Evaluating the Efficacy of Cannabidiol for Reducing Cigarette Use
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Evaluate the effects of CBD on nicotine intake
研究概览
简要总结
The goal of this research is to evaluate the efficacy of cannabidiol (CBD) in reducing cigarette smoking. Although there are safe and effective treatments for smoking cessation, not everyone who attempts smoking cessation is successful, even with these treatments. Relapse rates are high, leaving a need for new approaches. Despite justification to evaluate CBD for this indication, human research on the topic is scant. Larger, more extended studies are warranted and essential.
The investigators will recruit participants from CRI-Help, Inc., a substance abuse treatment program in North Hollywood, where residents who indicate the desire to stop smoking are prohibited from using other cannabis products which would affect recruitment.
The aims of this study are:
- Evaluate the effects of CBD on nicotine intake.
- Exploratory Aims. Measure plasma concentrations of CBD, N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) at baseline and day 7.
Participants who meet eligibility criteria will take part in a 56-day treatment phase during which they receive the study medication under supervision (CBD or placebo twice daily) and complete questionnaires on side effects, withdrawal, craving and mood symptoms. Blood, breath, and urine tests will also be performed throughout the study. Participants who complete the treatment will also be assessed at 1-month and 3-month follow up visits.
详细描述
General Experimental Design: This will be a randomized, double-blind, placebo-controlled, comparison study of Nantheia ATL5 (CBD) vs. placebo on smoking behavior in participants who have Tobacco Use Disorder (TUD) and have a desire for smoking cessation, conducted at CRI-Help, Inc., a residential substance use treatment center in N. Hollywood, CA. The investigators will instruct participants and provide support via text messages from the National Cancer Institute's Smokefree.gov website. Smokefree.gov offers free messaging programs that give encouragement, advice, and tips for becoming smoke-free and being healthier. The NCI website also helps people who smoke create a personalized quit plan that makes it easier to stay on track, get through hard times, and quit for good. Creating this plan will be part of baseline procedures.
Randomization to Treatment, Sample Size: Participants will receive CBD at a dose of 800 mg per day or placebo (n = 40/group). The investigators will randomize by sex and age (18-30, greater than/equal to 31 years) to ensure equal representation across the groups. The investigators will use an intention-to-treat analysis, including data from all participants who are randomized (see below for power analysis).
Dosing and Testing Schedule: After screening (Days -7 to 0) and baseline (Day 0) assessments, the study will comprise a 56-day (8-week) treatment period with follow up assessments at 1 and 3 months after termination of treatment as part of this trial. Measurements will be obtained at daily and weekly assessments during the 8-week treatment period.
Measures Collected: A baseline assessment will include assay of blood plasma cotinine to indicate heaviness of smoking, and self-reports of smoking-related behaviors on the following smoking-related questionnaires:
- Fagerström Test for Nicotine Dependence (FTND). This 6-item survey (~2 min) is closely linked to nicotine intake.
- Smoking History Questionnaire. Developed in Dr. London's Lab, this 25-item survey (~5 min) queries age at initiation, longest quit attempt, number of quit attempts, reasons for quitting, and current smoking behavior (e.g., preferred brand, cigarettes per day, etc.).
- Minnesota Nicotine Withdrawal Scale (MNWS) measures withdrawal symptoms: craving, irritability, anxiety, difficulty concentrating, restlessness, headache, drowsiness, and GI disturbances. These symptoms are scored on an ordinal scale [0 (not present) to 3 (severe)].
- General Anxiety Screener (GAD-7). This is a self-administered seven-item questionnaire that is used to measure or assess the severity of generalized anxiety disorder (GAD). The GAD-7 takes ~1-2 min to complete.
- Patient Health Questoinnaire-9 (PHQ-9). This self-administered nine-item scale measures the degree of depression. The PHQ-9 only takes ~1-2 min to complete.
- State-Trait Anxiety Inventory Y1 (STAI-Y1). This self-administered 20-item scale measures the degree of anxiety and takes ~1-2 min to complete.
- Positive and Negative Affect Schedule (PANAS). This self-administered 30-item scale measures current affective state and takes ~2-3 min to complete.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The investigators will study equal numbers of males and females betweeen 18 - 65 years of age who have Tobacco Use Disorder and express a desire for smoking cessation. Participants will be recruited from the clientele base at Cri-Help Treatment Center in North Hollywood, CA, where the investigators have a long-standing relationship and where the investigators have conducted other research protocols. This study will be conducted at Cri-Help Treatment Center.
- •Participants will not be recruited from the general population for this study because common use of cannabis in the greater Los Angeles area would confound measurements of CBD, interfering with evaluation of the association of plasma level from treatment with efficacy. This problem is avoided in studying participants who are receiving treatment at a facility where cannabis use is not allowed.
