title: Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. Electronic address: mak2102@columbia.edu.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Kelly
authors.affiliation: Department of Biostatistics, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Pavlicova
authors.affiliation: Division of Biostatistics in the Department of Psychiatry, 722 West 168th Street, New York, NY 10032, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.affiliation: 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.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mariani
authors.affiliation: 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.
authors.forename: Adam
authors.initials: A
authors.lastname: Bisaga
authors.affiliation: 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.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.affiliation: 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.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Nunes
authors.affiliation: 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.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Levin
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000188:drug therapy* / Q000523:psychology; D008875:Middle Aged; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride
keywords: Cannabis; Cannabis Withdrawal; Marijuana; Marijuana Withdrawal; Treatment; Venlafaxine