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Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol.
Drug Alcohol Depend 2008; 94(1-3):191-8DA

Abstract

Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Delta(9)-tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids (e.g., cannabidiol (CBD)) has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC's abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC's discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, PO Box 980613, Richmond, VA 23298-0613, United States. revann@vcu.eduNo affiliation info availableNo affiliation info availableNo 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

18206320

Citation

Vann, Robert E., et al. "Divergent Effects of Cannabidiol On the Discriminative Stimulus and Place Conditioning Effects of Delta(9)-tetrahydrocannabinol." Drug and Alcohol Dependence, vol. 94, no. 1-3, 2008, pp. 191-8.
Vann RE, Gamage TF, Warner JA, et al. Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2008;94(1-3):191-8.
Vann, R. E., Gamage, T. F., Warner, J. A., Marshall, E. M., Taylor, N. L., Martin, B. R., & Wiley, J. L. (2008). Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug and Alcohol Dependence, 94(1-3), pp. 191-8. doi:10.1016/j.drugalcdep.2007.11.017.
Vann RE, et al. Divergent Effects of Cannabidiol On the Discriminative Stimulus and Place Conditioning Effects of Delta(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2008 Apr 1;94(1-3):191-8. PubMed PMID: 18206320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. AU - Vann,Robert E, AU - Gamage,Thomas F, AU - Warner,Jonathan A, AU - Marshall,Ericka M, AU - Taylor,Nathan L, AU - Martin,Billy R, AU - Wiley,Jenny L, PY - 2007/10/17/received PY - 2007/11/12/revised PY - 2007/11/19/accepted PY - 2008/1/22/pubmed PY - 2008/6/28/medline PY - 2008/1/22/entrez SP - 191 EP - 8 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 94 IS - 1-3 N2 - Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Delta(9)-tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids (e.g., cannabidiol (CBD)) has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC's abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC's discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios. SN - 0376-8716 UR - https://www.unboundmedicine.com/medline/citation/18206320/Divergent_effects_of_cannabidiol_on_the_discriminative_stimulus_and_place_conditioning_effects_of_Delta_9__tetrahydrocannabinol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(07)00490-5 DB - PRIME DP - Unbound Medicine ER -