- •The investigators will include all racial and ethnic groups. Based on the population of the surrounding communities in the Los Angeles region, the investigators anticipate a racial and ethnic makeup of approximately 26% White, 9% Black/African American, 49% Hispanic/Latino, 14% Asian American, and 2% multi-racial/unknown. These percentages align with our recent studies.
- •Smoking cigarettes and at least moderate nicotine dependence, as indicated by smoking 5 or more cigarettes per day and/or a score of at least 4 on the Fagerström Test for Nicotine Dependence are inclusion criteria. Although vaping is popular and a high proportion of participants who vape also report cigarette smoking (58%), the investigators will exclude participants who vape nicotine. Vaping is not allowed at Cri-Help, Inc.
排除标准
- •Physiological dependence on alcohol or any drug, requiring medical detoxification and/or showing signs of acute withdrawal symptoms from opioids, alcohol or benzodiazepines.
- •Treatment of Opioid Use Disorder with buprenorphine or methadone to avoid potential drug-drug interactions. CBD interacts with CYP3A. Opioid drugs metabolized by cytochrome P450 (CYP450), and cytochrome P450 isoenzyme CYP3A4 (CYP3A4) in particular, include fentanyl, methadone, oxycodone, and buprenorphine.
- •Meeting DSM-5 criteria for schizophrenia, Bipolar I disorder, psychotic disorder, having active suicidal ideation, or suicide attempt in the past 12 months. NOTE: Participants with other psychiatric conditions, such as major depression, generalized anxiety, dysthymia, social phobia or specific phobia can enroll if they are clinically stable.
- •AIDS or current HIV medication treatment with antiviral and/or non-antiviral therapy (due to the interaction of CBD with antiviral therapy).
- •Clinically significant abnormalities on EKG (such as evidence of arrhythmia or MI).
- •Clinically significant cardiovascular, hematologic, hepatic, renal, neurological, or endocrine abnormalities [specific exclusion criteria: AST greater than or equal to 3Xs ULN, Bilirubin greater or equal to 1.5 X ULN, Prothrombin time/International Normalized Ratio (INR) > 1.
- •Pregnancy and/or lactation. Contraception methods required at time of enrollment, and throughout the duration of the study medication period include abstinence, oral contraceptives, depot contraceptives, condom with spermicide, cervical cap with spermicide, diaphragm with spermicide, intrauterine device, surgical sterilization (e.g. tubal ligation, vasectomy).
- •Because of evidence that CBD affects ovarian function in rats, women with values outside the reference ranges on a hormonal battery [estradiol, follicle- stimulating hormone, free thyroxine index, luteinizing hormone, prolactin, total T3 and total T4, thyroid-stimulating hormone], followed by an abnormal ovarian ultrasound finding will be excluded.
- •Based on data obtained using Epidiolex® (CBD) oral solution label section 7, "Drug Interactions", the investigators will exclude participants who are taking the following medications: a) strong inducers of CYP3A4 or CYP2C19, which may decrease CBD plasma levels; and b) substrates of UGT1A9, UGT2B7, CYP2B6, CYP2C19 due to the potential of CBD to inhibit enzyme activity.
研究组 & 干预措施
Placebo
Sixty participants who meet all eligibility criteria will be randomized to receive placebo.
干预措施: Placebo (Drug)
Cannabidiol (CBD) 800 mg
Sixty participants who meet all eligibility criteria will be randomized to receive CBD (ATL5; Ananda Scientific) at a dose of 800 mg.
干预措施: Cannabidiol (CBD) 800 mg (Drug)
结局指标
主要结局
Evaluate the effects of CBD on nicotine intake
时间窗: 8 weeks
Nicotine intake will be determined by levels of plasma cotinine (ng/mL).
Evaluate the effects of CBD on change in cigarette use
时间窗: 24 weeks
Change in cigarette use will be indexed by self-reported number of cigarettes/day.
Validate self-reported effects of CBD on change in cigarette use
时间窗: 24 weeks
Plasma levels of cotinine (ng/mL) will be measured to validate self-reported tobacco use.
次要结局
- Nicotine dependence(24 weeks)
- Nicotine withdrawal(24 weeks)
- Mood state - depression(24 weeks)
- Mood state - anxiety(24 weeks)
- Mood state - positive and negative affect(24 weeks)
- Abstinence from smoking during the last 2 weeks of the trial(2 weeks (Days 42-56))
- Confirmation of abstinence from smoking during the last 2 weeks of the trial(2 weeks (Days 42-56))
- Validation of abstinence from smoking during the last 2 weeks of the trial(2 weeks (Days 42-56))
- Change in nicotine dependence(8 weeks)
- Change in nicotine withdrawal(8 weeks)
- Changes in mood state - depression(24 weeks)
- Changes in mood state - anxiety(24 weeks)
研究者
Edythe London
Distinguished Professor in Residence
University of California, Los Angeles