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In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa.
Sci Rep. 2020 11 23; 10(1):20405.SR

Abstract

The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

Authors+Show Affiliations

College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada.Aurora Prairie Research Centre, Aurora Cannabis, Saskatoon, SK, Canada.ZYUS Life Sciences, Saskatoon, SK, Canada.College of Pharmacy and Nutrition, University of Saskatchewan, 3B36, Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 2Z4, Canada. robert.laprairie@usask.ca. Department of Pharmacology, College of Medicine, Dalhousie University, Halifax, NS, Canada. robert.laprairie@usask.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33230154

Citation

Zagzoog, Ayat, et al. "In Vitro and in Vivo Pharmacological Activity of Minor Cannabinoids Isolated From Cannabis Sativa." Scientific Reports, vol. 10, no. 1, 2020, p. 20405.
Zagzoog A, Mohamed KA, Kim HJJ, et al. In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa. Sci Rep. 2020;10(1):20405.
Zagzoog, A., Mohamed, K. A., Kim, H. J. J., Kim, E. D., Frank, C. S., Black, T., Jadhav, P. D., Holbrook, L. A., & Laprairie, R. B. (2020). In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa. Scientific Reports, 10(1), 20405. https://doi.org/10.1038/s41598-020-77175-y
Zagzoog A, et al. In Vitro and in Vivo Pharmacological Activity of Minor Cannabinoids Isolated From Cannabis Sativa. Sci Rep. 2020 11 23;10(1):20405. PubMed PMID: 33230154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa. AU - Zagzoog,Ayat, AU - Mohamed,Kawthar A, AU - Kim,Hye Ji J, AU - Kim,Eunhyun D, AU - Frank,Connor S, AU - Black,Tallan, AU - Jadhav,Pramodkumar D, AU - Holbrook,Larry A, AU - Laprairie,Robert B, Y1 - 2020/11/23/ PY - 2020/10/06/received PY - 2020/11/05/accepted PY - 2020/11/24/entrez PY - 2020/11/25/pubmed PY - 2021/4/17/medline SP - 20405 EP - 20405 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33230154/In_vitro_and_in_vivo_pharmacological_activity_of_minor_cannabinoids_isolated_from_Cannabis_sativa_ DB - PRIME DP - Unbound Medicine ER -