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The growing dilemma of legalized cannabis and heart transplantation

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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.

Section snippets

Disparities in clinical practice

There are wide variations in clinical practice among transplant centers regarding cannabis. The American Society of Transplantation surveyed members and noted variations in transplant candidacy policy (28% rejected all patients, 52% varied by organ), cannabis screening (55% screened all candidates, 20% screened based on organ), and concern for route of administration (11% allowed edibles only).6 An electronic survey of adult solid organ transplant centers in the United States (U.S.) reflecting

Recreational versus medical cannabis

Should transplant centers make a distinction between recreational versus medicinal cannabis usage? Medical conditions for medicinal usage vary despite evidence only supporting a few conditions such as chronic pain, chemotherapy induced nausea and emesis, and spasticity due to multiple sclerosis.9 In the U.S., chronic pain remains the most common reason for medicinal usage, accounting for 68% of license holders.10 Unfortunately, this symptom is common and subjective. Among the remainder U.S.

Addiction and cannabis use disorder

Cannabis addiction is often compared to other drug abuse which adversely affect transplant outcome (Table 1). Cannabis addiction occurs with long-term use, increases in prevalence among users starting during adolescence,11 and is associated with underlying psychiatric disorders and history of polysubstance abuse.12,13 In one study of 61 transplant candidates referred for abuse and dependence, 42% had depression, 27% had anxiety, and 31% had polysubstance abuse.12 Tolerance as well as

Cannabis active and inactive ingredients

The main molecules responsible for the various effects of cannabis are cannabinoids. More than 100 exist9 including Δ9-tetrahydrocannabinol (THC) which is responsible for the psychoactive effects, cannabidiol (CBD) which has anti-inflammatory and anti-proliferative effects, and other minor cannabinoid molecules such as cannabinol.24 Cannabinoids are naturally produced by plants and humans and synthetically produced such as prescription medications like dronabinol or illicit drugs like “Spice.”25

Transplant drug interactions

THC and CBD have been reported to modulate the effects of many CYP enzymes and drug transporters in in-vitro and in-vivo studies.25 CBD may also mediate interactions with enzymes in the UGT system.25 These potential drug interactions may interfere with immunosuppressant therapy and other drugs (Table 3). Calcineurin inhibitors, like tacrolimus, make up the backbone of chronic immunosuppression therapy. CBD products can raise tacrolimus levels by inhibiting the CYP3A4 and P-glycoprotein, a

Transplant outcomes

Data on cannabis and transplantation is sparse and limited by small sample size, retrospective analyses, and limited outcome data. This literature review combines transplant data from different organs and includes case reports.

Potential cardiovascular complications

Although the cannabis literature for transplantation is sparse, there are cardiovascular adverse effects concerning for potential transplant complications. These concerns are described below.

Future considerations

Cannabis usage remains controversial because it is widely accessible, legalized for medicinal and/or recreational purposes in several states and countries, and adverse events may be attributable to a lack of regulatory standards for the cultivation of cannabis products, leading to impurities and infections. To address cannabis in future transplant guidelines we should consider route of administration, frequency of usage, and dependency. Inhaled cannabis is more deleterious than edible cannabis

Disclosures

None.

Dr. Hsich is supported by the National Heart, Lung and Blood Institute of the National Institute of Health under Award Number R01HL141892 to study disparities in survival among heart transplant candidates and recipients. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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