Possible Receptor Mechanisms Underlying Cannabidiol Effects on Addictive-like Behaviors in Experimental Animals

• Published in: International journal of molecular sciences Vol. 22; no. 1; p. 134
• Main Authors: Galaj, Ewa, Xi, Zheng-Xiong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.12.2020; MDPI
• Subjects: 5-TH; Allosteric properties; Analgesics; Animals; Attenuation; Cannabidiol; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Cannabinoids; Cannabis; Capsaicin receptors; CB1 receptor; CB2 receptor; Cocaine; Convulsions & seizures; Dopamine; Drug abuse; Drug addiction; Drug self-administration; Drug withdrawal; Heroin; In vivo methods and tests; Intravenous administration; Legislation; Marijuana; Medicine; Morphine; Narcotics; Pharmacology; Place preference conditioning; Public health; Receptor mechanisms; Reinforcement; Review; Schedules; Serotonin; Serotonin S1 receptors; Substance abuse treatment; Tetrahydrocannabinol; THC; Transient receptor potential proteins; TRPV1; CB2 receptor; cannabidiol; 5-TH; CB1 receptor; cocaine; addiction; TRPV1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22010134

Substance use disorder (SUD) is a serious public health problem worldwide for which available treatments show limited effectiveness. Since the legalization of cannabis and the approval of cannabidiol (CBD) by the US Food and Drug Administration, therapeutic potential of CBD for the treatment of SUDs and other diseases has been widely explored. In this mini-review article, we first review the history and evidence supporting CBD as a potential pharmacotherapeutic. We then focus on recent progress in preclinical research regarding the pharmacological efficacy of CBD and the underlying receptor mechanisms on addictive-like behavior. Growing evidence indicates that CBD has therapeutic potential in reducing drug reward, as assessed in intravenous drug self-administration, conditioned place preference and intracranial brain-stimulation reward paradigms. In addition, CBD is effective in reducing relapse in experimental animals. Both in vivo and in vitro receptor mechanism studies indicate that CBD may act as a negative allosteric modulator of type 1 cannabinoid (CB1) receptor and an agonist of type 2 cannabinoid (CB2), transient receptor potential vanilloid 1 (TRPV1), and serotonin 5-HT receptors. Through these multiple-receptor mechanisms, CBD is believed to modulate brain dopamine in response to drugs of abuse, leading to attenuation of drug-taking and drug-seeking behavior. While these findings suggest that CBD is a promising therapeutic candidate, further investigation is required to verify its safety, pharmacological efficacy and the underlying receptor mechanisms in both experimental animals and humans.