Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change in peak plasma concentration of THC
研究概览
简要总结
This is a crossover, randomized, double-blinded clinical pharmacology study enrolling dual cannabis-tobacco smokers to better understand the combined effects of co-administering cannabis and tobacco. The project aims to describe the pharmacokinetics and pharmacodynamics of marijuana-tobacco co-administration by delivering THC and nicotine in various combinations. This foundational study will establish a research program focused on elucidating the public health consequences of marijuana-tobacco co-use.
详细描述
This is a single-center, within-subject (crossover), randomized, double-blinded clinical pharmacology study of over 8 study visits (days). Participants will be non-treatment-seeking, healthy frequent users of both marijuana and tobacco/nicotine, age 21 to 65 years (21 years because of California tobacco control law). Participants will be marijuana users of any race who smoke or vape marijuana or THC extracts at least three days a week for the past 3 months or more. The study investigators will use positive urine toxicology THC results and self-report of marijuana smoking/vaping to determine eligibility. Participants must also be current users of inhaled forms of tobacco/nicotine (cigarettes, cigars, e-cigarettes) who use the product daily over the past 3 months.
Each study day will consist of a standardized session of 5 puffs of one of 8 study conditions using a PAX-3 vaporizer (PAX Labs, Inc.). Blood will be sampled multiple times for plasma THC, nicotine, and catecholamines, questionnaires administered for sensory and subjective effects, and heart rate, skin blood flow, and skin temperature will be measured. After 6 hours of abstinence, participants will have 60 minutes of ad libitum access to the assigned study condition, during which heart rate and blood pressure will be continuously monitored, blood sampled before and after for THC, nicotine, and platelet aggregation measured, and questionnaires administered.
Studies will be conducted at the Clinical & Translational Science Institute (CTSI) Clinical Research Services-supported research ward at Zuckerberg San Francisco General.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Heart rate < 105 beats per minute (BPM)*
- •Systolic Blood Pressure < 160 and > 90*
- •Diastolic Blood Pressure < 100 and > 50*
- •*Considered out of range if both machine and manual readings are above/below these thresholds.
- •Body Mass Index (BMI) ≤ 38.0 (at investigator's discretion for higher BMI if no other concurrent health issues)
- •Current regular user of cannabis who smokes or vapes cannabis or THC extracts at least three days a week for the past 3 months or more
- •Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use
- •Current user of inhaled forms of tobacco/nicotine (cigarette, cigars, e-cigarettes) who use the product daily for the past 3 months or more
- •Saliva cotinine ≥ 30 ng/mL
排除标准
- •Unstable medical conditions:
- •Heart disease
- •Thyroid disease (okay if controlled with medication)
- •Hepatitis B or C or Liver disease
- •Kidney disease or urinary retention
- •An ulcer in the past year
- •Active use of an inhaler for asthma or Chronic Obstructive Pulmonary Disease (COPD)
- •Hypertension if uncontrolled (meaning participant has a diagnosis, but they are not taking medication/under treatment (e.g., diet or exercise plan)
- •Drug/Alcohol Dependence
- •Alcohol or illicit drug dependence within the past 12 months (currently in treatment) with the exception of those who recently completed an alcohol/drug treatment program
- •Positive toxicology test at the screening visit (THC & prescribed medications okay)
- •Opioid replacement therapy (including methadone, buprenorphine, or other)
- •Psychiatric conditions
- •Current or past schizophrenia, and/or current or past bipolar disorder
- •Major depression, current or within the past year
- •Major personality disorder
- •Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the PI [study physician] and considered for inclusion
- •History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's [study physician's] approval
- •Current regular use of any psychiatric medications with the exception of Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) and current evaluation by the PI that the participant is otherwise healthy, stable, and able to participate
- •Congenital or acquired immunodeficiency disorders (i.e. HIV, congenital immune deficiency syndrome, chronic diseases)
- •Other disorders (i.e. ICU, malnutrition, immunosuppressive therapy)
- •Traumatic brain injury
- •Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks
- •Medications
- •Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs)
- •Concurrent use of nicotine-containing medications
- •Any stimulant medications (ex. Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
- •Other/Misc. Chronic Health Problems
- •Oral thrush
- •Other "life threatening illnesses" as per study physician's discretion
- •Pregnancy
- •Pregnancy (self-reported and urine pregnancy test)
- •Breastfeeding (determined by self-report)
- •Concurrent participation in another clinical trial
- •Inability to communicate in English
- •History of marijuana-induced psychosis or paranoia after smoking marijuana
- •Scoring a 7 or higher on the Severity of Dependence Scale (SDS) for cannabis use
- •Planning to quit smoking or vaping within the next 60 days
