Amphetamine-Induced Psychosis

Amphetamines are stimulants of the central nervous system that are prescribed to treat attention-deficit/hyperactivity disorder (ADHD), obesity, and narcolepsy. In addition to their prescribed usage, amphetamines are sometimes used to boost athletic, cognitive, and creative performance.

Commonly encountered amphetamines include amphetamine itself, methamphetamine, MDMA (also known as Ecstasy), phentermine, and ephedrine, among many others. According to the National Survey on Drug Use and Health from 2012, more than 12 million Americans have used some form of amphetamines. Amphetamines are also used recreationally as they produce euphoria, especially in higher doses.

Though most people recover from amphetamine induced psychosis, the presence of several factors make it less likely that a person will fully recover, including long-term usage, co-occurring substance use disorders, genetic predisposition to psychosis, and psychiatric comorbidities. It is these higher doses that make it much more likely that a person using amphetamines will experience symptoms of psychosis.

Psychosis refers to the state of being disconnected from reality and is the trademark symptom of disorders such as schizophrenia. Examples of psychotic symptoms include paranoia, delusions, agitation, ideas of reference (this refers to when people experience coincidence or routine events as having special significance for them, e.g., believing that special messages are being broadcast to them from a highway billboard or through a radio host), and hallucinations.

Hallucinations can involve any of the senses—auditory, visual, tactile (touch), olfactory (smell), or gustatory (taste)—and are often among the more obvious and distressing signs of psychosis. Some classic examples of amphetamine-induced psychosis symptoms include the perception of seeing insects and of feeling them crawling on or underneath the skin. These perceptions are referred to as formacanopia and formication, respectively.

Amphetamine-induced psychosis belongs to a larger family of mental health conditions called substance-induced psychotic disorders. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (commonly known as the DSM-5) provides the gold standard for describing and diagnosing amphetamine-induced psychosis. According to the DSM-5, a substance-induced psychotic disorder is present under the following circumstances:

• Prominent hallucinations or delusions are present.
• Hallucinations or delusions develop during, or soon after, intoxication or withdrawal from a substance or medication known to cause psychotic symptoms.
• Psychotic symptoms are not actually part of a psychotic disorder (such as schizophrenia, schizophreniform disorder, or schizoaffective disorder) that is not substance-induced.
• Psychotic symptoms do not only occur during a delirium.

To understand how and why the symptoms of psychosis develop during or after amphetamine use, it is important to understand the basic mechanism of amphetamines on the central nervous system (CNS). Like all stimulants, amphetamines increase the activity of the sympathetic nervous system, which is responsible for the “fight or flight” response that all animals experience to aid survival. This confers the treatment benefits of stimulants, as it results in increased focus and alertness, improved concentration, higher energy levels, and higher rates of metabolism. Amphetamines in particular accomplish these benefits by increasing the availability of the chemical messengers called monoamines to the CNS, allowing acceleration or amplification of the processes that the CNS normally controls. The primary monoamines that are amplified by amphetamines are dopamine and norepinephrine.

However, many structures of the midbrain and forebrain that are responsible for both emotional regulation and for processing information about the external environment are sensitive to changes in dopamine levels. Psychotic symptoms can occur when such information is either corrupted, overloaded, or poorly integrated, and researchers generally believe this phenomenon occurs when excess dopamine over stimulates the dopamine receptors of the midbrain and forebrain. The primary evidence for this mechanism of action is that most antipsychotic medications block or limit the activity of these dopamine receptors.

Symptoms of amphetamine-induced psychosis closely parallel those of organic psychotic disorders like schizophrenia, and often have to be treated in highly controlled settings, such as a medical hospital’s emergency department or in an inpatient psychiatric hospital. Usually, symptoms from this type of psychosis subside within one to two weeks of initiating treatment. If the symptoms do not abate, then other diagnoses need to be considered.

