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Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.
Br J Pharmacol 2016; 173(1):53-65BJ

Abstract

BACKGROUND AND PURPOSE

It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC. However, our understanding of CBD and THC interactions is limited and the brain circuitry mediating interactions between CBD and THC are unknown. The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

EXPERIMENTAL APPROACH

Male C57BL/6 mice were treated with vehicle, CBD, THC or a combination of CBD and THC (10 mg·kg(-1) i.p. for both cannabinoids) to examine effects on locomotor activity, anxiety-related behaviour, body temperature and brain c-Fos expression (a marker of neuronal activation).

KEY RESULTS

CBD potentiated THC-induced locomotor suppression but reduced the hypothermic and anxiogenic effects of THC. CBD alone had no effect on these measures. THC increased brain activation as measured by c-Fos expression in 11 of the 35 brain regions studied. CBD co-administration suppressed THC-induced c-Fos expression in six of these brain regions. This effect was most pronounced in the medial preoptic nucleus and lateral periaqueductal gray. Treatment with CBD alone diminished c-Fos expression only in the central nucleus of the amygdala compared with vehicle.

CONCLUSIONS AND IMPLICATIONS

These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC.

Authors+Show Affiliations

Brain and Mind Centre, University of Sydney, Sydney, Australia. Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, Australia.Brain and Mind Centre, University of Sydney, Sydney, Australia. Discipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, Australia.

Pub Type(s)

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

Language

eng

PubMed ID

26377899

Citation

Todd, S M., and J C. Arnold. "Neural Correlates of Interactions Between Cannabidiol and Δ(9) -tetrahydrocannabinol in Mice: Implications for Medical Cannabis." British Journal of Pharmacology, vol. 173, no. 1, 2016, pp. 53-65.
Todd SM, Arnold JC. Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis. Br J Pharmacol. 2016;173(1):53-65.
Todd, S. M., & Arnold, J. C. (2016). Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis. British Journal of Pharmacology, 173(1), pp. 53-65. doi:10.1111/bph.13333.
Todd SM, Arnold JC. Neural Correlates of Interactions Between Cannabidiol and Δ(9) -tetrahydrocannabinol in Mice: Implications for Medical Cannabis. Br J Pharmacol. 2016;173(1):53-65. PubMed PMID: 26377899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis. AU - Todd,S M, AU - Arnold,J C, Y1 - 2015/11/18/ PY - 2015/04/27/received PY - 2015/09/01/revised PY - 2015/09/06/accepted PY - 2015/9/18/entrez PY - 2015/9/18/pubmed PY - 2016/10/14/medline SP - 53 EP - 65 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 173 IS - 1 N2 - BACKGROUND AND PURPOSE: It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC. However, our understanding of CBD and THC interactions is limited and the brain circuitry mediating interactions between CBD and THC are unknown. The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols. EXPERIMENTAL APPROACH: Male C57BL/6 mice were treated with vehicle, CBD, THC or a combination of CBD and THC (10 mg·kg(-1) i.p. for both cannabinoids) to examine effects on locomotor activity, anxiety-related behaviour, body temperature and brain c-Fos expression (a marker of neuronal activation). KEY RESULTS: CBD potentiated THC-induced locomotor suppression but reduced the hypothermic and anxiogenic effects of THC. CBD alone had no effect on these measures. THC increased brain activation as measured by c-Fos expression in 11 of the 35 brain regions studied. CBD co-administration suppressed THC-induced c-Fos expression in six of these brain regions. This effect was most pronounced in the medial preoptic nucleus and lateral periaqueductal gray. Treatment with CBD alone diminished c-Fos expression only in the central nucleus of the amygdala compared with vehicle. CONCLUSIONS AND IMPLICATIONS: These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/26377899/Neural_correlates_of_interactions_between_cannabidiol_and_Δ_9___tetrahydrocannabinol_in_mice:_implications_for_medical_cannabis_ L2 - https://doi.org/10.1111/bph.13333 DB - PRIME DP - Unbound Medicine ER -