What are the potential interactions between ibuprofen (nonsteroidal anti-inflammatory drug (NSAID)) - paracetamol (acetaminophen) 200/325mg and cannabis?

Potential Interactions Between Ibuprofen-Paracetamol 200/325mg and Cannabis

The combination of ibuprofen-paracetamol 200/325mg with cannabis carries moderate risk of interactions, primarily through pharmacokinetic mechanisms involving cytochrome P450 enzymes, with potential for increased side effects but generally low probability of severe clinical consequences.

Pharmacokinetic Interactions

Cytochrome P450 Enzyme Interactions

• Cannabis and cannabinoids inhibit several cytochrome P450 enzymes, including CYP2C9, CYP1A1/2, and CYP1B1 1
• Ibuprofen is primarily metabolized by CYP2C9, which can be inhibited by THC and CBD, potentially leading to increased ibuprofen levels and side effects 2
• Paracetamol metabolism may be affected by cannabis through CYP1A2 and CYP2D6 pathways, though this interaction is less clinically significant 2

Metabolism and Clearance

• Cannabis smoking can induce CYP1A2, potentially increasing the metabolism of some drugs, though this effect is more relevant for chronic cannabis smokers 2
• The overall probability of clinically relevant drug interactions between cannabis and NSAIDs is generally considered moderate 3

Pharmacodynamic Interactions

Pain Management Effects

• Paracetamol's analgesic effect involves indirect activation of cannabinoid CB1 receptors, which could theoretically lead to enhanced analgesic effects when combined with cannabis 4
• Some evidence suggests potential synergistic analgesic effects between cannabinoids and ibuprofen, primarily mediated through peripheral CB2 receptors 5

Cardiovascular Effects

• Both cannabis (particularly THC) and NSAIDs can independently increase cardiovascular risk
• Combining these substances may potentially increase the risk of adverse cardiovascular events, especially in patients with pre-existing cardiovascular disease 1

Gastrointestinal Effects

• NSAIDs like ibuprofen increase the risk of gastrointestinal bleeding and ulceration 1
• Cannabis has antiemetic properties but can also cause cannabinoid hyperemesis syndrome with chronic use
• The combination may mask early symptoms of NSAID-induced gastric irritation 1

Special Considerations

Dosing and Administration

• The risk of interactions increases with higher doses of both substances
• Patients consuming greater than 1.5g/day of inhaled cannabis or 20mg/day of THC-dominant cannabis oil may experience more pronounced interactions 1
• Administration of oral cannabinoids with high-fat meals significantly increases their absorption, potentially enhancing interaction effects 1

Risk Factors for Adverse Effects

• Patients at higher risk for NSAID toxicities (age >60, history of peptic ulcer disease, renal impairment, concomitant use of anticoagulants) should exercise particular caution 1
• Patients with liver disease should be monitored closely as both cannabinoids and acetaminophen can affect liver function 1

Safety Recommendations

Monitoring

• Monitor for signs of increased sedation, dizziness, and confusion, which may be enhanced when these substances are combined 1
• Be alert for gastrointestinal symptoms that could indicate NSAID-related complications 1
• Consider baseline and follow-up liver function tests if chronic use of both substances is anticipated 1

Practical Advice

• Avoid driving or operating heavy machinery when using this combination due to potential enhanced impairment 1
• Start with lower doses of both substances when using them concurrently
• Consider spacing administration times to minimize peak interaction effects

Alternative Approaches

• For patients requiring both cannabis and pain relief, consider using paracetamol alone (without ibuprofen) as it has fewer potential interactions and side effects 6
• For patients with significant pain requiring anti-inflammatory effects, consider consulting with a healthcare provider about adjusting cannabis dosing or timing

While the combination of ibuprofen-paracetamol and cannabis is not absolutely contraindicated, patients should be aware of the potential for enhanced side effects and exercise caution, particularly regarding sedation, cardiovascular effects, and gastrointestinal complications.