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.

项目总结