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，处方阿片类药物历史上一直如此 是标准的治疗方法。这种方法导致了阿片类药物使用障碍和死亡的惊人比率。 过量，并对我们的经济产生了过大的金融影响。识别非阿片类药物治疗 以最低限度的滥用责任管理慢性疼痛是公共卫生的需要，而大麻类药物是 这是一个很有前途的药物类别。超过80%的医用大麻使用者报告说疼痛是他们的主要症状 适应症，他们报告经历了最小的精神活动影响。然而，几乎没有得到很好控制的 评估大麻在滥用情况下止痛效果的人体实验室研究更是鲜为人知 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。小心地- 需要进行对照研究。这项修订的随机、受试者内、安慰剂对照的16天交叉试验 住院的人体实验室研究(N=20；10男，10女)将解决我们的三个重要差距 了解大麻对疼痛的潜在治疗作用：1)耐受性是否会发展到每天重复 吸烟大麻(6.58%THC)对实验性疼痛和滥用责任的管理措施；2)如果是，是 对活性大麻戒断7天后的耐受性逆转；3)突然戒除 与基线相比，活性大麻增加了实验性的疼痛敏感性，即痛觉过敏，并产生了这些影响 大麻戒断的平行措施，如情绪紊乱和睡眠？全面解决这些问题 问题，将测量两种不同形式的实验性疼痛：冷加压试验和定量 感官测试热时间总和。在入住当天，研究将从一天开始 “标准化”(第1天)，参与者每天抽6.58%THC 3次，使大麻暴露标准化 在下一阶段强制禁欲之前，所有参与者都要参加。接下来是7天的“非活动期”(第2-8天)，在 哪些参与者每天3次吸食非活性大麻(0.00%THC)；这一阶段将决定大麻是否 戒断诱导的痛觉过敏是由于活性大麻突然停止而导致的，并将决定 禁欲一周是否会逆转止痛耐受性。接下来，参赛者将进行为期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)，每天3次；这一阶段将确定 是否对大麻的止痛作用产生耐受性。在整个研究过程中，实验性的疼痛和虐待- 相关影响将被评估，睡眠和主观情绪也将被评估。随着慢性疼痛的比率增加和有限 提供安全有效的治疗替代阿片类药物，这项研究将有助于确定大麻的潜力 作为止痛药的治疗作用。如果医用大麻患者正在使用大麻来缓解疼痛 调查数据显示的比率，关键是要确定反复使用对止痛效果有什么影响 和滥用责任，因为这可能导致疼痛恶化和增加其他止痛药的使用。