Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons

Uma Anand,1 Christian Oldfield,1 Barbara Pacchetti,2 Praveen Anand,1 Mikael H Sodergren1,2 1Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, W12 ONN, UK; 2EMMAC Life Sciences Ltd, London, UKCorrespondence: Uma AnandFaculty of Medicine, Imperial College London, Hammersmith...

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Autores principales:	Anand U, Oldfield C, Pacchetti B, Anand P, Sodergren MH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cannabinoid cbg cbd thc trpv1 drg neurons pain Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c79a2660b4574334ae6db17a2044e025
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spelling	oai:doaj.org-article:c79a2660b4574334ae6db17a2044e0252021-11-23T18:43:01ZDose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons1178-7090https://doaj.org/article/c79a2660b4574334ae6db17a2044e0252021-11-01T00:00:00Zhttps://www.dovepress.com/dose-related-inhibition-of-capsaicin-responses-by-cannabinoids-cbg-cbd-peer-reviewed-fulltext-article-JPRhttps://doaj.org/toc/1178-7090Uma Anand,1 Christian Oldfield,1 Barbara Pacchetti,2 Praveen Anand,1 Mikael H Sodergren1,2 1Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, W12 ONN, UK; 2EMMAC Life Sciences Ltd, London, UKCorrespondence: Uma AnandFaculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 ONN, UKEmail u.anand@imperial.ac.ukBackground: 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.Conclusion: 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.Keywords: cannabinoid, CBG, CBD, THC, TRPV1, DRG neurons, painAnand UOldfield CPacchetti BAnand PSodergren MHDove Medical Pressarticlecannabinoidcbgcbdthctrpv1drg neuronspainMedicine (General)R5-920ENJournal of Pain Research, Vol Volume 14, Pp 3603-3614 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cannabinoid cbg cbd thc trpv1 drg neurons pain Medicine (General) R5-920
spellingShingle	cannabinoid cbg cbd thc trpv1 drg neurons pain Medicine (General) R5-920 Anand U Oldfield C Pacchetti B Anand P Sodergren MH Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
description	Uma Anand,1 Christian Oldfield,1 Barbara Pacchetti,2 Praveen Anand,1 Mikael H Sodergren1,2 1Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, W12 ONN, UK; 2EMMAC Life Sciences Ltd, London, UKCorrespondence: Uma AnandFaculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 ONN, UKEmail u.anand@imperial.ac.ukBackground: 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.Conclusion: 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.Keywords: cannabinoid, CBG, CBD, THC, TRPV1, DRG neurons, pain
format	article
author	Anand U Oldfield C Pacchetti B Anand P Sodergren MH
author_facet	Anand U Oldfield C Pacchetti B Anand P Sodergren MH
author_sort	Anand U
title	Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
title_short	Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
title_full	Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
title_fullStr	Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
title_full_unstemmed	Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons
title_sort	dose-related inhibition of capsaicin responses by cannabinoids cbg, cbd, thc and their combination in cultured sensory neurons
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/c79a2660b4574334ae6db17a2044e025
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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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