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Of the medications that have been studied to treat problem marijuana use, none have proved effective, a new analysis shows.
The review, of 26 trials, found that no tested drugs -- including antidepressants, anxiety medication and synthetic cannabinoids -- showed clear benefits for people with cannabis use disorder, or CUD.
CUD may be diagnosed when a marijuana habit becomes a consuming part of life, where people let work or personal responsibilities slide, ignore problems that their drug use is causing, or find themselves needing more and more marijuana to get high.
In 2015, about 4 million Americans had CUD, according to the U.S. National Institute on Drug Abuse, or NIDA. Research suggests it affects around 30 percent of marijuana users at some point.
And while people often see marijuana as a nonaddictive drug, regular users can develop withdrawal symptoms if they try to stop, including nervousness and irritability, insomnia, depressed mood, and physical symptoms like abdominal pain, tremors and headache.
"There is a misperception that marijuana is benign," said Dr. Frances Levin, chief of the division on substance use disorders at the New York State Psychiatric Institute/Columbia University, in New York City.
What doctors see tells a different story.
People with milder CUD symptoms are less likely to seek treatment, noted Levin, who was not involved in the study. So, those who do seek help typically have a more serious dependence on the drug that is disrupting their lives.
"We need to look at [CUD] as we would any other substance use disorder," Levin said.
That includes studying whether medication can help people deal with withdrawal and reduce their marijuana use.
The new review, published online March 2 in the Annals of Internal Medicine, found that a few drug classes have failed to help patients abstain from marijuana, or cut down on consumption. Those include antidepressants, the anti-anxiety drug buspirone, and prescription-grade cannabinoids.
Some other medications have been studied, such as mood stabilizers, antiseizure medications and the dietary supplement N-acetylcysteine. And the evidence on them was deemed "insufficient."
However, Levin said, the individual studies in the review were small, and not of the size that can be definitive. They also varied in the duration of treatment, the use of behavioral therapy, and the groups of patients they studied: In some, people had a co-existing psychiatric condition, like depression; some focused on teenagers, while others on long-time marijuana users.
So it's difficult to draw conclusions, according to Levin.
"I don't think things are as pessimistic as this [review] might suggest," she said. "There are some promising signals based on human laboratory and treatment studies that are worth pursuing."
Karli Kondo, a researcher with the VA Portland Health Care System, led the review. She agreed it's too soon to reach a verdict.
The bottom line, Kondo said, is that larger studies are needed. She pointed to the example of cannabinoids, saying there was some "promising data" that they might ease withdrawal symptoms.
Beyond that, she added, studies of different combinations of medication and behavioral therapy are needed.
Dr. Timothy Brennan is director of the Addiction Institute at Mount Sinai West and Mount Sinai St. Luke's Hospitals, in New York City.
He said that, in general, behavioral therapies for marijuana use disorder are "quite effective." One is cognitive behavioral therapy, which helps people reshape the negative thought patterns that drive their behavior, and develop healthier ways of coping.
Some people use marijuana to "essentially self-medicate" for disorders like anxiety or depression, Brennan noted. That's, in part, the rationale behind testing antidepressants and anxiety medication for CUD, he explained.
But, Kondo said, behavioral therapy alone may not be the "right fit" for everyone. It's also time-consuming, she noted, and may be costly or simply unavailable in a patient's local area.
Brennan agreed on the need for more research, partly because Americans increasingly see marijuana as "safe" and use of the drug is rising. Between 2002 and 2014, the number of daily marijuana users in the United States almost doubled, according to the NIDA.
One concern is that the marijuana in circulation today can be about 10 times as potent as what was available decades ago, Brennan added.
And while other drugs -- like opioids -- certainly cause more severe problems, that doesn't mean marijuana is harmless, Brennan said.