Effects of Repeated Cannabis Administration on Experimental Pain and Abuse Liability in Humans

重复使用大麻对人类实验疼痛和滥用责任的影响

• 批准号: 10265556
• 负责人: Caroline A Arout
• 金额: $ 19.89万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265556
• 关键词: Absence of pain sensation; Abstinence; Acute; Address; Adult; Analgesics; Anorexia; Cannabinoids; Cannabis; Centers for Disease Control and Prevention (U.S.); Clinical Research; Data; Desire for food; Dose; Experimental Models; Guidelines; Human; Hyperalgesia; Inpatients; Laboratories; Laboratory Study; Lead; Light; Measures; Medical; Medical Marijuana; Medication Management; Methodology; Modality; Modeling; Moods; Neurobiology; Opioid; Opioid Analgesics; Oral; Overdose; Pain; Pain management; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Placebos; Plants; Population; Process; Public Health; Randomized; Reporting; Research; Sensory; Sleep; Sleep disturbances; Smoke; Spinal Cord; Standardization; Surveys; Symptoms; Techniques; Testing; Tetrahydrocannabinol; Therapeutic; Therapeutic Effect; Time; United States; Withdrawal; Withdrawal Symptom; Woman; alternative treatment; cannabinoid treatment; cannabis cessation; cannabis withdrawal; central sensitization; chronic pain; chronic pain management; clinically relevant; common treatment; design; effective therapy; experience; inflammatory pain; innovation; marijuana legalization; marijuana smoker; marijuana use; marijuana user; men; negative mood; non-opioid analgesic; novel; opioid epidemic; opioid use disorder; pain perception; pain relief; pain sensitivity; painful neuropathy; pre-clinical; prescription opioid; recruit; response; reverse tolerance; standard care; substance use; treatment strategy

Project Summary Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This approach has contributed to the striking rates of opioid use disorders and fatal overdoses and has had an exorbitant financial impact on our economy. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary indication, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis’ efficacy for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. Carefully- controlled research is needed. This revised randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis (6.58% THC) administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed following 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep? To comprehensively address these questions, two distinct modalities of experimental pain will be measured: The Cold Pressor Test and Quantitative Sensory Testing Thermal Temporal Summation. Following move-in day, the study will start with one day of “standardization” (Day 1), where participants will smoke 6.58% THC 3x/day, standardizing cannabis exposure across participants before enforced abstinence in the next phase. A 7-day “inactive phase” will follow (Day 2-8), in which participants will smoke inactive cannabis (0.00% THC) 3x/day; this phase will determine whether cannabis withdrawal-induced hyperalgesia develops as a result of abrupt cessation from active cannabis, and will determine whether analgesic tolerance is reversed with one week of abstinence. Next, participants will undergo a 7-day “active phase” (Day 9-15) during which they will smoke active cannabis (6.58% THC) 3x/day; this phase will determine whether tolerance develops to cannabis’ analgesic effects. Throughout the study, experimental pain and abuse- related effects will be assessed, as will sleep and subjective mood. With rates of chronic pain increasing and limited availability of safe and effective treatment alternatives to opioids, this study will help define cannabis’ potential therapeutic utility as an analgesic medication. If medical cannabis patients are using cannabis to relieve pain at the rates suggested by survey data, it is critical to determine what effect repeated use has on analgesic efficacy and abuse liability, as this could lead to worsened pain and increased use of other pain medications.

项目概要 慢性疼痛是美国的一个重大公共卫生问题，处方阿片类药物历来都用于治疗慢性疼痛 一直是标准治疗。这种方法导致阿片类药物使用障碍和致命率惊人 用药过量并对我们的经济造成了巨大的财务影响。识别非阿片类药物 以最小的滥用可能性管理慢性疼痛是公共卫生的必需品，而大麻素是 用于此目的的一类有前途的药物。超过 80% 的药用大麻使用者表示疼痛是其主要症状 迹象，并且他们报告说经历了最小的精神影响。但控制良好的却很少 人体实验室研究评估了大麻在滥用情况下对疼痛的功效，但我们知之甚少 关于每天重复使用大麻对疼痛的影响及其与滥用倾向的关系。小心- 需要进行受控研究。这项修订后的随机、受试者内、安慰剂对照的 16 天交叉试验 住院人体实验室研究（N = 20；10 名男性，10 名女性）将解决我们的研究中的三个重要差距 了解大麻对疼痛的潜在治疗效用：1）耐受性是否会发展到每天重复使用？ 吸食大麻（6.58% THC）管理实验性疼痛和滥用倾向的措施； 2）如果是的话，是 戒断活性 THC 大麻 7 天后，耐受性逆转； 3）是否突然戒烟 活性大麻相对于基线增加实验性疼痛敏感性，即痛觉过敏，并产生这些效果 大麻戒断的并行措施，例如扰乱情绪和睡眠？为全面解决这些问题 问题，将测量两种不同的实验疼痛方式：冷加压测试和定量测试 感官测试热时间总和。入住日后，研究将从一天开始 “标准化”（第一天），参与者每天吸 3 次 6.58% THC，标准化大麻暴露 在下一阶段强制禁欲之前跨参与者进行。随后将进入为期 7 天的“非活动阶段”（第 2-8 天）， 哪些参与者将吸食非活性大麻 (0.00% THC) 3 次/天；此阶段将确定大麻是否 戒断引起的痛觉过敏是由于突然停止使用活性大麻而产生的，并且将决定 禁欲一周是否会逆转镇痛耐受性。接下来，参与者将经历为期7天的“活跃 阶段”（第 9-15 天），在此期间他们将吸食活性大麻 (6.58% THC) 3 次/天；此阶段将确定 是否会对大麻的镇痛作用产生耐受性。在整个研究过程中，实验性的疼痛和虐待—— 将评估相关影响，以及睡眠和主观情绪。随着慢性疼痛发生率的增加和有限 提供安全有效的阿片类药物治疗替代品，这项研究将有助于确定大麻的潜力 作为镇痛药物的治疗用途。如果医用大麻患者使用大麻来缓解疼痛 根据调查数据显示的比率，确定重复使用对镇痛功效有何影响至关重要 和滥用倾向，因为这可能导致疼痛加剧并增加其他止痛药物的使用。