Don’t Worry, Be Happy:Endocannabinoids and Cannabis at the Intersection of Stress and Reward

Nora D. Volkow, Aidan J. Hampson, and Ruben Baler



The search for a state of mental relaxation and well-being is one of the factors driving the widespread consumption of cannabis. The most frequently abused illicit substance worldwide, cannabis is consumed regularly by about 2.4% of the world population (approximately 181 million people in 2013) (1).

The principal psychoactive component of cannabis is_9-tetrahydrocannabinol (THC), which acts as an orthosteric agonist for cannabinoid receptors and mediates both the positive and negative effects of cannabis. The cannabinoid receptors are part of the brain’s endocannabinoid system (ECS), which modulates multiple neurobiological processes including reward and stress, a fact that is relevant for understanding not just the recreational use of cannabis but also its therapeutic potential.

This review focuses on the role of the ECS in the modulation of stress responses, its interaction with the reward system in the brain, and the implications of this emerging understanding for cannabis abuse, mental illnesses, and therapeutics.


Cannabis has been used for centuries across the globe. However, the recent changes in laws regarding legalization of recreational or medicinal cannabis, along with the availability of cannabis with increasingly higher THC levels (94, 163), are generating a sense of urgency for understanding the potential adverse effects of cannabis exposure as well as its purportedly medicinal actions.

Although many studies have been published on deleterious effects of chronic cannabis vis-´a-vis cognition, emotion, and psychiatric symptoms, the findings are inconsistent, which has made it easier for proponents of cannabis legalization to dismiss them and wrongly claim that cannabis use has no harmful effects. At the same time, major advances in our understanding of ECS neurobiology have opened exciting new opportunities for the development of novel, smarter medications for psychiatric and neurological disorders.

Source:     Annu. Rev. Pharmacol. Toxicol. 2017. 57:2.1–2.23

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