Chronic methamphetamine use can induce pathological brain changes in the brain. Users can develop thought, mood, and behavioral disorders, including psychosis. Such effects may persist even after extended abstinence. Because cognitive deficits can affect how well patients respond to treatment, interventions should include approaches that improve cognitive ability.

The basis for methamphetamine abuse/dependence lies with the basic biochemical effects of the drug on the brain, where it functions as a potent releaser of monoamines, including dopamine, in brain regions that subsume rewarding effects of various substances, including food and sexual activities. These biochemical effects occur through the binding of the drug to dopamine transporters and vesicular monoamine transporter 2.

Although FDA-approved for treating attention-deficit/hyperactivity disorder, methamphetamine is taken recreationally for its euphoric effects; however, it also produces anhedonia, paranoia, and a host of cognitive deficits and other adverse effects.

Methamphetamine causes psychiatric diseases that resemble naturally occurring illnesses but are more difficult to treat. Dependence occurs over a period of escalating use. Long-term exposure to the drug has been shown to cause severe neurotoxic and neuropathological effects with consequent disturbances in several cognitive domains.

Psychiatric symptoms. Patients under the influence of methamphetamine may present with clinical symptoms that mimic psychiatric disorders. For example, the drug can cause marked euphoria, hyperactivity, and disturbed speech patterns, thus mimicking a manic state. Patients also may present with anxiety, agitation, and irritability or aggressiveness. Although an individual may take methamphetamine for sexual enhancement, the drug can cause hyper­sexuality, which often is associated with unintended and unsafe sexual activities. These signs and symptoms are exacerbated during drug binges that can last for days, during which time large quantities of the drug are consumed.

Methamphetamine users may become preoccupied with their own thought patterns, and their actions can become compulsive and nonsensical. For example, a patient may become obsessed with an object of no specific value in his (her) environment, such as a doorknob or a cloud. Patients also may become suspicious of their friends and family members or think that police officers are after them. Less commonly, a patient also may suffer from poverty of speech, psychomotor retardation, and diminished social engagement similar to that reported in some patients with schizophrenia with deficit syndrome. Usually, acute symptoms will last 4 to 7 days after drug cessation, and then resolve completely with protracted abstinence from the drug.

Neurologic signs of methamphetamine use include hemorrhagic strokes in young people without any evidence of previous neurologic impairments. Studies have documented similarities between methamphetamine-induced neurotoxicity and traumatic brain injury. Postmortem studies have reported the presence of arteriovenous malformation in some patients with hemorrhagic strokes.

Hyperthermia is a dangerous acute effect of methamphetamine use. High body temperatures can cause both peripheral and central abnormalities, including muscular and cardiovascular dysfunction, renal failure secondary to rhabdomyolysis, heat stroke, and other heat-induced malignant syndromes. Some of the central dysfunctions may be related to heat-induced production of free radicals in various brain regions. There are no pharmacologic treatments for methamphetamine-induced thermal dysregulation. Therefore, clinicians need to focus on reducing body temperature by using cooling fans or cold water baths. Efforts should be made to avoid overhydrating patients because of the risk of developing the syndrome of inappropriate antidiuretic hormone secretion.

Chronic methamphetamine abuse

Psychosis is a long-term complication of chronic abuse of the drug. Although psychosis has been a reported complication of methamphetamine use since the 1950s, most of the subsequent literature is from Japan, where methamphetamine use was highly prevalent after World War II. The prevalence of methamphetamine-induced psychosis in methamphetamine-dependent patients varies from 13% (in the United States) to 50% (in Asia). This difference might be related to variability in the purity of methamphetamine used in different locations.

Methamphetamine users may experience a pre-psychotic state that consists of ideas of reference and delusional moods. This is followed by a psychotic state that includes hallucinations and delusions. The time it takes to develop these symptoms can vary from a few months up to >20 years after starting to use methamphetamine.^10,13 Psychosis can occur in patients who do not have a history of psychiatric illness.

The clinical presentation of methamphetamine-induced psychosis includes delusions of reference and persecutions. Paranoid delusions may be accompanied by violent behavior. Some patients may present with grandiose or jealousy delusions. Patients may experience auditory, tactile, or visual hallucinations. They may exhibit mania and logorrheic verbal outputs, symptoms consistent with a diagnosis of methamphetamine-induced mood disorder with manic features. Patients who use large daily doses of the drug also may report that there are ants or other parasites crawling under their skin (eg, formication, “meth mites”) and might present with infected excoriations of their skin as a result of attempting to remove insects. This is clinically important because penicillin-resistant bacteria are common in patients who use methamphetamine, and strains tend to be virulent.

Psychotic symptoms can last from a few days to several weeks after stopping methamphetamine use, although methamphetamine-induced psychosis can persist after long periods of abstinence. Psychotic symptoms may recur with re-exposure to the drug or repeated stressful life events. Patients with recurrent psychosis in the absence of a drug trigger appear to have high levels of peripheral norepinephrine. Patients with psychosis caused by long-term methamphetamine use will not necessarily show signs of sympathomimetic dysfunction because they may not have any methamphetamine in the body when they first present for clinical evaluation. Importantly, patients with methamphetamine-induced psychosis have been reported to have poor outcomes at follow-up. They have an increased risk of suicide, recurrent drug-induced psychosis, and comorbid alcohol abuse.

Doses required to induce psychosis vary from patient to patient and may depend on the patient’s genetic background and/or environmental conditions. Methamphetamine can increase the severity of many psychiatric symptoms and may expedite the development of schizophrenia in first-degree relatives of patients with schizophrenia.

The diagnosis of methamphetamine-induced psychosis should focus on differentiating it from schizophrenia. Wang et al found similar patterns of delusions in patients with schizophrenia and those with methamphetamine-induced psychosis. However, compared with patients with schizophrenia, patients with methamphetamine-induced psychosis have a higher prevalence of visual and tactile hallucinations, and less disorganization, blunted affect, and motor retardation. Some patients may present with depression and suicidal ideation; these features may be more prominent during withdrawal, but also may be obvious during periods of active use.

Although these clinical features may be helpful initially, more comparative neurobiologic investigations are needed to identify potential biologic differences between schizophrenia and methamphetamine-induced psychosis because these differences will impact therapeutic approaches to these diverse population groups.

Neurologic complications. Chronic methamphetamine users may develop various neurologic disorders. They may present with stereotypies involving finger movements or repeated rubbing of mouth or face, orofacial dyskinesia, and choreoathetoid movements reminiscent of classical neurologic disorders. These movement disorders can persist after cessation of methamphetamine use. In some cases, these movement abnormalities may respond to dopamine receptor antagonists such as haloperidol.

Neuropsychological findings. Chronic methamphetamine users show mild signs of cognitive decline that affects a broad range of neuropsychological functions. There are deficits in several cognitive processes that are dependent on the function of frontostriatal and limbic circuits. Specifically, episodic memory, executive functions, complex information processing speed, and psychomotor functions all have been reported to be negatively impacted.

Methamphetamine use often results in psychiatric distress that impacts users’ interpersonal relationships. Additionally, impulsivity may exacerbate their psychosocial difficulties and promote maintenance of drug-seeking behaviors. Cognitive deficits lead to poor health outcomes, high-risk behaviors, employment difficulties, and repeated relapse.

Partial recovery of neuropsychological functioning and improvement in affective distress can be achieved after sustained abstinence from methamphetamine, but recovery may not be complete. Because cognitive dysfunction can influence treatment outcomes, clinicians need to be fully aware of the cognitive status of those patients, and a thorough neuropsychological evaluation is necessary before initiating treatment.