Cover Story

As efforts to make marijuana legal for medicinal use gain momentum, psychologists are studying the effects of the nation’s most popular illicit drug — and several are sounding notes of caution.

As researchers, psychologists are exploring the risks of dependence, developing more effective interventions for marijuana users who want to quit, studying withdrawal and evaluating medicinal uses of marijuana’s main active chemical, delta-9-tetrahydrocannabinol (THC).

That research is more relevant than ever: 14 states have already legalized marijuana for medical purposes, with voters in nine of those states approving medical marijuana by ballot initiative. A dozen more states are considering legislation this year to make marijuana available for medical use.

In California, the epicenter of what some describe as de facto legalization, voters will decide in November on whether marijuana’s recreational use should be legalized, taxed and regulated.

Meanwhile, public opinion polls continue to show growing acceptance for legalizing marijuana for personal use. An October Gallup poll found that 44 percent of adults favored legalizing marijuana, a group that’s grown between 1 percent and 2 percent every year since 2000. In six Western states, most poll respondents favored outright legalization.

Support for medicinal uses for marijuana is even stronger: According to a January ABC News/Washington Post poll, 81 percent of Americans would allow physicians to prescribe marijuana for their patients, up from 69 percent in 1997.

But as the nation debates legalization, the public should know that about 10 percent of users go on to develop marijuana dependence, says Barbara Mason, PhD, co-director of the Pearson Center for Alcoholism and Addiction Research at the Scripps Research Institute in San Diego.

“Ninety percent of individuals will be able to use it in a way they find nonproblematic in terms of dependence but 10 percent will run the risk of developing dependence, and for that, effective treatments should be available,” says Mason, the principal investigator for a National Institute on Drug Abuse-funded study of the neurobiological effects of marijuana use.

A secondary analysis of the 2005 National Survey on Drug Use and Health found that among people who had used heroin in the past year, 45.4 percent met the criteria for dependence. Among those who had smoked cigarettes in the past year, 35.3 percent were dependent on nicotine, and 20.4 percent of past-year cocaine users were dependent. The analysis, included in Chapter 22 of “Psychiatry Third Edition, Volume 1” (Wiley, 2008) found that 9.7 percent of people who used cannabis met criteria for dependence. Among past-year alcohol users, 4.9 percent met criteria for dependence.

While the percentage of American users who become dependent on marijuana wouldn’t change after legalization, the absolute numbers probably would, says Columbia University neuroscience professor and marijuana researcher Margaret Haney, PhD. “Clearly, the more available something is, the more likely people will try it, and therefore a higher number will go on to develop problems with it,” she says.

But some addiction researchers, including renowned researcher G. Alan Marlatt, PhD, aren’t troubled by the trend toward legalization. In his view, many marijuana users who want to quit or cut back avoid treatment for fear of criminal repercussions.

“If it’s decriminalized ... that’s going to open the door for more people to seek help,” says Marlatt, who directs the University of Washington’s Addictive Behaviors Research Center.

As society moves toward greater acceptance of marijuana, psychologists should make sure their research results are available to people who are considering using it, particularly adolescents and young adults, says Mason. They also need to develop more effective interventions for dependent users who want to stop.

“When an individual makes that decision that they want to quit, I want to meet them with the best possible strategy,” she says.

Use and abuse on the rise

About 6 percent of Americans age 12 and older have used marijuana in the past month, according to the Substance Abuse and Mental Health Services Administration’s 2008 National Survey on Drug Use and Health — a trend that’s held steady for the last seven years. However, the National Institute on Drug Abuse “Monitoring the Future” survey found that past-month marijuana use among high school seniors edged slightly upward over the past three years to 20.6 percent in 2009, reversing a decade-long downward trend. Although it’s a concerning trend, it’s a far cry from the peak of 37 percent in 1978. NIDA officials think use might continue to increase given the increasing percentage of high school seniors surveyed who don’t view regular marijuana use as risky.

Marijuana use is, however, risky for some: About 4.2 million people are dependent on or abuse marijuana, almost twice the number of prescription drug abusers and three times the number of cocaine abusers, says Joseph Gfroerer, director of SAMHSA’s Division of Population Surveys.

Complicating the picture is the fact that marijuana’s main psychoactive component, THC, has FDA-approved medicinal uses in a non-smoked form. People being treated for HIV smoke marijuana to deal with the nausea, anorexia, stomach upset and anxiety associated with the disease and antiretroviral therapy. Cancer patients smoke it to relieve the side effects of chemotherapy. By relieving nausea and boosting appetite, marijuana can help patients in both groups avoid severe weight loss.

New research has found more potential uses for the drug. Five clinical trials funded by the University of California’s Center for Medicinal Cannabis Research revealed that marijuana significantly decreases neuropathic pain — notoriously difficult-to-treat chronic discomfort, which can result from injuries, side effects of anti-HIV drugs and diabetes, says Igor Grant, MD, executive vice chair of the department of psychiatry at the University of California, San Diego, School of Medicine.

