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Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.
Drug Alcohol Depend. 2009 Nov 01; 105(1-2):42-7.DA

Abstract

Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Delta(9)-THC and CBN bound to the CB(1) receptor and produced antinociceptive effects. The CB(1) receptor antagonist, rimonabant, but not the CB(2) receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB(1) receptor with similar affinity as Delta(9)-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Delta(9)-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19679411

Citation

Booker, Lamont, et al. "Evaluation of Prevalent Phytocannabinoids in the Acetic Acid Model of Visceral Nociception." Drug and Alcohol Dependence, vol. 105, no. 1-2, 2009, pp. 42-7.
Booker L, Naidu PS, Razdan RK, et al. Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception. Drug Alcohol Depend. 2009;105(1-2):42-7.
Booker, L., Naidu, P. S., Razdan, R. K., Mahadevan, A., & Lichtman, A. H. (2009). Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception. Drug and Alcohol Dependence, 105(1-2), 42-7. https://doi.org/10.1016/j.drugalcdep.2009.06.009
Booker L, et al. Evaluation of Prevalent Phytocannabinoids in the Acetic Acid Model of Visceral Nociception. Drug Alcohol Depend. 2009 Nov 1;105(1-2):42-7. PubMed PMID: 19679411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception. AU - Booker,Lamont, AU - Naidu,Pattipati S, AU - Razdan,Raj K, AU - Mahadevan,Anu, AU - Lichtman,Aron H, Y1 - 2009/08/12/ PY - 2009/02/21/received PY - 2009/06/03/revised PY - 2009/06/03/accepted PY - 2009/8/15/entrez PY - 2009/8/15/pubmed PY - 2009/12/16/medline SP - 42 EP - 7 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 105 IS - 1-2 N2 - Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Delta(9)-THC and CBN bound to the CB(1) receptor and produced antinociceptive effects. The CB(1) receptor antagonist, rimonabant, but not the CB(2) receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB(1) receptor with similar affinity as Delta(9)-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Delta(9)-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/19679411/Evaluation_of_prevalent_phytocannabinoids_in_the_acetic_acid_model_of_visceral_nociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(09)00221-X DB - PRIME DP - Unbound Medicine ER -