Methamphetamine, developed in 1893, is a synthetic stimulant that affects the central nervous system and other major organ systems. Until the 1950s, no prescription was necessary to obtain methamphetamine or other amphetamine-containing products. Prescriptions for variants of these drugs were freely dispensed in the 1960s. Different versions of methamphetamine became popular in the 1960s, and “ice,” a smokable derivative, emerged in the late 1980s in Hawaii. The evolution of methamphetamine use since 1988 has varied. The early to mid-1990s witnessed escalating problems with methamphetamine throughout many parts of the world. In the United States the highest rates of use were in the Western region of the country, particularly in suburban and rural communities. Australia also saw increases in use and, in the same region, Southeast Asia also reported escalating prevalence. Relatively little use is reported in the United Kingdom and the rest of Europe.
One of the key enablers of the growth of methamphetamine use was the wide availability of pseudoephedrine, the primary precursor of methamphetamine, which was contained in many over-the-counter cold medications including Sudafed, Nyquil, and Claritin-D. Methamphetamine was manufactured and distributed by small homemade “kitchen chemists,” as well as larger syndicates and drug cartels. Those exposed to active methamphetamine production sites, including children, can have serious health consequences from explosions, fires, and toxic gases and wastes. Consequently, methamphetamine use and methamphetamine use disorder have had a substantial impact on the treatment, health care, criminal justice, and social welfare systems. From 2003 to 2006, many jurisdictions around the world, including the United States, imposed strict precursor control laws that restrict the retail sales of medications that contain pseudoephedrine. These efforts have substantially reduced the availability of methamphetamine and increased its price in many areas of the United States.
In the United States, from the early 1990s through 2005, numerous indicators have shown steady increases in the use of methamphetamine. However, in the early to mid-2000s, many areas in the world have started to show a reduction in people who use the drug. In 2007 in the United States, 529,000 people 12 years of age or older were current users of methamphetamine, a reduction from 731,000 in 2006. Similarly, the Community Epidemiology Work Group of the National Institute on Drug Abuse reported that methamphetamine indicators from law enforcement (arrests and seizures) and emergency room data from 20 of 22 metropolitan areas, showed either a stable or downward trend of methamphetamine use during 2006 and 2007. Similarly, treatment admissions for methamphetamine, which increased dramatically from the 1990s to 2005, showed a decline in 2006.
In other parts of the world, similar declines have been reported. In Australia, for example, there has been a decreasing trend in reported methamphetamine use since 1998, and the 2016 National Drug Strategy Household Survey shows methamphetamine at its lowest point since recording began. However, harm indicators have continued to increase, including ambulance callouts, treatment presentations, and drug-related deaths, largely due to a change in reported preference for the more potent and pure crystal form (ice) over the powdered form (speed).
Neurobiological Impact of Methamphetamine Use
Some caution is required in interpreting neurocognitive studies, as most are cross-sectional and cannot confirm whether cognitive deficits are predrug or postdrug use. In addition, some longitudinal studies show that childhood deficits in executive function can predict adolescent drug use, suggesting that some of the cognitive problems could be premorbid. Frequency, duration, and quantity of use does not appear to predict level of cognitive impairment, suggesting a vulnerability to the toxic effects of methamphetamine among some people who use it. However, regular long-term methamphetamine use has been associated with significant impairment relative to age- and education-matched controls on a range of cognitive domains and self-reported functional impairments correspond with neurocognitive deficits.
Methamphetamine has a significant impact on the structure and chemistry of the brain, largely through disruption of the dopamine system. Methamphetamine releases stores of dopamine into the synapse, and then blocks its reuptake, resulting in significantly increased levels of dopamine in the synapse of neurons, particularly in the prefrontal cortex and the limbic regions of the brain. Among people who use methamphetamine occasionally, these changes to the dopamine system correct themselves after a few days, and dopamine stores return to preuse levels once the methamphetamine has been eliminated from the body. However, among people who use methamphetamine regularly, depleted dopamine stores do not have sufficient time to replenish. Methamphetamine also increases the cytoplasmic concentration of dopamine, which promotes oxidation products that are toxic to the nerve terminals, and long-term use has been associated with a fourfold increase in risk of Parkinson disease. The neurotoxicity of methamphetamine is further accentuated by its prolonged half-life and long duration of action.
