Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model

Mitchell, Vanessa; Harley, Juliette Cornelia; Casey, Sherelle L.; Vaughan, Arabella C.; Winters, Bryony L.; Vaughan, Christopher W.

doi:10.1016/j.neuropharm.2021.108529

Cited by 26 publications

(16 citation statements)

References 39 publications

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“…While both THC and CBD were highly efficacious against mechanical allodynia, they had only partial effectiveness against cold allodynia. This differs to systemic administration where THC has high efficacy, compared to CBD which has only partial efficacy against both mechanical and cold allodynia [ 6 , 21 ]. This difference may be due a relatively greater role of spinal pain pathways in the suppressive actions of THC and CBD on mechanical allodynia, compared to cold allodynia.…”

Section: Discussionmentioning

confidence: 99%

“…The difference between THC and selective agonists may be due to the lower affinity and efficacy of THC for cannabinoid receptors, or other experimental factors (see Section 3.3 ). The lack of side-effects of intrathecal THC and CBD might also be contrasted to systemic THC which has a relatively poor therapeutic window [ 6 , 21 ]. This is consistent with prior studies that have demonstrated a major role of the brain in the side-effects of THC.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, systemically injected THC and CBD synergistically reduce allodynia in neuropathic pain models [ 6 , 7 ]. However, the systemic actions of THC-containing phytocannabinoid preparations in neuropathic pain models are associated with substantial cannabinoid-like side-effects, when injected or administered orally [ 6 , 10 , 19 , 20 , 21 ]. These side-effect issues are reflected by the problems with adverse reactions reported in clinical studies which are largely focused on systemic administration [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…These side-effect issues are reflected by the problems with adverse reactions reported in clinical studies which are largely focused on systemic administration [ 4 , 5 ]. One approach to avoiding side-effects associated with cannabis has been the use of non-psychoactive phytocannabinoid constituents such as CBD [ 6 , 13 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

Casey

Mitchell

Sokolaj

et al. 2022

IJMS

Self Cite

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(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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

Casey

Mitchell

Sokolaj

et al. 2022

IJMS

Self Cite

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“…Cannabis sativa contains a multitude of phytocannabinoids, such as the psychoactive constituent Δ9-tetrahydrocannabinol (THC), plus other constituents such as cannabidiol (CBD) that do not produce THC-like psychotropic side effects. Agonism at CB1 and CB2 receptors by cannabis-based medicines have shown analgesia in rodent models of neuropathic pain [ 135 ]. Cancer patients have reported favourable outcomes for managing chemotherapy-induced nausea and vomiting as well as symptoms due to cancer such as pain [ 136 ], but there are differing views as to their clinical efficacy and safety in light of the limited number of high-quality clinical trials evaluating these benefits being currently available [ 137 , 138 ].…”

Section: Current Approaches To the Pharmacotherapy Of Chronic Pain In...mentioning

confidence: 99%

Pharmacologic Management of Persistent Pain in Cancer Survivors

Glare

Aubrey

Gulati

et al. 2022

Drugs

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Improvements in screening, diagnosis and treatment of cancer has seen cancer mortality substantially diminish in the past three decades. It is estimated there are almost 20 million cancer survivors in the USA alone, but some 40% live with chronic pain after completing treatment. While a broad definition of survivorship that includes all people living with, through and beyond a cancer diagnosis-including those with active cancer-is often used, this narrative review primarily focuses on the management of pain in people who are disease-free after completing primary cancer treatment as adults. Chronic pain in this population needs a different approach to that used for people with a limited prognosis. After describing the common chronic pain syndromes caused by cancer treatment, and the pathophysiologic mechanisms involved, the pharmacologic management of entities such as post-surgical pain, chemotherapy-induced neuropathy, aromatase inhibitor musculoskeletal syndrome and checkpoint inhibitor-related pain are described. The challenges associated with opioid prescribing in this population are given special attention. Expert guidelines on pain management in cancer survivors now recommend a combination of pharmacologic and non-pharmacologic modalities, and these are also briefly covered.

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Natural Products Derived from Cannabis sativa for Pain Management

Liktor-Busa,

Largent-Milnes

2024

Handbook of Experimental Pharmacology

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Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model

Cited by 26 publications

References 39 publications

Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

Pharmacologic Management of Persistent Pain in Cancer Survivors

Natural Products Derived from Cannabis sativa for Pain Management

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