36.10 - Bupropion

Authors: Sadock, Benjamin James; Sadock, Virginia Alcott

Title: Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition

Copyright ©2007 Lippincott Williams & Wilkins

> Table of Contents > 12 - Substance-Related Disorders > 12.5 - Cannabis-Related Disorders

12.5

Cannabis-Related Disorders

Cannabis preparations are obtained from the Indian hemp plant Cannabis sativa, a hardy, aromatic annual herb (Fig. 12.5-1). The cannabis plant has been used in China, India and the Middle East for approximately 8,000 years for its fiber and as a medicinal agent. It is the most commonly used illicit drug in the United States and, by most estimates, around the world as well.

Cannabis Preparations

All parts of Cannabis sativa contain psychoactive cannabinoids, of which (-)-Δ9-tetrahydrocannabinol (Δ9-THC) is most abundant. The most potent forms of cannabis come from the flowering tops of the plants or from the dried, black-brown, resinous exudate from the leaves, which is referred to as hashish or hash. The cannabis plant is usually cut, dried, chopped, and rolled into cigarettes (commonly called “joints”), which are then smoked. The common names for cannabis are marijuana, grass, pot, weed, tea, and Mary Jane. Other names, which describe cannabis types of various strengths, are hemp, chasra, bhang, ganja, dagga, and sinsemilla. The potency of marijuana preparations has increased in recent years because of improved agricultural techniques used in cultivation so that plants may contain up to 15 or 20 percent THC.

FIGURE 12.5-1 Marijuana (Cannabis sataiva).

Epidemiology

Prevalence and Recent Trends

Based on the 2003 National Surveys on Drug Use and Health (NSDUH), an estimated 90.8 million adults (42.9 percent) aged 18 years or older had used marijuana at least once in their lifetime. Among this group, about 2 percent used the drug before age 12, about 53 percent between 12 and 17 and about 45 percent after age 18.

The Monitoring the Future survey of adolescents in school indicates recent increases in lifetime, annual, current (within the past 30 days), and daily use of marijuana by eighth and tenth graders, continuing a trend that began in the early 1990s. In 1996, about 23 percent of eighth graders and about 40 percent of tenth graders reported having used marijuana and, in 1998 and 1999, more that a quarter of marijuana initiates were aged 14 years or younger. The average age was 17.

According to the text revision of the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), there is a 5 percent lifetime rate of cannabis abuse or

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dependence, but that figure may be too low according to NSDUH surveys.

FIGURE 12.5-2 Autoradiography of cannabinoid receptor distribution in a sagittal section of rat brain. Binding of tritiated ligand is dense in the hippocampus (Hipp), the globus pallidus (GP), the entopeduncular nucleus (EP), the substantia nigra pars reticulata (SNr), and the cerebellum (Cer). Binding is moderate in the cerebral cortex (Cx) and the caudate putamen (CP) and sparse in the brainstem (Br St) and spinal cord. (From

Howlett AC, Bidaut-Russell M, Devane WA, et al. The cannabinoid receptor: Biochemical anatomical, and behavioral characterization. Trends Neurosci. 1990;13:422

, with permission.)

Demographic Correlates

The rate of past year and current marijuana use by males was almost twice the rate for females overall among those aged 26 and older. This gap between the sexes narrows with younger users; at ages 12 to 17, there are no significant differences.

Race and ethnicity were also related to marijuana use, but the relationships varied by age group. Among those aged 12 to 17, whites had higher rates of lifetime and past-year marijuana use than blacks. Among those 17 to 34 years of age, whites reported higher levels of lifetime use than blacks and Hispanics. But among those 35 and older, whites and blacks reported the same levels of use. The lifetime rates for black adults were significantly higher than those for Hispanics.

Neuropharmacology

As stated above, the principal component of cannabis is Δ9-THC; however, the cannabis plant contains more than 400 chemicals, of which about 60 are chemically related to Δ9-THC. In humans, Δ9-THC is rapidly converted into 11-hydroxy-Δ9-THC, the metabolite that is active in the central nervous system (CNS).

A specific receptor for the cannabinols has been identified, cloned, and characterized. The cannabinoid receptor, a member of the G protein-linked family of receptors, is linked to the inhibitory G protein (Gi), which is linked to adenylyl cyclase in an inhibitory fashion. The cannabinoid receptor is found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the cerebral cortex (Fig. 12.5-2). It is not found in the brainstem, a fact consistent with cannabis's minimal effects on respiratory and cardiac functions. Studies in animals have shown that the cannabinoids affect the monoamine and γ-aminobutyric acid (GABA) neurons.