After regular use, there is evidence of damage to the structures of the dopamine system, significantly affecting executive functioning, episodic memory, and motor functioning. The magnitude of the impairments is significant compared to other drugs such as cocaine and cannabis.
For regular and dependent methamphetamine users who enter treatment, attention, memory, and executive function seem to decline further in the first 2 weeks of abstinence potentially due to the deprivation of the acute benefits of methamphetamine on cognition, sleep disturbance, or neuropsychiatric sequelae. After 6 months of abstinence, cognitive test performance is worse than in people who had either relapsed or continued to use, with little significant improvement in the first 12 months. However, one study showed some improvement after an average of 13 months, with the range up to 42 months, on some domains (motor functioning and information processing speed but not learning, memory, and executive functioning).
The level of dopamine depletion is a predictor of relapse risk. People who use methamphetamine over a long period also demonstrate attentional bias for drug-related stimuli, which has been shown to predict poorer treatment outcomes. Cognitive impairment is generally associated with poorer treatment retention.
Effects of Methamphetamine Use and Methamphetamine Use Disorder
Acute and Chronic Physical Effects of Methamphetamine Use
At low doses, euphoria, increased blood pressure, elevated body temperature, and rapid heart and breathing rates are commonly experienced acute effects of methamphetamine use. Other immediate clinical symptoms include reduced fatigue, reduced hunger, increased energy, increased sexual drive, and increased self-confidence.
At higher doses causing moderate intoxication, negative acute physiological effects can include intense stomach cramps, shaking, bruxism, disrupted menstrual cycles, formication (i.e., the sensation of insects creeping on the skin), and insomnia.
Toxicity, or overdose, can manifest in cardiovascular, central nervous system, and respiratory problems. Death is relatively rare but can occur. Cardiopulmonary consequences are among the more common health complications among people who use methamphetamine, with chest pain, hypertension, shortness of breath, tachycardia and acute coronary syndrome common in emergency room cases involving methamphetamine toxicity. Turnipseed and colleagues documented acute coronary syndrome in 25% of people who use methamphetamine regularly and admitted for chest pain, possibly resulting from myocardial ischemia and the risk of arrhythmias and cardiogenic shock. Cardiomyopathy related to methamphetamine use may be reversible; if drug use ceases. Pulmonary edema was found in over 70% of methamphetamine-related deaths. Damage to small blood vessels in the brain can result in stroke, paralysis, and brain damage. Central nervous system manifestations of methamphetamine use include agitation, violent behavior, and self-harm; coma; seizure; movement disorders; confusion, psychosis, paranoia, hypersexuality, and hallucinations; and headache. Respiratory manifestations of methamphetamine use include dyspnea (shortness of breath), wheezing, and pneumothorax. “Meth mouth” and other oral complications are common among people who use methamphetamine regularly. Like many drugs, methamphetamine reduces saliva production, increasing risk of dental caries, enamel erosion, and gum disease. Studies also suggest poor oral hygiene, teeth grinding, and jaw clenching (bruxism), and direct caustic effects of methamphetamine may also contribute to oral problems.
Compulsive skin picking can occur among people who use methamphetamine regularly, resulting in sores and ulcers. This is commonly in response to sensations of bugs crawling below the skin (formication). Formication is essentially a tactile hallucination accompanied by the delusion that insects are causing the sensation. Methamphetamine also raises body temperature and increases perspiration, and restricts blood flow to the surface of the skin, which can contribute to both skin irritation, resulting in picking, and poor skin health. Cellulitis and abscesses resulting from injection of methamphetamine may also affect skin condition.
Many people who use methamphetamine have psychiatric comorbidity, particularly psychosis, depression, and suicidal ideation. Nearly 25% of people who use methamphetamine at least monthly have experienced a clinically significant symptom of psychosis, with people who are dependent on methamphetamine three times more likely to have experienced symptoms of psychosis. There is some evidence that methamphetamine increases risk of mental health problems, rather than merely co-occurring.
