Methamphetamine Abuse: Consequences and Treatment

Jun 01, 2007

Methamphetamine (MA) abuse is not a new problem in the United States, but the current epidemic is more widespread and presents with more pernicious consequences than in the past. MA, frequently called "speed," "crystal," "crank," "ice," or "tina," is a potent psychostimulant that can be swallowed in pill form or administered via intranasal, intravenous, or smoking route.

Methamphetamine (MA) abuse is not a new problem in the United States, but the current epidemic is more widespread and presents with more pernicious consequences than in the past. MA, frequently called "speed," "crystal," "crank," "ice," or "tina," is a potent psychostimulant that can be swallowed in pill form or administered via intranasal, intravenous, or smoking route.

Epidemiologic data on the extent and consequences of MA use among increasingly involved populations-women, men who have sex with men, rural residents, and youths-indicate a need for additional efforts to effectively treat persons who use MA and those with problems related to MA use. Recent research has influenced the way we think about MA and the related medical consequences of its use. For example, neuroimaging research and new information on the cellular mechanisms of MA's action indicate new targets for the development of pharmacotherapies. While pharmacotherapy research is still in a formative stage, behavioral therapies that have been developed for the treatment of stimulant use disorders have considerable empiric support.

EPIDEMIOLOGY
Geographic spread

In the late 1960s, MA became known as a dangerous drug, creating substantial health threats to persons who used it and prompting the drug prevention slogan "speed kills." During the late 1970s and early 1980s, MA use in the United States was, for the most part, limited to several cities in California (primarily San Francisco and San Diego), since the primary manufacturers and suppliers of MA at the time were members of Hells Angels and other motorcycle gangs that were headquartered in California.1

In the mid-1980s, MA use escalated dramatically in Honolulu as "ice," a smokable form of the drug, was imported to the island from the Philippines.2 In the 1990s, MA spread throughout the western states and began to surface in substantial amounts in the Midwest (eg, Iowa and Missouri).3

Today, MA has emerged as one of the most dangerous "homegrown" drugs in the country, and its use and dependence pose significant public health challenges.4 MA is the most widely used illicit drug in the world after cannabis,5 and it has become established as the most dominant drug problem in many western and midwestern states, severely impacting rural and suburban areas, as well as small to mid-sized cities.

MA's availability and use have migrated from the western states to mid-America and the southeastern states.6 In 2003, 14 states cited more admissions to substance abuse treatment programs resulting from MA use than from heroin and cocaine use combined; nationally, admissions related to MA use increased 10% between 2002 and 2003 (from 105,754 to 116,604).7

High-risk populations

Women use MA at rates almost equal to those of men. While the use of other major illicit drugs is characterized by ratios such as 3:1 (heroin) or 2:1 (cocaine) for men to women, in many large data sets, the ratio for persons who use MA approaches 1:1. Surveys among women suggest that they are more likely than men to be attracted to MA for reasons such as weight loss and for the control of symptoms of depression. More than 70% of women who use MA report histories of physical and sexual abuse, and women are more likely than men to present for treatment of MA abuse with greater psychological distress.8

MA use is also associated with high-risk sexual behaviors, which has been shown to be a major factor in HIV transmission among men who have sex with men.9 Research by Shoptaw and colleagues10 showed that MA use poses the biggest threat of producing a renewed spread of HIV in the gay community because of the increase in high-risk sexual behaviors. The researchers have developed treatment programs for this group that have shown the successful treatment of MA dependence to be an extremely effective HIV prevention strategy.

There appears to be an increase in MA use among adolescents in some parts of the country, particularly on the West Coast. Phoenix House, a large treatment center for adolescents in Southern California, reported that MA use accounted for almost half of the center's admissions in 200511; there was particular concern in the center regarding MA use among young women.

In another report on MA use among adolescents, 63% of girls who were admitted to substance abuse treatment received a primary diagnosis of MA abuse/dependence while only 36% of boys received MA abuse/dependence as a primary diagnosis.12

Acute and Chronic Effects

The euphoric feelings (described as a "high" or "rush") that accompany the use of MA appear to be the result of dopamine release in the reward/pleasure centers of the brain. The timing and intensity of such stimulant effects depend largely on the drug's route of administration. The effects of the drug are almost instantaneous when it is smoked or injected.