One study funded by the center and published in the April 2008 Journal of Pain (Vol. 9, No. 6) found that both low-dose cannabis cigarettes (3.5 percent THC) and high-dose (7 percent THC) effectively reduced neuropathic pain from a variety of causes. According to NIDA, the average THC content of marijuana confiscated from the U.S. market was about 10 percent last year.

Two clinical trials examining the analgesic effects of THC on neuropathic pain will be completed by 2011, Grant says.

Overall, several of the studies showed that smoked marijuana reduced patient pain by more than 30 percent. That finding is important because in pain research, reducing pain by at least 30 percent is associated with “meaningful improvement in quality of life” for people dealing with chronic pain, according to a report Grant presented to the California Legislature in January.

Nationwide, 5 percent to 10 percent of Americans suffer some form of neuropathic pain, says Grant, so millions of people need more relief than they’re currently receiving. “This pain doesn’t respond as well to traditional pain medication, the opioid-type drugs, so what our studies showed is that cannabis has benefits with this kind of pain over and above the standard treatments patients were already receiving,” says Grant.

Center-sponsored research also found that cannabis side effects were mild, not any worse than with other medications and that they ceased once a participant stopped using marijuana. A separate, as-yet-unpublished study funded by the University of California center found that cannabis reduced muscle spasticity and pain intensity in people with multiple sclerosis beyond the relief available through conventional medication, Grant says.

Investigating medical benefits without smoking

For all of the debate over the legalization of marijuana and the drug’s possible medicinal uses, not enough is being done to study the possible benefits of the drug in its nonsmoked forms, says Haney.

In her research, Haney led a study comparing the relief offered by smoked marijuana with dronabinol, an oral form of THC, an FDA-approved treatment for nausea and disease-related weight loss.

In the study, a group of HIV patients who regularly smoked marijuana were given different concentrations of oral THC and smoked marijuana, or a placebo form of either drug. The researchers evaluated the effects THC had on diet, mood, cognitive performance and sleep.

Her volunteers were all taking at least two antiretroviral medications, and a physician was managing their HIV.

When taken at doses eight times stronger than the current recommended dose, dronabinol achieved the same effects as smoked marijuana, Haney says. Participants ate more often, gained an average of almost one pound in four days and experienced less anxiety on both forms of the drug as compared with a placebo, according to results published in the August 2007 Journal of Acquired Immune Deficiency Syndrome (Vol. 45, No. 5).

“What we found is that both oral THC and smoked marijuana work very nicely, they both increased appetite, and both were very well tolerated and had few side effects,” she says. The results suggest that oral forms of THC, and a new form of delivery through a botanically derived oral spray called Sativex that combines cannabidiol and THC may have many as-yet-unexplored medicinal uses, Haney says.

In her view, the state-by-state drive to legalize medical marijuana and promote its smoked form as the first choice for medical needs has diverted attention from finding better ways to use synthetic THC and nonsmoked marijuana — delivery methods that don’t expose a patient to the harmful effects of smoking.

“From a scientist’s perspective, it’s been very frustrating that there hasn’t been more science behind these [legalization] policies …. There’s an awful lot of anecdote driving these policy changes,” she says.

Living dependent

For all of marijuana’s possible medical benefits, it’s an addictive drug for some people who try it, researchers say. Mason is looking at whether a nonaddictive, neuromodulating medication called gabapentin, prescribed for epilepsy and for some forms of neuropathic pain, can help people get through the initial withdrawal and avoid relapse. Results so far are promising, with less marijuana use and decreased withdrawal severity among a pilot study of 25 daily marijuana users, compared with 25 who received a placebo, she says. Both groups received behavioral therapy during treatment, but the users who took gabapentin had less severe withdrawal symptoms and were more successful at avoiding relapse longer. That’s important because finding a way to ease withdrawal symptoms and decrease relapse, while starting behavioral therapy could boost the percentage of people staying abstinent longterm, Mason says.

“There are a lot of individuals, perhaps leading lives of quiet desperation, who are really engaged in the marijuana culture and can’t find their way out of it,” Mason says.

A second study, with 150 participants given either gabapentin or a placebo, is now under way, she says.

Meanwhile, psychologists have also studied the life experiences of long-term, heavy marijuana users compared with people who briefly smoked marijuana — less than 50 times in adolescence and early adulthood. A case-control study of 108 long-term heavy cannabis users published in 2003 in Psychological Medicine (Vol. 33, No. 8) found that when compared with people who smoked marijuana briefly, matched by age and similar family backgrounds, heavy users reported lower income and lower educational achievement.

Heavy users — who reported smoking marijuana an average of 18,000 times in their lives — also rated their own quality of life much more negatively than study participants who used marijuana for only a short period of time and stopped. They had lower ratings across 10 measures, including quality of diet, overall satisfaction with self and life, and general happiness.

For users who become dependent, stopping brings a constellation of withdrawal symptoms that may lead to relapse, says Alan Budney, PhD, of the Center for Addiction Research at the University of Arkansas College of Medicine.

