Cannabinoids

Use, Abuse, and Addiction

For some time, a common belief was that marijuana abuse and dependence rarely occurred as a primary problem. Many people believed that cannabis did not produce a true dependence syndrome. Beginning in the 1980s, however, an increasing number of individuals who could not stop smoking cannabis on their own have sought treatment primarily for cannabis dependence. When subjects present for treatment, various rationales for discontinuing marijuana use are given, including fear of the physical consequences of smoking cannabis, difficulty expressing emotions, difficulty experiencing feelings of intimacy or closeness with a partner, and dissatisfaction with a failure in achieving life goals (Box 8.3). Chronic users are described as having mild boredom, a lack of zest, or a low level of depression that resolves during marijuana abstinence. Subjects readily respond to advertisements for the treatment of cannabis dependence, and the majority are not abusing other substances.

TABLE 8.8

Peak Plasma Levels of Δ9-THC After Smoked vs. Oral Administration

Route

_9-THC Dose

Mean Peak Plasma Level (Range)

Smoked

16 mg

84.3 (50.0–129.0) ng/m (Huestis et al.)

 

34 mg

162.2 (76.0–267.0) ng/m (Huestis et al.)

Oral

2.5 mg

2.01 (0.6–12.5) ng/m (Timpone et al.)

 

15 mg

3.9 (2.7–6.3) ng/m (Frytak et al.)

 

20 mg

6.0 (4.4–11.0) ng/m (Ohlsson et al.)

 

30 mg

15.5 ng/m_ (Haney et al.)

Cannabis Use Disorder has a characteristic clinical course that can be identified, is predictable, and has elements common to Substance Use Disorders for other drugs of abuse. A user will typically begin with social use, often enjoying the pleasurable effects of cannabis in a social setting while learning to use the drug to enhance such effects (for example, learning to inhale). Marijuana use can then increase to the point where the drug is no longer used socially, and users begin smoking whenever possible (for example, on the way to school or even between classes or during work). Tolerance develops, and more and more marijuana is smoked, possibly because of the effect of tolerance. Performance in social settings and occupational/academic functioning decline, and denial and resistance to considering cannabis use as a problem develop. An important criterion for clinically diagnosing Substance Dependence on cannabis, as defined by the DSM-IV and DSM-5, is that marijuana use affects a person’s ability to function. Abnormal or compulsive marijuana use is often argued to be the result of a given problem rather than the cause of it, but the converse may also be true (see below). Difficulty sleeping, depression, and stress fall into this category. Both social users and dependent users may use marijuana for the same reasons:

FIGURE 8.8 Metabolic pathways of Δ9-THC. The highlighted compounds signify psychoactive metabolites. The bold arrows indicate the predominate metabolic pathway. The 11-OH ➔ COOH pathway is where most of the Δ9-THC ends up going. This is why it is often the primary choice for detection in drug testing.

Box 8.3

VOLUNTEER WITH UNSUCCESSFUL TREATMENT

JS was an 18-year-old male who voluntarily presented because he “wanted to stop.” Consumption of drugs consisted of about 3.5 grams of marijuana and hashish per day for one year prior to seeking treatment. He self-administered every one to four hours while awake and complained of chronic cough, anorexia, depression, and weight loss. When he had tried abruptly to cease marijuana by himself, he had hallucinations, depression, and anergy. Urinalysis testing revealed the presence of marijuana, but no other drugs. The patient entered a counseling program, but received no medications. Only one return appointment was kept, and he was lost to followup.

From: Tennant FS Jr, The clinical syndrome of marijuana dependence, Psychiatric Annals, 1986, (16), 225–234.

“The reason addicts use marijuana abnormally is because marijuana apparently provides an unusual reinforcement to those with a vulnerability to marijuana not possessed by others.”

TABLE 8.9

Peak Plasma Levels of Δ9-THC After Smoked vs. Oral Administration

Taken with permission from Tennant FS. The clinical syndrome of marijuana dependence. Psychiatric Annals, 1986, (16), 225–234.

Box 8.4

MANDATORY WORK-SITE DETECTION AND REFERRAL

HS was a 37-year-old male salesperson. He was reported to the management of his company to be a marijuana user who also sold it to other employees while on company premises. A mandatory urine test revealed the presence of marijuana metabolites, and in order to retain employment he was required to undergo withdrawal and enter a periodic urine-testing program. Upon interview, he stated that he had used marijuana every evening for approximately 22 years. He believed this habit had not been injurious to himself until approximately three months prior to treatment when he began to notice some defects in his short-term memory. Physical examination was normal. Plasma analysis showed there to be 148 ng/ml of 11-OH THC and 80 ng/ml of THC-C. He was administered desipramine, 25 mg, three times per day and tyrosine. During the first three weeks following cessation of marijuana, he reported mild insomnia, depression, anergy, and craving. Urine analysis showed no marijuana metabolite after about 30 days. After six weeks of abstinence, he reported improvement of short term memory and improved job performance.

From: Tennant FS Jr, The clinical syndrome of marijuana dependence, Psychiatric Annals, 1986, (16), 225–234.

(Miller NS, Gold MS. The diagnosis of marijuana (cannabis) dependence. Journal of Substance Abuse Treatment, 1989, (6), 183–192.)

Two clinical forms of dependence have been described: Type 1 and Type 2 (Table 8.9). Such a prior distinction seemed to foretell the diagnostic changes adopted by the DSM-5 by considering cannabis use disorder on a continuum of severity. Type 1 involves an individual who smokes or uses marijuana several times per day at approximately 2–4 h intervals, except during sleep, and who escalates intake. Such subjects exhibit significant impairment in social and occupational functioning and often ultimately seek treatment. Type 2 presents at mandatory screening and involves individuals who usually use marijuana every 24–36 h (Box 8.4). Although they present with impairment in social and occupational functioning, these individuals have less withdrawal symptoms and less perceived dependence.

Most of the DSM-III-R criteria for Substance Dependence were met by individuals diagnosed with Substance Dependence on cannabis. Preoccupation with obtaining and using marijuana is represented by the persistent presence of marijuana in the individual’s daily living and choices of activities. Compulsivity is represented by continued use despite marijuana-related consequences. Relapse or the propensity to relapse is reflected by a return to marijuana use after a period of abstinence and may provide confirmation of the suspected diagnosis. In a study of adolescents who were referred for substance abuse and conduct problems, the most frequently observed criteria were a substantial time spent obtaining marijuana, using marijuana, or recovering from its effects, continued use despite problems in social and occupational functioning, and tolerance or withdrawal (Figure 8.9).

The treatment of cannabis dependence has relied almost exclusively on behavioral therapies. No pharmacological treatments for cannabis dependence have been approved by the US Food and Drug Administration. Few pharmacological treatments have shown any success. There is some evidence that dronabinol (Marinol) can be used as a substitution therapy, similar to methadone treatment for heroin dependence, and a successful clinical trial has been conducted with gabapentin. Cognitive behavioral therapy, motivational enhancement therapy, relapse prevention support groups, social support groups, and motivational interviewing have all significantly reduced marijuana use compared with baseline, but no single therapy has stood out as being significantly more effective than any other. A large-scale, multi-site clinical trial found that approximately 23% of the people in an experimental group that received extended cognitive behavioral therapy combined with motivational enhancement therapy remained abstinent at 4 months compared with 9% of people in a brief intervention group and 4% of people in a delayed treatment group, suggesting some semblance of a treatment “dose” response.

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