• Cannabis use could cause harmful drug in

    From ScienceDaily@1:317/3 to All on Mon Dec 13 21:30:44 2021
    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

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