Gabapentin shows promise for cannabis dependence.

HOLLYWOOD, FLA. -- Gabapentin significantly decreases weekly cannabis use while significantly improving craving, depression, and sleep quality symptoms, compared with placebo, the results of a phase II, double-blind, randomized study show.

Cannabis dependence is the most common illicit substance disorder in the United States, Barbara J. Mason, Ph.D., said. However, there are no medications approved by the Food and Drug Administration for withdrawal or relapse prevention in this population.

Dr. Mason placed an advertisement in a free newspaper in San Diego in which she invited potential participants to contact her. She received 745 telephone inquiries. Of those, almost half--350 people--did not return a subsequent telephone call. After excluding a similar number (for example, for comorbid depression and/or anxiety), the final cohort was 50 treatment-seeking outpatients who met DSM-IV criteria for cannabis dependence.

The cohort was "solidly dependent," according to Dr. Mason. "Nearly every one of the seven criteria for dependence were met, despite a need for only three," she said at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Compared with placebo, gabapentin significantly reduced cannabis use and tetrahydrocannabinol (THC)/creatinine levels, improved mood and sleep quality, and improved executive function.

The participants reported an average 12-year history of daily marijuana smoking. At baseline, they had average urine TCH/creatinine ratio of 673 ng/mg and reported smoking an average 11 grams a week. Dr. Mason said this amount was equivalent to about one to two marijuana cigarettes a day. The gabapentin group demonstrated significant decreases in grams/week of cannabis smoking (P less than .01) and in THC/creatinine levels (P less than .02), compared with placebo.

Similarly, those in the gabapentin group showed significantly greater improvements in marijuana craving severity (P less than .01), Beck Depression Inventory scores (P less than .05), and the Pittsburgh Sleep Quality Index components. "Gabapentin had a rather dramatic effect on daytime dysfunction for week 1 to 8," said Dr. Mason, professor and member of the Committee on the Neurobiology of Addictive Disorders at the Scripps Research Institute in La Jolla, Calif.

A neuropsychologist joined the study to assess executive function. There was a statistically significant higher number of improvements on the various executive function tasks in the gabapentin group than in the placebo group.

The participants were equally randomized to 12 weeks of 1,200 mg/day gabapentin (available as a generic) or placebo. Men comprised 92% of the treatment and 84% of the placebo cohort. The mean age was 34 years, and 76% of the participants were white. Participants were not paid.

Dr. Mason was surprised at how motivated participants were to quit cannabis use. "Over the course of 12 weeks, between screening and week 0, people cut back on grams-per-week use, with a decrease in THC/creatinine ratio," Dr. Mason said. "So they were motivated to cut down from their first call to their clinic."

Before randomized, they underwent 4 weeks of motivational interviewing to set a quit date. This cognitive-behavioral relapse prevention therapy was included "because we thought there would not be a willingness to set a quit date, and we were wrong," said Dr. Mason, who plans to change the protocol in future study.

"We are not starting with 4 weeks of motivational interviewing. This is a group already coming in willing to start, and it's a mixed signal to tell them to wait 4 weeks."

A meeting attendee asked Dr. Mason why she chose to study gabapentin.

"It normalizes some CRF [corticotrophin-releasing factor] systems associated with drug withdrawal, as well as the profile with mood and sleep, so we thought we would give it a try," Dr. Mason said. When it came to sleep, somnolence associated with gabapentin could improve the protracted insomnia typically experienced when people stop using marijuana.

"This is one area where a side effect of a drug ... was in the service of the greater good in this population," Dr. Mason said.

Gabapentin was well tolerated, Dr. Mason said. Dizziness was the only adverse event significantly higher in the treatment group and was reported by 22%, compared with none of the placebo participants.

Dr. Mason said she had no relevant financial disclosures. The study was funded by National Institute on Drug Abuse.