Despite broad implications, there is limited data on clinical outcomes for patients who use marijuana before and after LT and no consensus within the transplant community surrounding marijuana use. Approximately 15,000 patients are currently listed for LT in the US according to the Organ Procurement and Transplantation Network . Therefore, given the rising prevalence of marijuana use, LT listing policies around marijuana use may affect several thousand patients in the US alone. Using psychosocial assessment and urine toxicology, our study is the first report on the prevalence and frequency of marijuana use and its effect on LT wait list outcomes among a cohort of LT candidates in the Unites States. In the only prior study evaluating LT-related outcomes among marijuana users, Ranney et al 17 found that marijuana users were less likely to receive LT but had similar overall survival rates as nonusers. Their study, however, was limited by the exclusion of a large portion of LT wait list candidates. They also did not assess wait list outcomes like rate of delisting in this study and their use of urine toxicology alone to define marijuana led to a low prevalence estimate and may have led to misclassification of marijuana users. In contrast, we used a more robust definition of marijuana use based on psychosocial interviews combined with urine toxicology to describe the frequency and patterns of marijuana and other substance use among LT candidates. We also used a competing risk model to assess for rates of death or delisting in addition to receiving LT among marijuana users and nonusers. Our study, and that of Ranney et al.,rolling tables did not find clear evidence of harm associated with historical marijuana use, and raises the question whether ongoing marijuana use could be considered safe on the LT wait list.
This question is especially relevant given recent passage of laws that protect medical marijuana users from transplant restrictions across several states in the United States. Further, could medical marijuana have a potential therapeutic role for LT candidates? A recent report documents successful use of prescription marijuana to decrease opiate use following liver transplantation. Perhaps marijuana could be effectively used for appetite stimulation, treating nausea, reducing opiate addiction, or postoperative pain relief. This is especially relevant considering that almost a quarter of LT candidates at our institution had recent opiate/BDZ prescriptions. It is important to note that our understanding of the metabolism and effects of marijuana is still developing – marijuana use affects the endocannabinoid system, including the hepatic cannabinoid receptors, which are also modulated by chronic liver disease. Upregulation of the CB1 receptor in chronic liver disease has been implicated in progression of liver fibrosis. However, CB2 is also upregulated in liver disease and prevents fibrosis progression. It has been postulated that the balance between CB1 and CB2 receptor activation may modulate liver fibrosis – if both receptors are targeted equally then they may not be any net effect on liver fibrosis. However, there have been isolated cases of invasive aspergillosis related to marijuana use among post transplant patients. Our study has several important limitations and should be interpreted with caution. We could not assess impact of ongoing marijuana use on wait list outcomes because our institutional policy did not allow LT listing for active marijuana users. Those with active marijuana use, including heavy users, had to demonstrate abstinence prior to listing for LT. Therefore, based on our data we cannot comment on active marijuana use and our results should only be applied to historical marijuana use prior to LT listing.
Those subjects who were able to satisfy the selection committee concerns and demonstrate abstinence from marijuana use were classified as ‘recent’ users in our study. All outcomes are presented in strata of ‘recent’ and ‘prior’ marijuana use to capture any differences between these 2 groups. Accordingly, we also cannot provide relevant data on the effects of ongoing marijuana use on post-LT outcomes. Though we attempt to adjust for confounding variables, given the limited prior work in this field there is potential for unmeasured confounding in our analysis. Further, our definition of marijuana use does not incorporate duration or method of marijuana use, as these data were not collected systematically at our institution. Finally, we defined marijuana use via combination of self-report in a psychosocial assessment and urine toxicology, which likely yields an underestimate of the true prevalence since patients had a conflict of interest in self-reporting marijuana use and urine toxicology to detect marijuana is an imperfect test. In conclusion, we found a high prevalence of historical marijuana use that did not have clear adverse effects on LT wait list outcomes. Recent use of illicit substances was, however, associated with higher risk of death or delisting from the LT wait list. This suggests historical marijuana use alone may not be equivalent to use of other illicit drugs. Yet, this data should be interpreted with restraint as further research is needed to assess the impact of ongoing marijuana use among candidates on the LT wait list. Further, post transplant outcomes must also be followed in these patients to determine safety of continued marijuana use after LT. Recent passage of laws protecting medical marijuana users has created an urgent need to further study LT-related outcomes among this population. MARIJUANA, THE MOST used illicit drug in the United States and the world, is frequently used in association with alcohol. Marijuana use is prospectively associated with both heavy drinking and with the development and maintenance of alcohol use disorders as well as with the deleterious AUD treatment outcomes . Couse of marijuana and alcohol is associated with heavy episodic drinking and AUDs .