Sexual Behavior and Communicable Diseases
Several surveys have shown high rates of methamphetamine use among men who have sex with men, estimated to be around 11%. Men who have sex with men and who use methamphetamine are more likely to report a greater number of sex partners, greater likelihood of sex with an HIV-infected partner, and unprotected anal intercourse than men who have sex with men who do not use methamphetamine. There is some evidence that methamphetamine use directly increases sexual risk behavior among men who have sex with men, rather than just co-occurring
A study by Rawson and colleagues found that both men and women who use methamphetamine tend to engage in frequent sexual activity, to have multiple, anonymous sexual partners, and to report low rates of condom use and high rates of unprotected anal and vaginal sex, increasing HIV risk.
Studies of people who use methamphetamine in general also show strong associations between methamphetamine use and communicable disease risk, including HIV; hepatitis A, B, C; and other sexually transmitted infections, due to risky sexual and drug use practices. Risky drug use practices among people who use methamphetamine, including injection and drug-sharing behaviors (e.g., sharing water for needle or pipe preparations and/or to rinse syringes/pipes and cotton) have also significantly increased the risk of infectious diseases.
Methamphetamine use is low among teenagers, but young people in their 20s have the highest rate of use. However, there is a worldwide downward trend in use in this group. The literature on clinical risk factors associated with methamphetamine use among youth suggests that young people who use methamphetamine have a high rate of past history of physical and sexual abuse/trauma, family history of substance use problems, and current psychological problems, including affective emotional and conduct disorders.
Research indicates that women use methamphetamine at rates similar to those of men, and suggests that compared to men, women tend to begin use earlier, are more prone to dependence, experience greater psychological distress, but also have better treatment outcomes. Almost half (46%) of national admissions to publicly funded treatment in the United States are adult women who use methamphetamine, compared with 31% of admissions for other drugs (i.e., heroin, alcohol, marijuana). A large body of literature comparing drug-dependent women with drug-dependent men indicates that women are more likely than men to report extensive histories of trauma, neglect, and abuse. Between 70% and 85% of women who develop methamphetamine dependence have reported a history of sexual and physical abuse. Such histories have been linked to an increased likelihood of domestic violence in adult relationships, chronic addiction, criminal activity, homelessness, and psychiatric cooccurring illness. Women offenders who are dependent on methamphetamine tend to have had significantly greater exposure to childhood abuse and household dysfunction than have methamphetamine-dependent men, and more often reported sexual abuse in adolescence and as an adult.
Pregnant Women and Their Children
There is limited evidence on the impact of prenatal methamphetamine exposure on the developing fetus and most is complicated by the high level of polydrug use and poor social conditions to which women who are dependent on methamphetamine may be exposed. Studies that are available suggest higher rates of preterm birth, placental abruption, cardiac anomalies, smaller head circumference, fetal distress, and fetal growth restriction. Women who use methamphetamine tend to have a lower body mass index, increasing risk of pregnancy complications, and more frequent and longer hospital stays. Women who use methamphetamine risk intrauterine growth retardation and insufficient amount of oxygen to the fetus, resulting in low birth weight, relatively small gestational size, and increased risk of neurodevelopmental problems. Around 4% of babies born to women who use methamphetamine go through withdrawal. There is some limited evidence of longer-term behavioral effects of children born to women who use methamphetamine.
The numbers of incarcerations and other problems within the criminal justice system among methamphetamine-dependent individuals have increased, which supports the strong association between methamphetamine use disorder and participation in illegal behaviors. Since 2002, the criminal justice system has been the top referral source for methamphetamine treatment. The latest national statistics indicate that a large proportion of admissions for primary methamphetamine/amphetamine use across the country was from the criminal justice system (49%), compared with 34% for other categories of drugs. In California, more than half of offenders who used drugs and were diverted from the judicial system to treatment in lieu of incarceration primarily used methamphetamine.
