What is the effect of marijuana on antipsychotic (anti-psychotic) medications, such as olanzapine (olanzapine), risperidone (risperidone), or quetiapine (quetiapine)?

Effect of Marijuana on Antipsychotic Medications

Marijuana use can reduce the effectiveness of antipsychotic medications, potentially leading to treatment resistance and poorer clinical outcomes in patients with psychotic disorders. 1

Interactions Between Marijuana and Antipsychotics

Reduced Treatment Efficacy

• Cannabis use is associated with an increased number of unique antipsychotic medications prescribed, suggesting reduced response to initial antipsychotic treatment 1
• Patients with first-episode psychosis who use cannabis have higher rates of hospital admissions and longer hospital stays, partly mediated by reduced antipsychotic effectiveness 1
• Cannabis contains THC (delta-9-tetrahydrocannabinol), which at high doses may be associated with psychosis, potentially counteracting the therapeutic effects of antipsychotics 2

Neurological and Psychiatric Effects

• The combination of cannabis with antipsychotics like olanzapine and risperidone can increase the risk of central nervous system (CNS) depression 3
• There have been reports of delirium with anticholinergic symptoms when cannabis is used alongside combinations of antipsychotics (e.g., olanzapine and paliperidone) 3
• Cannabis use in early youth is associated with neuropsychological decline and elevated risk for psychotic disorders in adulthood 2

Specific Antipsychotic Interactions

Olanzapine

• Olanzapine has high central anticholinergic activity, which may compound cognitive effects when combined with cannabis 2
• Case reports indicate that combining olanzapine with cannabis can lead to delirium and anticholinergic symptoms 3
• Olanzapine is associated with significant weight gain, which may be affected by cannabis use patterns 2

Risperidone

• No significant difference has been found between olanzapine and risperidone in terms of efficacy on psychotic symptoms or effect on cannabis use in first-episode patients with co-occurring cannabis use disorders 4
• Both olanzapine and risperidone show similar improvements in subjective well-being and similar decreases in craving for cannabis in patients with schizophrenia who use cannabis 5

Quetiapine

• Like olanzapine, quetiapine has high central anticholinergic activity, which may interact with cannabis effects 2
• Quetiapine is sedating, which could compound the sedative effects of cannabis 2

Clinical Implications

Dosing Considerations

• Some studies suggest that cannabis use does not significantly impact the doses of antipsychotics required during acute exacerbations of schizophrenia or schizoaffective disorder 6
• However, cannabis users often require multiple antipsychotic medication trials, suggesting treatment resistance 1

Monitoring Recommendations

• Patients using both cannabis and antipsychotics should be monitored more closely for:
  • Treatment resistance requiring medication changes 1
  • Increased risk of hospital admissions 1
  • Potential delirium and anticholinergic symptoms 3
  • Sedation and cognitive impairment, especially with olanzapine and quetiapine 2

Risk Mitigation Strategies

• Consider discussing cannabis cessation with patients on antipsychotics, as continued use may reduce treatment effectiveness 1
• For patients who continue cannabis use while on antipsychotics:
  • Monitor for signs of reduced medication efficacy 1
  • Be vigilant for symptoms of CNS depression and delirium 3
  • Consider more frequent follow-up to assess treatment response 1
  • Be aware that cannabis with high THC content (which has increased from 9% in 2008 to 17% in 2017, with concentrates reaching 70%) may pose greater risks for psychosis and medication interactions 2

Special Considerations

Mental Health Impact

• Long-term cannabis use is associated with mental health problems that may complicate antipsychotic treatment 2
• Cannabis use in adolescence is linked to major depression and suicidal ideation, which may affect overall treatment outcomes in patients also requiring antipsychotics 2
• Regular cannabis use can lead to cannabis use disorder (CUD), potentially complicating adherence to antipsychotic regimens 2

Physical Health Considerations

• Cannabis smoking may affect lung function and is associated with pulmonary conditions 2
• Cannabis use may be associated with adverse cardiovascular events, including myocardial infarction and stroke, which could interact with the cardiovascular effects of some antipsychotics 2