Abstract
Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs' therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD's promise, further investigation and validation of CBD's efficacy, across preclinical and clinical trials will be necessary.
Highlights
Substance use disorder (SUD) is a global problem, with over 30 million individuals estimated to have an SUD [1]
The endocannabinoid system (ECS) consists of cannabinoid receptors (e.g., CB1R, CB2R), the endogenous ligands that bind to these cannabinoid receptors [e.g., anandamide and 2-arachidonoylglycerol (2-AG)], and enzymes for their biosynthesis and degradation [e.g., fatty acid amide hydrolase (FAAH) and monoacylglyrecol lipase (MAGL)] [8]
CBD shows some promise in alleviating negative withdrawal effects and reducing motivation to self-administer or reinstatement of drug use in animals
Summary
Substance use disorder (SUD) is a global problem, with over 30 million individuals estimated to have an SUD [1]. Within the United States alone, SUD-related expenditure (e.g., treatment and productivity cost) exceeded 23 billion USD per year [2], presenting a worrisome issue. SUD has been conceptualized as a maladaptive and relapsing cycle of intoxication, binging, withdrawal and craving that results in excessive substance use despite adverse consequences [6]. Recent models implicate major brain circuits involved in reward saliency, motivation, and memory/learned associations in maintaining addiction [7]. These circuits may largely be modulated by the endocannabinoid system (ECS), presenting a promising pharmaceutical avenue for treating SUDs
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