Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression

Wong, Stanley Sau Ching; Chan, Wing Shing; Cheung, Chi Wai

doi:10.1007/s11481-020-09905-y

Cited by 38 publications

(30 citation statements)

References 75 publications

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“…Clinically, studies appear to support a role for cannabinoids, including Δ 9 -THC, for the treatment of chronic, noncancer pain (for a review see, Wong et al, 2020). For example, Nabilone, an FDA approved analog of Δ 9 -THC for the treatment of chemotherapy-induced nausea and vomiting, was found to be superior to both placebo and/or an active control in relieving pain associated with chronic headaches (Pini et al, 2012), diabetic neuropathy (Toth et al, 2012), and Multiple Sclerosis (MS)-induced chronic pain (Turcotte et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

Henderson-Redmond

Crawford

Sepulveda

et al. 2021

Front. Mol. Biosci.

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Tolerance to the pain-relieving effects of cannabinoids limits the therapeutic potential of these drugs in patients with chronic pain. Recent preclinical research with rodents and clinical studies in humans has suggested important differences between males and females in the development of tolerance to cannabinoids. Our previous work found that male mice expressing a desensitization resistant form (S426A/S430A) of the type 1 cannabinoid receptor (CB1R) show delayed tolerance and increased sensitivity to the antinociceptive effects of delta-9-tetrahydrocannabinol (∆9-THC). Sex differences in tolerance have been reported in rodent models with females acquiring tolerance to ∆9-THC faster than males. However, it remains unknown whether the S426A/S430A mutation alters analgesic tolerance to ∆9-THC in mice with chemotherapy-evoked chronic neuropathic pain, and also whether this tolerance might be different between males and females. Male and female S426A/S430A mutant and wild-type littermates were made neuropathic using four once-weekly injections of 5 mg/kg cisplatin and subsequently assessed for tolerance to the anti-allodynic effects of 6 and/or 10 mg/kg ∆9-THC. Females acquired tolerance to the anti-allodynic effects of both 6 and 10 mg/kg ∆9-THC faster than males. In contrast, the S426A/S430A mutation did not alter tolerance to ∆9-THC in either male or female mice. The anti-allodynic effects of ∆9-THC were blocked following pretreatment with the CB1R antagonist, rimonabant, and partially blocked following pretreatment with the CB2R inverse agonist, SR144528. Our results show that disruption of the GRK/β-arrestin-2 pathway of desensitization did not affect sensitivity and/or tolerance to ∆9-THC in a chronic pain model of neuropathy.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

Henderson-Redmond

Crawford

Sepulveda

et al. 2021

Front. Mol. Biosci.

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“…inflammatory pain)? Indeed, a recent meta‐regression that compared the efficacy of cannabinoids for NP to its efficacy for other chronic pain aetiologies found no significant difference between them (Wong et al., 2020). Second, can predictors for treatment success be identified?…”

Section: Introductionmentioning

confidence: 99%

“…So far, over 20 randomized controlled trials (RCTs) have been conducted, some on cannabis-based medicines and others on herbal cannabis (Aviram & Samuelly-Leichtag, 2017). The inconsistent results of these studies have led to numerous meta-analyses (Andreae et al, 2015;Aviram & Samuelly-Leichtag, 2017;Iskedjian et al, 2007;Martín-Sánchez et al, 2009;Meng et al, 2017;Mücke et al, 2018;Nugent et al, 2017;Stockings et al, 2018;Whiting et al, 2015;Wong et al, 2020), altogether showing limited-to-modest analgesic effects at best with relatively frequent adverse effects. Hence, the effectiveness of MC for chronic pain remains questionable.…”

Section: Introductionmentioning

confidence: 99%

Medical cannabis treatment for chronic pain: Outcomes and prediction of response

Aviram

Pud

Gershoni

et al. 2020

European Journal of Pain

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BackgroundAlthough studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire‐based prospective cohort was aimed to assess the long‐term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success.MethodsPatients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity).ResultsA total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12‐month follow‐up. At 1 year, average pain intensity declined from baseline by 20% [−1.97 points (95%CI = −2.13 to −1.81; p < 0.001)]. All other parameters improved by 10%–30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = −34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non‐serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite.ConclusionsThis prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild‐to‐modest long‐term improvement of the tested measures and identifying possible predictors for treatment success.

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“…However, CB2R agonists were reported to reduce thermal hyperalgesia associated with inflammation [ 442 , 443 ]. A recently performed meta-analysis of randomized controlled trials revealed cannabinoids produced a small, yet significant, improvement in pain reduction in individuals with neuropathic and non-neuropathic pain [ 444 ].…”

Section: Biological Role Of the Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

Haspula

Clark

2020

IJMS

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The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

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Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression

Cited by 38 publications

References 75 publications

Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

Medical cannabis treatment for chronic pain: Outcomes and prediction of response

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

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