Offenders who are dependent on methamphetamine and who are seeking treatment may require different treatment options and plans tailored to their special characteristics. It has been suggested that drug courts may be an effective tool for promoting successful treatment outcomes for methamphetamine-dependent offenders. Drug courts are governed by a number of key components, including the integration of treatment with criminal case processing; early identification and prompt placement of eligible drug offenders into the program; provision of a continuum-of-services treatment plan; alcohol and drug testing; and ongoing judicial interaction. One study examined the treatment response of methamphetamine-dependent individuals within a drug court setting and found that drug court participation was associated with better rates of engagement, retention, completion, and abstinence compared with people who use methamphetamine who did not participate in a drug court treatment setting. Follow-up analyses revealed that participants who were enrolled in the drug court intervention used methamphetamine significantly less frequently compared with people who use methamphetamine without drug court supervision.
People With Co-occurring Disorders
Many people who are dependent on methamphetamine present for treatment with symptoms of psychiatric problems. Although distinguishing the degree to which these symptoms can be attributed to methamphetamine use versus a premorbid disorder is often difficult, the treatment is the same. Clinically, high rates of depression coupled with impulsivity put people who use methamphetamine regularly at higher risk of suicidal behavior. Some research has implicated methamphetamine-related intoxication, withdrawal, and psychiatric symptoms in elevating risk of depression and suicide.
Reducing Harms Associated With Methamphetamine Use
By far the majority of people who use methamphetamine do so infrequently and irregularly, and for a short period in their lives. More than weekly use is associated with dependence and the dependence rate among people who currently use methamphetamine is around 10%–15%, with use of the crystal form resulting in higher rates of regular use and methamphetamine use disorder. Numerous harms can affect people who use methamphetamine, whether they are dependent or not, including high rates of polydrug use, mental health problems, and acute toxicity effects.
Around 10% of people inject the drug, with the majority smoking or using other routes of administration. Clean needle programs have been shown to be effective in reducing harms associated with injecting, such as bloodborne viruses, and can be an effective way to provide health information to people who use drugs, but with low rates of injecting among people who use methamphetamine, access to this group is more difficult. Our understanding of harm reduction strategies for this group is more limited than for other drugs.
Toxicity, or overdose, can happen to anybody, including people using for the first-time and those who use regularly. Useful harm reduction messages to reduce the risk of toxicity include using only a small amount in the first instance to test the strength of the methamphetamine; avoiding mixing of methamphetamine with alcohol or other drugs; avoiding lengthy binge sessions that put the body under extreme stress; taking as many breaks as possible from using methamphetamine; and understanding the actions and effects of methamphetamine and being vigilant for early warning signs of overdose. An ambulance should be called immediately if overdose is suspected. In the event of overdose, keep the person cool (e.g., moist towels) and reduce stimulation in the environment (e.g., lower the lights, turn off music, speak quietly and calmly, and reassure the person) until the ambulance arrives.
Methamphetamine use reduces the sedating effects of alcohol, and some people use methamphetamine so they can drink more. A lethal dose of alcohol is around 4 grams of alcohol per 100 mL of blood (i.e., a blood alcohol concentration [BAC] of ≥0.4) and this does not change in the presence of methamphetamine. However, methamphetamine may mask the effects of alcohol so people feel less drunk at the same BAC. People should be informed of the risk of alcohol poisoning and should be advised to monitor their drinking to reduce that risk.
Sharing equipment increases risk of bloodborne viruses, including HIV and hepatitis. Sharing pipes to smoke crystal meth also increases potential exposure to blood through cracked or cut lips. Methamphetamine use can reduce inhibitions and increase sexual desire and risk taking. Some use methamphetamine specifically to enhance sexual encounters; for others sex may be spontaneous. This effect of methamphetamine puts people who use methamphetamine at high risk of sexually transmitted infections. People who use methamphetamine should be encouraged to use their own equipment and be prepared at all times and have access to condoms, dental dams, and lubricant.
