Numerous substances can induce psychotic states through direct neurochemical alterations, with specific mechanisms varying by drug class. Understanding these substance-induced psychotic disorders is crucial for accurate diagnosis and appropriate intervention, as treatment approaches differ significantly from primary psychotic disorders.

Dopamine-Activating Stimulants

Substances that increase dopamine transmission frequently produce paranoid psychosis.

• Amphetamines and Methamphetamine. These powerful stimulants directly force dopamine release, commonly causing paranoid delusions, tactile hallucinations (formication), and intense agitation. Chronic use can produce psychotic states indistinguishable from schizophrenia.
• Cocaine. Through dopamine reuptake inhibition, cocaine can induce transient paranoid psychosis, particularly during binge patterns of use. These symptoms demonstrate how certain drugs cause psychosis through direct alteration of reward pathway signaling.
• Synthetic Cathinones ("Bath Salts"). These potent stimulants cause severe, often prolonged psychotic episodes through combined effects on dopamine, norepinephrine, and serotonin systems.

Glutamate and Cannabinoid System Disruptors

Other substances primarily affect different neurotransmitter systems.

• NMDA Receptor Antagonists. Phencyclidine (PCP) and ketamine produce a unique psychotic state with both positive and negative symptoms through glutamate system disruption. These cases illustrate how drugs cause psychosis by altering critical excitatory neurotransmission.
• High-Potency Cannabis. THC-dominant strains, particularly with concentrations exceeding 15%, significantly increase psychosis risk through CB1 receptor activation and secondary dopamine effects. Adolescent use demonstrates particular vulnerability for how drugs cause psychosis in developing brains.
• Synthetic Cannabinoids. Compounds like Spice and K2 frequently cause severe, unpredictable psychotic reactions due to their full agonist activity at cannabinoid receptors.

Additional Psychotogenic Substances

Several other substance categories carry significant psychosis risk.

• Hallucinogens. While classic psychedelics like LSD primarily cause perceptual alterations, they can trigger persistent psychotic disorders in vulnerable individuals through 5-HT2A receptor activation.
• Corticosteroids. High-dose prednisone and related medications induce psychotic symptoms in approximately 5% of patients through unclear mechanisms, typically resolving with discontinuation.
• Anticholinergic Substances. Medications and plants with strong anticholinergic properties can cause delirium with psychotic features through acetylcholine disruption.

The duration of substance-induced psychotic symptoms varies considerably, with most resolving within days to weeks of abstinence. However, approximately 10-15% of cases transition to chronic psychotic disorders, particularly with adolescent exposure or genetic vulnerability. Clinical assessment must carefully distinguish substance-induced symptoms from primary psychiatric conditions, as this distinction carries significant implications for treatment planning and prognostic accuracy.