What are the risks of smoking cannabis for a patient taking Vraylar (cariprazine) for schizophrenia or bipolar disorder?

Cannabis Use with Vraylar (Cariprazine): Strong Recommendation Against Concurrent Use

Patients taking Vraylar for schizophrenia or bipolar disorder should avoid smoking cannabis entirely, as cannabis directly undermines antipsychotic treatment by worsening psychotic symptoms, precipitating severe anxiety, and fundamentally counteracting the therapeutic effects of the medication. 1

Critical Psychiatric Risks

Direct Antagonism of Antipsychotic Effects

• Cannabis worsens positive psychotic symptoms and total psychiatric symptoms in patients being treated for psychosis, fundamentally undermining antipsychotic treatment goals. 1
• High doses of THC are associated with psychotic symptoms and can precipitate severe anxiety, directly counteracting the therapeutic effects of antipsychotic medications in vulnerable individuals. 1
• The potency of cannabis products has increased dramatically, with average THC concentration almost doubling from 9% in 2008 to 17% in 2017, and cannabis concentrates may have THC levels as high as 70%, significantly elevating all risks for medication interactions and psychiatric destabilization. 1, 2

Specific Contraindication for Psychotic Disorders

• Cannabis should be avoided if there is a history of psychotic episodes or breaks with reality, as it fundamentally undermines antipsychotic treatment. 1
• The American Psychiatric Association recommends that treatment focus should center on cannabis cessation for patients with bipolar disorder or psychotic disorders who are using cannabis while on psychiatric medications. 1

Pharmacological Interaction Concerns

Medication Potentiation Effects

• Cannabis can potentiate the unwanted side effects of psychiatric medications, creating a dangerous synergistic effect. 1
• Cannabis inhibits several cytochrome P450 enzymes (specifically CYP3A4, CYP2C19, and others) that metabolize many medications, potentially affecting cariprazine metabolism and increasing adverse effects. 3

Compounding Side Effects

• Common side effects of cannabis that may compound with cariprazine effects include dizziness, confusion, dry mouth, and fatigue, as well as more serious effects like tachycardia, orthostatic hypotension, severe confusion, and paranoia. 3
• Cannabis use may be associated with adverse cardiovascular events including arrhythmias and orthostatic hypotension, which could compound with cariprazine's cardiovascular effects. 2

Long-Term Psychiatric Consequences

Risk of Cannabis Use Disorder

• Approximately 10% of adults with chronic cannabis use develop cannabis use disorder, characterized by clinically significant impairment that complicates psychiatric treatment. 1, 2
• A randomized trial found that participants who received a medical cannabis card had almost twice the incidence (17% versus 9%) of developing cannabis use disorder within 12 weeks compared to controls. 2

Worsening of Underlying Conditions

• Cannabis use may be associated with increased risk for developing depressive disorders and may exacerbate psychiatric disorders in vulnerable individuals. 1, 2
• Early onset of cannabis use, especially weekly or daily use, strongly predicts future dependence, neuropsychological decline, and elevated risk for psychotic disorders in adulthood. 2

Neurological Damage from Cannabis

Cognitive Impairment

• Cannabis causes persistent cognitive deficits with regular use, including executive function impairment, deficits in inhibitory control, decision-making, and reduced processing speed. 2
• Cannabis causes measurable brain alterations, particularly altered gray matter volume in key brain regions, changes in cortical thickness, and disrupted connectivity in the prefrontal cortex affecting decision-making and impulse control. 2

Mechanism of Neurological Harm

• Neurological harm occurs through glutamate excitotoxicity, where cannabis inhibits GABAergic inhibitory action on glutaminergic neurons, increasing susceptibility to excitotoxic damage. 2
• Changes in glutamate and dopamine signaling contribute to cognitive deficits and psychosis risk. 2

Additional Medical Risks

Cardiovascular Concerns

• Cannabis affects heart rhythm through multiple mechanisms, including blocking reuptake of catecholamines, causing sympathetic stimulation, increasing heart rate and blood pressure in a dose-dependent fashion, causing coronary vasoconstriction, and promoting a prothrombotic state. 2
• Long-term cannabis use is associated with adverse cardiovascular events, including myocardial infarction, stroke, and arrhythmias. 2

Cannabinoid Hyperemesis Syndrome

• Long-standing cannabis use (more than 4 times per week for over a year) can lead to cannabinoid hyperemesis syndrome, characterized by cyclical emetic episodes that are relieved by hot showers, with treatment focusing on cannabis cessation. 4, 2

Clinical Management Approach

Primary Recommendation

• The treatment focus should center on cannabis cessation for patients with bipolar disorder or psychotic disorders who are using cannabis while on psychiatric medications. 1

If Patient Continues Cannabis Use Despite Counseling

• Monitor closely for worsening psychotic symptoms, increased anxiety, and treatment failure. 1
• Be vigilant for signs of severe confusion, paranoia, or psychotic breaks. 3
• Consider monitoring liver function tests if CBD products are being used, particularly at higher doses (>300 mg/day). 3
• Assess for development of cannabis use disorder and provide appropriate interventions. 1

Safety Counseling Points

• Avoid driving when feeling effects of cannabis, which may be compounded by cariprazine—wait at least 5-8 hours after cannabis use, though for some it may take longer. 4
• Older adults may be at higher risk of confusion and falls when using cannabis. 3, 2
• Store cannabis safely away from children and pets. 4, 3

Critical Pitfall to Avoid

The most dangerous clinical error is minimizing the severity of this interaction or treating cannabis as a benign substance in patients with psychotic disorders. Cannabis is not simply contraindicated due to theoretical concerns—it actively worsens the disease state that cariprazine is prescribed to treat, making successful psychiatric treatment nearly impossible. 1