- •Planning to quit cannabis use within the next 60 days
- •Uncomfortable with getting blood drawn
- •Willingness to abstain from tobacco smoking and all combustible products for 13 hours before admission
- •Willingness to abstain from smoking/ingestion of cannabis 13 hours before
- •Willingness to abstain from nicotine products 13 hours before each admission
研究组 & 干预措施
High marijuana and regular cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Cannabis (Drug)
Placebo marijuana and regular cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Nicotine (Drug)
Placebo marijuana and regular cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
Placebo marijuana and regular cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Placebo Marijuana (Other)
Placebo marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Nicotine (Drug)
Placebo marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
Placebo marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Placebo Marijuana (Other)
Medium marijuana and regular cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Cannabis (Drug)
Medium marijuana and regular cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Nicotine (Drug)
Medium marijuana and regular cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
Medium marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Cannabis (Drug)
Medium marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Nicotine (Drug)
Medium marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
High marijuana and regular cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Nicotine (Drug)
High marijuana and regular cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and regular cigarette (25.94 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
High marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Cannabis (Drug)
High marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Nicotine (Drug)
High marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
High marijuana only
Participants will vape high marijuana (>10% THC)
干预措施: Cannabis (Drug)
High marijuana only
Participants will vape high marijuana (>10% THC)
干预措施: Pax Loose Leaf Vaporizer (Device)
Regular cigarette only
Participants will vape a regular cigarette (25.94 mg/g nicotine content)
干预措施: Nicotine (Drug)
Regular cigarette only
Participants will vape a regular cigarette (25.94 mg/g nicotine content)
干预措施: Pax Loose Leaf Vaporizer (Device)
结局指标
主要结局
Change in peak plasma concentration of THC
时间窗: From Day 7 to Day 8
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 7 to Day 8
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 5 to Day 6
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 6 to Day 7
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Baseline to Day 1
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 1 to Day 2
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 2 to Day 3
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 3 to Day 4
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 4 to Day 5
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 5 to Day 6
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in Peak plasma concentration of nicotine
时间窗: From Day 6 to Day 7
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Baseline to Day 1
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 1 to Day 2
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 2 to Day 3
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 3 to Day 4
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
Change in peak plasma concentration of THC
时间窗: From Day 4 to Day 5
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
次要结局
- Cardiovascular effects among dosages using heart rate as a measure(From Day 7 to Day 8)
- Area under the plasma concentration versus time curve (AUC)(From Day 7 to Day 8)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 7 to Day 8)
- Cardiovascular effects among dosages using heart rate as a measure(From Baseline to Day 1)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 1 to Day 2)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 2 to Day 3)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 3 to Day 4)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 4 to Day 5)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 5 to Day 6)
- Cardiovascular effects among dosages using heart rate as a measure(From Day 6 to Day 7)
- Area under the plasma concentration versus time curve (AUC)(From Baseline to Day 1)
- Area under the plasma concentration versus time curve (AUC)(From Day 1 to Day 2)
- Area under the plasma concentration versus time curve (AUC)(From Day 2 to Day 3)
- Area under the plasma concentration versus time curve (AUC)(From Day 3 to Day 4)
- Area under the plasma concentration versus time curve (AUC)(From Day 4 to Day 5)
- Area under the plasma concentration versus time curve (AUC)(From Day 5 to Day 6)
- Area under the plasma concentration versus time curve (AUC)(From Day 6 to Day 7)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Baseline to Day 1)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 1 to Day 2)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 2 to Day 3)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 3 to Day 4)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 4 to Day 5)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 5 to Day 6)
- Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)(From Day 6 to Day 7)