“In controlled outpatient studies, we observe increased irritability and anger,” says Budney. “We observe sleep difficulties, and many [people] start to report strange or unusual dreaming. Restlessness, nervousness and decreased appetite are also frequently reported.”

Inpatient withdrawal research by Haney supports Budney’s observations. Haney’s team has regular users smoke marijuana under controlled conditions. When they’re switched to marijuana free of THC (see sidebar on page 53), they experience irritability, restlessness, anxiety, sleep disturbances and changes in appetite, with food intake dropping by as much as 1,000 calories a day.

Those effects were reversed when oral THC was administered or marijuana smoking was resumed, demonstrating the pharmacologic specificity of THC, according to a study published in 2004 in Neuropsychopharmacology (Vol. 29, No. 1).

“Once you do become dependent, it’s difficult to stop,” Haney says. “People who are seeking treatment relapse at rates as high as they are for cocaine, heroin and alcohol.”

Treating marijuana dependence is especially difficult when users don’t believe they have a problem, says Gregory Brigham, PhD, a clinical psychologist at Maryhaven, a substance abuse and mental health treatment center in Columbus, Ohio.

Marijuana users often see it as fun and a key ingredient to an entire subculture, Brigham says. “With the relatively mild intoxication they experience, they’re not alarmed by the consequences of being under the influence. It’s difficult for them to make a connection between the problems in their life and the use of marijuana, and that’s different from other drugs,” he says.

Helping users quit

Despite these challenges, psychologists and other researchers have found that three types of interventions help people quit marijuana. According to a 2007 study in Addictive Behaviors (Vol. 32, No. 6), when used together, these three interventions can result in an abstinence rate of about 27 percent, as measured at 14 months from treatment:

  • Motivational enhancement therapy. This approach uses motivational interviewing to get a person to consider the rewards and drawbacks of marijuana use. It focuses on helping clients acknowledge how marijuana use has affected their work, school and family life. The goal is to help users see how marijuana use might conflict with their goals — such as completing college or applying for a job that requires drug testing. That realization helps many clients develop motivation to change.

  • Cognitive behavioral therapy. Following one to four sessions of motivational interviewing, if a client decides to quit, a therapist can help him or her develop skills to stay marijuana-free. For example, clients role-play situations where friends offer them marijuana. In a typical scenario, a friend invites them to get high. Combining a firm “no” with an explanation of “I’m not smoking pot anymore,” the client proposes an alternative activity that doesn’t involve smoking pot. The therapy includes relaxation techniques for falling asleep without using marijuana, as well as steps to alleviate depressed moods.

  • Contingency management. Adapted from techniques developed for people who abuse cocaine and other drugs, this intervention sets a client on a schedule of earning vouchers with a predetermined cash value that escalates in value, if urinalysis indicates abstinence, during a 14-week monitoring period. Contingency management provides a structure to abstain from marijuana through urine monitoring and, through the vouchers, an incentive to stay abstinent. One 2006 study found that combining an abstinence-based voucher program with cognitive behavioral therapy resulted in 37 percent abstinence at one year (Journal of Consulting and Clinical Psychology, Vol. 74, No. 2).

Looking to the future, even better interventions may come from boosting people’s feelings of self-efficacy, says researcher Ronald Kadden, PhD, of the University of Connecticut Health Center. Previous research has found that marijuana users who reported significant improvements in feelings of self-efficacy while using coping skills learned to curtail cravings for marijuana stayed abstinent longer, says Kadden. To capitalize on this finding, Kadden is leading a NIDA-funded study to boost marijuana-dependent participants’ self-efficacy using a more intense regimen of daily homework assignments.

“If we can enhance that in people, maybe we’ll have better outcomes,” he says.

Another area that needs further study is whether marijuana users whose cognitive abilities have been impaired by smoking large amounts daily can benefit from cognitive behavioral therapy delivered in shorter and more frequent sessions, says Karen Bolla, PhD, director of neuropsychology at Johns Hopkins Bayview Medical Center in Baltimore.

The potential costs of legalization

Kadden’s experiences working with people who are dependent on marijuana convinces him that legalization isn’t a wise course to follow.

“We’ve got alcohol, and we’re stuck with it. We do marijuana, and it’s going to be another Pandora’s box,” he says.

A psychologist with very strong opinions on whether legalization is a wise course is A. Thomas McLellan, PhD, deputy director for the White House Office of National Drug Control Policy. As McLellan sees it, making marijuana more available will lead to more use, and more use will lead to greater dependence.

“Are you willing to say, ‘Let’s expand use, let’s add another intoxicant into the public?’ I don’t like the odds,” he says.

While noting that the cannabinoids found within marijuana show medicinal promise and will eventually be developed as a new class of pain reliever, smoked marijuana is not the best way to deliver those medical benefits, he says.

“Put it this way: We’ve got record unemployment, two wars, we have a bank collapse, a housing catastrophe. Oh, I know, let’s add marijuana, let’s add another intoxicant — that ought to fix things,” McLellan says.