Amphetamine-induced Psychosis

A Separate Diagnostic Entity or Primary Psychosis Triggered in the Vulnerable?

Jørgen G Bramness; Øystein H Gundersen; Joar Guterstam; Eline B Rognli; Maija Konstenius; Else-Marie Løberg; Sigrid Medhus; Lars Tanum; Johan Franck

Disclosures

BMC Psychiatry. 2012;12(221) 

In This Article

Background

Amphetamine and methamphetamine (hereafter amphetamines) can prolong wakefulness, increase focus and feelings of energy as well as decrease fatigue. They can produce euphoria, induce anorexia, and be used to treat narcolepsy and attention deficit/hyperactivity disorder (ADHD). Adverse effects include anxiety, aggression, paranoia, hyperactivity, reduced appetite, tachycardia, increased breathing rate, dilated pupils, increased blood pressure, headache, insomnia, palpitations, arrhythmia and others.[1]

Amphetamines inhibit dopamine reuptake by interacting with the dopamine transporter (DAT), thereby increasing the concentration of dopamine in the synaptic cleft.[2] Amphetamines also interact with the vesicular monoamine transporter 2 (VMAT2), leading to increasing amounts of dopamine in the cytosol, a possible mechanism of action for the neurotoxicity of amphetamines. Neurotoxic effects are seen also in serotonergic and noradrenergic neurons.

Amphetamines are highly addictive drugs. Both amphetamine and methamphetamine act directly on the mesolimbic dopaminergic "reward system"[3] by inducing release of dopamine, and to some extent norepinephrine, in the synaptic clefts of the Nucleus Accumbens (NAc) and other terminal areas provoking a euphoric state, but also addiction.

Abuse of amphetamines is widespread in the general population.[4–9] It is also common among psychiatric patients,[10–11] where a high percentage test positive for amphetamines.[12]

There is overwhelming evidence that patients with psychotic disorders have an increased vulnerability to compulsive use of drugs of abuse,[13–14] including psycho stimulants like amphetamines.[15] This may be especially true for patients with schizophrenia like disorders.[16] There may be several explanations for this increased co morbidity, but there is convincing evidence from animal studies that this may be due to shared vulnerabilities for both psychosis and drug use disorders.[17] These animal studies also point to possible neural mechanisms explaning the increased co morbidity.[18]

The association between amphetamine use and psychosis has received much attention,[19] but several questions about this complex relationship remain unanswered. In the following, we review some of these questions and propose a new model for understanding the relationship between amphetamine use and psychosis.

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