Not all instances of amphetamine-induced psychosis are severe enough to warrant intervention, and symptoms often subside shortly after drug usage has ceased; however, treatment of this type of psychosis is recommended if symptoms are distressing or obviously disruptive. Several different antipsychotic medications, almost all of which limit the activity at one or both types of dopamine receptors in the brain, can be used to treat. All antipsychotic medications have roughly equal levels of effectiveness (except for the highly effective but side-effect laden medication clozapine, the use of which is generally reserved for cases of organic psychotic disorders that don’t respond to other antipsychotics), so treatment is often governed by the side effect profile of the selected medication.

A common feature of first-generation (also known as “typical”) antipsychotics, which block the activity of the dopamine type 1 receptor in the brain, is the tendency to create movement disturbances like motor tics or other involuntary movements. For this reason, second-generation (also known as “atypical”) antipsychotics, nearly all of which preferentially block the activity of the dopamine type 2 receptor, are often chosen. For example, the second-generation antipsychotics olanzapine and quetiapine are often selected to treat amphetamine-induced psychosis because their common side effect of sedation helps counter the agitation of psychosis. Second-generation antipsychotics do have a tendency to cause weight gain over time, but this is less worrisome because of the short course of treatment usually required to treat amphetamine-induced psychosis.

Though amphetamine-induced psychosis usually is eliminated by the cessation of drug use or by the treatment of psychotic symptoms, occasionally such psychosis can last for weeks, months, or even years beyond its initial onset. When amphetamine-induced psychosis does persist beyond treatment or stopping amphetamine use, several potential situations must be considered. The presence of any of the following conditions can increase the risk of amphetamine-induced psychosis becoming permanent:

• Meeting criteria for severe stimulant use disorder in the DSM-V makes it far more likely that a person will develop psychosis when taking any amphetamines and have worse long-term behavioral outcomes.
• At least seven genes are associated with the potential for amphetamine use to trigger psychosis; moreover, when psychosis does develop, the presence of these genes predicts poorer outcomes.
• Using amphetamine or other substances has the potential to “unlock” a person’s genetic predisposition for organic psychotic disorders, like bipolar disorder or schizophrenia—this is also referred to by the terms sensitization, priming effect, and reverse tolerance.
• The DSM-5 outlines criteria for considering psychotic symptoms to be part of a primary psychotic disorder, even if psychosis develops while using methamphetamine: (1) symptoms are substantially in excess of what would be expected given the type or amount of substance used or the duration of use; (2) there is a history of psychotic episodes that are not substance-related; (3) psychotic symptom onset precedes the onset of substance use; (4) psychotic symptoms persist for at least one month after the cessation of intoxication or acute withdrawal.
• Those with a previous history of primary psychotic symptoms (as a result of schizophrenia, bipolar disorder, or related conditions) before ever using amphetamine display a greater likelihood of experiencing persistent psychotic symptoms.
• Research based on studies of psychosis development in users of methamphetamine suggests that at least two types of amphetamine-induced psychosis exist, including a more severe “delayed lasting type” with symptoms that persist a month or more after stopping amphetamine use. This form is associated with using methamphetamine for five years or longer.

Researchers believe that, in the long term, the most effective way to treat amphetamine-induced psychosis is to treat the underlying stimulant use disorder. Unlike opioid or alcohol use disorders, however, no medications have been approved to help treat stimulant use disorders, though several have been studied.

Psychotherapy is the treatment of choice for stimulant disorders. The well-validated treatment approach cognitive behavioral therapy (CBT) is one of the primary types of therapy utilized, demonstrating excellent efficacy in reducing methamphetamine usage. CBT is a treatment method that helps people change patterns of unhealthy behavior by examining the situations, thoughts, feelings, assumptions, and actions that lead to those behaviors. It can be performed by an individual with a therapist, in a group setting, or alone with a textbook.

If you suspect that you are or a loved one is experiencing amphetamine-induced psychosis, residential treatment for substance-induced psychosis is the safest and most accurate way to properly diagnosis and treat the psychotic symptoms and address any underlying co-occurring mental health disorders.