Background

The acceptability and use of cannabis—both medically and recreationally—is growing. In the U.S., cannabis is legal in 38 of 50 states for medical use and 24 states for recreational use. At the federal level, cannabis is classified as a Schedule I drug under the Controlled Substances Act, determined to have a high potential for abuse and no accepted medical use, prohibiting its use for any purpose.

Uncertainty exists regarding heart transplant (HT) eligibility among patients with heart failure (HF) who use cannabis. Transplant societies have historically listed tobacco use and alcohol addiction/use disorder as contraindications to HT but provide limited guidance for patients who use cannabis and defer candidacy to individual centers [1]. Differing U.S. state cannabis legislations, inadequate knowledge about cannabis pharmacotherapy, and lack of safety data surrounding cannabis continues to worsen this uncertainty [2]. Key concerns by transplant clinicians regarding cannabis use include lack of outcomes data, concerns for poor medication adherence after transplantation, unpredictable variability in calcineurin inhibitor immunosuppressant levels (due to pharmacokinetic interaction with cannabis), concerns about cardiac allograft dysfunction, rejection, and fungal infections [3].

In a survey of HT programs, 59% allowed pre or post-HT patients to use medically prescribed cannabis products and 60% of programs required 6 months of abstinence prior to considering HT [4]. Another survey by Neyer et al. demonstrated that most respondents from states with laws prohibiting cannabis-using patients from being denied transplant listing reported denying all cannabis-using patients or mandating abstinence before transplant listing [5]. In a survey of the membership of a major transplant society, transplant centers varied in their approval processes for cannabis and transplant and there were differences regarding various organ types within the same institutions [6]. The purpose of this study was to assess the opinions and practice patterns of transplant clinicians and transplant center policies in relation to cannabis use in HT.

Methods

We conducted an anonymous, cross-sectional, web-based survey of HT healthcare professionals between December 18, 2021, and September 30, 2022. The survey was developed by the authorship team. Survey questions were developed based on the most important questions arising at transplant selection committee meetings and the questions were pre-tested once before survey administration to a group of HT clinicians. The final survey contained 16 optional multiple-choice questions (Fig 1), and it could be submitted without completing all the questions. The survey assessed basic general demographic information including professional role, and self-identified gender. The data was analyzed using Microsoft Office 365 Excel software (Microsoft, Redmond, Washington, USA). The Indiana University Institutional Review Board approved the survey which contained questions designed to assess practice patterns for patients using cannabis referred for HT. A survey link was posted to the Heart Failure Society of America and the International Society of Heart and Lung Transplant websites. Respondents were asked to select whether cannabis is “illegal in my state”, “legal for medical and recreational use in my state,” or “legal for medical use in my state.” Those not responding to this question (n = 2) were excluded. We then tested for a difference in response between those in “illegal” versus “legal” states using Fisher’s exact test for nominal variables and the Brunner-Munzel test [7] for ordinal variables. Missing data for individual questions are reported but excluded from analysis. Informed consent was not obtained as it was a voluntary survey.

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Fig 1. Key survey findings regarding cannabis use and heart transplant listing.

https://doi.org/10.1371/journal.pone.0310778.g001

Results

A total of 140 HT healthcare professionals were included in the analysis—cardiologists (41.4%, n = 58), surgeons (7.1%, n = 10), pharmacists (9.3%, n = 13), advanced practice providers and coordinators (23.6%, n = 33) Broken down by gender–females (60.7%, n = 85), males (33.6%, n = 47) and undisclosed (5.7%, n = 8) (Table 1). Their responses to the survey questions, grouped into 2 categories: i) illegal by whether they responded that cannabis is “illegal in my state/jurisdiction”, or ii) legal—“legal for medical and recreational use in my state/jurisdiction,” or “legal for medical use in my state/jurisdiction” with legal (n = 86; 61.4%) and illegal (n = 54; 38.6%) (Table 1).

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Table 1. Opinions regarding cannabis use and heart transplant listing.

