Cannabis use could cause harmful drug interactions

Date:
December 13, 2021
Source:
Washington State University
Summary:
Using cannabis alongside other drugs may come with a significant
risk of harmful drug-drug interactions, new research suggests. The
researchers looked at cannabinoids--a group of substances found in
the cannabis plant -- and their major metabolites found in cannabis
users' blood and found that they interfere with two families of
enzymes that help metabolize a wide range of drugs prescribed for
a variety of conditions. As a result, either the drugs' positive
effects might decrease or their negative effects might increase
with too much building up in the body, causing unintended side
effects such as toxicity or accidental overdose. While more research
needs to be done, the authors said one early takeaway from these
studies is that it's important to be careful when using cannabis
with other prescription drugs.



FULL STORY ========================================================================== Using cannabis alongside other drugs may come with a significant risk of harmful drug-drug interactions, new research by scientists at Washington
State University suggests.


==========================================================================
The researchers looked at cannabinoids -- a group of substances found
in the cannabis plant -- and their major metabolites found in cannabis
users' blood and found that they interfere with two families of enzymes
that help metabolize a wide range of drugs prescribed for a variety
of conditions. As a result, either the drugs' positive effects might
decrease or their negative effects might increase with too much building
up in the body, causing unintended side effects such as toxicity or
accidental overdose.

While more research needs to be done, the authors said one early
takeaway from these studies is that it's important to be careful when
using cannabis with other prescription drugs.

"Physicians need to be aware of the possibility of toxicity or lack of
response when patients are using cannabinoids," said Philip Lazarus,
senior author on the papers and Boeing distinguished professor of pharmaceutical sciences. "It's one thing if you're young and healthy
and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact
their treatment." The findings were described in a pair of studies
published in the journal Drug Metabolism and Disposition. One study
focused on a family of enzymes known as cytochrome P450s (CYPs), whereas
the other looked at UDP- glucuronosyltransferases (UGTs), another enzyme family. Together, these two enzyme families help metabolize and eliminate
more than 70 percent of the most commonly used drugs from the body.

While there has been limited previous research focused on potential
drug interactions caused by cannabinoids, this new research provides the
first known comprehensive look at the interaction between three of the
most abundant cannabinoids -- tetrahydrocannabinol (THC), cannabidiol
(CBD) and cannabinol (CBN) -- and their metabolites and all of the
major CYP enzymes. This is also the first known research that looked
for interactions between these cannabinoids and UGT enzymes, specifically.



========================================================================== "Cannabinoids stay in your body only for about 30 minutes before they
are rapidly broken down," said first author Shamema Nasrin, a graduate
student in the WSU College of Pharmacy and Pharmaceutical Sciences. "The metabolites that result from that process stay in your body for much
longer -- up to 14 days - - and at higher concentrations than cannabinoids
and have been overlooked in previous studies, which is why we thought we
should focus on those as well." The researchers used manipulated human
kidney cells that allowed them to look at a single enzyme at a time and validated their results in human liver and kidney specimens in which many
of these enzymes were present. They found that cannabinoids and the major
THC metabolites strongly inhibited several CYP enzymes. One key discovery
was that one of the most abundant THC metabolites, called THC-COO-Gluc
-- which had not been previously studied in this context - - appears to
play a major role in inhibiting several key enzymes in the liver.

Looking at the UGT enzyme family, the researchers found that all three cannabinoids, but especially CBD, inhibited two of the primary UGT
enzymes present in the liver. CBD was also found to block three enzymes
that account for about 95 percent of kidney UGT metabolism, which helps
clear toxins and certain drugs from the body.

"If you have a kidney disease or you are taking one or more drugs that
are metabolized primarily through the kidney and you're also smoking
marijuana, you could be inhibiting normal kidney function, and it may
have long-term effects for you," Lazarus said.

Nasrin added that these interactions between CBD and UGT enzymes could
be inhibiting kidney function in patients with acute kidney disease or
kidney cancer, who may be using CBD to treat pain or to try to reduce
the side effects from anti-cancer drugs.

"Taking CBD or marijuana might help your pain but could be making the
other drug you're taking more toxic, and that increase in toxicity
may mean that you can't continue taking that drug," Nasrin said. "So,
there could be serious ramifications for anti-cancer drugs, and that's
only one example of the many drugs that could potentially be affected
by the cannabinoid-enzyme interactions we're seeing." Others who worked
with Nasrin and Lazarus on this research include Christy Watson, Yadira Perez-Paramo, Keti Bardhi, Gabriela Fort and Gang Chen, all of whom are,
or previously were, at the WSU College of Pharmacy and Pharmaceutical
Sciences.

Funding for these studies came from the Health Sciences and Services
Authority of Spokane County and the State of Washington's Initiative
Measure No. 502, which funds the university's Alcohol and Drug Abuse
Research Program.

========================================================================== Story Source: Materials provided by Washington_State_University. Original written by Judith Van Dongen. Note: Content may be edited for style
and length.


========================================================================== Journal References:
1. Shamema Nasrin, Christy J.W. Watson, Yadira X Perez-Paramo, Philip
Lazarus. Cannabinoid Metabolites as Inhibitors of Major
Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug
Interactions. Drug Metabolism and Disposition, 2021; 49 (12):
1070 DOI: 10.1124/ dmd.121.000442
2. Shamema Nasrin, Christy J. W. Watson, Keti Bardhi, Gabriela Fort,
Gang
Chen, Philip Lazarus. Inhibition of UDP-Glucuronosyltransferase
Enzymes by Major Cannabinoids and Their Metabolites. Drug Metabolism
and Disposition, 2021; 49 (12): 1081 DOI: 10.1124/dmd.121.000530 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211213095020.htm

--- up 1 week, 2 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)