Analgesic and subjective effects of terpenes administered alone and in combination with THC: Potential THC- and opioid-sparing effects of myrcene and ß-caryophyllene

萜烯单独使用以及与 THC 联合使用的镇痛和主观效果：月桂烯和 α-石竹烯的潜在 THC 和阿片类药物节约作用

基本信息

批准号：
10559580
负责人：
ZIVA D COOPER
金额：
$ 74.16万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-15 至 2026-01-31
项目状态：
未结题

项目摘要

Project Summary: Chronic pain is a significant public health burden for which there are few effective treatments; individuals with chronic pain are a central component to the current opioid epidemic. Delta-9- tetrahydrocannabinol (THC), the primary psychoactive chemical of cannabis, holds promise as a therapeutic candidate to treat chronic pain. However, analgesia is accompanied by intoxication and abuse liability, thus limiting its clinical utility. Terpenes are organic compounds that contribute to the aromatic nature and flavor of cannabis; it has been hypothesized that these compounds may interact synergistically with THC to enhance its therapeutic effects with reduced adverse consequences. As such, terpenes may increase the analgesic effects of low, minimally intoxicating, doses of THC, and/or reduce adverse consequences of higher THC doses. Preclinical research demonstrates that the terpenes myrcene and ß-caryophyllene (BCP) elicit antinociceptive effects and have opioid-sparing properties. These effects are, in part, mediated by the mu-opioid receptor. It is unknown if these findings translate to humans. Understanding if these terpenes have analgesic properties alone, or in combination with THC, is fundamental to developing novel cannabinoid-based therapeutics to treat pain. In addition, investigating adverse effects of these terpenes (abuse liability, intoxication) will clarify their clinical potential. At a time when pharmacotherapeutic strategies to decrease reliance on opioids for pain relief are desperately needed, probing the 1) analgesic effects, 2) potential THC- and opioid-sparing properties, and 3) mechanism of these terpenes is of significant interest. The proposed double-blind, placebo-controlled studies will be the first to rigorously assess the dose-dependent analgesic effects of ecologically-relevant doses of myrcene and BCP and determine their THC- and opioid-sparing effects. Study findings will be essential in understanding the clinical potential of terpenes alone and in conjunction with THC for pain management. The proposed double-blind, placebo-controlled, within-subject studies in recreational cannabis smokers (N=30, 15M, 15F in each study) will first ascertain the dose-dependent analgesic potential of vaporized myrcene and BCP alone and in combination with sub-analgesic (5 mg) and analgesic (15 mg) doses of THC (Specific Aim 1). The myrcene/THC and BCP/THC dose combinations that produce the greatest analgesia and minimal intoxication and abuse liability will then be tested for their opioid sparing effects (Specific Aim 2). Opioid modulation of combined terpene/THC analgesia will be assessed with co-administration of naltrexone, an opioid antagonist (Specific Aim 2). Findings from these studies address a significant public health priority by investigating terpenes as a safe, well tolerated novel pharmacotherapeutic strategy to manage pain. This is an urgent area of research as alternatives to opioids and strategies to decrease use of high opioid doses are desperately needed.

项目摘要：慢性疼痛是很少有效的公共卫生烧伤治疗；患有慢性疼痛的个体是当前阿片类药物流行病的核心组成部分。 delta-9- 四氢大麻酚（THC）是大麻的主要精神活性化学物质，其保证是一种疗法治疗慢性疼痛的候选人。但是，镇痛是通过陶醉和滥用责任来实现的限制其临床实用性。萜烯是有机化合物，有助于芳香的性质和风味大麻；已经假设这些化合物可能与THC协同相互作用以增强其治疗作用减少了不良后果。因此，萜烯可能会增加镇痛作用低剂量的低剂量和/或减少较高THC剂量的不良后果。临床前研究表明，萜烯霉菌和β-氯苯乙烯（BCP）引起了抗伤害感受效果并具有消除阿片类药物的特性。这些作用部分是由MU-阿片受体介导的。这是未知这些发现是否转化为人类。了解这些萜烯是否具有镇痛特性单独或与THC联合使用，是开发基于大麻素的新型治疗的基础疼痛。此外，调查这些萜烯的不良影响（滥用责任，中毒）将澄清他们的临床潜力。在减少阿片类药物缓解疼痛的药物治疗策略迫切需要1）镇痛作用，2）潜在的THC和阿片类药物的特性，以及 3）这些萜烯的机制具有重大关注。提议的双盲，安慰剂控制研究将是第一个严格评估与生态相关的剂量依赖性镇痛作用的研究霉菌和BCP的剂量，并确定其THC和阿片类药物的影响。研究结果将是对于单独理解萜烯的临床潜力以及与THC结合使用，至关重要管理。拟议的双盲，安慰剂对照的，受试者在休闲大麻吸烟者中的研究（n = 30，每项研究中15m，15F）首先确定蒸发霉菌和剂量依赖性镇痛电位单独使用BCP，并与亚氨基糖（5 mg）和镇痛（15 mg）的THC结合使用（特定目的 1）。霉菌/THC和BCP/THC剂量组合产生最大的镇痛和最小然后，将对其阿片类药物的保留作用进行测试（特定目标2）。联合萜烯/THC镇痛的调节将与Naltrexone的共同给药（一种阿片类药物）进行评估对手（特定目标2）。这些研究的发现涉及大量公共卫生优先事项将萜烯作为一种安全，耐受性良好的新型药物治疗策略来控制疼痛。这是一个紧急研究领域是杀菌剂的替代方案，以及减少使用高蛋白剂量使用的策略是迫切需要。