Beta-caryophyllene (BCP) and cannabidiol (CBD) combination: HIV-1 chronic neuropathic pain

β-石竹烯 (BCP) 和大麻二酚 (CBD) 组合：HIV-1 慢性神经性疼痛

• 批准号: 10490249
• 负责人: Khalid Benamar
• 金额: $ 1.16万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490249
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adult; Affect; Affective; Analgesics; Animal Model; Animals; Anti-Anxiety Agents; Anxiety; Area; Attention; Behavior; Beta-caryophyllene; Cannabidiol; Cannabinoids; Cannabis; Cannabis sativa plant; Caring; Catalepsy; Chronic; Combined Modality Therapy; Data; Dependence; Development; Dimensions; Dose; Drug Combinations; Epidemic; Exhibits; Family; Feeling; Female; Food Additives; Goals; HIV; HIV Seropositivity; HIV-1; Health; Helping to End Addiction Long-term; Herb; Hypersensitivity; Individual; Lead; Link; Medical; Mental Depression; Minor; Modeling; National Institute of Drug Abuse; Natural Products; Nature; Needles; Neurologic; Numbness; Opioid; Outcome; Outcome Measure; Pain; Pain management; Patients; Performance; Persistent pain; Persons; Pharmaceutical Preparations; Pharmacology; Plants; Prevalence; Proteins; Quality of life; Rattus; Research; Role; Safety; Sedation procedure; Sensory; Shock; Shoes; Sleep Deprivation; Terpenes; Testing; Therapeutic; Therapeutic Agents; Touch sensation; Transgenic Organisms; Translations; United States Food and Drug Administration; Virus Diseases; abuse liability; antiretroviral therapy; base; chronic neuropathic pain; chronic pain; chronic pain management; clinically relevant; combat; comorbidity; depressive symptoms; effective therapy; experience; improved; innovation; male; mechanical allodynia; nerve injury; new combination therapies; novel; opioid epidemic; pain model; pain reduction; painful neuropathy; phytocannabinoid; pre-clinical; response; side effect

ABSTRACT Human Immunodeficiency Virus-1 (HIV)-related neuropathic pain affects 55-67% of the 37.9 million infected individuals worldwide. Although antiretroviral therapy has successfully reduced the prevalence of AIDS, neuropathic pain continues to affect many individuals with HIV. Treatment options are limited and often ineffective, and adverse side effects are common. Better outcomes may be achieved by identifying favorable combinations of drugs that are already available or emerging as potential new analgesics or by developing new and more effective drugs. We propose to test a novel pharmacological combination therapeutic strategy involving constituents of cannabis, Beta-caryophyllene (ΒCP, a terpene), and cannabidiol (CBD, a minor cannabinoid), to effectively inhibit HIV-related chronic neuropathic pain without side effects and/or abuse potential. A preclinical dose-response study of the analgesic effect of CBD in a nerve-injury pain model showed that, although CBD has the potential to alleviate a chronic neuropathic pain state, it showed moderate efficacy. However, the analgesic effect of CBD was not associated with catalepsy, and did not impair motor performance or produce sedation over a wide range of doses. Interestingly, BCP also showed potential in managing chronic pain, but it exhibited moderate efficacy. Furthermore, a strategy to increase the analgesic efficacy of CBD without inducing potential side effects or abuse potential is urgently needed. The rationale for choosing this dual CBD-ΒCP strategy is based on its individual analgesic effects and safety profiles. Aim 1 will test the hypothesis that in comparison with CBD alone, BCP and CBD in combination will produce an enhanced analgesic effect (synergistic) in an improved and clinically relevant HIV chronic neuropathic pain model. We will assess multiple outcome measures capturing sensory and affective dimensions of chronic pain. Isobolographic analysis will demonstrate the nature of interaction (e.g. synergistic). Aim 2 will screen for any side effects, abuse potential and development of analgesic tolerance. The proposed studies will significantly impact the field of HIV-related chronic pain management by providing a new combination therapy, CBD and BCP, that has critical advantages over current therapies. It is safe, effective, and non-addictive. The anxiolytic and anti-depressive effects of CBD and BCP are of additional benefit to target chronic pain comorbidities. Furthermore, this combination therapy will have a significant impact on the opioid epidemic, because one of the key strategies to combat this epidemic (HEAL initiative) is through improved pain management by the development of non-addictive approaches . The natural product, BCP, is approved by the Food and Drug Administration (FDA) as a food additive, known for its favorable safety profile. Therefore, combination of the BCP with CBD for the treatment of HIV-related chronic neuropathic pain could lead to a rapid translation to patients.

抽象的 人类免疫缺陷病毒-1（HIV）相关的神经性疼痛影响3790万感染的3790万个 全球个人。尽管抗逆转录病毒疗法已成功降低了艾滋病的患病率，但 神经性疼痛继续影响许多艾滋病毒的人。治疗选择有限，并且经常 无效和不良副作用很常见。通过确定有利的结果可以实现更好的结果 已经可以作为潜在的新镇痛药或开发新的药物组合 和更有效的药物。我们建议测试一种新型的药物组合疗法策略 大麻的成分，β-蛋黄（Becp，萜烯）和大麻二醇（CBD，次要大麻素）的成分 有效地抑制HIV相关的慢性神经性疼痛，而没有副作用和/或滥用潜力。临床前 CBD在神经伤害疼痛模型中CBD镇痛作用的剂量反应研究表明，尽管CBD具有 减轻慢性神经性疼痛状态的潜力，表现出适度的有效性。但是，镇痛药 CBD的效果与蠕虫术无关，也不会损害运动性能或生产镇静 多种剂量。有趣的是，BCP还表现出在管理慢性疼痛方面的潜力，但暴露了 中等效率。此外，提高CBD镇痛效率的策略而没有诱导的潜力 迫切需要副作用或滥用潜力。选择这种双CBD-BETACP策略的理由是 基于其单独的镇痛作用和安全性。 AIM 1将检验以下假设 仅使用CBD，BCP和CBD组合将产生增强的镇痛作用（协同作用） 改善和临床相关的HIV慢性神经性疼痛模型。我们将评估多种结果指标 捕获慢性疼痛的感觉和情感维度。同胞分析将证明性质 相互作用（例如协同作用）。 AIM 2将筛选任何副作用，滥用潜力和发展 镇痛耐受性。 拟议的研究将通过提供一种 与当前疗法相比，新的组合疗法CBD和BCP具有重要优势。这是安全，有效的， 和非依恋。 CBD和BCP的抗焦虑和抗抑郁作用是目标的其他好处 慢性疼痛合并症。此外，这种组合疗法将对阿片类药物产生重大影响 流行病，因为打击这种流行病的关键策略之一（治愈倡议）是通过改善疼痛 管理 非依恋方法的发展 。天然产品BCP已由 食品药品监督管理局（FDA）是一种食品添加剂，以其有利的安全性而闻名。所以， BCP与CBD结合治疗HIV相关的慢性神经性疼痛可能会导致快速 转化为患者。