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Cochrane

Cannabis use is relatively common and widespread worldwide. Demand by cannabis users for treatment has been increasing in most regions of the world. Moves in some countries to decriminalise or legalise cannabis use is likely to result in this trend continuing. Currently there are no medicines specifically for the treatment of cannabis use. This review sought to assess the effectiveness and safety of medicines for the treatment of cannabis dependence.

Search date

We searched the scientific literature in March 2018.

Study characteristics

We identified 21 randomised controlled trials (clinical studies where people are allocated at random to one of two or more treatment groups) involving 909 participants treated with active medicines, and 846 who received placebo (a pretend treatment). Key features of dependent drug use are compulsive use, loss of control over use and withdrawal symptoms on cessation of drug use. This review included studies where participants were described as dependent or were likely to be dependent based on cannabis use occurring several days a week, or daily.

The mean age of participants in individual studies ranged from 22 to 41 years, excluding three studies that targeted young people. Most (75%) study participants were male. Most (16) of the studies were undertaken in the USA, with three occurring in Australia, one in Canada and one in Israel. The studies tested a wide range of medicines to reduce the symptoms of cannabis withdrawal and to promote cessation or reduction of cannabis use.

Four studies received study medicines from the manufacturing pharmaceutical company but none were funded by pharmaceutical companies. One study did not report funding or medicine source.

Key results

For the outcome of abstinence at the end of treatment, Δ 9 -tetrahydrocannabinol (THC, the major constituent in cannabis) preparations were probably ineffective; antidepressants called selective serotonin reuptake inhibitors, mixed action antidepressants, a medicine called buspirone and a medicine called N-acetylcysteine may also have been ineffective; and we are uncertain about the effect of anticonvulsants and mood stabilisers.

For the outcome of completion of the scheduled period of treatment, THC preparations, mixed action antidepressants, anticonvulsants and mood stabilisers may not have been effective, we were uncertain about the effect of SSRI antidepressants, and N-acetylcysteine probably did not support treatment completion. The use of anticonvulsants and mood stabilisers may have increased the likelihood that people left treatment early.

THC preparations and N-acetylcysteine were probably no more likely to cause side effects than placebo, mixed action antidepressants and buspirone may have been no more likely to cause side effects than placebo, and we were uncertain about SSRI antidepressants.

Based on current research, all medicines should be considered still experimental.

Quality of the evidence

The quality of the evidence for many of the outcomes in this review was low or very low because each medicine was investigated by a small number of studies (ranging from one to four), each study involved small numbers of participants, there was some inconsistency in the findings and there was a risk of bias due to study participants dropping out of treatment.

There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.

Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.

This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014.

To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use.

We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science.

Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent.

We used standard methodological procedures expected by Cochrane.

We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.

All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.

Abstinence at end of treatment was no more likely with Δ 9 -tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).

There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.

Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).

There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).

There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).

Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness.

Cochrane Cannabis use is relatively common and widespread worldwide. Demand by cannabis users for treatment has been increasing in most regions of the world. Moves in some countries to

Cannabis Use Disorder: Know the Signs

As marijuana use becomes increasingly mainstream, with many states legalizing the drug for medicinal and/or recreational use, consumption is on the rise—leading to the question, how much marijuana is too much?

In 2020, cannabis, or marijuana, is legal for recreational use in 11 states, with several others attempting to follow suit. Despite its prevalence and increasing legalization, however, marijuana remains classified by the U.S. Drug Enforcement Administration as a Schedule I drug, along with heroin and LSD, due to its high potential for abuse and the absence of currently accepted medical use. As such, marijuana is still federally illegal and, according to research on substance abuse disorders, potentially dangerous.

“Cannabis use disorders are often associated with dependence—in which a person feels withdrawal symptoms when not taking the drug. People who use marijuana often report irritability, mood and sleep difficulties, decreased appetite, cravings, restlessness, and/or various forms of physical discomfort that peak within the first week after quitting and last up to two weeks,” explains Nora Volkow, M.D., director of the National Institute on Drug Abuse (NIDA).

“When dependence and other factors escalate to cannabis use disorder, a person cannot stop using the drug even though it interferes with many aspects of his or her life,” Dr. Volkow continues. “Some studies suggest that nine percent of people who use marijuana will become dependent on it, with higher rates in those who start using in their teens.” Other studies show even higher rates.

What Is Cannabis Use Disorder?

Among other substance abuse disorders, cannabis use disorder (CUD) is classified in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5) using a series of criteria that determine a user’s patterns of behavior. These criteria include:

  • Cannabis is often taken in larger amounts or over a longer period than intended
  • There is a persistent desire or unsuccessful efforts to cut down or control cannabis use
  • A great deal of time is spent in activities necessary to obtain cannabis, use cannabis or recover from its effects
  • Craving or a strong desire to use cannabis
  • Recurrent cannabis use results in failure to fulfill role obligations at work, school or home
  • Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis
  • Important social, occupational or recreational activities are given up or reduced because of cannabis use
  • Recurrent cannabis use in situations in which it is physically hazardous
  • Cannabis use continues despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis.
  • Tolerance, as defined by either: (1) a need for markedly increased cannabis to achieve intoxication or desired effect or (2) a markedly diminished effect with continued use of the same amount of the substance.
  • Withdrawal, as manifested by either (1) the characteristic withdrawal syndrome for cannabis or (2) cannabis is taken to relieve or avoid withdrawal symptoms.

CUD is defined as either mild (two to three symptoms present), moderate (four to five symptoms present) or severe (six or more symptoms present). According to NIDA, in 2015 roughly 4 million people in the United States met the criteria for cannabis use disorder.

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Treatments For Cannabis Use Disorder

According to NIDA, CUD is similar to other substance abuse disorders in that people with the disorder often suffer from other psychiatric disorders or substance abuse problems. For that reason, treating underlying mental health concerns may help treat the marijuana use disorder. Behavioral health treatments include:

  • Cognitive-behavioral therapy, which teaches people strategies to identify and correct behaviors that lead to substance abuse
  • Contingency management, which monitors target behaviors and rewards positive behavior changes
  • Motivational enhancement therapy, which is designed to mobilize a person’s internal motivations for change

Is Any Amount of Marijuana OK?

Cannabis has long had the reputation of being non-addictive, unlike other “harder” drugs. Scientists, however, disagree–particularly in today’s environment that produces stronger strains. Simply stated, this isn’t your parents’ weak weed.

“The potency of cannabis products used to be much weaker, perhaps contributing to the impression that marijuana is not addictive,” explains Deborah Hasin, Ph.D., professor of epidemiology at Columbia University, in New York City. “However, potency has increased greatly over the last few decades. Updated figures show that 20 to 30 percent of cannabis users develop CUD, so the risk for addiction is real.” It is for that reason that Dr. Hasin feels that marijuana consumption of any amount can be cause for concern.

“I think the very idea that there is a ‘healthy’ amount of any psychoactive substance is problematic,” says Dr. Hasin. “Some people can use marijuana without harm, just as some people can drink without harm, especially if use is infrequent, but others run the risk of adverse consequences, including CUD, impaired social or operational functioning, respiratory problems, motor vehicle crashes and cannabis reactions requiring visits to the emergency room.”

Marijuana use is common: National Institutes of Health. “Marijuana Use Disorder Is Common And Often Untreated.”

Cannabis and withdrawal: StatPearls, (2019) “Cannabis Use Disorder.”

Marijuana is classified as a serious, hard drug: United States Drug Enforcement Administration. “Drug Scheduling.”

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Cannabis use disorder (CUD) – or, marijuana addiction – is increasingly common in the United States. Know the signs and learn which treatments can help.