Methamphetamine affects sleep, nutrition, and dental hygiene. Because of the stimulating effects of methamphetamine, people often have trouble maintaining a healthy sleeping pattern. Methamphetamine can keep people who use it awake for long periods of time and also disrupt the timing of sleep. People who use methamphetamine should be encouraged to go to bed and get up at regular times, even if they cannot sleep, rest without sleep still allows the body some recovery time. Lack of appetite is typical among people who use methamphetamine and they may go for several days without eating. Eating something (healthy) like a banana or a healthy shake is beneficial even if appetite is poor. Regular exercise has been shown to reduce symptoms of depression and anxiety among people newly abstinent from methamphetamine. Brushing and flossing of teeth, drinking a sufficient amount of water each day, and chewing sugar-free gum can help to reduce the risk of dental caries often associated with regular methamphetamine use.
Acute Management of Methamphetamine Problems
Managing Methamphetamine Intoxication
Acute agitation from methamphetamine intoxication is most often the condition that leads people who use methamphetamine to seek medical attention, and talking down the patient in a calm environment is a first course of action if possible. For mild agitation, administration of benzodiazepines can useful. For severe behavioral disturbances, droperidol is the recommended agent; the addition of olanzapine may also be helpful in some cases.
Managing Acute Methamphetamine Psychosis
Symptoms of methamphetamine-induced psychosis can be difficult to differentiate from those of other disorders that may predate drug use, and so a definitive diagnosis is required before commencing treatment. People who use methamphetamine regularly frequently report auditory hallucinations, which is more typical of schizophrenia, in addition to visual (flashing lights, peripheral artifacts), olfactory, and tactile sensations. Symptoms of methamphetamine psychosis include persecutory delusions, ideas of reference, hallucinations (visual and auditory, olfactory, tactile) , relative clear sensorium, stereotypy and compulsive acts, anhedonia and depression, blunt affect, poverty of speech, and being prone to excited delirium and violence.
Methamphetamine-induced acute psychosis, which generally is transient, can require use of either a benzodiazepine or an antipsychotic, both of which may be halted when acute symptoms have resolved. Low-dose antipsychotics between psychotic episodes may be useful, but there is no empirical guidance on the efficacy or appropriateness of such treatment. Such agents are contraindicated for adolescents and young adults, in whom methamphetamine-induced psychosis has increased more than fivefold from 1993 to 2002. Treatment of this population should follow the treatment described above for intoxication.
Managing Chronic Methamphetamine Psychosis
Symptoms of persistent or chronic methamphetamine psychosis are often so similar to those of schizophrenia that some clinicians may regard them as clinically equivalent conditions, and most likely in these cases methamphetamine has acted as the trigger for schizophrenia. Symptoms of schizophrenia and of persistent methamphetamine-related psychosis are not readily distinguishable, and the treatment for this condition remains basically the same as in recent practice.
Managing Methamphetamine Withdrawal
Methamphetamine withdrawal symptoms consist of severe fatigue, cognitive impairment, feelings of depression and anxiety, anergia, confusion, and paranoia. For the majority of individuals experiencing acute withdrawal/early phase abstinence, most symptoms resolve over 7–14 days. Often the physical withdrawal symptoms are mild, and rest, exercise, and a healthy diet may be a suitable management approach for most people. Those with heightened agitation and sleep disturbance may respond to benzodiazepines, but acute depression and anhedonia associated with early abstinence generally resolve without intervention. Clinicians should be aware of possible dehydration and hyperthermia. Drug craving may be addressed via behavioral treatments or periods of residential care. No pharmacotherapy has been shown to be effective in other symptoms of methamphetamine withdrawal.
Certain groups of individuals present for treatment with special concerns, as detailed below:
Women who use methamphetamine —higher rates of depression, often with histories of sexual and physical abuse; responsibilities for children.
People who inject methamphetamine —very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis.
Homeless, chronically mentally ill individuals —high levels of psychiatric symptoms at admission and during treatment.
Individuals under the age of 21 —antipsychotic medications and other mediations should be avoided or used with caution .
Men who have sex with men —at very high risk for HIV, hepatitis, and other sexually transmitted diseases.
