Cannabis Relapse: Influence of Tobacco Cessation

目前，接受药物治疗的患者中有17%被诊断为大麻使用障碍（CUD），但很少有 实现持续的禁欲。使用CUD的住院患者人体实验室模型，我们已经表明， 每日吸食大麻者：（1）烟草卷烟吸烟者在大麻复吸率方面明显较高， 实验室相对于那些不使用烟草（61%对15%），平行的临床证据表明， 和大麻吸烟者有较差的CUD治疗结果，（2）那些谁有他们的第一个烟草香烟 在16岁之前，戒烟7天后大麻复吸率高于那些开始戒烟的人。 吸烟> 16年（55%对21%），尽管其他烟草或大麻严重程度没有差异 特色当我们比较大麻复发率在这项研究中相比，我们早期的研究使用 非常相似的程序，我们发现，对于那些开始吸烟在> 16岁，7天， 戒烟与大麻复吸率的相关性与非吸烟者一样低。 吸烟者。然而，对于那些开始吸烟香烟较早（<16岁），7天的烟草 戒烟似乎没有影响;大麻复吸率与正在吸烟的人相匹配 吸烟者。因此，第一支烟草香烟的年龄是大麻复吸的一个强有力的预测因素， 短期戒烟。可能是那些更难对付的大麻吸食者（那些开始吸烟的人） 早期使用）需要更长的戒烟时间才能影响大麻复吸，而不是晚发型 吸烟者/大麻吸食者。在小鼠中，每天给予尼古丁增强了与滥用相关的行为， 刺激剂和酒精的作用，以及尼古丁戒断14天逆转了这些作用。的目标 这一更新申请是为了测试大麻戒断前戒烟的持续时间和年龄 大麻复吸时的烟草发病率我们将比较戒烟7天和21天对吸烟者的影响。 每日吸食大麻后的大麻复吸（在实验室和自然生态中评估）， 大麻吸烟者，每组中有一半的参与者早期开始吸烟（<16 另一半（>16岁）。将在研究时采集组蛋白乙酰化的血液指标 发病后14天确认戒烟。我们假设（1）晚发型烟草 吸烟者在7岁以后的大麻复吸率将显著低于早发性烟草吸烟者， 戒烟21天后，（2）组蛋白乙酰化水平会随着戒烟的进行而降低。到目前为止， 对大麻和烟草吸烟者的临床研究已经使患者同时戒断了两种药物， 而不是减少大麻的复吸据我们所知，没有研究测试过在大麻之前戒烟 治疗，但这可能是实现长期大麻戒断的更有效方法。的 这项研究的结果有可能显着影响CUD治疗和减少大麻复发， 相当大比例的烟草依赖患者寻求CUD治疗。

Currently, ∼17% of patients entering drug treatment has a diagnosis of Cannabis Use Disorder (CUD), yet few achieve sustained abstinence. Using an inpatient human laboratory model of CUD, we have shown that among daily cannabis smokers: (1) tobacco cigarette smokers have markedly higher rates of cannabis relapse in the laboratory relative to those who do not use tobacco (61% vs 15%), paralleling clinical evidence that tobacco and cannabis smokers have poorer CUD treatment outcome, (2) those who had their first tobacco cigarette prior to age 16 had higher rates of cannabis relapse after 7-days of tobacco cessation relative to those starting cigarettes at > 16 years (55% vs 21%), despite no differences in other tobacco- or cannabis-severity characteristics. When we compare cannabis relapse rates in this study as compared to our earlier study using closely similar procedures, we find that for those who started smoking cigarettes at > 16 years of age, 7 days of tobacco cessation was associated with rates of cannabis relapse as low as those seen in non-cigarette smokers. Yet for those who started smoking tobacco cigarettes earlier (<16 years of age), 7 days of tobacco cessation appeared to have no impact; cannabis relapse rates matched those seen in ongoing cigarette smokers. Thus, the age of first tobacco cigarette is a robust predictor of cannabis relapse following short-term tobacco cessation. It may be that the more intractable cannabis smokers (those initiating tobacco use early) require a longer period of tobacco cessation to impact cannabis relapse than later-onset tobacco/cannabis smokers. In mice, daily nicotine administration enhanced the abuse-related behavioral effects of stimulants and alcohol, and nicotine abstinence for 14 days reversed these effects. The objective of this renewal application is to test both the duration of smoking cessation prior to cannabis abstinence and age of tobacco onset on cannabis relapse. We will compare the effects of 7- and 21-days of tobacco cessation on cannabis relapse (assessed both in the laboratory and the natural ecology) in daily cigarette-smoking, cannabis smokers, with half the participants in each group initiating tobacco cigarette smoking early (<16 years) and the other half later (>16 years). Blood measures of histone acetylation will be collected at study onset and following 14 days of confirmed tobacco abstinence. We hypothesize that (1) later-onset tobacco smokers will have significantly lower cannabis relapse rates than early-onset tobacco smokers after 7- but not 21 days of tobacco cessation, (2) histone acetylation will decrease as a function of tobacco cessation. To date, clinical studies with cannabis and tobacco smokers have had patients quit both drugs concurrently, and have not reduced cannabis relapse. No studies to our knowledge have tested tobacco cessation prior to cannabis treatment, yet this may be a more effective approach to achieving long-term cannabis abstinence. The outcome of this study has the potential to significantly impact CUD treatment and reduce cannabis relapse in the sizable proportion of tobacco-dependent patients seeking treatment for CUD.