According to most studies, animals do not self-administer cannabinoids as they do most other substances of abuse. Moreover, some debate questions whether the cannabinoids stimulate the so-called reward centers of the brain, such as the dopaminergic neurons of the ventral tegmental area. Tolerance to cannabis does develop, however, and psychological dependence has been found, although the evidence for physiological dependence is not strong. Withdrawal symptoms in humans are limited to modest increases in irritability, restlessness, insomnia, and anorexia and mild nausea; all these symptoms appear only when a person abruptly stops taking high doses of cannabis.

When cannabis is smoked, the euphoric effects appear within minutes, peak in about 30 minutes, and last 2 to 4 hours. Some motor and cognitive effects last 5 to 12 hours. Cannabis can also be taken orally when it is prepared in food, such as brownies and cakes. About two to three times as much cannabis must be taken orally to be as potent as cannabis taken by inhaling its smoke. Many variables affect the psychoactive properties of cannabis, including the potency of the cannabis used, the route of administration, the smoking technique, the effects of pyrolysis on the cannabinoid content, the dose, the setting, and the user's past experience, expectations, and unique biological vulnerability to the effects of cannabinoids.

Diagnosis and Clinical Features

The most common physical effects of cannabis are dilation of the conjunctival blood vessels (red eye) and mild tachycardia.

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At high doses, orthostatic hypotension may appear. Increased appetite—often referred to as “the munchies”—and dry mouth are common effects of cannabis intoxication. That no clearly documented case of death caused by cannabis intoxication alone reflects the substance's lack of effect on the respiratory rate. The most serious potential adverse effects of cannabis use are those caused by inhaling the same carcinogenic hydrocarbons present in conventional tobacco, and some data indicate that heavy cannabis users are at risk for chronic respiratory disease and lung cancer. The practice of smoking cannabis-containing cigarettes to their very ends, so-called “roaches,” further increases the intake of tar (particulate matter). Many reports indicate that long-term cannabis use is associated with cerebral atrophy, seizure susceptibility, chromosomal damage, birth defects, impaired immune reactivity, alterations in testosterone concentrations, and dysregulation of menstrual cycles; these reports, however, have not been conclusively replicated, and the association between these findings and cannabis use is uncertain.

Table 12.5-1 DSM-IV-TR Cannabis-Related Disorders

Cannabis use disorders
Cannabis dependence
Cannabis abuse
Cannabis-induced disorders
Cannabis intoxication
   Specify if:
      With perceptual disturbances
Cannabis intoxication delirium
Cannabis-induced psychotic disorder, with delusions
   Specify if:
      With onset during intoxication
Cannabis-induced psychotic disorder, with hallucinations
   Specify if:
      With onset during intoxication
Cannabis-induced anxiety disorder
   Specify if:
      With onset during intoxication
Cannabis-related disorder not otherwise specified
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

The DSM-IV-TR lists the cannabis-related disorders (Table 12.5-1), but has specific criteria within the cannabis-related disorders section only for cannabis intoxication (Table 12.5-2). The diagnostic criteria for the other cannabis-related disorders are contained in those DSM-IV-TR sections that focus on the major phenomenological symptom—for example, cannabis-induced psychotic disorder, with delusions, in the DSM-IV-TR section on substance-induced psychotic disorder (see Table 14.4-7).

Cannabis Dependence and Cannabis Abuse

The DSM-IV-TR includes the diagnoses of cannabis dependence and cannabis abuse (see Tables 12.1-3, 12.1-4, and 12.1-5). The experimental data clearly show tolerance to many of the effects of cannabis, but the data are less supportive of the existence of physical dependence. Psychological dependence on cannabis use does develop in long-term users.

