Kelly Meredith A, Pavlicova Martina, Glass Andrew, Mariani John J, Bisaga Adam, Sullivan Maria A, Nunes Edward V, Levin Frances R
New York State Psychiatric Institute, Division of Substance Abuse, 1051 Riverside Drive, New York, NY 10032, USA; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Department of Biostatistics, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
Drug Alcohol Depend. 2014 Nov 1;144:42-6. doi: 10.1016/j.drugalcdep.2014.06.040. Epub 2014 Jul 11.
Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group.
We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis.
The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models.
Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use.
患有抑郁症的大麻依赖参与者采用文拉法辛缓释剂（VEN-XR）治疗时，实现戒断的可能性较小。服用VEN-XR的个体报告称戒断症状更严重，尽管他们并未减少吸烟行为。我们推测，类似戒断的症状（可能是药物副作用）导致该组人群继续吸食大麻。
我们使用大麻戒断检查表（MWC）评分和尿液四氢大麻酚（THC）进行了一项二次分析，以测试类似戒断症状的严重程度是否介导了VEN-XR治疗与继续吸食大麻之间的关系。我们纳入了103名参与者（VEN-XR组=51人，安慰剂组=52人）。大麻使用情况被分为吸烟周（THC>100纳克/毫升）和非吸烟周（THC≤100纳克/毫升）。每周获取MWC评分。我们在基于回归的中介分析中使用了三个模型。
即使在控制MWC评分的情况下，VEN-XR组个体在第7至9周吸食大麻的估计风险更高（第7周风险差异[RD]=0.11，p=0.034；第8周RD=0.20，p=0.014），且更高的评分介导了这种效应。在第10周和第11周，估计效应更强（第10周RD=0.03，p=0.380；第11周RD=0.07，p=0.504），根据模型，更严重的类似戒断症状更充分地解释了VEN-XR组继续吸食大麻的情况。
接受VEN-XR治疗的个体有更严重的类似戒断症状，这介导了他们继续吸食大麻的行为。去甲肾上腺素能药物，如VEN-XR，可能会对试图减少或停止使用大麻的依赖大麻患者的治疗结果产生负面影响。
