Department of Pharmacology, College of Medicine (A.M.S., D.K., J.A.M., V.M.-R., C.S., T.B., A.W. J.C., J.M.S.) and Comprehensive Center for Pain and Addiction (J.M.S.), University of Arizona, Tucson, Arizona.
Department of Pharmacology, College of Medicine (A.M.S., D.K., J.A.M., V.M.-R., C.S., T.B., A.W. J.C., J.M.S.) and Comprehensive Center for Pain and Addiction (J.M.S.), University of Arizona, Tucson, Arizona
J Pharmacol Exp Ther. 2024 Oct 18;391(2):214-221. doi: 10.1124/jpet.124.002212.
Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to for pain management. contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within : cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), Δ8-tetrahydrocannabinol (Δ8-THC), and Δ9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose Δ8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose Δ8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. SIGNIFICANCE STATEMENT: Minor cannabinoids are poorly studied ligands present in lower levels in than cannabinoids like THC. In this study, we evaluated five minor cannabinoids (CBN, CBDV, CBG, THCV, and Δ8-THC) for their cannabimimetic and analgesic effects in mice. We found that four of the five minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.
慢性疼痛状况影响了美国近 20%的人口。目前的医学干预措施，如阿片类药物，在缓解疼痛方面是有效的，但伴随着许多不良的副作用。这也是越来越多的慢性疼痛患者转而寻求大麻素治疗的原因之一。大麻含有许多生物活性化学物质；然而，目前对大麻中研究较少的次要大麻素的研究缺乏实验组之间的一致性，或者将雌性小鼠排除在研究之外。这使得很难在不同实验室之间用不同的次要大麻素化合物进行的实验之间得出结论，也很难梳理出可能存在的潜在性别差异。我们选择了大麻中含量较低的五种次要大麻素：大麻酚（CBN）、大麻二酚（CBDV）、大麻萜酚（CBG）、Δ8-四氢大麻酚（Δ8-THC）和Δ9-四氢大麻酚（THCV）。然后，我们在大麻素四联体测定法和雄性和雌性 CD-1 小鼠的化疗诱导周围神经病变（CIPN）疼痛模型中测试了这些化合物的类大麻素作用和止痛作用。我们发现，我们测试的次要大麻素在引起的类大麻素行为以及程度上有所不同。我们发现，CBN、CBG 和高剂量Δ8-THC 在两性中都引起了一些四联体行为，而 THCV 和低剂量Δ8-THC 仅在雌性中表现出类大麻素四联体行为。只有 CBN 有效地缓解了 CIPN 疼痛，这与其他研究人员的报告相反。这些发现为次要大麻素的药理学提供了进一步的清晰度，并表明需要进一步研究它们的机制和治疗潜力。 意义声明：次要大麻素是在大麻中比大麻素（如 THC）水平低的研究较少的配体。在这项研究中，我们评估了五种次要大麻素（CBN、CBDV、CBG、THCV 和 Δ8-THC）在小鼠中的类大麻素和镇痛作用。我们发现，五种次要大麻素中的四种表现出类大麻素活性，而一种对缓解慢性神经性疼痛有效。这项工作对于进一步评估这些药物的活性非常重要，随着大麻合法化，这些药物的使用越来越广泛。
