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Molecular Mechanism and Cannabinoid Pharmacology

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Substance Use Disorders

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 258))

Abstract

Since antiquity, Cannabis has provoked enormous intrigue for its potential medicinal properties as well as for its unique pharmacological effects. The elucidation of its major cannabinoid constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), led to the synthesis of new cannabinoids (termed synthetic cannabinoids) to understand the mechanisms underlying the pharmacology of Cannabis. These pharmacological tools were instrumental in the ultimate discovery of the endogenous cannabinoid system, which consists of CB1 and CB2 cannabinoid receptors and endogenously produced ligands (endocannabinoids), which bind and activate both cannabinoid receptors. CB1 receptors mediate the cannabimimetic effects of THC and are highly expressed on presynaptic neurons in the nervous system, where they modulate neurotransmitter release. In contrast, CB2 receptors are primarily expressed on immune cells. The endocannabinoids are tightly regulated by biosynthetic and hydrolytic enzymes. Accordingly, the endocannabinoid system plays a modulatory role in many physiological processes, thereby generating many promising therapeutic targets. An unintended consequence of this research was the emergence of synthetic cannabinoids sold for human consumption to circumvent federal laws banning Cannabis use. Here, we describe research that led to the discovery of the endogenous cannabinoid system and show how knowledge of this system benefitted as well as unintentionally harmed human health.

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Acknowledgments

This work was supported by R01 DA039942 (DAK, LD, AHL), R01 DA042157 (ACH), P50 DA006634 (ACH), and VCU School of Pharmacy start-up funds (AHL).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA

    Lesley D. Schurman & Aron H. Lichtman

  2. Rangel College of Pharmacy, Health Science Center, Texas A&M University, Kingsville, TX, USA

    Dai Lu

  3. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA

    Debra A. Kendall

  4. Department of Physiology and Pharmacology and Center for Research on Substance Use and Addiction, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Allyn C. Howlett

  5. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA

    Aron H. Lichtman

Authors
  1. Lesley D. Schurman
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  2. Dai Lu
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  3. Debra A. Kendall
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  4. Allyn C. Howlett
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  5. Aron H. Lichtman
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Correspondence to Aron H. Lichtman .

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Editors and Affiliations

  1. Wake Forest School of Medicine, Winston-Salem, NC, USA

    Michael A. Nader

  2. Addiction Institute of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yasmin L. Hurd

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Schurman, L.D., Lu, D., Kendall, D.A., Howlett, A.C., Lichtman, A.H. (2019). Molecular Mechanism and Cannabinoid Pharmacology. In: Nader, M., Hurd, Y. (eds) Substance Use Disorders. Handbook of Experimental Pharmacology, vol 258. Springer, Cham. https://doi.org/10.1007/164_2019_298

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