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.

Youth

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.

Women

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.

Criminal Offenders

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.

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:

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  Women who use methamphetamine —higher rates of depression, often with histories of sexual and physical abuse; responsibilities for children.

  
  
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  People who inject methamphetamine —very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis.

  
  
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  Homeless, chronically mentally ill individuals —high levels of psychiatric symptoms at admission and during treatment.

  
  
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  Individuals under the age of 21 —antipsychotic medications and other mediations should be avoided or used with caution .

  
  
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  Men who have sex with men —at very high risk for HIV, hepatitis, and other sexually transmitted diseases.

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:

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  Functional analyses of substance use

  
  
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  Individualized training in recognizing emotional states

  
  
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  Exercises, such as thought stopping and managing thoughts about drug use

  
  
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  Coping skills, problem-solving, planning for emergencies, and refusal skills

  
  
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  Examination of the client’s cognitive processes related to substance use

  
  
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  Identification and debriefing of past and future high-risk situations

  
  
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  Encouragement and review of extrasession implementation of skills

  
  
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  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.

Contingency Management

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.