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Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice.
Br J Pharmacol. 2019 05; 176(10):1552-1567.BJ

Abstract

BACKGROUND AND PURPOSE

It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of Δ9 -tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB1 /CB2 receptor agonists or produces these pharmacological effects on its own.

EXPERIMENTAL APPROACH

The effects of THC or the CB1 /CB2 receptor full agonist WIN55212 alone, CBD alone or their combination were tested across a range of doses. Cognitive effects were assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes maze. Cannabinoid withdrawal signs were assessed following precipitated withdrawal by acute administration of the CB1 receptor antagonist SR141716, the 5-HT1A receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine or the adenosine A2A receptor antagonist SCH58261.

KEY RESULTS

THC produced significant motor and cognitive impairment in the Barnes maze task, none of which were attenuated by the addition of CBD. CBD alone did not affect cognitive performance. Precipitation of withdrawal signs by SR141716 occurred in mice chronically treated with THC or WIN55,212. These withdrawal signs were not attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD treatment also produced anxiolysis, which was not altered by attempting to precipitate withdrawal-induced anxiety with a range of antagonists.

CONCLUSIONS AND IMPLICATIONS

CBD as a monotherapy may prove to be a safer pharmacological agent, than CB1 receptor agonists alone or in combination with CBD, for the treatment of several disorders.

LINKED ARTICLES

This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.

Authors+Show Affiliations

Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.

Pub Type(s)

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

Language

eng

PubMed ID

29338068

Citation

Myers, Alyssa M., et al. "Single and Combined Effects of Plant-derived and Synthetic Cannabinoids On Cognition and Cannabinoid-associated Withdrawal Signs in Mice." British Journal of Pharmacology, vol. 176, no. 10, 2019, pp. 1552-1567.
Myers AM, Siegele PB, Foss JD, et al. Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. Br J Pharmacol. 2019;176(10):1552-1567.
Myers, A. M., Siegele, P. B., Foss, J. D., Tuma, R. F., & Ward, S. J. (2019). Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. British Journal of Pharmacology, 176(10), 1552-1567. https://doi.org/10.1111/bph.14147
Myers AM, et al. Single and Combined Effects of Plant-derived and Synthetic Cannabinoids On Cognition and Cannabinoid-associated Withdrawal Signs in Mice. Br J Pharmacol. 2019;176(10):1552-1567. PubMed PMID: 29338068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. AU - Myers,Alyssa M, AU - Siegele,Patrick B, AU - Foss,Jeffrey D, AU - Tuma,Ronald F, AU - Ward,Sara Jane, Y1 - 2018/03/01/ PY - 2017/07/24/received PY - 2017/10/04/revised PY - 2017/10/11/accepted PY - 2018/1/18/pubmed PY - 2020/7/22/medline PY - 2018/1/17/entrez SP - 1552 EP - 1567 JF - British journal of pharmacology JO - Br J Pharmacol VL - 176 IS - 10 N2 - BACKGROUND AND PURPOSE: It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of Δ9 -tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB1 /CB2 receptor agonists or produces these pharmacological effects on its own. EXPERIMENTAL APPROACH: The effects of THC or the CB1 /CB2 receptor full agonist WIN55212 alone, CBD alone or their combination were tested across a range of doses. Cognitive effects were assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes maze. Cannabinoid withdrawal signs were assessed following precipitated withdrawal by acute administration of the CB1 receptor antagonist SR141716, the 5-HT1A receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine or the adenosine A2A receptor antagonist SCH58261. KEY RESULTS: THC produced significant motor and cognitive impairment in the Barnes maze task, none of which were attenuated by the addition of CBD. CBD alone did not affect cognitive performance. Precipitation of withdrawal signs by SR141716 occurred in mice chronically treated with THC or WIN55,212. These withdrawal signs were not attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD treatment also produced anxiolysis, which was not altered by attempting to precipitate withdrawal-induced anxiety with a range of antagonists. CONCLUSIONS AND IMPLICATIONS: CBD as a monotherapy may prove to be a safer pharmacological agent, than CB1 receptor agonists alone or in combination with CBD, for the treatment of several disorders. LINKED ARTICLES: This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/29338068/Single_and_combined_effects_of_plant_derived_and_synthetic_cannabinoids_on_cognition_and_cannabinoid_associated_withdrawal_signs_in_mice_ DB - PRIME DP - Unbound Medicine ER -