Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward.
Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.
National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892; email: nvolkow@nida.nih.gov.
Nora D
ND
Volkow
National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892; email: nvolkow@nida.nih.gov.
Aidan J
AJ
Hampson
National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892; email: nvolkow@nida.nih.gov.
Ruben D
RD
Baler
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002188:Cannabis; D063388:Endocannabinoids / Q000378:metabolism*; D006240:Happiness; D006801:Humans; D064086:Medical Marijuana / Q000008:administration & dosage / Q000378:metabolism*; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*
D063388:Endocannabinoids; D064086:Medical Marijuana; D043884:Receptor, Cannabinoid, CB1
THC; cannabis; endocannabinoids; marijuana; reward; stress