While transplant societies may refuse liver transplants based on cannabis use, they may be harming patients in the process

1. 19
About 50% of liver transplants are performed due to
complications of alcohol toxicity. Liver transplants are
often delayed in these patients until they achieve sobriety.
While the primary reason for this is to ensure that the
new liver is not consigned to the same fate as the
previous, it is also to soothe the emotions of those who
are morally disturbed by people getting a liver transplant
for a condition that is seen to be self-inflicted.
Policies have been enacted to decrease the wait time
for hepatic transplants as many patients may not survive.
Ontario is launching a pilot program this year to convene
a panel with a nurse practitioner, social worker, transplant
surgeon, hepatologist and addiction specialist to
individually assess patients without a mandatory 6-month
abstinence. There is evidence that patients do well with
this approach, however this has had to be balanced with
concerns about decreasing levels of public donations of
organs if alcohol-related deaths persist after transplant.
For alcohol and the liver, the harms are clear and severe;
this makes it easier to deny an available organ to an active
user, even without the moral dimension. Many transplant
societies also demand a cessation of cannabis use before
being considered for a liver transplant – is this justified,
or should it be seen as an infringement of the Canadian
Charter of Rights and Freedoms?
On top of this, the protocols are not always clear. To
qualify for a liver transplant in BC, you cannot be a smoker
or vaper of cannabis, but it appears you could use edibles,
oils or topicals and remain listed for an organ, as long as it
has not been illegally purchased.
In America, Federal guidelines for transplantation
consider cannabis to be a drug of abuse and a reason
to deny a life-saving organ transplant. With changing
state laws around medical and recreational cannabis this
is proving problematic. In one case, a young man with
primary sclerosing cholangitis (PSC) was denied a liver
transplant due to a positive drug screen for opiates and
THC. However, both had been authorized by his physician,
oxycodone for the pain and medical cannabis (legal in the
state) for the pain, nausea and cachexia caused by the
CANNABIS, ALCOHOL AND LIVER HEALTH
Cannabis,AlcoholandLiverHealth/IanMitchell,MD
Ian Mitchell, MD
Ian Mitchell is an emergency physician practising in
Kamloops, British Columbia. His area of interest is
reducing opiate deaths with the use of take-home
Naloxone and the substitution of opiates with cannabis
for chronic pain. He is a qualified investigator for an RCT
of cannabis for PTSD and is also involved with
research as the site scholar for the Kamloops Family
Medicine program. He blogs less often than he
should at www.clinicalcannabisincontext.tumblr.com
EXCLUSION CRITERIA
1) Use of alcohol within last six months in patients with
addition history
2) Use of illicit drugs and/or excessive use of therapeutic
drugs within the last six months
3) Ongoing smoker (cigarettes, e-cigarettes, marijuana)
and unwilling to quit

2. 20PSC. The transplant team accepted the opiate use but
refused the transplant on the basis of drug abuse and
potential worse outcomes due to cannabis use.
Aside from the fact that the above case is more
representative of stigma than legitimate medical concern,
what are the effects of cannabis on the liver? Health
Canada’s Information for Health Professionals on Cannabis
(2013)1
has this to say: “A number of studies have strongly
implicated the endocannabinoid system in chronic liver
disease. Studies in patients with chronic hepatitis C have
found a significant association between daily cannabis
smoking and moderate to severe fibrosis, as well as
cannabis smoking being a predictor of fibrosis progression.”
On top of this, The College of Physicians and Surgeons
of Alberta urges physicians to follow guidelines from the
Canadian Family Physicians and states that cannabis use
is inappropriate for those with severe liver disease. But
is this advice harming patients? Overall, there is very
little literature supporting any adverse effects of smoking
cannabis on the liver. It seems that in normal liver tissue,
there are relatively few cannabinoid receptors. However,
cannabinoid receptors are upregulated and much more
common in the presence of liver disease such as hepatitis
and cirrhosis. This has led researchers to focus on the
effects of cannabis on people with these disease states.
There has been an interesting trend in cannabis
research over the years. Early studies showing harms
have been shown to have overestimated the risks, and
new better-done studies are revealing less harms and
occasionally potential benefits from cannabis use. This
has been the case with cannabis and cognition, brain
morphology changes, schizophrenia and cancer, and
it turns out to be the case in liver disease also. In vitro
studies have suggested that cannabinoids could be
protective in liver injury, however in humans three
cross-sectional studies published between 2005-20082,3,4
have suggested cannabis use could accelerate the
development of liver fibrosis and steatosis in those with
chronic hepatitis C infection. This was the basis of the
“significant association” of fibrosis with cannabis use.
Amajorarticleappearedin2013tochallengethisnarrative.5
This study came out of the Canadian Coinfection Cohort,
a population composed of patients suffering from both
HIV and HCV. HIV positive patients are known to use
cannabis frequently to treat their symptoms and HIV has
been shown to accelerate the progression of fibrosis,
making this an excellent patient population.The research
group also tried to correct for reverse causation bias by
using a longitudinal cohort and ensuring that cannabis
use was measured prior to developing fibrosis rather
than concurrently.
After examining almost 700 patients, the group concluded
that there was no increased risk of developing fibrosis due
to cannabis use.While cannabis use did appear to increase
as cirrhosis developed, the longitudinal analysis showed
that this was due to symptom treatment. In addition,
there was no evidence of a dose response relationship
with cannabis and the development of fibrosis, further
weakening any connection.
Several recent studies have come to a more radical
conclusion – that cannabis use appears to decrease
the progression to cirrhosis and hepatocellular cancer.
Cirrhosis is linked to recurrent episodes of inflammation
and scarring of the liver. Cannabinoids often express
anti-inflammatory properties and preclinical work has
demonstrated that cannabinoids can protect the liver in
ischemic injury. Ahmed, et al6
examined the records of
14,000 patients from the NHANES database. They found
that cannabis was associated with a decreased risk of
developing non-alcoholic fatty liver disease.The largest risk
reduction was associated with current heavy users and
occurred despite increased alcohol consumption and poor
ANUMBEROFSTUDIESHAVESTRONGLY
IMPLICATEDTHEENDOCANNABINOID
SYSTEMINCHRONICLIVERDISEASE.
STUDIESINPATIENTSWITHCHRONIC
HEPATITISCHAVEFOUNDASIGNIFICANT
ASSOCIATIONBETWEENDAILYCANNABIS
SMOKINGANDMODERATETOSEVERE
FIBROSIS,ASWELLASCANNABIS
SMOKINGBEINGAPREDICTOROF
FIBROSISPROGRESSION
Cannabis,AlcoholandLiverHealth/IanMitchell,MD

