Withdrawal

Withdrawal is a core feature of substance dependence, with the most severe withdrawal phenomena generally associated with alcohol, benzodiazepine, and opioid use. Withdrawal from marijuana is not recognized in DSM-IV, purportedly because at the time of publication it was not felt that this was a clinically significant phenomenon. Since then, however, substantial evidence has developed that supports the existence and clinical relevance of marijuana withdrawal.41-44 Marijuana withdrawal syndrome is most frequently characterized by a constellation of emotional, behavioral, and physical symptoms that include anger and aggression, anxiety, decreased appetite and weight loss, irritability, restlessness, and sleep difficulty.45 Less frequent but sometimes present are depressed mood, stomach pain and physical discomfort, shakiness, and sweating.

Onset of withdrawal symptoms typically occurs within 24 hours of cessation. Symptoms may last days to approximately 1 to 2 weeks.43,44 The specificity of these withdrawal symptoms to marijuana's active ingredient—Δ-9-tetrahydrocannabinol—is supported by pharmacological studies. In nonhuman species, cannabis withdrawal has been reliably precipitated after the administration of a cannabinoid 1-receptor antagonist.46 In humans, oral Δ-9-tetrahydrocannabinol has been demonstrated to suppress marijuana withdrawal symptoms.47,48

Adolescents have been the focus of recent investigations of marijuana withdrawal. Initial reports noted the above symptoms among cannabis-dependent adolescents with comorbid conduct problems in residential treatment49,50 and in adolescents with cannabis use disorders in a community sample.51 More recent literature reveals that adolescents who seek treatment may experience clinically significant withdrawal symptoms.52 A brief report also described withdrawal symptoms in adolescents presenting for nontreatment research.53 Further work is needed to elucidate similarities and differences between adolescent and adult presentations of marijuana withdrawal.

Craving

Craving is typically thought of as a subjective desire to use a substance and is often associated with drug dependence, including cannabis dependence.54 Cravings and urges are considered to reflect the fundamental motivational processes that maintain continued drug use.55-57

A well-established laboratory method for evaluating craving is the cue reactivity paradigm, in which the researcher attempts to induce craving of a substance in patients by presenting them with cues associated with their respective substance of use and/or abuse (eg, sight or smell of a substance, films of drug-taking locations, and drug-related paraphernalia). This paradigm is designed to approximate levels of craving that an individual experiences in his or her substance use environment, rather than the comparatively lower levels of craving experienced in an ordinary clinical setting. In general, this approach leads to robust increases in craving, along with modest increases in objective physiological measures, such as skin conductance (reflecting perspiration) and heart rate.58 Several studies have demonstrated that cue reactivity can be predictive of drug relapse.59-66 Investigation of cue reactivity in adolescents is a relatively recent development. Initial reports suggest that adolescents with nicotine and alcohol use disorders react to cues in a manner similar to their adult counterparts.67-71

Marijuana cue reactivity research is also in its early stages and has yielded promising results. Small-scale studies have demonstrated reliable reactivity to marijuana-related cues in adults72,73 and adolescents74,75 with cannabis use disorders.

Conclusion

Marijuana use in adolescence remains a significant problem. Frequent use and early initiation of use during adolescence are associated with poor outcome. Existing treatments have demonstrated generally modest results. Research is needed to further elucidate factors involved in relapse among adolescents attempting to abstain.

Marijuana withdrawal and craving are 2 potential targets of focused investigation, from both experimental and treatment standpoints. These phenomena are increasingly recognized in adults with cannabis use disorders, and recent preliminary investigation is yielding compelling data pointing toward their validity in adolescents.

Treatments being developed for adolescent cannabis use disorders, both psychosocial and pharmacological, should consider craving and withdrawal symptoms as potential targets to reduce relapse. Similarly, clinicians treating adolescents with cannabis use disorders should not disregard marijuana craving and withdrawal symptoms as potential factors complicating treatment.

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