What drugs can cause hallucinations?

Drugs That Cause Hallucinations

Hallucinations can be caused by multiple drug classes including classic hallucinogens (LSD, psilocybin, PCP), medications with anticholinergic properties (diphenhydramine, tricyclic antidepressants), opioids (especially meperidine), benzodiazepines, corticosteroids, first-generation antipsychotics, and CNS stimulants (cocaine, amphetamines). 1

Classic Hallucinogens

Illicit hallucinogenic drugs are specifically designed to produce hallucinations and include:

• Indolealkylamines: LSD, psilocybin (magic mushrooms), psilocin, DMT, and DET produce characteristic visual hallucinations, pseudohallucinations, and illusions through serotonin 5-HT2A receptor activation 2, 3
• Phenylethylamines: Mescaline and peyote 2
• Phenylisopropylamines: MDA, MMDA, MDMA (ecstasy), MDEA 2
• Dissociative anesthetics: Phencyclidine (PCP) produces complex hallucinations analogous to paranoid psychosis through NMDA receptor blockade 2, 3

Clinical Characteristics by Drug Type

• LSD produces a combination of hallucinations, pseudohallucinations, and illusions, with effects occurring within 0.5-1 hour and commonly presenting with agitation (42.4%) and tachycardia (38.6%) 3, 4, 5
• Psilocybin causes hallucinations in 45.8% of exposures, with agitation (24.1%) and tachycardia (18.0%) being common 4, 5
• Cocaine produces simple hallucinations through dopaminergic activity 3
• PCP can cause complex hallucinations with paranoid features 3

Prescription Medications That Cause Hallucinations

Anticholinergic Medications (Highest Risk)

Anticholinergic drugs are strongly associated with delirium and hallucinations, particularly in elderly patients:

• Antihistamines: Diphenhydramine, hydroxyzine 1
• Tricyclic antidepressants 1
• Muscle relaxants: Cyclobenzaprine (due to anticholinergic effects) 1
• Urinary antispasmodics: Oxybutynin 1

Opioids

Opioids are well-known to cause hallucinations, particularly at higher doses:

• Meperidine has the highest risk among opioids for causing hallucinations 1
• All opioids can cause hallucinations, with 80-90% response rates to opioid rotation when this occurs 1
• Common opioids include morphine, codeine, methadone, oxycodone, hydrocodone, fentanyl, and heroin 2

Benzodiazepines

• Benzodiazepines can cause delirium with associated hallucinations, especially in elderly patients 1
• Critical caveat: Abrupt discontinuation of benzodiazepines can cause withdrawal hallucinations 1, 6
• Alcohol and barbiturate withdrawal can also produce hallucinations 2

Other Prescription Medications

• First-generation antipsychotics: Haloperidol and chlorpromazine may paradoxically induce hallucinations 1
• Corticosteroids are implicated as risk factors for delirium with potential hallucinations 1
• Muscle relaxant: Carisoprodol has CNS depressant properties that can lead to hallucinations, and abrupt discontinuation can cause withdrawal hallucinations 1

CNS Stimulants

Stimulants cause hallucinations through dopamine D2 receptor activation:

• Amphetamines: Dextroamphetamine, methamphetamine, amphetamine sulfate 2, 3
• Cocaine 2, 3
• Methylphenidate (Ritalin, Concerta) 2
• Dose-dependent relationship exists with amphetamines, where higher doses produce more intense hallucinatory experiences 3

Cannabinoids

• Marijuana and hashish can cause hallucinations 2

Inhalants

Volatile substances that can cause hallucinations include:

• Solvents and aerosols: glues, gasoline, paint thinner, cleaning solutions, nail polish remover, Freon 2
• Nitrites and nitrous oxide 2

Risk Factors for Medication-Induced Hallucinations

Certain patient populations are at significantly higher risk:

• Advanced age increases susceptibility due to altered pharmacokinetics and pharmacodynamics 1
• Polypharmacy, especially combinations of medications with hallucination potential 1
• Pre-existing psychiatric conditions 1
• Hepatic insufficiency increases benzodiazepine half-life 2-5 fold, increasing toxicity risk 6
• Renal impairment increases risk with renally-excreted drugs 6

Management Approach

When hallucinations are suspected to be medication-induced:

1. Identify and discontinue the offending medication when possible 1
2. For opioid-induced hallucinations: Consider opioid rotation (80-90% effective) 1
3. For antipsychotic-induced hallucinations: Switch from first-generation to atypical antipsychotics 1
4. Avoid combining multiple medications that can cause hallucinations 1
5. Use standardized assessment tools like CAM-ICU or ICDSC when medication-induced hallucinations are suspected 1
6. For acute panic reactions: May require benzodiazepine or haloperidol 3
7. Ensure adequate pain control while minimizing opioid doses, as untreated pain can also contribute to delirium 1

Critical Pitfalls to Avoid

• Never abruptly discontinue benzodiazepines or carisoprodol as withdrawal can cause hallucinations 1, 6
• Elderly patients require dose reduction to 2-2.5 mg initially for benzodiazepines to prevent oversedation and hallucinations 6
• Monitor for orthostatic hypotension when using sedating antipsychotics for hallucination management 1
• Serious effects from hallucinogens are infrequent but include hyperthermia, seizures, coma, increased creatinine, and cardiac arrest 4, 7
• Most hallucinogen exposures occur in adolescents and young adults (ages 13-29), requiring age-appropriate assessment 4