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Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.
Br J Pharmacol 2013; 170(3):679-92BJ

Abstract

BACKGROUND AND PURPOSE

Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors.

EXPERIMENTAL APPROACH

The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1)) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays.

KEY RESULTS

CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1)) and audiogenic seizure models (≥87 mg·kg(-1)), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1)). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV.

CONCLUSIONS AND IMPLICATIONS

CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

Authors+Show Affiliations

Reading School of Pharmacy, University of Reading, Reading, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23902406

Citation

Hill, T D M., et al. "Cannabidivarin-rich Cannabis Extracts Are Anticonvulsant in Mouse and Rat Via a CB1 Receptor-independent Mechanism." British Journal of Pharmacology, vol. 170, no. 3, 2013, pp. 679-92.
Hill TD, Cascio MG, Romano B, et al. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Br J Pharmacol. 2013;170(3):679-92.
Hill, T. D., Cascio, M. G., Romano, B., Duncan, M., Pertwee, R. G., Williams, C. M., ... Hill, A. J. (2013). Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. British Journal of Pharmacology, 170(3), pp. 679-92. doi:10.1111/bph.12321.
Hill TD, et al. Cannabidivarin-rich Cannabis Extracts Are Anticonvulsant in Mouse and Rat Via a CB1 Receptor-independent Mechanism. Br J Pharmacol. 2013;170(3):679-92. PubMed PMID: 23902406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. AU - Hill,T D M, AU - Cascio,M-G, AU - Romano,B, AU - Duncan,M, AU - Pertwee,R G, AU - Williams,C M, AU - Whalley,B J, AU - Hill,A J, PY - 2013/05/23/received PY - 2013/07/19/revised PY - 2013/07/27/accepted PY - 2013/8/2/entrez PY - 2013/8/2/pubmed PY - 2014/8/20/medline KW - anticonvulsant KW - cannabidiol KW - cannabidivarin KW - cannabinoid KW - epilepsy KW - isobologram KW - radioligand binding assays KW - seizure KW - tolerability SP - 679 EP - 92 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 170 IS - 3 N2 - BACKGROUND AND PURPOSE: Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. EXPERIMENTAL APPROACH: The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1)) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. KEY RESULTS: CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1)) and audiogenic seizure models (≥87 mg·kg(-1)), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1)). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS: CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/23902406/Cannabidivarin_rich_cannabis_extracts_are_anticonvulsant_in_mouse_and_rat_via_a_CB1_receptor_independent_mechanism_ L2 - https://doi.org/10.1111/bph.12321 DB - PRIME DP - Unbound Medicine ER -