https://doi.org/10.1371/journal.pone.0310778.t001

Most respondents 96.3% and 90.7% of the respondents in both the illegal and legal categories stated that a combination of history-taking and toxicology is the optimal modality to assess potential HT recipients for cannabis use respectively. (p = 0.2075). There was a statistically significant difference in responses between the groups in the frequency of cannabis use that should preclude a patient from HT listing (Table 1, Q6, p = 0.0330), with respondents where cannabis is legal tending to answer that higher frequencies were acceptable. The groups also differed in whether a validated cannabis use disorder screening questionnaire could evaluate HT eligibility in patients with cannabis use (Table 1, Q8, p = 0.0111), with those in the legal group tending to more towards agreement. As expected, there was a substantial difference between groups in response to whether their program allows pre- or post-transplant patients to use prescribed cannabis products (Table 1, Q11, p<0.0001), with a majority in the illegal group responding “No”. Similarly, there was a substantial difference between groups in response to “Does your HT center’s current selection criteria policy address medical cannabis use in potential transplant candidates?” (Table 1, Q14, p = 0.0001), with a majority in the illegal group responding “No” while the majority in the legal group responded “Yes”. In contrast, there was no difference between groups in response to having a policy on recreational cannabis use (Table 1, Q13, p = 0.7612). There was a significant difference between groups to the question “If your program considers patients who use cannabis for transplant, after what duration of cannabis abstinence are they considered for HT?” (Table 1, Q15, p = 0.0025) For both groups, most respondents selected “6 months;” notably more in the legal than the illegal group selected “We transplant then anyway” or “Other” while more in the illegal group than the legal group selected “12 months.” There was no statistically significant (α = 0.05) difference between groups in the remaining questions (Table 1).

Discussion

Our survey demonstrates the heterogeneity regarding cannabis use among HT team members, while comparing the respondents in states where cannabis is legal versus illegal. Respondents in states with legal cannabis believed that higher frequency of use is acceptable and that a validated cannabis questionnaire (Cannabis Use Disorders Identification Test-Revised survey) could identify problematic cannabis use even though most were unaware of this validated tool. Respondents in states where cannabis is illegal were less likely to allow prescribed cannabis products and to have policies surrounding medical cannabis use. Both groups agreed that 6 months of abstinence is appropriate to proceed with transplantation. The 6-month rule is arbitrary and is backed by expert consensus. Respondents believe that patients using prescribed opioids and cannabis should be considered similarly for HT. Respondents were wary of transplanting patients on long-term opioids for pain without tapering/considering less addictive analgesics. Our study found that respondents were not aware of a validated cannabis use disorder questionnaire that can be used prior to transplant. The difference in opinion in respondents from legal versus illegal cannabis use states reflects the heterogeneous attitudes of respondents. This suggests that legality of cannabis may influence respondent’s views on this subject.

Our paper adds on to an earlier work by Neyer et al. (2016) which found that most respondents supported HT listing for patients using legal medical cannabis [5] suggesting that attitudes remain unchanged. Our survey also illustrates a disconnect between the equivocal transplant guidelines in the face of increasing cannabis use and the uncertainty facing HT programs as they evaluate these patients for HT. Nevertheless, there is no data that pre-surgical cannabis use causes worse outcomes after transplantation. Some states have passed laws that prohibit transplant centers from denying transplant listing based solely on a patient’s use of medical cannabis [8].

Clinical outcomes data of cannabis use in other solid organ transplants has been inconsistent. A study of a national kidney transplant database to Medicare claims demonstrated that cannabis dependence or abuse was rare in kidney transplant recipients. Dependence or abuse in the year before transplant was not associated with death or graft failure in the year after transplant. However use in the first year posttransplant was associated with approximately 2-fold increased risk of death-censored graft failure, all-cause graft loss, and death (aHR, 1.79; 95% CL, 1.06–3.04) in the subsequent 2 years [9]. In a single center study of kidney transplant recipients, patients with isolated cannabis use had similar overall graft survival compared to nonusers (aHR 1.00, P = 0.994) [10]. Cannabis use disorder (abuse and dependence) is however associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance [9]. However, it must be noted that many patients assessed for HT use recreational cannabis which should be considered differently from medical cannabis.

Limitations

This study has limitations. First, as a convenience survey it is at risk for responder and selection bias towards individuals more interested in HT cannabis use. Attitudes may be inadequately assessed by categorical responses which may not properly contextualize perception and practice. Finally, to preserve anonymity HT centers and their locations were not captured.

Conclusion

Our study provides contemporary insight into the variability that exists among HT clinicians regarding cannabis use and heart transplantation. This highlights the need for further study to inform consistent guidance and recommendations across transplant centers to ensure standardized and equitable care for all transplant patients. This highlights the urgent need for development of data-driven approach regarding cannabis use and transplantation. These data-driven approaches should assess the impact of cannabis use on post-HT outcomes—allograft rejection and survival and accurately characterize the pharmacokinetic variability of the interaction between cannabis and calcineurin inhibitors. Finally, it is worth noting that the growing acceptance of cannabis in the US is ahead of nearly all other countries worldwide, such that better characterization of transplant eligibility in the US should be informative to countries who later follow the US example in relaxing cannabis laws.

Supporting information