Reck Antonio Matt, Siderovski David P, Kinsey Steven G
School of Nursing, University of Connecticut, Storrs, CT, USA; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
Neuropharmacology. 2025 Feb 15;264:110216. doi: 10.1016/j.neuropharm.2024.110216. Epub 2024 Nov 16.
Pruritus (i.e., the experience that evokes a desire to scratch) is an adaptive process that can become maladaptive, leading to a persistent scratch-itch cycle that potentiates pruritus and increases the risk of infection. Cannabinoid drugs have been reported to decrease pruritus, but often at doses that also decrease locomotor activity, which confounds assessments of utility. To determine the utility of cannabinoids in treating pruritus without undesirable adverse effects, the current preclinical study investigated a range of doses of the synthetic cannabinoid agonist, WIN 55,212-2, and two minor Cannabis phytoconstituents, Δ-tetrahydrocannabinol and β-caryophyllene, in experimentally induced pruritus in male and female C57BL/6J adult mice. WIN 55,212-2 reduced compound 48/80-induced scratching, and this antipruritic effect was prevented by either chemically blocking (via SR144528 antagonism) or genetically deleting the CB cannabinoid receptor. The CB receptor selective agonist, JWH-133, also attenuated compound 48/80-induced scratching, while the CB positive allosteric modulator, ZCZ011, had no effect. Similarly, the minor phytocannabinoid Δ-tetrahydrocannabinol reduced scratching at doses that did not affect locomotor activity. In contrast, the sesquiterpene cannabis constituent β-caryophyllene induced scratching, acting as a pruritogen. These preclinical data support the continuing investigation of cannabinoid receptor modulation as a potential therapeutic strategy for pruritus.
瘙痒（即引发搔抓欲望的感觉）是一个可能会变得适应不良的适应性过程，会导致持续的搔抓-瘙痒循环，从而加剧瘙痒并增加感染风险。据报道，大麻素类药物可减轻瘙痒，但通常所用剂量也会降低运动活性，这给效用评估带来了困扰。为了确定大麻素类药物在治疗瘙痒时不会产生不良副作用的效用，当前的临床前研究在雄性和雌性C57BL/6J成年小鼠实验性诱导的瘙痒模型中，研究了一系列剂量的合成大麻素激动剂WIN 55,212-2以及两种次要的大麻植物成分Δ-四氢大麻酚和β-石竹烯。WIN 55,212-2减少了化合物48/80诱导的搔抓行为，并且通过化学阻断（通过SR144528拮抗作用）或基因敲除CB大麻素受体，均可阻止这种止痒作用。CB受体选择性激动剂JWH-133也减弱了化合物48/80诱导的搔抓行为，而CB正变构调节剂ZCZ011则没有效果。同样，次要植物大麻素Δ-四氢大麻酚在不影响运动活性的剂量下减少了搔抓行为。相比之下，倍半萜类大麻成分β-石竹烯却引发搔抓，起到致痒原的作用。这些临床前数据支持继续研究大麻素受体调节作为瘙痒潜在治疗策略的可能性。
