Addictive potential of cannabinoids: the underlying neurobiology.
Drugs that are addictive in humans have a number of commonalities in animal model systems-(1). they enhance electrical brain-stimulation reward in the core meso-accumbens reward circuitry of the brain, a circuit encompassing that portion of the medial forebrain bundle (MFB) which links the ventral tegmental area (VTA) of the mesencephalic midbrain with the nucleus accumbens (Acb) of the ventral limbic forebrain; (2). they enhance neural firing of a core dopamine (DA) component of this meso-accumbens reward circuit; (3). they enhance DA tone in this reward-relevant meso-accumbens DA circuit, with resultant enhancement of extracellular Acb DA; (4). they produce conditioned place preference (CPP), a behavioral model of incentive motivation; (5). they are self-administered; and (6). they trigger reinstatement of drug-seeking behavior in animals behaviorally extinguished from intravenous drug self-administration behavior and, perforce, pharmacologically detoxified from their self-administered drug. Cannabinoids were long considered 'anomalous', in that they were believed to not interact with these brain reward processes or support drug-seeking and drug-taking behavior in these animal model systems. However, it is now clear-from the published data of several research groups over the last 15 years-that this view of cannabinoid action on brain reward processes and reward-related behaviors is untenable. This paper reviews those data, and concludes that cannabinoids act on brain reward processes and reward-related behaviors in strikingly similar fashion to other addictive drugs.
Gardner
Eliot L
EL
National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Building C, Room 272, 5500 Nathan Shock Drive, Baltimore, MD 20850, USA. egardner@intra.nida.nih.gov
D000818:Animals; D016739:Behavior, Addictive; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002186:Cannabinoids / Q000009:adverse effects* / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D009714:Nucleus Accumbens / Q000378:metabolism; D012201:Reward; D019966:Substance-Related Disorders / Q000209:etiology* / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000378:metabolism
D002186:Cannabinoids; D004298:Dopamine