Numerous substances can induce transient or persistent psychotic states through various neurochemical mechanisms. These drug-induced psychoses typically result from direct alterations in dopamine, glutamate, or serotonin systems, though individual vulnerability varies significantly based on genetic factors, dosage, and duration of use.

Primary Dopamine-Activating Substances

Stimulants that increase dopamine transmission frequently produce paranoid psychosis.

• Amphetamines and Methamphetamine. These directly force dopamine release, commonly causing paranoid delusions, formication (sensation of insects crawling under skin), and auditory hallucinations with chronic use.
• Cocaine. Particularly in binge patterns, cocaine blocks dopamine reuptake and can produce transient psychotic states indistinguishable from acute paranoid schizophrenia.
• Prescription Stimulants. When misused or taken at high doses, medications for ADHD like methylphenidate and adderall can cause psychosis through similar dopaminergic mechanisms.

Glutamate and Serotonin System Disruptors

Other substances act through non-dopamine pathways to alter reality perception.

• Phencyclidine (PCP) and Ketamine. These NMDA receptor antagonists create a unique psychotic state with both positive and negative symptoms, closely resembling schizophrenia's neurochemical profile.
• Cannabis with High THC Content. Modern cultivars with 15-25% THC significantly increase psychosis risk, particularly in adolescent users, through combined CB1 receptor activation and subtle dopamine elevation.
• Classic Hallucinogens. LSD and psilocybin primarily act on serotonin 5-HT2A receptors, which can cause psychosis-like states during acute intoxication and occasionally trigger persistent psychotic disorders in predisposed individuals.

Medication-Induced Psychotic Reactions

Several therapeutic agents carry psychosis as a potential adverse effect.

• Corticosteroids. High-dose prednisone and related medications frequently induce manic and psychotic states through unclear mechanisms, typically resolving upon discontinuation.
• Antiparkinsonian Medications. Dopamine agonists used for Parkinson's disease commonly produce visual hallucinations and paranoid ideation, particularly in elderly patients.
• Certain Antibiotics. Fluoroquinolones and other CNS-penetrating antibiotics rarely cause psychosis as an idiosyncratic reaction, though the mechanism remains poorly understood.

The duration and severity of substance-induced psychotic episodes vary considerably. While most resolve with abstinence and supportive care, approximately 10-15% of cases transition to chronic psychotic disorders, particularly in individuals with genetic vulnerability or adolescent exposure. Clinical assessment must carefully distinguish substance-induced symptoms from primary psychiatric disorders, as treatment approaches differ significantly. Understanding which drugs can cause psychosis enables better prevention strategies and informed clinical decision-making regarding substance use in vulnerable populations.