Treatment for People Who Use Methamphetamine
A body of literature has been developed on treatment outcomes for methamphetamine use. Engagement in treatment, retention in treatment for at least 90 days, abstinence during treatment, and treatment completion have consistently been shown to successfully predict positive treatment outcomes with methamphetamine-dependent populations. One study found that people who use methamphetamine have better treatment outcomes than people who use alcohol or other drugs, demonstrating at least that treatment for this group is effective.
Risk factors for poor treatment outcomes have been identified as daily methamphetamine use, injection methamphetamine use, having less than a high school education, young age at treatment admission, having a disability, polydrug use, childhood trauma and abuse, and having an underlying psychotic disorder or major depression. Treatment participation and active recovery efforts, including frequent 12-step program participation, have been associated with successful treatment outcomes. Research has also shown that women and men respond to treatment similarly in terms of retention and completion, although women tend to have slightly better treatment outcomes, including more improved relationships with family and fewer medical problems as compared with men.
Few studies to date have examined the longer-term impact of treatment, including patterns of use and psychosocial outcomes. Despite the success in treatment, McKetin et al. showed that posttreatment relapse rates are high among people who use methamphetamine. Three months after residential treatment, for example, relapse rates were around 45%, after 1 year around 80%, and by 3 years after treatment rates of relapse were similar to those who did not enter treatment, at around 90%. In one longitudinal examination of outcomes over a 10-year period, Hser and colleagues found that quitting was predicted by current treatment and self-help participation among people who use stimulants (including people who use methamphetamine and cocaine), and that cessation of drug use was less likely among people who use methamphetamine with an early drug-use onset relative to people who use cocaine or heroin. Lubman et al. also found that engagement with posttreatment support such as SMART Recovery or other mutual aid groups increased the likelihood of abstinence.
The majority of studies investigating the effectiveness of treatment for stimulant addiction have focused on cocaine use and methamphetamine use disorder, with fewer studies on methamphetamine. Despite differences between the two stimulants in individual health, psychological, and cognitive effects, both groups tend to show comparable responses to psychosocial behavioral treatments.
Evidence-based behavioral treatment for methamphetamine-dependent individuals does work, as documented by the authors and colleagues. Treatment has profound effects, including reductions in methamphetamine use during treatment, increased treatment retention, decreased use of other drugs, decreased criminal involvement, and reduced high-risk sexual practices among gay and heterosexual people who use methamphetamine.
Cognitive Behavioral Therapy
Cognitive behavioral therapy is a short-term, focused approach to help people who use alcohol and other drugs reduce use, become abstinent, or avoid relapse. The underlying assumption is that learning processes play an important role in the development and continuation of substance use. Key elements of cognitive behavioral therapy are:
Functional analyses of substance use
Individualized training in recognizing emotional states
Exercises, such as thought stopping and managing thoughts about drug use
Coping skills, problem-solving, planning for emergencies, and refusal skills
Examination of the client’s cognitive processes related to substance use
Identification and debriefing of past and future high-risk situations
Encouragement and review of extrasession implementation of skills
Practice of skills within sessions.
Cognitive behavioral therapy promotes abstinence via skill training, including learning and practicing strategies for: (1) reducing availability and exposure to drugs and related cues, (2) fostering resolution to stop drug use by exploring positive and negative consequences of continued use, (3) self-monitoring to identify high-risk situations and to conduct functional analyses of substance use, (4) recognition of conditioned craving and development of strategies to cope with craving, (5) identification of seemingly irrelevant decisions that can culminate in high-risk situations, (6) preparing for emergencies and coping with relapse to substance use, (7) drug refusal skills, and (8) identifying and confronting thoughts about drugs. Several versions or packages of cognitive behavioral therapy–based interventions are available in manual form.
Cognitive behavioral therapy ranges from very brief to longer more intensive interventions, all within the same broad theoretical approach.
A brief therapy trialed in Australia showed significant increases in abstinence rates among people who received only two sessions of motivational interviewing and cognitive behavioral therapy compared to a self-help booklet. People who received four sessions of motivational interviewing and cognitive behavioral therapy showed the same outcomes, and also significantly reduced symptoms of depression.
