Background There is potential for a wide array of cannabidiol (CBD) drug-drug interactions (DDIs) through modulation of hepatic cytochrome P450 enzymes and various other membrane proteins. Potential DDIs with CBD have been described, but few clinical interaction data exist outside of medications prescribed for epilepsy. Polypharmacy in cancer and palliative care patients increases the likelihood of DDIs. It is therefore important to consider possible drug interactions when prescribing medicinal cannabis.

Objective To look for evidence of drug-drug interactions between concomitant medications and CBD oil in participants with advanced cancer recruited to a placebo-controlled trial of medicinal cannabis for symptom control.

Methods Participants were those recruited to a randomised controlled trial of synthetic CBD versus placebo (MedCan-1, ACTRN 12618001220257, J Clin Oncol 2023;41(7);1444–1452). All participants provided a list of concomitant medications taken in conjunction with trial medications and were advised to continue them throughout the study. Adverse events were recorded throughout the trial. Surrogate measures were used to identify possible drug interactions: 1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to specific drug groups or individual agents (on the basis that co-administration of other drugs might limit the dose of CBD tolerated), 2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest.

Results The dose of CBD self-selected by participants was not related to opioid use or medications including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect whilst on study or when taking specific medications was not increased by the use of CBD. There was a suggestion that paracetamol could be protective against the side-effects of CBD but this was not supported by all analyses.

Discussion Although there is potential for CBD to interact with multiple medications, the findings of this sub-study suggest that concerns regarding clinically significant drug interactions with CBD may be unfounded.