Table 12.5-2 DSM-IV-TR Diagnostic Criteria for Cannabis Intoxication

  1. Recent use of cannabis.
  2. Clinically significant maladaptive behavioral or psychological changes (e.g., impaired motor coordination, euphoria, anxiety, sensation of slowed time, impaired judgment, social withdrawal) that developed during, or shortly after, cannabis use.
  3. Two (or more) of the following signs, developing within 2 hours of cannabis use:
    1. conjunctival injection
    2. increased appetite
    3. dry mouth
    4. tachycardia
  4. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.
Specify if:
   With perceptual disturbances
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Cannabis Intoxication

The DSM-IV-TR formalizes the diagnostic criteria for cannabis intoxication (Table 12.5-2). These criteria state that the diagnosis can be augmented with the phrase “with perceptual disturbances.” If intact reality testing is not present, the diagnosis is cannabis-induced psychotic disorder.

Cannabis intoxication commonly heightens users' sensitivities to external stimuli, reveals new details, makes colors seem brighter and richer than in the past, and subjectively slows the appreciation of time. In high doses, users may experience depersonalization and derealization. Motor skills are impaired by cannabis use, and the impairment in motor skills remains after the subjective, euphoriant effects have resolved. For 8 to 12 hours after using cannabis, users' impaired motor skills interfere with the operation of motor vehicles and other heavy machinery. Moreover, these effects are additive to those of alcohol, which is commonly used in combination with cannabis.

Cannabis Intoxication Delirium

Cannabis intoxication delirium is a DSM-IV-TR diagnosis (see Table 10.2-6). The delirium associated with cannabis intoxication is characterized by marked impairment on cognition and performance tasks. Even modest doses of cannabis impair memory, reaction time, perception, motor coordination, and attention. High doses that also impair users' levels of consciousness have marked effects on cognitive measures.

Cannabis-Induced Psychotic Disorder

Cannabis-induced psychotic disorder (see Table 14.4-7) is diagnosed in the presence of a cannabis-induced psychosis. Cannabis-induced psychotic disorder is rare; transient paranoid ideation is more common.

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A 35-year-old white married male who was naïve to cannabis use was given two “joints” by a friend. He smoked the first of the two in the same manner that he normally smoked a cigarette (in about 3 to 5 minutes). Noting no major effects, he proceeded immediately to smoke the second in the same amount of time. Within 30 minutes, he began to experience rapid heartbeat, dry mouth, mounting anxiety and the delusional belief that his throat was closing up and that he was going to die. That belief induced further panic and the patient was brought to the emergency room in the midst of a psychotic experience. Reassurance that he would not die had no effect. He was sedated with diazepam and some of his anxiety diminished. He eventually went to sleep and on awakening in about 5 hours he was asymptomatic with full recall of pervious events.

Florid psychosis is somewhat common in countries in which some persons have long-term access to cannabis of particularly high potency. The psychotic episodes are sometimes referred to as “hemp insanity.” Cannabis use rarely causes a “bad-trip” experience, which is often associated with hallucinogen intoxication. When cannabis-induced psychotic disorder does occur, it may be correlated with a preexisting personality disorder in the affected person.

Cannabis-Induced Anxiety Disorder

Cannabis-induced anxiety disorder (see Table 16.7-3) is a common diagnosis for acute cannabis intoxication, which in many persons induces short-lived anxiety states often provoked by paranoid thoughts. In such circumstances, panic attacks may be induced, based on ill-defined and disorganized fears. The appearance of anxiety symptoms is correlated with the dose and is the most frequent adverse reaction to the moderate use of smoked cannabis. Inexperienced users are much more likely to experience anxiety symptoms than are experienced users.

Cannabis-Related Disorder Not Otherwise Specified

The DSM-IV-TR does not formally recognize cannabis-induced mood disorders; therefore, such disorders are classified as cannabis-related disorders not otherwise specified (Table 12.5-3). Cannabis intoxication can be associated with depressive symptoms, although such symptoms may suggest long-term cannabis use. Hypomania, however, is a common symptom in cannabis intoxication.

Table 12.5-3 DSM-IV-TR Diagnostic Criteria for Cannabis- Related Disorder Not Otherwise Specified

The cannabis-related disorder not otherwise specified category is for disorders associated with the use of cannabis that are not classifiable as cannabis dependence, cannabis abuse, cannabis intoxication, cannabis intoxication delirium, cannabis-induced psychotic disorder, or cannabis-induced anxiety disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

The DSM-IV-TR also does not formally recognize cannabis-induced sleep disorders or cannabis-induced sexual dysfunction; therefore, both are classified as cannabis-related disorders not otherwise specified. When either sleep disorder or sexual dysfunction symptoms are related to cannabis use, they almost always resolve within days or a week after cessation of cannabis use.

