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要的公共卫生问题，处方阿片类药物历来 这是标准治疗。这种方法导致了阿片类药物使用障碍和致命的 过量服用，对我们的经济产生了巨大的财政影响。识别非阿片类药物 以最小的滥用倾向管理慢性疼痛是公共卫生必需品， 这是一种很有前途的药物类别。超过80%的药用大麻使用者报告疼痛是他们的主要症状 适应症，他们报告说经历了最小的精神影响。然而，很少有控制良好的 人类实验室研究评估大麻在滥用情况下对疼痛的疗效，甚至更少有人知道 关于每日重复使用大麻对疼痛的影响及其与滥用责任的关系。小心- 需要有控制的研究。这项修订后的随机化、受试者内、安慰剂对照16天交叉研究 住院患者的人类实验室研究（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）耐受性是否发展到重复，每天 吸烟大麻（6.58%THC）管理实验疼痛和滥用倾向的措施; 2）如果是， 耐受性逆转后，7天的禁欲从积极的四氢大麻酚大麻; 3）突然禁欲从 活性大麻相对于基线增加了实验性疼痛敏感性，即痛觉过敏，并且这些效应 大麻戒断的平行措施，如情绪和睡眠中断？为了全面解决这些问题， 问题，将测量两种不同的实验疼痛模式：冷加压试验和定量 感官测试热时间总和。在搬入日之后，研究将开始一天， “标准化”（第1天），参与者将每天吸食6.58%的THC 3次，使大麻暴露标准化 在下一阶段强制禁欲之前，随后将进行为期7天的“非活动期”（第2-8天）， 参与者将吸食非活性大麻（0.00%THC）3x/天;这一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，并将决定 镇痛耐受是否在禁欲一周后逆转。接下来，参与者将进行为期7天的“活动 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;这一阶段将决定 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。随着慢性疼痛率的增加和限制 安全有效的阿片类药物治疗替代品的可用性，这项研究将有助于确定大麻的潜力 作为镇痛药物的治疗效用。如果医用大麻患者使用大麻来缓解疼痛， 根据调查数据所建议的比率，确定重复使用对镇痛效果的影响至关重要 和滥用倾向，因为这可能导致疼痛加剧和其他止痛药的使用增加。