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Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ9-tetrahydrocannabinol
Gerald T. DeLonga, 1, Carl E. Wolfb, Alphonse Poklisb and Aron H. Lichtmana, Corresponding Author Contact Information, E-mail The Corresponding Author, E-mail The Corresponding Author
a Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
b Department of Pathology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Received 12 February 2010;
revised 25 May 2010;
accepted 31 May 2010.
Available online 9 July 2010.
Abstract
In contrast to the numerous reports on the pharmacological effects of Δ9-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 CB1 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 CB2 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 CB1 or CB2 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 0.3 mg/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.
Keywords: Cannabis sativa; Marijuana; Phytocannabinoid; Cannabichromene; Delta-9-tetrahydrocannabinol (THC); CB1 cannabinoid receptor; CB2 cannabinoid receptor; Anti-inflammatory
Article Outline
1.
Introduction
2.
Materials and methods
2.1. Animals
2.2. Drugs
2.3. Tetrad procedure
2.4. Extraction procedure, GC/MS analysis
2.5. Inflammation induction and measurement procedure
2.6. Statistical analyses
3.
Results
3.1. CBC elicits pharmacological effects through a non-CB1 receptor mechanism of action in the tetrad assay
3.2. THC enhances the pharmacological effects of CBC
3.3. Evaluation of CBC and THC on LPS-induced paw edema
3.4. Combination of CBC and THC on LPS-induced paw edema
4.
Discussion
4.1. Evaluation of pharmacological effects of CBC in the tetrad assay.
4.2. Evaluation of CBC in the LPS-induced paw edema model
4.3. Conclusions
Role of funding source
Contributors
Conflict of interest
Acknowledgements
Appendix A.
Supplementary data
References
star, openA supplementary data figure is available with the online version of this article at doi:10.1016/j.drugalcdep.2010.05.019. Please see Appendix A.
Corresponding Author Contact InformationCorresponding author at: Virginia Commonwealth University, Department of Pharmacology & Toxicology, 410 N. 12th Street, Smith Building P.O. Box 980613, Richmond, VA 23298-0613, USA. Tel.: +1 804 828 8480; fax: +1 804 828 2117.
1 Now at Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Source: Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ9-tetrahydrocannabinol
Gerald T. DeLonga, 1, Carl E. Wolfb, Alphonse Poklisb and Aron H. Lichtmana, Corresponding Author Contact Information, E-mail The Corresponding Author, E-mail The Corresponding Author
a Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
b Department of Pathology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Received 12 February 2010;
revised 25 May 2010;
accepted 31 May 2010.
Available online 9 July 2010.
Abstract
In contrast to the numerous reports on the pharmacological effects of Δ9-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 CB1 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 CB2 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 CB1 or CB2 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 0.3 mg/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.
Keywords: Cannabis sativa; Marijuana; Phytocannabinoid; Cannabichromene; Delta-9-tetrahydrocannabinol (THC); CB1 cannabinoid receptor; CB2 cannabinoid receptor; Anti-inflammatory
Article Outline
1.
Introduction
2.
Materials and methods
2.1. Animals
2.2. Drugs
2.3. Tetrad procedure
2.4. Extraction procedure, GC/MS analysis
2.5. Inflammation induction and measurement procedure
2.6. Statistical analyses
3.
Results
3.1. CBC elicits pharmacological effects through a non-CB1 receptor mechanism of action in the tetrad assay
3.2. THC enhances the pharmacological effects of CBC
3.3. Evaluation of CBC and THC on LPS-induced paw edema
3.4. Combination of CBC and THC on LPS-induced paw edema
4.
Discussion
4.1. Evaluation of pharmacological effects of CBC in the tetrad assay.
4.2. Evaluation of CBC in the LPS-induced paw edema model
4.3. Conclusions
Role of funding source
Contributors
Conflict of interest
Acknowledgements
Appendix A.
Supplementary data
References
star, openA supplementary data figure is available with the online version of this article at doi:10.1016/j.drugalcdep.2010.05.019. Please see Appendix A.
Corresponding Author Contact InformationCorresponding author at: Virginia Commonwealth University, Department of Pharmacology & Toxicology, 410 N. 12th Street, Smith Building P.O. Box 980613, Richmond, VA 23298-0613, USA. Tel.: +1 804 828 8480; fax: +1 804 828 2117.
1 Now at Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Source: Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ9-tetrahydrocannabinol
