Pharmacokinetics and Pharmacodynamics of Oral and Vaporized Delta-9-Tetrahydrocannabinol (THC) in Older Adults
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Peak concentration (Cmax)
研究概览
简要总结
The overarching goal of this double-blind, placebo-controlled, crossover study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of the main analgesic and psychoactive constituent of cannabis, delta-9 tetrahydrocannabinol (THC), among older adults - the fastest growing population of cannabis consumers, and the most likely age cohort to use cannabinoids to relieve pain. This protocol includes two sub-studies, each randomizing 20 men and women aged 65 years or older to receive two administration routes of THC; oral administration and vaporized administration.
详细描述
This is a double-blind, placebo-controlled, crossover study, with two sub-studies each focusing on different routes of THC administration.
Oral THC Sub-Study: 20 men and women aged 65 years or older, will be randomized to two doses of oral THC (5 mg and 10 mg). Across three, 8-hour test sessions, participants will receive a random sequence of 3 conditions: 5 mg oral THC; 10 mg oral THC; oral placebo.
Vaporized THC Sub-Study: 20 men and women aged 65 years or older will be randomized to two doses of vaporized THC (2 mg and 4 mg). Across three 8-hour test sessions, participants will receive a random sequence of 3 conditions: 2 mg vaporized THC; 4 mg vaporized THC; and vaporized placebo.
For both the Oral and Vaporized THC Sub-Studies, blood samples will be regularly collected from an intravenous line, up to 8 hours post-dose, and at 24 hours post-dose, to assess the PK of THC and its phase I and II metabolites. PD effects of THC on pain will be measured with Quantitative Sensory Testing (QST), a psychophysical technique used to reliably measure pain sensitivity and investigate pain modulatory mechanisms. The abuse liability of THC will be measured using an established drug reinforcement paradigm. General adverse, cardiovascular, and cognitive/psychomotor effects of THC will be thoroughly assessed with behavioral, physiological, and neuropsychological methods.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Study medication will be prepared by study pharmacy.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants aged 65 ≥ years old
- •Prior exposure to THC or cannabis least once in the last 10 years; 1-10 times in the last 20 years; or more than 20 times in their lifetime
- •Capable of providing informed consent in English.
排除标准
- •Meeting DSM-5 criteria for psychiatric/substance use disorders (SUD) other than tobacco use disorder, within the last year
- •Current use of cannabinoid products, as evidenced by a urine drug screen
- •Having a history of treatment for cannabis use disorder
- •History of intent or current intent of abstaining from cannabis use
- •Clinically significant medical disorders (e.g. liver/kidney dysfunction, immunosuppressing conditions, history or presence of epilepsy, seizures, head trauma with loss of consciousness)
- •Medical conditions that increase the risk of respiratory problems (e.g. COPD, asthma, recuring bronchitis, reactive airway disorder)* (does not apply to the Oral THC Sub-Study)
- •History of environmental sensitivities (e.g. bronchospastic allergies, multiple chemical sensitivities) or other airway sensitivities that require the use of an epi pen*(does not apply to the Oral THC Sub-Study)
- •Neurological conditions that may change the response to nociceptive stimuli (e.g., stroke, neuropathy), or that lead to loss of balance, evidenced by a neuro-sensory exam
- •Contraindications for exposure to nociceptive stimuli, such as untreated hypertension
- •Current regular use of drugs known to affect pain, or that are prominent inducers or inhibitors of CYP2C9, CYP3A4, or UGTA19 (e.g., carbamazepine, valproate, fluvoxamine, and paroxetine)
- •Major neurocognitive disorders precluding participation, evidenced by a clinical exam
- •Abnormal EKG, arrythmia, vasospastic disease, chronic heart failure, or presence of a pacemaker
- •Elevation of liver enzymes (ALT, AST) 2x the normal limit or higher
- •Personal or family history of primary psychotic disorders, or mood disorders with psychotic features
- •Current suicidal ideation
- •Allergy or serious adverse reactions to sesame oil, THC, or cannabis
- •Having received any drug as part of a research study within 30 days prior to receiving the study medication in the current study.
研究组 & 干预措施
Placebo
Masked oral placebo or vaporized saline
干预措施: Placebo (Drug)
Dronabinol 5mg
Dronabinol 5 mg
干预措施: Dronabinol 5 MG (Drug)
Dronabinol 10mg
Dronabinol 10 mg
干预措施: Dronabinol 10 MG (Drug)
Vaporized THC 4mg
Vaporized THC 4 mg
干预措施: 4mg Purified THC in an ethanolic solution (Drug)
Vaporized THC 2mg
Vaporized THC 2mg
干预措施: 2mg Purified THC in an ethanolic solution (Drug)
结局指标
主要结局
Peak concentration (Cmax)
时间窗: Up to 8 hours
Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the peak concentration (Cmax) will be derived using a linear noncompartmental analysis.
Area under the plasma concentration-time curve (AUC0-8h)
时间窗: Up to 8 hours
Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the area under the plasma concentration-time curve (AUC0-8h) will be derived using a linear noncompartmental analysis.
Nociception
时间窗: Up to 8 hours
Multimodal quantitative sensory testing (QST) will be used ensure that various types of afferent fibers are engaged, so that the analgesic efficacy of THC can be comprehensively investigated. A composite pain sensitivity measure as a Z-score (ranging from -1 to +1) will be derived from the QST battery, with greater scores indicating a higher sensitivity to pain.
Abuse Liability
时间窗: Up to 8 hours
A modified Multiple-Choice Procedure (MPC) will be used to measure abuse liability. The MCP was developed and validated by Roland Griffiths to efficiently assess drug reinforcement - including cannabinoid-induced reinforcement. In each of the 6 experimental sessions, participants will choose between forfeiting or receiving escalating sums of money, on a scale of values between -$20.00 and $20.00; or re-receiving the study medication assigned for that day. The primary outcome will be the crossover point, the value at which the participant chooses money rather than the study medication, which will be determined for each session.
Time to attain Cmax concentration (Tmax)
时间窗: Up to 8 hours
Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the time to attain Cmax concentration (Tmax) will be derived using a linear noncompartmental analysis.
次要结局
未报告次要终点
研究者
Joao De Aquino
Assistant Professor of Psychiatry
Yale University