Experts Learning Much About Cannabis-Use Disorders

Marijuana is the most widely used illegal substance in the United States, with 15 million or more current users, and approximately 10 percent of these users develop cannabis-use disorders, epidemiological data have shown. The extent of this problem for clinicians was evident at a symposium on cannabis-use disorder, as the session attracted a full house of attendees at APA's annual meeting in New Orleans in May.

It is often difficult to conduct and interpret epidemiological studies of the adverse consequences and risks of marijuana use, David Gorelick, M.D., Ph.D., chief of the Pharmacotherapy Section in the Intramural Research Program at the National Institute for Drug Abuse (NIDA), told the attendees.

The observed outcomes of chronic use are influenced by many factors, including genetic variations, differences in the potency of and cumulative exposure to marjuana use, concurrent use of other substances such as tobacco and alcohol, comorbid psychiatric conditions, and psychosocial risk factors.

Growing evidence supports a link between marijuana use and psychosis, said Gorelick, citing population research from the United Kingdom. The link appears to be particularly strong with early exposure to marijuana in adolescence. Epidemiological research by Stanley Zammit, Ph.D., M.B., of Cardiff University estimated that the effect size of this link translates to this: stopping approximately 3,000 cases of cannnabis-use disorder might prevent one case of schizophrenia.

Research so far has shown no association between in-utero exposure to marijuana and the development of psychotic disorders later in life, according to Gorelick. However, two longitudinal studies using brain imaging found subtle differences in brain activities during executive-function tests between young adults with and without in-utero exposure to marijuana, even though their performance did not differ.

Meanwhile, patients with schizophrenia have reported a high rate of cannabis use—up to 50 percent in some studies, Gorelick noted. Marijuana smoking in these patients is associated with significantly worse psychotic symptoms, poorer treatment compliance, and exacerbated metabolic side effects from antipsychotic medications. “It's clearly bad for them,” he said. “The question is why they use marijuana—and there is no clear answer.”

According to recent research, physical effects of long-term cannabis use are somewhat different from those of tobacco smoking, Gorelick pointed out. Respiratory symptoms such as cough, phlegm, and wheezing have been reported. The association with chronic obstructive pulmonary disease, lung cancer, and myocardial infarction appears to be smaller for marijuana smoking than for tobacco smoking.

Marijuana Use Poses Driving Hazard

Aviv Weinstein, Ph.D., of the Department of Nuclear Medicine at Hadassah Hospital Ein Kerem in Jerusalem, Israel, reported findings from a recent study to measure the acute effects of cannabis on cognitive-motor functions.

Weinstein and colleagues enrolled 14 volunteers who regularly smoked marijuana and tobacco and gave them a driving test in a virtual-reality maze after smoking a cigarette containing 17 mg of tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, a cigarette containing 13 mg of THC, and a tobacco cigarette with no THC. The virtual maze was designed to test their motor-cognitive functions.

The volunteers had a higher collision rate in the virtual-maze test, indicating reduced cognitive-motor skills, immediately after a dose of 17 mg THC, compared with 13 mg THC and with tobacco. On PET scans performed after the maze test, the researchers saw that brain areas associated with motor coordination and visuospatial attention showed increased metabolism, while areas related to visual integration of motion in the occipital lobes were decreased.

Weinstein also reported that after administering 17 mg THC, the subjects made more errors on a cognitive test than they did after taking 13 mg THC or placebo, suggesting reduced attention and working memory, and showed an increased tendency for risk-taking behaviors in a simulated gambling task.

Behavioral Treatments Prove Effective

A number of studies have demonstrated the effectiveness of behavioral therapies to treat cannabis-use disorder, according to Alan Budney, Ph.D., a professor of psychiatry and a research scientist at the Center for Addiction Research at the University of Arkansas for Medical Sciences.

Summarizing recent studies on motivational enhancement therapy (MET), cognitive-behavioral therapy (CBT), abstinence-based therapy, and contingency management strategies, Budney noted that a combination of MET and CBT has been shown to reduce cannabis use and promote abstinence in many patients.

MET techniques help strengthen the patient's motivation to change and quit, Budney explained. The key to the motivational interviewing style is to convey a nonjudgmental, accepting attitude toward the patient and not overstate the risk of marijuana use. “Combined with teaching coping skills [with CBT], this approach works well in the real-world setting,” he said.

Contingency management, which involves offering rewards to patients who maintain abstinence, has been extensively studied and shown to be effective in treating various addiction disorders. The reward may be vouchers to exchange for goods, assistance for work or housing, or nonmonetary incentives, Budney said. For adolescents in treatment, parents can be taught to implement contingency strategies effectively. For example, an adolescent may be rewarded with a gift or privilege for staying free of marijuana use.

Budney is a proponent of frequent urine testing to monitor treatment efficacy.

Perhaps most important, behavioral treatment for cannabis-use disorders should be tailored to each patient's situation, needs, motivation, and concerns.

Pharmacological Treatments Promising

Margaret Haney, Ph.D., a professor of clinical neurobiology at the College of Physicians and Surgeons of Columbia University, and colleagues have developed a human laboratory model to study marijuana withdrawal, relapse, and intoxication symptoms and to test medications that may be effective in treating the addiction. The model is “an intermediary between preclinical animal experiments and randomized, controlled clinical trials,” said Haney at the annual meeting session.

In this model, volunteers who were heavy marijuana smokers with no major psychiatric disorders and not seeking treatment were assessed and tested under confined, controlled, experimental conditions of simulated withdrawal and relapse.

During withdrawal conditions, the subjects were given placebo rather than marijuana, while medications were tested for their effectiveness to reduce withdrawal symptoms such as cravings, anxiety, irritability, restlessness, decreased food intake, and disrupted sleep. Researchers found that bupropion worsened the symptoms, divalproex worsened mood and cognitive performance, and nefazadone relieved such symptoms such as anxiety and muscle pain to an extent. “The medication showing the most promise in attenuating withdrawal symptoms was dronabinol, an oral THC,” Haney pointed out.

To study predictors of relapse after abstinence and possible treatment, the subjects were given placebo for three days and then given the option of purchasing “real” marijuana for a high cost. The amount of money subjects are willing to pay to smoke marijuana is a measure of the severity of their relapse.

The alpha₂ adrenergic receptor agonist lofexidine significantly reduced the amount of marijuana smoked during the simulated relapse condition, and the effect appeared to be more robust with the combination of lofexidine and dronabinol.

Taken alone, dronabinol did not appear to have a significant effect on relapse in the experimental condition. Baclofen, a gamma-aminobutyric acid type B (GABA-B) receptor agonist, did not affect marijuana relapse but significantly reduced tobacco smoking. Mirtazapine improved sleep disturbance during withdrawal but did not differ from placebo in relapse outcome, and it significantly increased tobacco smoking.

“We did not see any significant correlation between the magnitude of withdrawal symptoms and the likelihood of relapse,” Haney said, although certain withdrawal symptoms (especially disrupted sleep) increased the severity of relapse. She noted that, curiously, the degree of cravings and irritability during abstinence did not significantly predict relapse.