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.

项目摘要 慢性疼痛在美国是一个重大的公共卫生问题，在这种情况下，阿片类药物历来是 是标准处理。这种方法导致了阿片类药物使用障碍和致命的打击率 服药过量，对我们的经济产生了高昂的财务影响。确定非阿片类药物 慢性疼痛的管理最小的虐待责任是公共卫生的必要性，大麻素是 为此目的的有前途的毒品类。超过80％的医用大麻使用者报告疼痛为主要 迹象表明，他们报告了经历最小的精神活性作用。但是，很少有控制的 人类实验室研究评估大麻在滥用情况下疼痛的效率，甚至更少 关于每天反复使用大麻对疼痛及其与滥用责任的关系的影响。小心- 需要对照研究。这是修订的随机内部主体内安慰剂对照的16天跨界 住院的人类实验室研究（n = 20; 10名男性，10名女性）将解决我们的三个重要差距 了解大麻对疼痛的潜在治疗效用：1）每天都会出现耐受性 烟熏大麻（6.58％THC）对实验性疼痛和虐待责任的措施； 2）如果是这样，是 在戒酒7天之后，耐受性逆转了。 3）突然禁欲 主动大麻会增加实验性疼痛敏感性，即相对于基线的痛觉过敏，并执行这些影响 大麻戒断的平行度量，例如心情和睡眠中断？全面解决这些 问题，将测量两种不同的实验疼痛方式：冷压验和定量 感觉测试热时间求和。在搬家一天之后，该研究将从一天的一天开始 “标准化”（第1天），参与者将吸烟6.58％3x/天，标准化大麻暴露 7天的“非活动阶段”将随后（第2-8天） 哪些参与者将抽大麻（0.00％THC）3倍/天；此阶段将确定大麻是否 由于活跃大麻的突然停止，戒断引起的痛觉过敏的发生，并将确定 止痛耐受性是否会因禁欲而逆转。接下来，参与者将经历7天的“活跃” 阶段”（第9-15天），在此期间，他们将抽大麻（6.58％THC）3倍/天；此阶段将确定 耐受性是否会发展出大麻的镇痛作用。在整个研究中，实验性疼痛和虐待 - 将评估相关效果，睡眠和主观情绪也将进行评估。随着慢性疼痛的增加和有限 可用性可用于阿片类药物的安全有效治疗替代品，这项研究将有助于确定大麻的潜力 治疗用途作为一种镇痛药。如果医用大麻患者使用大麻来挽救疼痛 调查数据建议的速率至关重要，确定重复使用对镇痛效率有什么影响 和虐待责任，因为这可能导致疼痛恶化和增加其他止痛药的使用。