The growing dilemma of legalized cannabis and heart transplantation

Abstract

This in-depth review discusses cannabis as it relates to heart transplantation and the growing dilemma of legalization around the world creating disparities in transplant candidacy. One will learn about two of the most common cannabinoids: Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids are metabolized by cytochrome P-450 and P glycoprotein, which are essential for the metabolism of drugs for transplantation, such as calcineurin inhibitors. Addiction, withdrawal, and cannabis use disorder will be reviewed as well as hyperemesis syndrome. Maintaining adequate immunosuppression will depend on a variety of factors, including drug-drug interactions, pharmacokinetics of cannabinoids and chronicity of cannabis usage. These drug interactions are further confounded by varying concentrations of cannabis products available at medical dispensaries. One will also learn about the outcomes of transplant recipients using cannabis such as graft failure and the risk of infections. Although more research is needed to establish transplant guidelines, the available data is concerning and fairness in organ distribution should not vary by transplant program or institution.

Keywords: cannabis; heart failure; heart transplantation; substance abuse; transplant rejection.

Figure 1.. Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) Metabolism

The figure depicts two routes of cannabis administration, their bioavailability, metabolism, storage and excretion. Inhaled bioavailability of cannabinoids is variable depending on depth of inhalation, length of breath hold, and chronicity of use. Ingested bioavailability depends on the type of food product consumed and patient absorption. THC and CBD metabolites enter the enterohepatic circulation and are mainly excreted in the feces in their non-conjugated form. The enterohepatic circulation of metabolites and slow redistribution of long-chain metabolites into and out of storage tissues contribute to the wide range of systemic exposure. CYP = cytochrome P450; F= bioavailability; UGT = glucuronosyltransferase

Figure 2.. Adjusted Associations of Adverse Events in Kidney Transplant Recipients with Cannabis Dependence or Abuse

Analysis included 52, 689 Medicare kidney transplant recipients from 2007–2015 with 163 diagnosed with cannabis dependency or abuse in the first year post-transplantation. After multivariate adjustment for recipient, donor and transplant factors including recipient age, comorbidities, and HLA mismatch, cannabis dependence or abuse was associated with a higher adjusted hazard ratio of graft failure, hypotension, pneumonia, drug abuse, non-compliance, mental health concerns, and accidents between 1 and 3 years post-transplantation. Copied from Alhamad, et al. with permission. (28)