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Written by

Dr Karen H Simpson Dr Karen H Simpson is a consultant in anaesthesia and pain medicine, Leeds, UK

Research update: The role of the endocannabinoid system in depression, reward and pain control

Published 27 April 2017

Pain specialist and joint editor Dr Karen H Simpson reviews the role of the endocannabinoid system in depression, reward and pain control

Huang WJ, Chen WW, et al.

Endocannabinoid system: Role in depression, reward and pain control (Review)

Molecular Medicine Reports. 2016;14(4):2899–903.

It is well accepted that mood disorders eg depression and chronic pain co-exist in almost 80% of patients. These conditions are common and are both associated with impaired health-related quality of life, often contributing to high mortality.

It has been shown that the majority of patients who suffer from depression and pain are not responsive to pharmacological treatments that address either pain or depression. This comorbidity therefore causes a heavy burden on patients, the healthcare system and society.

In ancient times this depression-pain comorbidity was sometimes treated using extracts of the plant Cannabis sativa. Given that this extract has been used for 1000s of years, it is surprising that the mode of action of Δ9‑tetrahydrocannabinol, an active ingredient of marijuana, has only recently been elucidated. Cannabinoid receptor types CB1 and CB2 have been identified; these are located on presynaptic membranes in the central nervous system and in peripheral tissues, respectively. Subsequent investigations have led to the identification of endocannabinoids, anandamide and 2-arachidonoylglycerol; these exert cannabinomimetic effects through CB1 and CB2 receptors. These endocannabinoids are produced from membrane lipids; they are lipophilic molecules that are synthesised on demand and are eliminated rapidly by hydrolysing enzymes. Clinical studies have shown altered endocannabinoid signalling in patients with chronic pain.

The authors present some evidence suggesting involvement of the endocannabinoid system in eliciting potent effects on neurotransmission, neuroendocrine and inflammatory processes that are known to be altered in depression and chronic pain. Several synthetic cannabinomimetic drugs are being developed to treat pain and depression. The precise mode of action of endocannabinoids on different body targets and whether their effects on pain and depression follow the same or different pathways remains to be determined.  However, this paper highlights the need for more cannabinoid research that may prove these compounds to be useful in our armamentarium. In my view this type of research needs to be uncoupled from inhibition by social and juridical prejudice.

  • Dr Karen H Simpson is a consultant in anaesthesia and pain medicine, Leeds, UK


Date of preparation: April 2017; MINT/PAEU-17009