topiramate and Marijuana-Abuse

Theoretical models of behavior change argue that youth should decrease their time with cannabis-using friends and increase their time with non-using friends during treatment. Informed by behavior-change models of recovery and socialization and selection peer-influence models, the current study examined whether combining evidence-based psychosocial treatment with adjunctive pharmacotherapy helps youth decrease their affiliations with cannabis-using friends and increase their affiliations with non-using friends during cannabis misuse treatment.. Youth ages 15-24 years (51 % male), participated in a double-blind randomized clinical trial that tested the effects of motivational enhancement and cognitive behavioral therapy (MET-CBT) plus topiramate (N = 39) or placebo (N = 26) on cannabis craving and use. Ecological momentary assessment data, collected via smartphones throughout the six-week intervention, assessed youths' time with cannabis-using and non-using friends, cannabis use, and craving in daily life. Multiple group multilevel structural equation modeling tested study hypotheses.. Across the topiramate (48 % completion rate) and placebo (77 % completion rate) conditions, greater time spent with cannabis-using friends promoted greater next day cannabis use and craving (socialization effect). In turn, cannabis craving, but not use, promoted continued selection of cannabis-using friends. This indirect effect was only supported in the placebo condition due to the selection piece of this cycle not being significant for youth who received topiramate. Neither cannabis craving nor use were associated with time with non-using friends the next day.. MET-CBT and adjunctive topiramate pharmacotherapy interrupted youth selection processes. This finding suggests that changing peer affiliations could be one mechanism by which treatments can work.

Topics: Adolescent; Adult; Cannabis; Friends; Humans; Marijuana Abuse; Motivational Interviewing; Topiramate; Young Adult

Cannabis is the most commonly abused illicit drug and accounts for the greatest number of adolescent substance abuse treatment admissions. Despite urgent need for effective interventions, the best available psychosocial treatment options yield only modest effects. Topiramate showed promise as an adjunctive pharmacotherapy to a psychosocial intervention for cannabis misuse among adolescents and young adults in a recent clinical trial, but it was not well tolerated. This study investigated associations between clinical characteristics and side effects and dropout among adolescents and young adults randomized to topiramate.. This study involved secondary data analysis of a randomized placebo-controlled trial of topiramate for treating cannabis misuse (ages, 15-24 years; 50% female). We explored the interaction effects of baseline characteristics and medication condition (topiramate vs placebo) on treatment dropout. We also explored the relationship between side effects and dropout.. Higher cannabis problems were significantly associated with reduced hazard of dropout in the topiramate group (P = 0.048) and were nonsignificantly associated with increased hazard of dropout in the placebo group (P = 0.062). Results also showed that memory difficulties were an overwhelming predictor of dropout in the topiramate condition; 42% of participants who dropped out experienced memory difficulties, whereas none of those who remained in the study experienced these effects.. By identifying who may most benefit from and tolerate this medication, treatment for substance use disorders can become more individualized and positive outcomes may be enhanced.

Topics: Adolescent; Adolescent Behavior; Adult; Anticonvulsants; Combined Modality Therapy; Double-Blind Method; Female; Fructose; Humans; Male; Marijuana Abuse; Medication Adherence; Patient Dropouts; Psychotherapy; Topiramate; Young Adult

The present study used youth's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse.. Participants were 40 cannabis users (≥ twice weekly in past 30 days), ages 15-24 years (47.5% female), with at least one cannabis use episode during the final 3 weeks of a 6-week, randomized clinical trial. Youth reported subjective "high" while smoking, stimulation, sedation, stress, craving, and grams of marijuana used in the natural environment via wireless electronic devices. Bayesian multilevel structural equation modeling (MSEM) evaluated mediation via indirect effect tests.. Significant within (daily) and between (person) variability and distinctive within and between effects supported the MSEM approach. Subjective high while smoking was significantly reduced for youth in the topiramate condition, relative to placebo, and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant. Indirect effects through other subjective responses were not significant.. The results of this initial study suggest that altering subjective responses to smoking, specifically subjective high, may be a key target for developing adjunctive pharmacotherapies for cannabis misuse. More generally, this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data.

