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Dose-related inhibition of capsaicin responses by cannabinoids CBG, CBD, THC and their combination in cultured sensory neurons

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Title: Dose-related inhibition of capsaicin responses by cannabinoids CBG, CBD, THC and their combination in cultured sensory neurons
Authors: Anand, U
Oldfield, C
Pacchetti, B
Anand, P
Sodergren, MH
Item Type: Journal Article
Abstract: Abstract Background: The analgesic effects of Cannabis sativa are mediated by ∆9 tetrahydrocannabinol (THC), but the contributions of other bioactive complex components, including cannabigerol (CBG) and cannabidiol (CBD), are unclear. We describe the individual and combined effects of CBG, CBD and THC, on blocking capsaicin responses in dorsal root ganglion (DRG), neurons, in an in vitro model of nociceptor hypersensitivity. Materials and Methods: Adult rat DRG were dissected and enzyme digested to obtain a neuronal suspension in BSF2 medium containing 2% fetal calf serum, and the neurotrophic factors NGF and GDNF. After 48 h, cultured neurons were loaded with Fura-2 AM, to determine the effects of cannabinoids on capsaicin responses using calcium imaging. In control experiments, neurons were treated with vehicle, followed by 1 µM capsaicin. In cannabinoid treated cultures, CBG, CBD or THC were applied individually, or combined (1:1:1 ratio), followed by 1 µM capsaicin. Data from n=6 experiments were analysed with Student’s t-test, and Pearson’s correlation coefficient. Results: CBG, CBD and THC, applied individually, elicited dose-related calcium influx in a subset of DRG neurons, and a corresponding dose-related reduction of subsequent responses to capsaicin. Maximum inhibition of capsaicin responses was observed at 30 µM CBG, 100 µM CBD, and 100 µM THC individually, and with combined CBD+CBG+THC (1:1:1) at 90 µM. THC+CBD+CBG combined in a 1:1:1 proportion has the potential to enhance the potency of these compounds applied individually. There was a high correlation between cannabinoid-mediated calcium influx and reduction of capsaicin responses: CBG = -0.88, THC = -0.97, CBD = -0.99 and combined CBG + THC + CBD = -1.00. Conclusions: CBG, CBD and THC demonstrated potent dose-related inhibition of capsaicin responses in DRG neurons when applied individually in vitro, and enhanced when applied in combination, being most effective at 90 μM. Thus, efficacy and tolerability of THC could be improved in combination with CBG and CBD at optimal concentrations, which deserve further studies in vivo.
Issue Date: 24-Nov-2021
Date of Acceptance: 4-Nov-2021
URI: http://hdl.handle.net/10044/1/92866
DOI: 10.2147/JPR.S336773
ISSN: 1178-7090
Publisher: Dove Medical Press
Start Page: 3603
End Page: 3614
Journal / Book Title: Journal of Pain Research
Volume: 14
Copyright Statement: © 2021 Anand et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Sponsor/Funder: EMMAC U.K Limited
Funder's Grant Number: WSSS_P78476
Keywords: Cannabinoid, CBG, CBD, THC, TRPV1, DRG neurons, pain
1103 Clinical Sciences
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Conference Place: UK
Article Number: 336773
Appears in Collections:Department of Surgery and Cancer
Institute of Global Health Innovation
Department of Brain Sciences

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