Are there any interactions between escitalopram (Selective Serotonin Reuptake Inhibitor - SSRI) and medicinal cannabis?

Potential Interactions Between Escitalopram and Medicinal Cannabis

There is a significant potential for drug interactions between escitalopram and medicinal cannabis, primarily due to cannabidiol (CBD) inhibiting CYP3A4 and CYP2C19 enzymes that metabolize escitalopram, which can increase escitalopram plasma concentrations and potentially lead to adverse effects.

Pharmacokinetic Interactions

• CBD significantly inhibits CYP3A4 and CYP2C19-mediated metabolism of citalopram and its stereoisomer escitalopram at physiologically relevant concentrations, suggesting a clinically important drug-drug interaction 1
• In a clinical study of patients with anxiety disorders on stable treatment with citalopram or escitalopram who received CBD (200-800 mg daily), the addition of CBD significantly increased citalopram plasma concentrations 1
• Cannabis and cannabinoids inhibit several cytochrome P450 enzymes (specifically CYP3A4, CYP2C19, and others) that are responsible for metabolizing many medications, including escitalopram 2
• THC is primarily metabolized by CYP3A4 and CYP2C9, creating potential for bidirectional drug interactions with medications that affect these pathways 3

Potential Clinical Consequences

• Increased escitalopram levels may lead to enhanced serotonergic effects and potentially increase the risk of adverse effects including:

  • Behavioral activation/agitation (motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, aggression) 2
  • Sexual dysfunction (erectile dysfunction, delayed ejaculation, anorgasmia) in adolescents and adults 2
  • Increased risk of bleeding, especially with concomitant administration of aspirin or nonsteroidal anti-inflammatory drugs 2

• While not specifically documented with escitalopram and cannabis, there is theoretical concern for serotonin syndrome when combining serotonergic medications with other substances that may affect serotonin levels 2

Cannabis-Related Considerations

• Cannabis products have variable THC and CBD content, making drug interactions unpredictable 2
• CBD presents risks for hepatotoxicity, with dose-related, reversible transaminase elevations reported, though typically at higher doses (>300 mg/day) 2
• Common side effects of cannabis that may compound with escitalopram effects include:
  • Dizziness, confusion, dry mouth, and fatigue 2
  • More serious effects like tachycardia, orthostatic hypotension, severe confusion, and paranoia 2

Recommendations for Clinical Management

• Monitor for increased escitalopram-related side effects when initiating cannabis products, particularly CBD-containing preparations 1
• Start cannabis products at the lowest possible dose and increase slowly with sufficient time between doses to gauge effects 2
• Be vigilant for signs of serotonin syndrome (confusion, agitation, anxiety, tremors, hyperreflexia, muscle rigidity, hypertension, tachycardia, diaphoresis) 2
• Consider monitoring liver function tests when using CBD products, particularly at higher doses 2
• Avoid high-fat meals when taking oral cannabis products as this significantly increases cannabinoid absorption and may exacerbate drug interactions 2

Special Considerations

• The interaction may be more pronounced in individuals with genetic polymorphisms affecting CYP2C19 function, which is involved in escitalopram metabolism 3
• Elderly patients and those with hepatic impairment may be at higher risk for adverse effects due to reduced drug clearance 2
• The limited clinical data on these interactions suggests caution and close monitoring is warranted when combining these substances 2, 1