The popularity of medicinal cannabis is increasing the potential risk of hazardous pharmacokinetic interactions with commonly used anti-rheumatic drugs, rheumatologists have been told.

Many clinicians and patients may not appreciate that the cannabinoids used in management of chronic pain and musculoskeletal conditions may potentiate the effects of analgesics and anti-inflammatory drugs through an interaction with cytochrome P450 (CYP450) isoenzymes, says Dr Luke Williamson of the  Department of Rheumatology, Westmead Hospital, Sydney.

Writing in the International Journal of Rheumatic Diseases, he says that commonly used cannabis derivatives such as tetrahydrocannabinol (THC) and cannabidiol (CBD) may increase the plasma levels of many drugs that are metabolised by the cytochrome P450.

Because they are substrates of cytochrome P450, both THC and CBD can potentially increase serum levels of drugs metabolised by this pathway, thus increasing the sedative effect of analgesics, especially opioids, pregabalin, duloxetine, and tricyclic antidepressants.

And since both THC and CBD are metabolised by the liver, concomitant use of hepatotoxic medications, such as NSAIDs and methotrexate should also be carefully considered, he suggests.

The potential interactions include increasing serum levels of csDMARDs and tsDMARDs, NSAIDs, corticosteroids and also gout therapies  such as colchicine. The cytochrome p450 interactions may also apply to anticoagulants and opioid analgesics, he adds.

“Despite the currently scant evidence for major in vivo drug-drug interactions, clinicians need to be aware of these possible interactions due to the increasingly widespread use of often patient-initiated and patient-driven THC- and CBD-containing formulations” he advises.