New Replacement Therapies for Marijuana Addiction

By Laura Slot, 2009

Anne Badeni is a passionate and successful musician in New York City who loves to sing and play guitar. She’s an intelligent woman in her mid-fifties with short blonde curls and pale skin. She looks tough and unapproachable, but her songs are emotional and melodic, a little like Joni Mitchell or Jackson Browne. For the greater part of her life, Badeni has been addicted to marijuana until she decided to quit about five months ago.

Anne—who didn’t want her real name used because it may threaten her job—has smoked weed regularly since the age of 14, but the drug became a bigger problem when she moved out of her parent’s house four years later and her new roommate turned out to be a seasoned marijuana smoker. She gradually started smoking every day, from morning to evening. On multiple occasions, Badeni tried to quit, but failed. Problems in romantic relationships, she said, often made her addiction worse. Last New Year’s Eve, she decided to live her life without the emotional comfort of getting high. “Quitting was the single thing that was in my power to change,” she said. “I realized how weed complicated my life—it’s illegal, expensive, it takes up time, I had adjusted my whole life to the drug.”

But was there any reason, personal or medical, to think that this might be different from any of the other times she thought of quitting? Not immediately. But scientists are now pursuing a radical new approach of developing drugs for marijuana addicts that can be used as a so-called replacement therapy, like nicotine patches for cigarette smokers or methadone for heroin addicts. The proposed medication will gradually replace lower the levels of the addictive chemical in the body— tetrahydrocannabinol, or THC, in marijuana—so that withdrawal symptoms are less severe. With so many social and emotional aspects to addiction, it is questionable whether such a therapy alone will suffice to help people quit. But recent discoveries mark a dramatic shift in the treatment of marijuana addiction.

Scientists at Stony Brook University are heading down a unique path by investigating a group of chemicals similar to THC that already exist in the brain: the so-called endocannabinoids, the brain’s natural cannabis, a system first discovered in the 1980s. Last March, after more than 15 years of research, professor of cell biology and biochemistry Dale Deutsch and his team reported a novel way to manipulate the levels of two important endocannabinoid chemicals, 2-AG and anandamides, which influence processes like appetite, pain and memory, but also addictive behavior.

“It’s possible for people who take opiates, alcohol, or smoke marijuana, and who want to stop, that we can raise the levels of the endocannabinoid system, and replace them, something like a nicotine patch,” said Deutsch, the lead author of the study, in a telephone interview. Nora Volkow, the director of the National Institute of Drug Abuse, which has been funding Deutsch’s research since 2003, said in a statement that Deutsch’s discovery could eventually be used for treating marijuana addiction, but also chronic alcohol abuse, which is closely linked to the endocannabinoid system. “From a theoretical viewpoint, this approach could be used for treating marijuana addiction,” said Dr. Volkow. “Compounds that inhibit FABPs could produce an effect similar to nicotine patches for smokers or methadone for opiate replacement. This line of research may also be important for other types of addiction, such as chronic alcohol abuse, which also affects AEA levels,” she explained. “People who smoke marijuana can be alleviated a lot.”

Contrary to the expectations of many other scientists, Deutsch discovered that these marijuana-like chemicals circulate through the brain in a very different manner than most other neurotransmitters, and, as a result, he learned how to manipulate the levels—just as the anti-depressant drug Prozac manipulates the levels of serotonin, the neurotransmitter related to happiness and depression. The two chemicals (2-AG and anandamides) are transported by a very oily substance, Deutsch said, just like marijuana, which is a thick yellow oil. Deutsch and colleagues found that the endocannabinoids are ferried around the cells by proteins (faty acid binding proteins) that make them soluble. These proteins are new drug targets that can raise endocannabinoid levels. The results is that Due to these transports, they can trigger the so-called reward system in the brain, where addictions are brought into being.

The National Survey on Drug Abuse and Health, which is conducted annually among 67,500 people by the Department of Health and Human Services, shows that approximately 3.9 million Americans had a marijuana addiction in 2007. Weed is by far the most popular illicit drug in the United States with twice as many addicts as cocaine (1.6 million). An estimated 14 million Americans had used marijuana at least once in the month prior to the survey.

People who have an addiction continuously want to trigger that reward system in order to feel better. As they become physically dependent on the drug, they need increasingly higher levels of the chemical in order to feel “normal,” and even more to experience a high. It is important that any potential new medications ameloriate withdrawal symptoms while the levels of the addictive drug (marijuana, alcohol, nicotine) are gradually lowered after withdrawal. It is a balancing act since the replacement therapy should not make the levels too high, Deutsch said, because with an overdose of endocannabinoids “you may become too stress-free, too relaxed, you may not be remembering anything, and you may be too spacey.” The idea that replacement therapy is useful conforms to the ideology of the National Institute of Drug Abuse, a subdivision of the National Institute of Health, that addiction is in fact “a chronic, relapsing brain disease.”

To Badeni it certainly is a disease, although she sees the basis of her dependence as mainly psychological. Growing up gay made her confused and turn inward. And as a direct consequence of being raised by a severe mentally ill mother, her two brothers also became heavy marijuana users—one of whom is addicted. Her wayward upbringing gave her low self-esteem and she needed marijuana to heal some of her emotional pain. One of Badeni’s friends stared down at his shoes during a recent gathering for marijuana addicts and uttered that even with a replacement therapy, “You still have to face life.”