Conversely, it takes about 5 minutes after snorting MA or 20 minutes after ingesting it for the onset of such effects to occur. The half-life of MA is about 8 to 12 hours, and the acute effects of MA occur during this period.

Immediate physiological changes associated with MA use are similar to those that are produced in the fight-or-flight response: that is, increased blood pressure, body temperature, heart rate, and respiration rate. Even small doses of MA can increase wakefulness, attention, and physical activity and can decrease fatigue and appetite.

Negative physical effects of MA use typically include hypertension, tachycardia, headaches, cardiac arrhythmia, and nausea; the psychological impact is manifested by increased anxiety, insomnia, aggressive and violent tendencies, paranoia, and visual and auditory hallucinations. High doses can elevate body temperature to dangerous and sometimes lethal levels, causing convulsions, coma, stroke, vegetative states, and death.

In persons who use MA for prolonged periods, tolerance for the drug frequently develops, along with escalating dosage levels and dependence. Persons who chronically use MA can be anxious and exhibit violent behavior, confusion, and insomnia, which is a result of the direct effects of the drug plus the consequences associated with sleep deprivation, since persons who use MA often report sleeplessness for days and even weeks. When they are in a state of prolonged MA use and sleep deprivation, users commonly experience a number of psychotic features, including paranoia, auditory hallucinations, mood disturbances, and delusions. One of the most regularly reported features associated with MA use is "formication," the sensation of insects creeping on the skin. The paranoia that accompanies MA use can result in homicidal or suicidal thoughts.

In a recent sample of MA users who entered treatment in the Midwest, Hawaii, and California, the rate of hepatitis C was 22%. Of those administering MA via injection, 45% tested positive for hepatitis C.13 Clearly, there needs to be a stronger effort to inform persons about behaviors that expose them to hepatitis C (through blood-to-blood transfers) and to treat and prevent MA use and abuse. See the Table for a summary of MA's adverse effects.

Mechanisms of action

MA inhibits the reuptake of released dopamine; the drug is taken into the dopaminergic neurons and exerts its action intracellularly. MA causes the docking of dopamine-containing vesicles to the cell membrane, and the leakage of dopamine into the synaptic cleft increases its concentration. MA thus increases the cytoplasmic concentration of dopamine, which undergoes oxidation and produces oxidation products such as free radicals, peroxides, and hydroxyquinones, which are toxic to nerve terminals.14-16 This neurotoxicity is compounded by MA's prolonged half-life and duration (8 to 12 hours).

Effects on neuronal circuits

Findings from neuroimaging studies show that in persons who use MA, changes occur in the limbic and in the frontal and prefrontal cortical areas, further implicating chronic MA use in the failure of the frontal and prefrontal cortex to inhibit the limbic areas. Imaging research involving persons who are newly abstinent from MA17,18 has documented deficits in inhibitory control mechanisms, which can affect decision making and perhaps increase inhibitory control of the frontal lobe over the limbic reward circuitry.

TREATMENT
Intoxication

Treatment for acute intoxication does not always require medication. Instead, patients can be reassured of the imminent passage of symptoms and placed in a dark, quiet environment. When symptoms are severe, medications such as the benzodiazepines and/or a high-potency antipsychotic can be administered. Haloperidol (5 mg) administered orally or parenterally in repeated doses can be used, often in combination with 1 to 2 mg of lorazepam and 1 mg of the antidyski- netic benztropine. Droperidol has been shown to achieve more rapid and better sedation scores than lorazepam, requiring fewer repeated doses.19

Withdrawal

Withdrawal symptoms within 2 weeks after a person's last MA use includes unique psychiatric and physical symptoms (eg, anhedonia is a key symptom of acute withdrawal20). To help patients combat these symptoms, rest, exercise, and a healthy diet may be appropriate.21 No medications are available yet to address severe craving and the attendant risk of relapse.

Psychosis

Strategies used for the treatment of acute intoxication are also applicable to treatment of acute MA-induced psychosis. In US patients, psychosis is generally reported to be transient.

The appropriate duration of antipsychotic medication administration for the treatment of acute psychosis remains an issue. Administering low-dose antipsychotics between psychotic episodes may have some merit, but this is still open to question.22

Because the numbers of young users and the appearance of psychosis from MA use in adolescents are increasing (greater than 500% increase from 1993 to 200223), it is important to note that exposure to antipsychotics may have consequences in the maturing brain. Empiric support for the use of antipsychotics for the treatment of acute or chronic MA- induced psychosis is lacking.

