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

基本信息

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
项目类别：
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

项目摘要

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，处方阿片类药物对此有着历史性的影响这种方法导致阿片类药物使用障碍和致命率惊人。药物过量并对我们的经济产生了巨大的财务影响。以最小的滥用可能性管理慢性疼痛是公共卫生的必需品，而大麻素是超过 80% 的药用大麻使用者表示疼痛是他们的主要症状。适应症，并且他们报告说经历了最小的精神影响，但是很少有得到良好控制的影响。人体实验室研究评估了大麻在滥用情况下缓解疼痛的功效，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责任的关系。这项修订后的随机、受试者内、安慰剂对照的 16 天交叉研究是必要的。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，则戒断活性 THC 大麻 7 天后耐受性逆转；3) 是否突然戒断？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，以全面解决这些问题？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，参与者将进入为期 7 天的“不活动阶段”（第 2-8 天）。哪些参与者将吸食非活性大麻 (0.00% THC) 3 次/天，此阶段将确定是否吸食大麻；突然停止使用活性大麻会导致戒断引起的痛觉过敏，并将决定接下来，参与者将接受为期 7 天的“主动”治疗。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；在整个研究过程中，实验性疼痛和滥用是否会对大麻的镇痛作用产生耐受性。随着慢性疼痛发生率的增加和有限，相关影响也将被评估，睡眠和主观情绪也将被评估。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的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。