Scientists at The Scripps Research Institute have found clinical evidence that the drug gabapentin, currently on the market to treat neuropathic pain and epilepsy, helps people to quit smoking marijuana (cannabis). Unlike traditional addiction treatments, gabapentin targets stress systems in the brain that are activated by drug withdrawal.
In a 12-week trial of 50 treatment-seeking cannabis users, those who took gabapentin used less cannabis, experienced fewer withdrawal symptoms such as sleeplessness, and scored higher on tests of attention, impulse-control, and other cognitive skills, compared to patients who received a placebo. If these results are confirmed by ongoing larger trials, gabapentin could become the first FDA-approved pharmaceutical treatment for cannabis dependence.
"A lot of other drugs have been tested for their ability to decrease cannabis use and withdrawal, but this is the first to show these key effects in a controlled treatment study," said Barbara J. Mason, the Pearson Family Chair and Co-Director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research. "The other nice thing about gabapentin is that it is already widely prescribed, so its safety is less likely to be an issue."
Mason led the new gabapentin study, recently published online ahead of print by the journal Neuropsychopharmacology.
Addiction researchers have long known that recreational drugs hook users by disrupting the normal tuning of their brains' reward and motivation circuitry. But as scientists at Scripps Research and other institutions have shown in animal studies, cannabis withdrawal after prolonged heavy use also leads to the long-term activation of basic stress circuits. "In human cannabis users who try to quit, this stress response is reflected in reports of drug craving, sleep disturbances, anxiety, irritability, and dysphoria, any one of which can motivate a person to return to using, because cannabis will quiet these symptoms," said Mason.
A 2008 study by Pearson Center Co-Director George Koob and his colleagues found that gabapentin, an FDA-approved anticonvulsant drug that resembles the neurotransmitter GABA, can quiet this withdrawal-related activation in stress circuitry in alcohol-dependent rats. That finding motivated Mason to set up a pilot trial of gabapentin in cannabis-dependent individuals, whose withdrawal syndrome features a similar over-activation of stress circuits.
She and her colleagues recruited cannabis users with local newspaper and web ads headlined: "Smoking too much pot? We want to help you stop." "We needed only 50 subjects, but we quickly got more than 700 queries from cannabis users who were eager to quit," Mason said. "Some people deny that cannabis can be addictive, but surveys show that between 16 and 25 percent of substance use treatment admissions around the world every year involve people with primary cannabis dependence."
Twice as Many Abstinent from Cannabis Use
The trial was based at Mason's laboratory at The Scripps Research Institute. Half of the 50 recruits were randomly assigned to take 1,200 mg/day of gabapentin; the rest were given identical-looking placebo capsules. Over 12 weeks, Mason and her colleagues, including a medical team from the nearby Scripps Clinic, monitored the subjects with tests. Using standard behavioral therapy techniques, they also counseled the patients to stay off cannabis.