Cannabinoids and drug–drug pharmacokinetic interactions: Deciphering the risks

The relationship between cannabinoids and mental health has become a major focus of scientific inquiry and public discourse. Cannabinoids are diverse chemical compounds from the Cannabis species that have been explored for their therapeutic applications in treating chronic pain, psychiatric and neurological conditions, such as depression, schizophrenia, epilepsy and anxiety. Additionally, cannabinoids are frequently used for recreational purposes. The evolving legislation surrounding cannabis has added a layer of complexity to the understanding of its pharmacological effects. Societal attitudes shifting towards a more permissive acceptance of cannabis use make it essential to balance individual freedom with public health concerns. While the use of cannabinoids remains a subject of ongoing research, clinical data have shown promise in the treatment of mental health disorders. However, debates and concerns have been raised regarding the potential pharmacokinetic (PK) drug-drug interactions that may occur, involving changes in the absorption, distribution, metabolism and excretion (ADME) of the prescribed drugs. The future prospect of patients having unrestricted access to cannabis requires special attention in case of concurrent use with the common medical treatments they may be receiving for a cardiovascular or metabolic disease or with medications related to the treatment of psychiatric disorders. This comprehensive review aims to critically discuss the main PK interactions of major cannabinoids (tetrahydrocannabinol, cannabidiol, cannabinol, cannabichromene and cannabigerol) in relation to the drugs prescribed in neuropathic pain, depression, anxiety, schizophrenia, epilepsy and cancer, as well as with the most common cardiometabolic disease treatments such as statins, beta-blockers, warfarin, insulin analogues and metformin.