Cannabis Relapse: Influence of Tobacco Cessation

目前，在接受药物治疗的患者中，有17%的人被诊断为大麻使用障碍(CUD)，但很少有人被诊断为∼ 实现持续的禁欲。使用住院的CUD人体实验室模型，我们已经证明在 每日吸食大麻的人：(1)吸烟的人吸食大麻的复发率在 实验室相对于不使用烟草的人(61%对15%)，与临床证据相平行的烟草 吸食大麻的人有较差的CUD治疗结果，(2)第一次吸烟的人 在16岁之前，戒烟7天后的大麻复发率比开始戒烟的人高 在16岁时吸烟(55%对21%)，尽管其他烟草或大麻的严重性没有差异 特点。当我们将这项研究中的大麻复发率与我们之前的研究进行比较时，使用 类似的程序，我们发现，对于那些在16岁开始吸烟的人，7天 戒烟与大麻复发率的相关性与不吸烟的人一样低 吸烟者。然而，对于那些较早开始吸烟的人(16岁)，7天的烟草 戒烟似乎没有影响；大麻的复发率与正在吸烟的人相当 吸烟者。因此，第一次吸烟的年龄是大麻复发的有力预测因素。 短期戒烟。可能是更难对付的大麻吸烟者(那些开始吸食烟草的人 早期使用)需要更长的戒烟期才能影响大麻复发 吸烟/吸食大麻的人。在小鼠中，每天服用尼古丁增强了与滥用相关的行为 兴奋剂和酒精的影响，以及14天的尼古丁戒断，逆转了这些影响。的目标是 这项续签申请是为了测试戒烟前的戒烟持续时间和年龄。 烟草对大麻复发的影响。我们将比较戒烟7天和21天对 日常吸烟中的大麻复发(在实验室和自然生态中进行评估)， 吸食大麻的人，每组有一半的参与者很早就开始吸烟(&lt；16 年)和另一半(&gt；16年)。组蛋白乙酰化的血液测量将在研究中收集 在确诊戒烟14天后开始戒烟。我们假设(1)迟发烟草 7岁以后吸烟者的大麻复发率将显著低于早发性吸烟者--但不会 戒烟21天后，(2)组蛋白乙酰化程度会随着戒烟时间的延长而降低。到目前为止， 对大麻和吸烟者的临床研究已经让患者同时戒除这两种药物，并 而不是减少大麻的复发。据我们所知，还没有研究表明在吸食大麻之前戒烟。 然而，这可能是实现长期大麻戒断的更有效的方法。这个 这项研究的结果有可能显著影响CUD治疗和减少大麻复发 寻求治疗CUD的烟草依赖患者的相当大比例。

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.