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Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol.
Drug Alcohol Depend. 2010 Nov 01; 112(1-2):126-33.DA

Abstract

In contrast to the numerous reports on the pharmacological effects of Δ(9)-tetrahydrocannabinol (THC), the pharmacological activity of another substituent of Cannabis sativa, cannabichromene (CBC) remains comparatively unknown. In the present study, we investigated whether CBC elicits cannabinoid activity in the tetrad assay, which consists of the following four endpoints: hypomotility, antinociception, catalepsy, and hypothermia. Because cannabinoids are well documented to possess anti-inflammatory properties, we examined CBC, THC, and combination of both phytocannabinoids in the lipopolysaccharide (LPS) paw edema assay. CBC elicited activity in the tetrad that was not blocked by the CB(1) receptor antagonist, rimonabant. Moreover, a behaviorally inactive dose of THC augmented the effects of CBC in the tetrad that was associated with an increase in THC brain concentrations. Both CBC and THC elicited dose-dependent anti-inflammatory effects in the LPS-induced paw edema model. The CB(2) receptor, SR144528 blocked the anti-edematous actions of THC, but not those produced by CBC. Isobolographic analysis revealed that the anti-edematous effects of these cannabinoids in combination were additive. Although CBC produced pharmacological effects, unlike THC, its underlying mechanism of action did not involve CB(1) or CB(2) receptors. In addition, there was evidence of a possible pharmacokinetic component in which CBC dose-dependently increased THC brain levels following an i.v. injection of 0.3mg/kg THC. In conclusion, CBC produced a subset of behavioral activity in the tetrad assay and reduced LPS-induced paw edema through a noncannabinoid receptor mechanism of action. These effects were augmented when CBC and THC were co-administered.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20619971

Citation

DeLong, Gerald T., et al. "Pharmacological Evaluation of the Natural Constituent of Cannabis Sativa, Cannabichromene and Its Modulation By Δ(9)-tetrahydrocannabinol." Drug and Alcohol Dependence, vol. 112, no. 1-2, 2010, pp. 126-33.
DeLong GT, Wolf CE, Poklis A, et al. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2010;112(1-2):126-33.
DeLong, G. T., Wolf, C. E., Poklis, A., & Lichtman, A. H. (2010). Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. Drug and Alcohol Dependence, 112(1-2), 126-33. https://doi.org/10.1016/j.drugalcdep.2010.05.019
DeLong GT, et al. Pharmacological Evaluation of the Natural Constituent of Cannabis Sativa, Cannabichromene and Its Modulation By Δ(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2010 Nov 1;112(1-2):126-33. PubMed PMID: 20619971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol. AU - DeLong,Gerald T, AU - Wolf,Carl E, AU - Poklis,Alphonse, AU - Lichtman,Aron H, PY - 2010/02/12/received PY - 2010/05/25/revised PY - 2010/05/31/accepted PY - 2010/7/13/entrez PY - 2010/7/14/pubmed PY - 2011/5/3/medline SP - 126 EP - 33 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 112 IS - 1-2 N2 - In contrast to the numerous reports on the pharmacological effects of Δ(9)-tetrahydrocannabinol (THC), the pharmacological activity of another substituent of Cannabis sativa, cannabichromene (CBC) remains comparatively unknown. In the present study, we investigated whether CBC elicits cannabinoid activity in the tetrad assay, which consists of the following four endpoints: hypomotility, antinociception, catalepsy, and hypothermia. Because cannabinoids are well documented to possess anti-inflammatory properties, we examined CBC, THC, and combination of both phytocannabinoids in the lipopolysaccharide (LPS) paw edema assay. CBC elicited activity in the tetrad that was not blocked by the CB(1) receptor antagonist, rimonabant. Moreover, a behaviorally inactive dose of THC augmented the effects of CBC in the tetrad that was associated with an increase in THC brain concentrations. Both CBC and THC elicited dose-dependent anti-inflammatory effects in the LPS-induced paw edema model. The CB(2) receptor, SR144528 blocked the anti-edematous actions of THC, but not those produced by CBC. Isobolographic analysis revealed that the anti-edematous effects of these cannabinoids in combination were additive. Although CBC produced pharmacological effects, unlike THC, its underlying mechanism of action did not involve CB(1) or CB(2) receptors. In addition, there was evidence of a possible pharmacokinetic component in which CBC dose-dependently increased THC brain levels following an i.v. injection of 0.3mg/kg THC. In conclusion, CBC produced a subset of behavioral activity in the tetrad assay and reduced LPS-induced paw edema through a noncannabinoid receptor mechanism of action. These effects were augmented when CBC and THC were co-administered. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/20619971/Pharmacological_evaluation_of_the_natural_constituent_of_Cannabis_sativa_cannabichromene_and_its_modulation_by_Δ_9__tetrahydrocannabinol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(10)00207-3 DB - PRIME DP - Unbound Medicine ER -