug” to treat a drug addiction, many will struggle to understand how that could be beneficial. There are some important points to keep in mind when considering CBD for addiction:

Endocannabinoid signaling seems to modulate the rewarding effects of addictive drugs, so CBD is of interest for its ability to encourage homeostasis in the endocannabinoid system. However, much of what is known about CBD for addiction is inconclusive and the bulk of studies are being performed in mice and other laboratory animals. Please keep this in mind as you read! CBD is not approved as an addiction treatment and we do not recommend self-treating addiction (or any condition) with retail CBD products.

What is the Endocannabinoid System?

The endocannabinoid system (ECS or eCB) is distributed in the central and peripheral nervous system, and also in many other tissues [1, 4]. It works by regulating brain functions by acting on different cell types and cellular compartments. When cannabinoids interact with the ECS, they do so by bonding with cannabinoid receptors like CB1 and CB2, or by using other indirect signaling mechanisms.

All of that may sound pretty complicated, but you can think of the ECS like a switchboard operator for the nervous system. It directs signals and communications to other systems in the body to communicate about changes in the environment that it senses. The result of this is biological processes like sending anti-inflammatory cells to a site of inflammation or improving the production/circulation of serotonin when it is abnormally low.

Researchers Batalla, Janssen, Gangadin, and Bossong explain:

The eCB system consists of at least two types of receptors and their endogenous ligands (i.e., endocannabinoids). The cannabinoid receptors are predominantly present in the central nervous system, in particular, in several limbic and cortical brain structures. The eCB system is a retrograde messenger system that regulates both excitatory glutamate and inhibitory GABA neurotransmission according to an ‘on-demand’ principle: Endocannabinoids are released when and where they are needed. This endocannabinoid-mediated regulation of synaptic transmission is a widespread phenomenon in the brain and is thought to play an important role in higher brain functions, such as cognition, motor function, and processing of sensory input, reward, and emotions. eCB receptors are also present on immune cells in the central nervous system (i.e., microglia), which suggests their involvement in processes such as cytokine release, immune suppression, and induction of both cell migration and apoptosis.

Batalla, A., Janssen, H., Gangadin, S. S., & Bossong, M. G. (2019). The potential of cannabidiol as a treatment for psychosis and addiction: who benefits most?

How Does Addiction Work?

Body systems such as the mesolimbic dopamine (DA) system are dysregulated by drugs like opioids, cannabinoids, psychostimulants, alcohol, and nicotine [4]. These substances enhance the release of dopamine and create a hedonistic sensation in many who take them.

This “reward system” becomes further reinforced over time with continued drug use and ultimately rewires the brain [4]. This makes the users crave more and can even make them sick when they are without the substance. Likewise, the reward system dulls with time and will require more and more of the substance in order to feel the reward from it.

The “drug reward system” as it is commonly called is, therefore, a common target for addiction treatments because it is one of the main roots of addictive behavior. As mentioned, this is just one facet of a very complex condition, but it is thought to be key. Psychological and physical addiction symptoms also need to be addressed, but re-balancing brain function is a major key to addiction recovery.

CBD and the Endocannabinoid System for Addiction

Cannabinoid Receptor 1 and Cannabinoid Receptor 2 (CB1 and CB2) are the primary endocannabinoid system receptors for cannabinoids [4]. Researchers have discovered that both cannabinoid receptors play a role in addiction. CB1 receptor activators (agonists) have been historically targeted in older cannabinoid approaches to addiction treatment.

CB1 and Addiction

The CB1 cannabinoid receptor does not bind to CBD, this cannabinoid receptor interacts with the plant cannabinoid THC and the natural endocannabinoid anamidine.

Previous CB1 medications (Rimonabant) have not done well in treating addiction [4]. Their effectiveness and side effects have included serious psychiatric adverse effects. Why does CB1 (aka CB1R) play an integral role in addiction? That is because it is abundant in the brain’s reward pathway (mesocorticolimbic pathway) and also in the brain regions involved in decision-making, withdrawal symptoms, and relapse.

That is to say, CB1 is essential to drug addiction and enables drug abuse behaviors. While the drug Rimonabant turned out not to be a successful option, the development and study of the drug shed a lot of light on the role of CB1 in addiction [4].

…treatment with the CB1R antagonist rimonabant decreased conditioned place preference for morphine, heroin, ethanol and nicotine, suggesting an effect CB1R on primary reward-associated memories. On the other hand, drug self-administration experiments where animals freely operate a lever to self-administer drug also showed inhibition of this operant behavior when CB1R activity was inhibited, either pharmacologically or genetically. This effect was observed for all the drugs mentioned above, including morphine, heroin, ethanol and nicotine. Hence, CB1R seem essential for the reinforcing and motivational properties of these drugs of abuse, and are involved in the execution of the operant behavior that promotes its consumption.