3. 21dietary choices.The authors speculate that cannabidiol can
lead to increased insulin sensitivity. NAFLD is co-related
with obesity and diabetes and previous studies have
shown that cannabis users tend to be leaner than average.
Bukong, et al7
found a strong dose-dependent reduction
in non alcoholic fatty liver disease in those who used
cannabis; this is thought to account for some of the effect.
However, the benefit persisted even when controlling
for these other risk factors implying that there is some
other mechanism involved. The benefit of cannabis was
reduced in those who were dependent on alcohol.
The same group published a similar study8
looking at
the records of over 300,000 patients with a history of
alcohol abuse and looked at their progression to alcoholic
steatosis, alcoholic hepatitis, cirrhosis and hepatocellular
carcinoma. In each category there was a decreased risk
of progression in those who were using cannabis, with
heavy users being the most protected. The decrease in
hepatocelluluar carcinoma appeared to be predominantly
due to a much lower risk of cirrhosis, a precursor state to
cancer. These were cross-sectional studies, which does
limit the inference of causality, as mentioned above.
However, we now have 3 studies suggesting a benefit
from using cannabis in those with liver disease—what
Health Canada would term a “significant association”.
This new evidence should prompt transplant societies
in Canada to remove any restrictions based on cannabis
usage. Whether they begin to recommend cannabis as a
way to treat the symptoms of liver disease and prevent
progression remains to be seen. Even with evidence,
years of stigma and slow knowledge translation will likely
contribute to restrictive policies in the future.
REFERENCES:
1. Canada H, Canada H. Information for Health Care Professionals: Cannabis
(marihuana, marijuana) and the cannabinoids [Health Canada, 2013] [Internet].
aem. 2013 [cited 2018 May 15]. Available from: https://www.canada.ca/
en/health-canada/services/drugs-health-products/medical-use-marijuana/
information-medical-practitioners/information-health-care-professionals-
cannabis-marihuana-marijuana-cannabinoids.html
2. Ishida JH, Peters MG, Jin C, Louie K, Tan V, Bacchetti P, et al. Influence of
Cannabis Use on Severity of Hepatitis C Disease. Clin Gastroenterol Hepatol
Off Clin Pract J Am Gastroenterol Assoc. 2008 Jan;6(1):69–75.
3. Hézode C, Zafrani ES, Roudot-Thoraval F, Costentin C, Hessami A, Bouvier-Alias
M, et al. Daily cannabis use: a novel risk factor of steatosis severity in patients
with chronic hepatitis C. Gastroenterology. 2008 Feb;134(2):432–9.
4. Hézode C, Roudot-Thoraval F, Nguyen S, Grenard P, Julien B, Zafrani E-S, et al.
Daily cannabis smoking as a risk factor for progression of fibrosis in chronic
hepatitis C. Hepatol Baltim Md. 2005 Jul;42(1):63–71.
5. Brunet L, Moodie EEM, Rollet K, Cooper C, Walmsley S, Potter M, et al.
Marijuana smoking does not accelerate progression of liver disease in HIV-
hepatitis C coinfection: a longitudinal cohort analysis. Clin Infect Dis Off Publ
Infect Dis Soc Am. 2013 Sep;57(5):663–70.
6. Kim D, Kim W, Kwak M-S, Chung GE,Yim JY, Ahmed A. Inverse association of
marijuana use with nonalcoholic fatty liver disease among adults in the United
States. PLOS ONE. 2017 Oct 19;12(10):e0186702.
7. Adejumo AC, Alliu S, AjayiTO, Adejumo KL, Adegbala OM, Onyeakusi NE, et al.
Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver
disease: A cross-sectional study. PloS One. 2017;12(4):e0176416.
8. Adejumo AC, Ajayi TO, Adegbala OM, Adejumo KL, Alliu S, Akinjero AM, et al.
Cannabis use is associated with reduced prevalence of progressive stages of
alcoholic liver disease. Liver Int Off J Int Assoc Study Liver. 2018 Jan 17;
Cannabis,AlcoholandLiverHealth/IanMitchell,MD