PhD Candidate Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada, Canada
Background: Despite the increasing interest in the use of medical cannabis, and many possible underlying pharmacological mechanisms, little is known about the clinical relevance of medical cannabis-related drug-drug interactions in children.
Objectives: Our objective was to systematically review and generate evidence on medical cannabis-related drug-drug interactions in children.
Methods: This systematic review (PROSPERO ID: CRD42020187433) searched four databases; MEDLINE, Embase, PsychInfo, and Cochrane Library (May 2022). Abstracts and full text were screened in duplicate. Data on types of cannabis products, doses, frequency, routes of administration, concomitant drugs, interacting drugs, drug interaction findings, efficacy outcomes, safety outcomes were extracted.
Results: Of 34,611 identified citations, 8 unique studies with a total of 295 participants were included (7 studies included children only); 3 studies were interventional and 5 were observational. 7 studies reported Cannabidiol (CBD) related-pharmacokinetic drug interaction and 1 study reported CBD-related pharmacodynamic drug interaction. In the included studies, CBD was reported to interact with clobazam (4/8, 50%), stripentol (1/8, 12.5%), sodium valproate (1/8, 12.5%), everolimus(1/8, 12.5%), sirolimus (1/8, 12.5%), lithium (1/8, 12.5%), levetiracetam (1/8, 12.5%), methadone (1/8, 12.5%) and other anti-epileptic drugs . Concomitant administration of CBD and clobazam increased plasma levels of clobazam and n-clobazam. Cannabidiol also increased plasma levels of lithium and methadone. Most common adverse events reported in CBD related drug interaction studies were diarrhea, drowsiness, elevation in transaminase levels and ataxia.
Conclusions: Cannabidiol was associated with increased in plasma levels of clobazam, lithium, methadone stripentol and other anti-epileptic drugs. Given the increasing interest in using cannabis, there is urgent need for more research on medical cannabis related drug-drug interactions in children.
