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The Role of the Cannabinoid System in Pain Control: Basic and Clinical Implications


Purpose of Review

The purpose of this review is to provide a comprehensive update of the different known components of the endogenous cannabinoid system and the mechanisms of action, as it applies to analgesia.

Recent Findings

Following the discovery of the endogenous cannabinoid system in the early 1990s and the subsequent characterization of the cannabinoid receptor, there has been a renewed interest in cannabinoid research. Recent work has demonstrated its efficacy as a pharmacologic agent. There is limited evidence in the literature about the understanding of the endocannabinoid system and its role in the treatment and management of acute and chronic pain. Further work may elucidate additional roles for the endocannabinoid system within our nervous system and, moreover, additional subtypes of cannabinoid receptors have yet to be discovered.


Cannabinoid compounds mediate their biological effects via binding and subsequent activation of cannabinoid receptors. These receptors are located throughout the body and make up the endocannabinoid system. These receptors are best understood and have been cloned, type 1 (CB1) and type 2 (CB2) [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)] [ (1, 2)]. The CB2 receptor is located primarily in the immune system. CB1 receptors are primarily located in the nervous system with the highest concentrations in the brain and lower concentrations in the spine and peripheral nervous tissues. Cannabinoids may be promising treatments for neuropathic pain with limited evidence, whereas, the evidence for other uses is insufficient.

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Correspondence to Ivan Urits.

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John Wolf, Vwaire Orhurhu, Jacquelin Peck, Mariam Salisu Orhurhu, Stephen Giacomazzi, Daniel Smoots, Charlie Piermarini, Laxmaiah Manchikanti, Rachel J. Kaye, and Omar Viswanath declare no conflict of interest.

Alan Kaye is a Section Editor for Current Headache and Pain Reports. He has not been involved in the editorial handling of this manuscript. Dr. Kaye is also a speaker for Merck.

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Wolf, J., Urits, I., Orhurhu, V. et al. The Role of the Cannabinoid System in Pain Control: Basic and Clinical Implications. Curr Pain Headache Rep 24, 35 (2020).

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  • Endocannabinoid system
  • Cannabis
  • Cannabinoid receptor
  • Cannabinoids