Topiramate and Motivational Enhancement Therapy for Cannabis use among youth: a randomized placebo-controlled pilot study

Sylvia Okoma, Mercer University College of Pharmacy

It is stated that topiramate is a medication that treats depression and alcohol, nicotine and cocaine addiction. [1, 2]

It has been noted that topiramate shows a high efficacy in the treatment of alcohol dependence and has a unique pharmacodynamic profile that gives it a broad range of effects in substance abuse related disorders.  However, it is stated that heterogeneity limits the effects of the drug in various types of substance abuse disorders.  [3]

Title: Topiramate and Motivational Enhancement Therapy for Cannabis use among youth: a randomized placebo-controlled pilot study [4]
Design Randomized, double-blind, placebo-controlled pilot study, N = 66
Objective To evaluate the effects of combining topiramate with Motivational Enhancement Therapy (MET) for treating Cannabis misuse in youths
Study Groups Youths ages 15 to 24 years with an interest in receiving psychosocial intervention combined with a novel medication.

Topiramate (n = 40); placebo medication (n = 26)

Methods Topiramate was titrated to 200 mg daily over four weeks then used at a stabilized dose for two weeks.  Both the study and the control groups received three sessions of MET intervention that was designed to enhance motivation and build skills that would assist in reducing Cannabis use.  Patients’ plasma tetrahydrocannabinol levels were measured at baseline and at weeks three and six of the trial, and assessments of compliance and drug use during the trial consisted of urinalysis and estimating use with measurements of oregano.  Patients were randomized to one of two six-week treatments that consisted of topiramate plus MET or placebo plus MET in a two to one ratio.
Duration Twelve weeks
Primary Outcome Measure Reduction in abstinence rates provided by the self-reported frequency of use and quantity of Cannabis and with the biochemical verification of abstinence with urine toxicology tests
Baseline Characteristics   Topiramate users (n = 40)
Age, years 20.30  ±  2.03
Male, n 20
Under 18, n 19
Overall Intelligence Quotient (IQ) 102.80  ±  17.18
Baseline Cannabis percent use days 70.22  ±  26.89
Baseline grams of Cannabis used per day 0.53  ±  0.37
Results Overall, youths used Cannabis on 68.4 percent of the days in week one (p < 0.001) and the average rate of use decreased over the course of the study (p < 0.001).

Results of urine analysis also showed that the probability of positive urine screens decreased with time, p = 0.006.

The youth’s amount of Cannabis used, which averaged 0.51 g on use days, did not change significantly from the initial quantity used, p = 0.638.

However, the grams of use indicated a slight decrease in Cannabis compared to placebo during week six (p = 0.003).

Adverse Events Common Adverse Events: Drowsiness or sleepiness (41.7%), slow thinking or reactions (24.2%), word finding difficulties (22%), difficulty with concentration (19.7%), dizziness (18.2%), depression (16.7%), anxiety (15.2%), fatigue (27.3%), difficulty with memory (19.7%)
Serious Adverse Events: None
Percentage that Discontinued due to Adverse Events: 67% of the 52% whom discontinued the study
Study Author Conclusions Topiramate compared with placebo provided a modest reduction in the amount of Cannabis participants smoked on the use days but not the frequency of use.  However, topiramate was not well tolerated and resulted in adverse effects that resulted in discontinuation of therapy by some participants.  Topiramate is known for its adverse cognitive effects, and these effects were also shown in the self-reported adverse event data and from neurocognitive testing showed more impaired effects on brain information retrieval that affected the abilities to verbalize memories when compared with placebo.


Drug abuse intervention has been a growing field of study with the rising rates of drug abuse. Treatment strategies for this young population focused on addressing the motivations for the use of Cannabis during the MET sessions and addressing the influences that could potentially lead to use into adulthood.  Intervening strategies for future studies include incorporating larger population sizes and other pharmacological interventions that target the effects of Cannabis and other addictive substances that have a range of pharmacological effects on mood and cognition.



  1. Davenport, Liam.   Topiramate for substance use: upside/downside.    Medscape Medical News, Psychiatry.  WebMD, LLC: Jan 26, 2016.   Accessed 3 Feb 2016.
  2. Rezaei, Farzin; Ebrahim Ghaderi; Roya mardani; Seiran Hamidi; Kambiz Hassanzadeh.  Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.   Fundamental Clinical Pharmacology, pp 1-15.   2016 Jan 11.  Accessed 3 Feb 2016.
  3. Shinn, Ann and Shelly Greenfield.  Topiramate in the treatment of substance related disorders: a critical review of the literature.   Journal of Clinical Psychiatry, 71(5): 634-648.   May 2010.   Accessed 3 Feb 2016.
  4. Miranda Jr., Robert; Hayley Treloar; Alexander Blanchard; Alicia Justus; et al.  Topiramate and motivational enhancement therapy for Cannabis use among youth: a randomized placebo-controlled pilot study.   Addiction Biology, pp 1-12.   Jan 16, 2016.   Accessed 3 Feb 2016.



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