What is the effect of Lexapro (escitalopram) on cannabis use?

Lexapro and Cannabis: Potential Interactions and Considerations

Lexapro (escitalopram) can interact with cannabis by inhibiting the metabolism of escitalopram, potentially leading to increased drug levels, enhanced serotonergic effects, and greater risk of adverse effects. 1

Pharmacokinetic Interactions

• Cannabis and cannabinoids inhibit several cytochrome P450 enzymes (specifically CYP3A4, CYP2C19, and others) that are responsible for metabolizing escitalopram, potentially increasing its blood levels 1
• CBD significantly inhibits CYP3A4 and CYP2C19-mediated metabolism of citalopram and escitalopram at physiologically relevant concentrations, suggesting a clinically significant drug interaction 2
• In patients taking citalopram or escitalopram, the addition of CBD significantly increased citalopram plasma concentrations in a small clinical study 2

Clinical Consequences of the Interaction

• Increased escitalopram levels may lead to enhanced serotonergic effects and potentially increase the risk of adverse effects, including behavioral activation, sexual dysfunction, and increased risk of bleeding 1
• There is a theoretical concern for serotonin syndrome when combining serotonergic medications like escitalopram with substances that may affect serotonin levels 1
• Common side effects that may be compounded when using both substances include:
  • Dizziness, confusion, dry mouth, and fatigue 1
  • More serious effects like tachycardia, orthostatic hypotension, severe confusion, and paranoia 1

Cannabis-Related Considerations

• Cannabis products have variable THC and CBD content, making drug interactions unpredictable 1
• CBD presents risks for hepatotoxicity, with dose-related, reversible transaminase elevations reported, though typically at higher doses (>300 mg/day) 3
• Cannabis use may be associated with an increased risk for developing depressive disorders and may exacerbate psychiatric disorders in vulnerable individuals 3
• Cannabis users are at higher risk of motor vehicle accidents, with drivers who test positive for cannabis being more than twice as likely as other drivers to be involved in motor vehicle crashes 3

Clinical Management Recommendations

• Start cannabis products at the lowest possible dose and increase slowly with sufficient time between doses to gauge effects 1
• Be vigilant for signs of serotonin syndrome, including confusion, agitation, anxiety, tremors, hyperreflexia, muscle rigidity, hypertension, tachycardia, and diaphoresis 1
• Consider monitoring liver function tests when using CBD products, particularly at higher doses 1
• Avoid high-fat meals when taking oral cannabis products, as this significantly increases cannabinoid absorption and may exacerbate drug interactions 1
• Elderly patients and those with hepatic impairment may be at higher risk for adverse effects due to reduced drug clearance 1

Special Populations

• Older adults may be at higher risk of confusion and falls when using cannabis than younger people 3
• Patients with a history of psychiatric disorders should exercise particular caution, as cannabis may exacerbate these conditions 3
• Patients receiving immunotherapy for cancer should be advised to avoid cannabis use, as preliminary data suggest poorer clinical outcomes 3

Practical Advice for Patients

• If using both substances, maintain open communication with healthcare providers about all medications and substances being used 3
• Avoid driving when feeling the effects of cannabis, which may be compounded by escitalopram 3
• Store cannabis products safely away from children and pets 3
• Be aware of local and federal laws regarding cannabis use 3

The limited clinical data on these interactions suggests caution and close monitoring is warranted when combining these substances 1. Patients should be educated about potential interactions and advised to report any unusual symptoms promptly to their healthcare provider.