Manzanares, J., Cabañero, D., Puente, N., García-Gutiérrez, M. S., Grandes, P., & Maldonado, R. (2018). Role of the endocannabinoid system in drug addiction.

It should be noted that different substances have slight differences in how they create dependence in the body. Psychostimulant drugs such as cocaine, methamphetamine, or MDMA have different reward mechanisms [4]. While blocking CB1 activation may help for some substances, others such as cocaine and MDMA do not respond.

CB2 and Addiction

Since CB1 addiction medications have failed so far to produce good results, attention has turned to CB2 (aka CB2R). CB2 is partially activated by CBD, which also acts indirectly through other routes to balance the endocannabinoid system. CB2-responsive substances differ slightly from those that respond to blocking CB1 [4]. Namely, alcohol, cocaine, and nicotine.

A great deal of research has been focused in the study of the role of CB2R in the central and peripheral nervous system. The expression of CB2R is located in brain regions belonging to classical neuronal circuits involved in drug addiction, such as the VTA, NAc, amygdala and hippocampus which promotes studies to understand further its potential role in these pathological conditions. …we detailed the growing evidences suggesting that CB2R present a pivotal role in addictive behaviors, including cocaine, ethanol and nicotine addiction.

Manzanares, J., Cabañero, D., Puente, N., García-Gutiérrez, M. S., Grandes, P., & Maldonado, R. (2018). Role of the endocannabinoid system in drug addiction.

Studies have demonstrated that activating CB2 could block addictive impulses [4]. Researchers have found evidence in mice and humans that genetic mutations to CB2 may predispose addiction behavior, especially for alcohol. The specific mutation is believed to desensitize CB2 to substances like CBD and beta-caryophyllene and create an imbalance in the endocannabinoid system.

Interestingly, some studies are using the terpene beta-caryophyllene to test this because it has a stronger interaction with CB2 than CBD itself does. It just goes to show that cannabis terpenes play as big of a role as the cannabinoids themselves.

In addition to disrupting the reward pathway, researchers saw other additional benefits that could help support addiction recovery from activating CB2 with beta-caryophyllene:

Pharmacological modulation of CB2R also displayed anxiolytic and antidepressant-like effects along with antiinflammatory and neuroprotective properties that would be of interest for the treatment of substance use disorders.

Manzanares, J., Cabañero, D., Puente, N., García-Gutiérrez, M. S., Grandes, P., & Maldonado, R. (2018). Role of the endocannabinoid system in drug addiction.

CBD for Alcoholism and Other Addictions

Animal studies are suggesting that CBD may be particularly useful for alcoholism [2]. Experimental studies have found evidence that CBD reduces the overall level of alcohol drinking in animal models. The motivation to drink, relapse, and contributing factors like anxiety and impulsivity all appeared to be reduced in animal models treated with CBD for alcoholism. Other benefits such as reduced damage to the body and brain were also observed.

Highlights from CBD for addiction research studies have shown that CBD is a very safe option with the potential to aid in many aspects of addiction recovery [3]. While CBD is not officially medically recommended for addiction treatment at this time, studies like these are hinting in that direction.

Final Thoughts on CBD for Addiction and Recovery

Understanding what addiction is and how the endocannabinoid system plays a role in it is key to understanding which cannabinoids and other cannabinoid receptor binding compounds could be of benefit to addiction and recovery. While targeting CB1 has not worked out well in the past, it is still of interest.

CB2 activators like the terpene beta-caryophyllene and the cannabinoid CBD have demonstrated early hope for their use, but more human research is needed to truly assess the viability of using cannabinoids to support addiction recovery.


  1. Batalla, A., Janssen, H., Gangadin, S. S., & Bossong, M. G. (2019). The potential of cannabidiol as a treatment for psychosis and addiction: who benefits most? A systematic review. Journal of clinical medicine, 8(7), 1058.
  2. De Ternay, J., Naassila, M., Nourredine, M., Louvet, A., Bailly, F., Sescousse, G., … & Rolland, B. (2019). Therapeutic prospects of cannabidiol for alcohol use disorder and alcohol-related damages on the liver and the brain. Frontiers in Pharmacology, 10, 627.
  3. Iffland, K., & Grotenhermen, F. (2017). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and cannabinoid research, 2(1), 139–154.
  4. Manzanares, J., Cabañero, D., Puente, N., García-Gutiérrez, M. S., Grandes, P., & Maldonado, R. (2018). Role of the endocannabinoid system in drug addiction. Biochemical pharmacology, 157, 108-121.
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