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Drug may reduce marijuana dependency

Half of medicated participants drop out due to adverse side effects, experts doubtful of results

A University study released earlier this month suggests that an anti-epilepsy drug is effective in reducing the amount of marijuana smoked by young adults, but not necessarily the frequency of smoking.


Yet some scientists doubt the validity of the results, in part because half of the study’s medicated participants dropped out before the study concluded — some due to adverse side effects from the drug.


The study, published in the journal Addiction Biology, tested the effects of topiramate on heavy cannabis users ages 15 to 24. Topiramate was administered to 40 of the study participants, who also received three 50-minute sessions of motivational enhancement therapy, in which patients learn strategies to reduce their usage. The remaining 26 participants received only the therapy over the trial’s six weeks, in addition to a placebo pill.


The researchers used self-reports and urine toxicology to measure rates of marijuana use. Participants reported the amount of marijuana used on a particular day by weighing out oregano as an estimate, according to the study.


“In both conditions in the study, we saw significant reductions in how quickly people used,” said Robert Miranda, associate research professor of psychiatry and human behavior and lead author of the study. “But in the topiramate condition we also saw that when kids did smoke, they smoked less.”


Ryan Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, disagreed with that conclusion. There was no quantitative change in the amount of marijuana use by each group on days when participants smoked, Vandrey said. “There is a difference between groups, but that difference existed at the beginning.”


Miranda found the results to be “promising in some ways,” he said. “The biggest drawback of the study was that a lot of people didn’t really tolerate the medication very well.”


Sixty-six individuals began the six-week trial, but only 39 finished it — 52.5 percent of the topiramate group participants and 23.1 percent of the placebo group participants dropped out of the study.


Of the 21 dropouts from the topiramate group, 67 percent cited side effects as their reason for withdrawing. A multitude of side effects were reported by participants, including neurocognitive and gastrointestinal distress.


“The results show that this medication has one serious drawback in that it is poorly tolerated, and that’s something that has often been reported for topiramate,” said Margaret Haney, professor of neurobiology and co-director of the Substance Use Research Center at Columbia University Medical Center. “It certainly showed some interesting findings with a decrease in marijuana use, so that was encouraging. But the dropout rate would seem to make it a non-starter.”


In future research, Miranda would like to investigate who tolerates topiramate best and possibly direct the treatment toward that group, he said. “I’m not sure what our next steps will be,” he added.


These findings illustrate that further research could examine how anti-epileptic drugs influence marijuana dependence, Haney said.  “Anti-epilepsy drugs have shown promise for a lot of drugs of abuse, so there’s no reason not to pursue it for marijuana.”


Miranda is currently investigating topiramate’s possible impact on alcohol abuse. The study is expected to conclude later this year.


In her lab, Haney has studied a few drugs that could have potential as treatment for marijuana dependence, such as tetrahydrocannabinol agonists. These medications behave somewhat like THC, so they can “reduce the withdrawal and decrease the desire to use marijuana” without the same risk of abuse.


Still, the Food and Drug Administration has yet to approve any medication for treating cannabis dependence, Miranda said.


In treatment for marijuana dependency, a psychosocial intervention, such as the motivational enhancement therapy involved in the study, is used more commonly. “Lots of good scientists have been trying lots of medications, and we haven’t found one that works really well yet,” Vandrey said. “Exactly what those medications are is kind of the golden goose right now.”

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