Street Drugs That Cause Mania

Amphetamine (including methamphetamine) and cocaine are the street drugs most commonly associated with causing mania. 1, 2, 3

Primary Causative Agents

Amphetamine and methamphetamine are definitively established as causing manic symptoms, with methamphetamine being a central nervous system stimulant that produces euphoria, heightened attention, and increased energy that can progress to full manic episodes. 1, 4
Methamphetamine use produces a rapid, pleasurable rush followed by euphoria, heightened attention, and increased energy, which can manifest as clinical mania with increased activity, rapid speech, elevated mood, and insomnia. 4, 2
The mechanism involves effects on monoaminergic systems, particularly dopaminergic pathways, which are central to the pathophysiology of mania. 2
Chronic methamphetamine use is associated with neurologic and psychiatric symptoms including psychosis, paranoia, hallucinations, and manic-like presentations. 4, 5

Cocaine is recognized as a street drug capable of inducing mania, presenting with a clinical picture that includes increased activity, rapid speech, elevated mood, and insomnia. 6, 3
Cocaine's effects on sodium channels and subsequent ischemia can contribute to both acute manic presentations and longer-term mood destabilization. 6
The combination of cocaine with other substances (including methamphetamine, benzodiazepines, or cannabis) can worsen psychiatric presentations. 6

Phencyclidine (PCP) is probably capable of inducing mania, though the evidence is less scientifically secure than for amphetamines and cocaine. 1
Hallucinogens (including LSD and ecstasy/MDMA) commonly induce manic syndromes through their serotonergic effects. 6, 2

The most common characteristics of drug-induced manic episodes include increased activity, rapid speech, elevated mood, and insomnia. 2
Patients may present with psychosis, agitation, anxiety, paranoia, and hallucinations that accompany the manic symptoms. 4, 5
Mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity can occur, particularly with serotonergic drugs like ecstasy. 6

Accurate and complete history of both the present episode and past drug use is most valuable in differentiation, along with mental status examination, physical examination, and selected laboratory tests including urine drug screening. 3
Patients who develop drug-induced mania often have a prior history, family history, or current symptoms of mood disturbance, making them more vulnerable to substance-induced episodes. 2
It is advisable to withhold psychiatric drug therapy, if possible, until the initial evaluation is completed, as it may obscure the diagnosis. 3

Management involves discontinuation of the suspected drug (if medically possible) and treatment of manic symptoms with antipsychotic drugs or lithium. 1
Discontinuation of the inciting drug and treatment with neuroleptic agents are equally efficacious, while lithium treatment is less effective for acute drug-induced mania. 2
For cocaine-induced presentations, troponin measurement is essential as correlation of myocardial infarction with ECGs is low in this population, and risk stratification using established criteria (ECG changes and troponin) is critical. 6

Cocaine prolongs the QT interval for several days after ingestion, requiring avoidance of other QT-prolonging medications during this time. 6
Continuous cardiac monitoring should be considered for patients with cocaine-induced chest pain or significant electrolyte abnormalities. 6

Failing to obtain a complete substance use history can lead to misdiagnosis of primary bipolar disorder when the presentation is actually substance-induced. 3
Premature initiation of mood stabilizers before confirming substance-induced etiology may commit patients to unnecessary long-term treatment. 3
Overlooking polysubstance use (particularly combinations of stimulants with alcohol, benzodiazepines, or other CNS depressants) can complicate both diagnosis and treatment. 6
Missing comorbid substance use disorders in patients with established bipolar disorder, as stimulants can trigger manic episodes even in patients on maintenance therapy. 7