Behavioral treatment

Several behavioral therapies have been evaluated for the treatment of persons who are dependent on MA in multisite controlled randomized clinical trials and have shown evidence of efficacy.

The Matrix Model is a manualized behavioral therapy for MA dependence that proved effective in a large randomized clinical trial.24 The Matrix Model is a synthetic treatment approach that incorporates principles of social learning, cognitive-behavioral therapy (CBT), family education, motivational interviewing, and behavioral therapy. The Matrix Model has been modified and used to evaluate subgroups of MA abusers (gay and bisexual men)10 and was used as the behavioral treatment platform in pharmacotherapy trials for MA dependence.25

Contingency management (CM) entails the provision of reinforcements/ rewards for desired behaviors/performance (eg, drug-free urine test). Roll and associates26 recently conducted a multisite clinical trial in which a CM protocol was evaluated when added to an outpatient MA treatment program. Participants receiving treatment with the CM protocol demonstrated superior clinical performance on multiple outcome measures (number of MA-negative urine samples, number of consecutive weeks of abstinence, percentage of participants who completed the trial with continued abstinence).

In addition to the controlled evaluations of behavioral treatments in persons dependent on MA, there have been trials conducted in which CM and CBT27 and the Matrix Model28 have been evaluated with samples of persons who use MA and cocaine. In all cases, the treatment response of the 2 groups of stimulant users was indistinguishable. Similarly, in 2 data sets in which persons who used MA and cocaine were treated side-by-side in standard community treatment programs, the response of the 2 groups was comparable on all measures.29,30

It appears highly likely that persons who use MA and those who use cocaine respond quite similarly to psychosocial interventions, and treatments that produce positive outcomes for persons who use cocaine are likely to be equally effective for those who use MA. This conclusion would support the use of approaches such as the community reinforcement approach, 12-step facilitation therapy, and CBT. In addition, although there have been no controlled trial data to assess motivational interviewing/motivational enhancement therapy to date, this approach is recommended in the treatment of persons who use MA.

Medications

Efforts to develop and evaluate medications that may be useful in the treatment of MA dependence address the postulated mechanisms of action of MA at the cellular-molecular level and at the neuronal circuit level in order to amend dysregulation and inhibit relapse. Bupropion and modafinil have exhibited some potential as adjuncts to behavioral therapy in treating MA dependence. Other medications (gabapentin, lobeline, vigabatrin, ondansetron) are under consideration, but evidence of their efficacy is lacking. Also under consideration is agonist therapy (ie, with "replacement/substitution" medication).31

Bupropion. In a recent trial, treatment with bupropion was associated with a reduction in MA use; bupropion produced significant reductions in MA use compared with placebo treatment (P = .03) in subjects who reported using MA fewer than 18 days in the past month.25 Seventy-two participants were randomized to placebo and 79 were randomized to sustained-release bupropion 150 mg bid. Bupropion in combination with behavioral group therapy proved effective for the treatment of participants with low to moderate MA dependence (defined as using fewer than 18 days in the month before intake). Bupropion reduced the subjective effects of MA and cue-induced cravings.20

Modafinil. Modafinil is a non-amphetamine stimulant that is approved for managing symptoms of narcolepsy. The effects of modafinil may relieve acute depression accompanying recent abstinence,32 inhibiting relapse. As an adjunct to a behavioral therapy such as CBT, modafinil has been shown to significantly improve performance on cognitive tasks and executive system functioning33 in persons with schizophrenia34 and in persons with HIV.35 Modafinil also improves impulse control.36

Conclusions

MA use in the United States has created significant public health and safety concerns. Women, men who have sex with men, rural residents, and adolescents are at elevated risk for becoming addicted to this drug. Use of MA causes significant damage to the body and the brain. Treatment for persons who use MA is available, has been proved empirically effective, and works in real-world clinical settings. Notably, the Matrix Model and CM have demonstrated efficacy.

Other psychosocial approaches with empiric support for persons who abuse cocaine are likely to be similarly effective with persons who are dependent on MA. Several studies have provided support for the use of bupropion, and there is great interest in modafinil as pharmacotherapy for persons who use MA.

References:

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