Flashbacks

Persisting perceptual abnormalities after cannabis use are not formally classified in DSM-IV-TR, although there are case reports of persons who have experienced—at times significantly—sensations related to cannabis intoxication after the short-term effects of the substance have disappeared. Continued debate concerns whether flashbacks are related to cannabis use alone or to the concomitant use of hallucinogens or of cannabis tainted with phencyclidine (PCP).

Cognitive Impairment

Clinical and experimental evidence indicates that the long-term use of cannabis may produce subtle forms of cognitive impairment in the higher cognitive functions of memory, attention, and organization and in the integration of complex information. This evidence suggests that the longer the period of heavy cannabis use, the more pronounced the cognitive impairment. Nonetheless, because the impairments in performance are subtle, it remains to be determined how significant they are for everyday functioning. It also remains to be investigated whether these impairments can be reversed after an extended period of abstinence from cannabis.

Amotivational Syndrome

A controversial cannabis-related syndrome is amotivational syndrome. Whether the syndrome is related to cannabis use or reflects characterological traits in a subgroup of persons regardless of cannabis use is under debate. Traditionally, the amotivational syndrome has been associated with long-term heavy use and has been characterized by a person's unwillingness to persist in a task—be it at school, at work, or in any setting that requires prolonged attention or tenacity. Persons are described as becoming apathetic and anergic, usually gaining weight, and appearing slothful.

Treatment and Rehabilitation

Treatment of cannabis use rests on the same principles as treatment of other substances of abuse—abstinence and support. Abstinence can be achieved through direct interventions, such as hospitalization, or through careful monitoring on an outpatient basis by the use of urine drug screens, which can detect cannabis for up to 4 weeks after use. Support can be achieved through the use of individual, family, and group psychotherapies. Education should be a cornerstone for both abstinence and support programs. A patient who does not understand the intellectual reasons for addressing a substance-abuse problem has little motivation to stop. For some patients, an antianxiety drug may be useful for short-term relief of withdrawal symptoms. For other patients, cannabis use may be related to an underlying depressive disorder that may respond to specific antidepressant treatment.

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Medical Use of Marijuana

Marijuana has been used as a medicinal herb for centuries, and cannabis was listed in the US Pharmacopeia until the end of the 19th century as a remedy for anxiety, depression, and gastrointestinal disorders, among others. Currently, cannabis is a controlled substance with a high potential for abuse and no medical use recognized by the Drug Enforcement Agency (DEA); however, it is used to treat various disorders, such as the nausea secondary to chemotherapy, multiple sclerosis (MS) chronic pain, acquired immune deficiency syndrome (AIDS), epilepsy, and glaucoma. In 1996, California residents approved the California Compensation Use Act that allowed state residents to grow and use marijuana for these disorders: in 2001, however, the US Supreme Court ruled 8 to 0 that the manufacture and distribution of marijuana are illegal under any circumstances. In addition, the Court held that patients using marijuana for medical purposes can be prosecuted; however, as of 2006, eleven states—Alaska, California, Colorado, Hawaii, Maine, Maryland, Montana, Nevada, Oregon, Vermont and Washington—have passed laws exempting patients who use cannabis under a physician's supervision from state criminal penalties.

In addition to the Supreme Court ruling, periodically the federal government attempts to prosecute doctors who prescribe the drug for medical use with the threat of loss of licensure or jail sentences. In a strongly worded editorial, the New England Journal of Medicine urged that “Federal authorities should rescind their prohibition of the medical use of marijuana for seriously ill patients and allow physicians to decide which patients to treat.” The editorial concluded by commenting on the role of the physician: “Some physicians will have the courage to challenge the continued proscription of marijuana for the sick. Eventually, their actions will force the courts to adjudicate between the rights of those at death's door and the absolute power of bureaucrats whose decisions are based more on reflexive ideology and political correctness than on compassion.”

Dronabinol, a synthetic form of THC, has been approved by the US Food and Drug Administration (FDA); some researchers believe, however, that when taken orally, it is not as effective as smoking the entire plant product. In 2006, regulatory officials authorized the first US clinical trial investigating the efficacy of Sativex, an oral spray consisting of natural cannabis extracts, for the treatment of cancer pain. Sativex is currently available by prescription in Canada and on a limited basis in Spain and Great Britain for patients suffering from neuropathic pain, multiple sclerosis, and other conditions.

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