Does cannabis increase the side effects of lithium or interact with other medications, such as Selective Serotonin Reuptake Inhibitors (SSRIs) like fluoxetine (Prozac) or sertraline (Zoloft), and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen (Advil) or naproxen (Aleve)?

Cannabis and Lithium Interactions: Potential Side Effects and Risks

Cannabis can increase the side effects of lithium and potentially cause lithium toxicity, requiring careful monitoring and possible dose adjustments when used together.

Cannabis-Lithium Interactions

• Cannabis inhibits several cytochrome P450 enzymes that are responsible for metabolizing many medications, which could potentially affect lithium metabolism 1
• An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness, confusion, and extrapyramidal symptoms) has been reported with lithium when combined with certain substances, suggesting potential for similar neurological interactions with cannabis 2
• A case report documented lithium toxicity (with symptoms of hypersomnolence, ataxia, and decreased oral intake) developing several weeks after initiating CBD therapy in a patient on lithium 3

Specific Side Effects That May Be Exacerbated

• Cannabis and lithium can both cause neurological side effects that may be additive, including:
  • Dizziness and confusion 1
  • Drowsiness and fatigue 1, 2
  • Impaired coordination and ataxia 2, 3
• Both substances can affect cardiovascular function:
  • Cannabis can cause tachycardia and orthostatic hypotension 1
  • Lithium has potential cardiovascular effects that could be compounded 2, 4

Monitoring and Management Recommendations

• Start cannabis products at the lowest possible dose and increase slowly with sufficient time between doses to gauge effects 1, 5
• Monitor lithium serum levels more frequently when initiating, changing doses of, or discontinuing cannabis use 6, 3
• Be vigilant for signs of lithium toxicity, including:
  • Neurological symptoms (tremor, confusion, ataxia) 2, 3
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea) 2, 7
  • Changes in mental status or alertness 2, 3
• Consider temporary reduction of lithium dose when initiating cannabis, especially CBD products 3

Other Drug Interactions with Cannabis

• Cannabis may interact with SSRIs (like fluoxetine and sertraline):

  • May increase SSRI levels through inhibition of CYP enzymes 5
  • Potential for enhanced serotonergic effects and increased risk of adverse effects 5
  • Theoretical risk of serotonin syndrome 5

• Cannabis may interact with NSAIDs (like ibuprofen and naproxen):

  • NSAIDs are already known to increase lithium levels and risk of toxicity 2, 6
  • Combined use of cannabis, lithium, and NSAIDs may further increase risk of lithium toxicity 2, 6
  • NSAIDs may have altered effects due to cannabis's inhibition of cyclooxygenase enzymes 1

Special Considerations

• CBD specifically presents risks for hepatotoxicity, with dose-related, reversible transaminase elevations reported, though typically at higher doses (>300 mg/day) 1, 5
• Elderly patients and those with hepatic impairment may be at higher risk for adverse effects due to reduced drug clearance 5, 8
• Cannabis products have variable THC and CBD content, making drug interactions unpredictable 5, 8
• Avoid high-fat meals when taking oral cannabis products, as this significantly increases cannabinoid absorption and may exacerbate drug interactions 5, 8

Conclusion for Clinical Practice

• Inform patients about potential interactions between cannabis and lithium 1, 3
• Document cannabis use patterns (frequency, amount, type) to better assess risk 1
• Consider more frequent lithium level monitoring in patients who use cannabis 6, 3
• Be prepared to adjust lithium dosing if signs of toxicity appear 2, 3