Among marijuana users with cannabis use disorder , there is increased likelihood for development of a comorbid AUD , with nationally representative data indicating that 68% of individuals with current CUD and over 86% of those with a history of CUD meeting criteria for an AUD . Marijuana dependence doubles the risk for long-term persistent alcohol problems , and marijuana-dependent alcohol users are 3 times more likely to develop alcohol dependence than non-marijuana-involved drinkers . Co-use of marijuana and heavy alcohol use is linked to a number of behavioral problems with exceptionally heightened risk for impaired driving , psychiatric comorbidity , and poor clinical treatment outcomes . Importantly, the risk associated with the use of marijuana in combination with alcohol is greater than that from either drug alone . Thus, increased attention has been called to the importance of examining inter-relations among alcohol and marijuana use patterns and the impact of the use of one substance on risk of excessive use of the other . The majority of the epidemiological studies using individual-level outcomes indicate that marijuana use increases or complements alcohol consumption . Similarly, studies of economic policies that reduce access to alcohol or increase the price of alcohol demonstrate complementary reductions in both alcohol and marijuana use . However,growers solutions longitudinal general population studies that mostly used state-level data on marijuana policy suggest marijuana and alcohol can be substitutes . Research with individuals using marijuana for medicinal purposes also indicates that alcohol use is lower or less likely with concurrent marijuana use . These findings suggest that individuals who use marijuana for medicinal purposes may use it as a harm-reduction strategy to substitute for alcohol . Preliminary evidence of alcohol substitution was also noted in a clinical study where controlled abstinence from marijuana was linked with increased alcohol craving and consumption among individuals with AUD and also in an experimental study that demonstrated decreased alcohol consumption over time when smoked marijuana was available during an operant task . Collectively, this research indicates that marijuana use is strongly linked with alcohol use, although whether marijuana serves as a complement to or substitute for alcohol use remains unclear. These mixed findings on co-occurrence between alcohol and marijuana use behaviors may reflect methodological limitations of correlational research which precludes causal inference. Similarly, epidemiological and laboratory studies are not designed to determine whether marijuana and alcohol use are linked at the event-level within individuals in a natural setting. The few experimental studies have primarily focused on pharmacokinetic interactions or on performance impairments from combined use of marijuana and alcohol , and thus offer limited information on marijuana’s influence on alcohol consumption.
Although several studies have asked respondents to recall their most recent marijuana-alcohol use event , they cannot distinguish different use events within the same person. Therefore, it is critical to use nuanced methods that examine co-use of marijuana and alcohol, such as event or daily level. To our knowledge, there have been only a few event-level studies on the co-occurrence of marijuana and alcohol use. One recent study used ecological momentary assessment methods to characterize the context of adolescent simultaneous marijuana and alcohol use, but did not examine event-level associations between the 2 behaviors . Another study examining daily marijuana and alcohol use found that marijuana intoxication was greater on days when participants used any alcohol or had 5 or more alcoholic drinks on 1 occasion . However, whether marijuana use predicted heavy drinking was not examined. Furthermore, neither study examined whether meeting criteria for AUD or CUD moderated the concurrent marijuana and alcohol use. A recent online daily diary study showed evidence for complementary alcohol and marijuana use at both the within- and between-person levels . However, individuals with coping-oriented patterns of substance use showed evidence of substitution by increasing levels of drinking while decreasing marijuana use. Heterogeneous samples may have contributed to the mixed findings in research examining marijuana–alcohol associations. For example, marijuana use may be associated with worse drinking outcomes among heavy drinkers, especially those with AUD. For these individuals, learned associations of conjoint use may be particularly salient. Marijuana also impairs executive control functioning , which may already be reduced among chronic heavy drinkers . Thus, in individuals with AUD, marijuana use may increase alcohol craving and may result in heavy drinking. Likewise, given that individuals with CUD are known to be at greater risk for problematic drinking , and CUD and AUD are highly comorbid , alcohol involvement may be even greater in individuals with the dual diagnoses of CUD and AUD. This study extends the growing literature on the association of marijuana and alcohol use and use disorders using event-level data to examine daily associations between marijuana and alcohol use in a clinical population with high base rates of use of these substances. The sample was recruited from the Veterans Health Administration facility to capitalize on the disproportionately high rates of substance use disorders in veterans relative to the general population . Veterans are at increased risk for substance use disorders because of the significantly elevated rates of mental health disorders such as post traumatic stress disorder and major depressive disorder, which are strongly associated with using alcohol and marijuana specifically to cope with aversive psychological and mood states as well as with sleep disturbance . Returning veterans experience high rates of suicide and impaired psychosocial functioning post deployment, which further exacerbate the severity of substance use disorders in this vulnerable population . Participants were selected based on co-use of marijuana and alcohol with a full range of marijuana and alcohol involvement . As there may be different associations for any use versus level of alcohol use, we examined any alcohol use as well as heavy and moderate levels of drinking. There are 2 main hypotheses of this study. First, we hypothesized that marijuana use on a given day will be associated with greater alcohol consumption /4 drinks, versus moderate drinking ; and moderate drinking vs. None on that day. Second, we examined the potential moderating effects of AUD and CUD diagnosis, as ascertained by the Structured Clinical Interview for DSM , on the marijuana–alcohol relationship. Specifically, we expected that marijuana use on a given day will be associated with heavy alcohol use that day specifically among individuals with a diagnosis of AUD or CUD but not among individuals without these diagnoses. Furthermore, we expected that a dual diagnosis of CUD and AUD would amplify the association between marijuana and alcohol use relative to a single diagnosis of AUD or CUD.In the 1990s, states across the United States began to legalize marijuana for medical use, which helped usher in the transition to the legalization of non-medical marijuana use.In 2012, Colorado and Washington were the first states to legalize recreational marijuana for adult use and sales through voter-initiated ballots, with legal sales beginning in 2014.