Topics: Adolescent; Adult; Bayes Theorem; Ecological Momentary Assessment; Female; Humans; Male; Marijuana Abuse; Topiramate; Young Adult

Cannabis misuse accounts for nearly all of the substance abuse treatment admissions among youth in the United States. Most youth do not experience sustained benefit from existing psychosocial treatments; however, medication development research for treating adolescent cannabis misuse is almost nonexistent. We conducted a double-blind, placebo-controlled, pilot study to test the potential efficacy of topiramate plus motivational enhancement therapy (MET) for treating cannabis use among adolescents. Sixty-six heavy cannabis users, ages 15 to 24 years, were randomized to one of two 6-week treatment conditions: topiramate plus MET or placebo plus MET. Topiramate was titrated over 4 weeks then stabilized at 200 mg/day for 2 weeks. MET was delivered biweekly for a total of three sessions. Only 48 percent of youths randomized to topiramate completed the 6-week trial (n = 19), compared with 77 percent of youths in the placebo condition (n = 20). Adverse medication side effects were the most common reason for withdrawal among participants in the topiramate group. Latent growth models showed that topiramate was superior to placebo for reducing the number of grams smoked per use day, but it did not improve abstinence rates. The same pattern of results was found when values for missing outcomes were imputed. We show that topiramate combined with MET demonstrated efficacy for reducing how much cannabis adolescents smoked when they used but did not affect abstinence rates. The magnitude of this effect was modest, however, and topiramate was poorly tolerated by youths, which calls into question the clinical importance of these findings.

Topics: Adolescent; Adult; Double-Blind Method; Feasibility Studies; Feedback, Psychological; Female; Fructose; Humans; Male; Marijuana Abuse; Motivational Interviewing; Neuroprotective Agents; Pilot Projects; Topiramate; Treatment Outcome; Young Adult

This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance was induced in mice by administration of CP-55,940 (0.5 mg/kg/12 hours; i.p.; 7 days). Behavioural assessment of spontaneous cannabinoid withdrawal was performed by measuring motor activity, somatic signs and anxiety-like behaviour on days 1 and 3 after cessation of treatment with CP-55,940. On days 1-3 of cannabinoid withdrawal, mice received pregabalin (40 mg/kg/12 hours; p.o.) or topiramate (50 mg/kg/12 hours; p.o.) and their actions on signs of withdrawal and anxiety-like behaviour were evaluated. The administration of CP-55,940 decreased rectal temperature and motor activity on day 1. On day 1 after interruption of cannabinoid administration, motor activity and the number of rearings increased compared with control group. Anxiety-like behaviour induced by cessation of cannabinoid treatment increased significantly on days 1 and 3 of withdrawal. The administration of pregabalin or topiramate blocked the motor signs and reduced significantly anxiety-like behaviour. Cannabinoid withdrawal decreased tyrosine hydroxylase (TH) gene expression in the ventral tegmental area and µ-opioid receptor gene expression in the nucleus accumbens (NAcc) and increased CB1 receptor gene expression in the NAcc. Treatment with topiramate or pregabalin blocked the decrease of TH and the increase of CB1 gene expressions induced by cannabinoid withdrawal. Both drugs failed to alter µ-opioid receptor gene expression. These results suggest that pregabalin and topiramate may result useful for the treatment of anxiety-like behaviour and motor symptoms associated with spontaneous cannabinoid withdrawal.

Topics: Analysis of Variance; Animals; Anticonvulsants; Anxiety; Behavior, Animal; Body Temperature; Cannabinoids; Cyclohexanols; Dose-Response Relationship, Drug; Drug Tolerance; Fructose; gamma-Aminobutyric Acid; Male; Marijuana Abuse; Mice; Models, Animal; Motor Activity; Nucleus Accumbens; Pregabalin; Receptor, Cannabinoid, CB1; Receptors, Opioid, mu; Substance Withdrawal Syndrome; Topiramate; Transcription, Genetic; Tyrosine 3-Monooxygenase; Ventral Tegmental Area

Topics: Adolescent; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Fructose; Humans; Immunoassay; Marijuana Abuse; Patient Compliance; Quetiapine Fumarate; Topiramate