Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model
(1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8649 |
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| author | Sherelle L. Casey Vanessa A. Mitchell Eddy E. Sokolaj Bryony L. Winters Christopher W. Vaughan |
| author_facet | Sherelle L. Casey Vanessa A. Mitchell Eddy E. Sokolaj Bryony L. Winters Christopher W. Vaughan |
| author_sort | Sherelle L. Casey |
| collection | DOAJ |
| description | (1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination. (2) Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain. (3) Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630. (4) Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain. |
| first_indexed | 2024-03-09T05:20:39Z |
| format | Article |
| id | doaj.art-e3d534e5f8344225a1209868f6098472 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:20:39Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e3d534e5f8344225a1209868f60984722023-12-03T12:41:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315864910.3390/ijms23158649Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain ModelSherelle L. Casey0Vanessa A. Mitchell1Eddy E. Sokolaj2Bryony L. Winters3Christopher W. Vaughan4Pain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, NSW 2065, AustraliaPain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, NSW 2065, AustraliaPain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, NSW 2065, AustraliaPain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, NSW 2065, AustraliaPain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, NSW 2065, Australia(1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination. (2) Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain. (3) Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630. (4) Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.https://www.mdpi.com/1422-0067/23/15/8649cannabinoidneuropathic painTHCcannabidiolsynergyintrathecal |
| spellingShingle | Sherelle L. Casey Vanessa A. Mitchell Eddy E. Sokolaj Bryony L. Winters Christopher W. Vaughan Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model International Journal of Molecular Sciences cannabinoid neuropathic pain THC cannabidiol synergy intrathecal |
| title | Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model |
| title_full | Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model |
| title_fullStr | Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model |
| title_full_unstemmed | Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model |
| title_short | Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model |
| title_sort | intrathecal actions of the cannabis constituents δ 9 tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model |
| topic | cannabinoid neuropathic pain THC cannabidiol synergy intrathecal |
| url | https://www.mdpi.com/1422-0067/23/15/8649 |
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