A comparison of the 4-session brief intervention of Baker et al. with 12 weeks of acceptance and commitment therapy (ACT), a form of cognitive behavioral therapy incorporating mindfulness strategies, showed no significant differences. There was a high dropout in the ACT group and the average number of sessions attended was three.
Among intensive interventions, The Matrix Model offers a blended treatment approach that incorporates principles of cognitive behavioral therapy in individual and group settings, family education, motivational interviewing, and behavioral therapy; while not a pure cognitive behavioral therapy intervention, the Matrix Model employs cognitive behavioral therapy principles. This manualized therapy has been proven effective in reducing methamphetamine use during the 16-week application of the intervention, in comparison with a treatment as usual condition in a large Center for Substance Abuse Treatment–funded multisite trial. The Matrix Model also has been evaluated as a stand-alone treatment for subgroups of people who use methamphetamine (e.g., gay and bisexual men and heterosexuals) and as the behavioral treatment platform in pharmacotherapy trials for methamphetamine use disorder. The National Institute on Drug Abuse had also trialed a manualized cognitive behavioral therapy, based on coping skills therapy, of 12-sessions approach.
Also known as motivational incentives, contingency management is an intervention for drug use that employs immediate reinforcement for demonstration of desired behaviors (e.g., a drug-free urine test). Contingency management appears to produce the most robust reductions in methamphetamine use of any single technique. Roll and colleagues conducted an early multisite clinical trial in which a contingency management protocol was evaluated as an addition to an outpatient methamphetamine treatment program. Participants in the contingency management condition demonstrated a superior clinical performance on multiple outcome measures (number of methamphetamine-negative urine samples, number of consecutive weeks of abstinence, percent that completed the trial with continual abstinence). A later trial by the same group to determine whether varying the duration of contingency management produced different rates of abstinence. Participants received standard psychosocial treatment or psychosocial treatment plus either 1-month, 2-month, or 4-month of contingency management. They found that participants were more likely to remain abstinent with longer contingency management duration. Menza et al. found that among men who have sex with men and use methamphetamine, contingency management increased frequency of use, and the authors did not recommend the intervention for this group.
Medications for Treatment of Methamphetamine Use and Methamphetamine Use Disorder
Although multiple medications have been investigated for treating methamphetamine use disorder, none has shown to be sufficiently effective for widespread use. Brensilver and colleagues concluded that although some medications have shown promising results (methylphenidate, naltrexone, bupropion, and mirtazapine), no pharmacotherapy has been found to be broadly effective.
Reviews by Stoops and Rush of clinical and laboratory trials of agonist replacement medication and combination pharmacotherapies for stimulant use disorder identify potentially promising directions but no widely effective option.
A Cochrane Review of psychostimulant medications for amphetamine dependence reviewed 11 studies of dexamphetamine, bupropion, methylphenidate, and modafinil. No significant differences were found between these medications and placebo in effect on reducing amphetamine use or craving, increasing length of abstinence; the retention in treatment studies was low and a similar proportion of adverse events prompting dropout was evident for both psychostimulants and placebo groups.
Since the publication of these reviews, 12 new clinical studies have been published.
Overall, among the medications that have been subject to controlled trials, only five have more than three published reports, offering more confidence in the results: dexamphetamine, modafinil, methylphenidate, naltrexone, and bupropion. All had some studies in support and some finding no difference to placebo. Dexamphetamine may reduce the severity of dependence but not use; only short-acting dexamphetamine has been evaluated in clinical studies, and longer-acting formulations may yield different results. Methylphenidate may reduce use and craving. Modafinil may reduce use. Naltrexone may also reduce use and craving and improve retention. Bupropion may reduce use, and also has the benefit of reducing tobacco use. Bupropion may have more benefit for people whose use is lighter. Although all reported that these medications were safe and tolerable, studies tend to show a high dropout and low medication adherence.
Lower baseline amphetamine use is strongly related to benefit from treatment, suggesting that earlier intervention, at least with bupropion, may yield better results. The complex action of methamphetamine in the brain affects multiple systems, meaning a single medication may not be effective.