Yet everyone who claims that marijuana is not addictive, Badeni said, is lying. She couldn’t sleep or eat for months after she stopped using it, and because of those frustrating withdrawal symptoms, Badeni sees the benefit in taking a replacement drug. She would have been eager to try such a treatment, she said, if she hadn’t already quit five months ago. “It would have taken away the chemical desire,” she said. “But I could have become addicted to the pill form, too. I really enjoyed the high.”

Science backs up Badeni’s sense of marijuana’s addictive powers. New research by Ryan Vandrey, a faculty researcher in psychiatry and behavioral sciences at Johns Hopkins University School of Medicine, showed last December that the addictiveness of marijuana is similar to nicotine, and that withdrawal can be an annoying experience. There seems to be a set of symptoms that all addicts experience when they quit, he said, regardless of whether they used nicotine, alcohol, opiates, cocaine or other drugs. “The most common symptoms that you see are things like irritability, sleep difficulty or insomnia, anxiety, restlessness, agitation, aggression, things like that,” Vandrey said in a telephone interview. “In a subgroup, you get more physiological things like gastrointestinal distress, stomach pains, nausea, and in some cases vomiting, sweating, and chills.”

Badeni’s withdrawal symptoms were in fact similar to when she quit her two other long-term habits: alcohol (which she gave up in September) and smoking cigarettes. Marijuana Anonymous, where Badeni is one of the almost 200 New York City members, is helping a specific group of people that is very different from alcoholics, she said. Many heavy marijuana users also struggle with alcohol abuse, and so they first turn to Alcoholics Anonymous—a step that rarely works, she said. “Alcoholics I found to be a different set of complexes,” she explained, “much more drama, ego-posturing, disingenuous, and not as warm and fuzzy. Potheads understand social anxiety. Bar-flies are more interested in social interaction.”

Some people still consider marijuana a “soft” drug, but weed has become considerably more potent during the last 20 years, Vandrey said. The average THC concentration today is much higher than what hippies in the Sixties experienced when they smoked, but there is no evidence that this is in any way linked to the increase in the number of addicts seeking help. The number of marijuana users reaching out to aid groups doubled between 1993 and 2005 (going from 9 to 18 percent of all substance abuse treatment admissions), and the number of groups directed specifically towards marijuana users is also growing, Vandrey said, because the idea that a marijuana addiction can be problematic is starting to become more accepted in society. “Most people who come in for treatment are not successful in quitting, and that’s just plain and simple, fact,” said Vandrey. “A lot of people acknowledged that the withdrawal they experienced has contributed to them relapsing or failing to quit when they want to try to. They believe it’s hindering their success.”

Meanwhile, pharmaceutical companies are already waiting around the corner for scientists to finish their basic research and clinical trials. Deutsch said that large firms like Schering-Plough immediately expressed an interest in developing a drug that could manipulate the addiction-neurotransmitters. New medication—which could increase the endocannabinoid levels—could possibly create a better alternative to the medical marijuana that is currently in use in the 14 states where it’s legal. In Deutsch’s opinion, medical marijuana can help people in cases where the drugs don’t always work, like, in some instances, for chemotherapy. Yet in California, he said, medical marijuana is used for much too wide a variety of complaints, and for symptoms that other drugs can treat better. “I think it’s abused by some doctors,” he added. “I mean, what other medicine do you use for everything?”

Even though Deutsch is manipulating the brain’s very own neurotransmitters rather than giving addicts the same, non-biological, addictive substance, a drug based on his research could still be controversial. If the result is similar to getting high, the danger of abuse and addiction continues to loom. “The government would be happy to block levels (of marijuana’s active ingredient),” said Deutsch, “but I don’t know how much they want to raise levels. If they promoted it for pain or drug abuse—and that’s what the medication will be promoted for mainly—it may work.”

Vandrey’s vision is that the most successful treatments are a combination of a behavioral treatment with a pharmacological approach—a suitable replacement drug. One of Badeni’s friends, another woman who is also addicted to marijuana, is currently participating in a clinical test conducted by Columbia University, in which one group of people receives pills with THC, known under the brand name Marinol, while another group gets placebos.

While he is waiting for the results coming from scientists working on the drugs, Vandrey is investigating different psychological strategies like motivational interviewing, in which a counselor helps patients explore themselves, and community reinforcement, where social connections are improved, both of which Vandrey thinks are highly promising and “wonderful” techniques.

Badeni is following a 12-step recovery program via Marijuana Anonymous, and the meetings with other addicts helped her quit. “I try to develop other coping mechanisms,” she said. “People have become much more important in my life, and I try to be more creative in my music. I’d like to develop this as a new lifestyle, one day at the time.” At some moments, however, she admits that her attempt to stop is purely experimental. Her commitment to leaving weed behind forever, she said, is not very strong. Some people are simply predestined to become addicts, Badeni said, and whatever substance will be their drug of choice is not important. For some, a drug can be shopping, food, or sex, just like heroin or alcohol. “You’re just trying to replace something,” she said. “The addict lives in the person, even without any drugs.”