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Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews.
Psychopharmacology (Berl). 2020 Sep; 237(9):2621-2631.P

Abstract

RATIONALE

When acutely administered intraperitoneally, the non-psychoactive cannabinoid cannabidiol (CBD), its acidic precursor cannabidiolic acid (CBDA) and a stable methyl ester of CBDA (HU-580) reduce lithium chloride (LiCl)-induced conditioned gaping in male rats (a selective preclinical model of acute nausea) via activation of the serotonin 1A (5-HT1A) receptor.

OBJECTIVES

To utilise these compounds to manage nausea in the clinic, we must determine if their effectiveness is maintained when injected subcutaneously (s.c) and when repeatedly administered. First, we compared the effectiveness of each of these compounds to reduce conditioned gaping following repeated (7-day) and acute (1-day) pretreatments and whether these anti-nausea effects were mediated by the 5-HT1A receptor. Next, we assessed whether the effectiveness of these compounds can be maintained when administered prior to each of 4 conditioning trials (once per week). We also evaluated the ability of repeated CBD (7 days) to reduce LiCl-induced vomiting in Suncus murinus. Finally, we examined whether acute CBD was equally effective in male and female rats.

RESULTS

Both acute and repeated (7 day) s.c. administrations of CBD (5 mg/kg), CBDA (1 μg/kg) and HU-580 (1 μg/kg) similarly reduced LiCl-induced conditioned gaping, and these effects were blocked by 5HT1A receptor antagonism. When administered over 4 weekly conditioning trials, the anti-nausea effectiveness of each of these compounds was also maintained. Repeated CBD (5 mg/kg, s.c.) maintained its anti-emetic efficacy in S. murinus. Acute CBD (5 and 20 mg/kg, s.c.) administration reduced LiCl-induced conditioned gaping similarly in male and female rats.

CONCLUSION

When administered repeatedly (7 days), CBD, CBDA and HU-580 did not lose efficacy in reducing nausea and continued to act via agonism of the 5-HT1A receptor. When administered across 4 weekly conditioning trials, they maintained their effectiveness in reducing LiCl-induced nausea. Repeated CBD also reduced vomiting in shrews. Finally, CBD's anti-nausea effects were similar in male and female rats. This suggests that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance.

Authors+Show Affiliations

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada.Institute of Drug Research, Medical Facility, Hebrew University of Jerusalem, Jerusalem, Israel.Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G2W1, Canada. parkerl@uoguelph.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32488349

Citation

Rock, Erin M., et al. "Evaluation of Repeated or Acute Treatment With Cannabidiol (CBD), Cannabidiolic Acid (CBDA) or CBDA Methyl Ester (HU-580) On Nausea And/or Vomiting in Rats and Shrews." Psychopharmacology, vol. 237, no. 9, 2020, pp. 2621-2631.
Rock EM, Sullivan MT, Collins SA, et al. Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews. Psychopharmacology (Berl). 2020;237(9):2621-2631.
Rock, E. M., Sullivan, M. T., Collins, S. A., Goodman, H., Limebeer, C. L., Mechoulam, R., & Parker, L. A. (2020). Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews. Psychopharmacology, 237(9), 2621-2631. https://doi.org/10.1007/s00213-020-05559-z
Rock EM, et al. Evaluation of Repeated or Acute Treatment With Cannabidiol (CBD), Cannabidiolic Acid (CBDA) or CBDA Methyl Ester (HU-580) On Nausea And/or Vomiting in Rats and Shrews. Psychopharmacology (Berl). 2020;237(9):2621-2631. PubMed PMID: 32488349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews. AU - Rock,Erin M, AU - Sullivan,Megan T, AU - Collins,Stephen A, AU - Goodman,Hannah, AU - Limebeer,Cheryl L, AU - Mechoulam,Raphael, AU - Parker,Linda A, Y1 - 2020/06/02/ PY - 2020/03/05/received PY - 2020/05/18/accepted PY - 2020/6/4/pubmed PY - 2020/6/4/medline PY - 2020/6/4/entrez KW - 5-HT1A KW - Cannabidiol KW - Cannabidiolic acid KW - Conditioned gaping KW - HU-580 KW - Repeated SP - 2621 EP - 2631 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 237 IS - 9 N2 - RATIONALE: When acutely administered intraperitoneally, the non-psychoactive cannabinoid cannabidiol (CBD), its acidic precursor cannabidiolic acid (CBDA) and a stable methyl ester of CBDA (HU-580) reduce lithium chloride (LiCl)-induced conditioned gaping in male rats (a selective preclinical model of acute nausea) via activation of the serotonin 1A (5-HT1A) receptor. OBJECTIVES: To utilise these compounds to manage nausea in the clinic, we must determine if their effectiveness is maintained when injected subcutaneously (s.c) and when repeatedly administered. First, we compared the effectiveness of each of these compounds to reduce conditioned gaping following repeated (7-day) and acute (1-day) pretreatments and whether these anti-nausea effects were mediated by the 5-HT1A receptor. Next, we assessed whether the effectiveness of these compounds can be maintained when administered prior to each of 4 conditioning trials (once per week). We also evaluated the ability of repeated CBD (7 days) to reduce LiCl-induced vomiting in Suncus murinus. Finally, we examined whether acute CBD was equally effective in male and female rats. RESULTS: Both acute and repeated (7 day) s.c. administrations of CBD (5 mg/kg), CBDA (1 μg/kg) and HU-580 (1 μg/kg) similarly reduced LiCl-induced conditioned gaping, and these effects were blocked by 5HT1A receptor antagonism. When administered over 4 weekly conditioning trials, the anti-nausea effectiveness of each of these compounds was also maintained. Repeated CBD (5 mg/kg, s.c.) maintained its anti-emetic efficacy in S. murinus. Acute CBD (5 and 20 mg/kg, s.c.) administration reduced LiCl-induced conditioned gaping similarly in male and female rats. CONCLUSION: When administered repeatedly (7 days), CBD, CBDA and HU-580 did not lose efficacy in reducing nausea and continued to act via agonism of the 5-HT1A receptor. When administered across 4 weekly conditioning trials, they maintained their effectiveness in reducing LiCl-induced nausea. Repeated CBD also reduced vomiting in shrews. Finally, CBD's anti-nausea effects were similar in male and female rats. This suggests that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/32488349/Evaluation_of_repeated_or_acute_treatment_with_cannabidiol__CBD__cannabidiolic_acid__CBDA__or_CBDA_methyl_ester__HU_580__on_nausea_and/or_vomiting_in_rats_and_shrews_ L2 - https://dx.doi.org/10.1007/s00213-020-05559-z DB - PRIME DP - Unbound Medicine ER -