Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist

Bilir, K. A.; Anli, G.; Ozkan, Ekin; Gündüz, Özgür; Ulugöl, Ahmet

doi:10.1111/ced.13398

Cited by 20 publications

(13 citation statements)

References 25 publications

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“…106 Recently, it has been suggested that the antipruritic effects of cannabinoids are independent of descending inhibitory serotonergic pathways. 107…”

Section: Topical Cannabinoidsmentioning

confidence: 99%

Itch: From mechanism to (novel) therapeutic approaches

Yosipovitch

Rosen

Hashimoto

2018

Journal of Allergy and Clinical Immunology

251

307

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Itch is a common sensory experience that is prevalent in patients with inflammatory skin diseases, as well as in those with systemic and neuropathic conditions. In patients with these conditions, itch is often severe and significantly affects quality of life. Itch is encoded by 2 major neuronal pathways: histaminergic (in acute itch) and nonhistaminergic (in chronic itch). In the majority of cases, crosstalk existing between keratinocytes, the immune system, and nonhistaminergic sensory nerves is responsible for the pathophysiology of chronic itch. This review provides an overview of the current understanding of the molecular, neural, and immune mechanisms of itch: beginning in the skin, proceeding to the spinal cord, and eventually ascending to the brain, where itch is processed. A growing understanding of the mechanisms of chronic itch is expanding, as is our pipeline of more targeted topical and systemic therapies. Our therapeutic armamentarium for treating chronic itch has expanded in the last 5 years, with developments of topical and systemic treatments targeting the neural and immune systems.

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“…106 Recently, it has been suggested that the antipruritic effects of cannabinoids are independent of descending inhibitory serotonergic pathways. 107…”

Section: Topical Cannabinoidsmentioning

confidence: 99%

Itch: From mechanism to (novel) therapeutic approaches

Yosipovitch

Rosen

Hashimoto

2018

Journal of Allergy and Clinical Immunology

251

307

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“…The pathogenesis of pruritis is well researched and is described comprehensively in various recent review articles. [64][65][66] Though most of the ECS research indicates that the itch response is primarily modulated through CB1 receptors in the CNS, [67][68][69] some reports argue the involvement of peripheral CB1 receptors could also be a potent contributor to itch. 70,71 The available data thus far for the involvement of peripheral CB2 receptors are conflicting and more research is needed to conclusively determine its role in pruritis.…”

Section: Itch (Pruritis)mentioning

confidence: 99%

<p>Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders</p>

Baswan¹,

Klosner²,

Glynn³

et al. 2020

CCID

123

113

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Though there is limited research confirming the purported topical benefits of cannabinoids, it is certain that cutaneous biology is modulated by the human endocannabinoid system (ECS). Receptors from the ECS have been identified in the skin and systemic abuse of synthetic cannabinoids, and their analogs, have also been associated with the manifestation of dermatological disorders, indicating the effects of the ECS on cutaneous biology. In particular, cannabidiol (CBD), a non-psychoactive compound from the cannabis plant, has garnered significant attention in recent years for its anecdotal therapeutic potential for various pathologies, including skin and cosmetic disorders. Though a body of preclinical evidence suggests topical application of CBD may be efficacious for some skin disorders, such as eczema, psoriasis, pruritis, and inflammatory conditions, confirmed clinical efficacy and elucidation of underlying molecular mechanisms have yet to be fully identified. This article provides an update on the advances in CBD research to date and the potential areas of future exploration.

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“…Attenuation of itching replies by augmenting endocannabinoid tonus via the inhibition of the endocannabinoid degradative enzymes, such as fatty acid amide hydrolase and monoacylglycerol lipase which is a different promising method for treating pruritus (14)(15)(16). Our research group also indicated that the synthetic cannabinoid agonist WIN 55,212-2 exerts dose-dependent antipruritic effects and this effect is partially mediated by spinal cannabinoid receptors CB1 (17,18).…”

Section: Systemic Cannabidiol Does Not Reduce Compound 48/80-induced Itching Behavior In Micementioning

confidence: 77%

Systemic Cannabidiol Does Not Reduce Compound 48/80-Induced Itching Behavior in Mice

Demirel¹,

Baksın²,

Özgür³

et al. 2019

tmsj

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Aims: Cannabinoids are chemical compounds including natural cannabinoids found in the Cannabis plant, their synthetic counterparts, and endocannabinoids. Cannabidiol, a phytocannabinoid derived from the Cannabis plant, exerts anticonvulsant, anxiolytic, anti-inflammatory, neuroprotective, analgesic effects. Although there are many similarities between the pathophysiological mechanisms of pain and itch, researches that investigate the effect of cannabinoids on itching are insufficient. Here, we aimed to examine the antipruritic effect of cannabidiol and the contribution of spinal cannabinoid receptors. Methods: Male Balb/c mice, weighing 20-30 g, were used. Itching behavior was produced by intradermal injection of compound 48/80 (100 μg/50 μl); cannabidiol (1, 3, 10 mg/kg, ip) was administered 30 minutes before compound 48/80 injections. Then, scratching of the injected site by the hind paws was videotaped for 30 minutes. Locomotor performances were assessed using a rotarod apparatus. Results: Cannabidiol had no effect on compound 48/80-induced itching behavior at any dose given; moreover, cannabidiol did not produce any impairment on motor function. AM-251, a cannabinoid receptor type 1 antagonist, and AM-630, a cannabinoid receptor type 2 antagonist were administered intrathecally to observe the contribution of spinal cannabinoid receptors to the antipruritic action of cannabidiol. We observed that cannabidol did not possess any effect on itching behaviour. Conclusion: Our results indicate that systemic administration of cannabidiol does not attenuate compound 48/80 induced itching behavior in mice.

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Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist

Abstract: Our findings support prior researches indicating that cannabinoids exert antipruritic effects. Moreover, our results show that the antipruritic effects of cannabinoids are partially mediated by spinal CB1 receptors.

Cited by 20 publications

References 25 publications

Itch: From mechanism to (novel) therapeutic approaches

Itch: From mechanism to (novel) therapeutic approaches

<p>Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders</p>

Systemic Cannabidiol Does Not Reduce Compound 48/80-Induced Itching Behavior in Mice

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