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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Pharmacogenetics of Cannabinoids.

Szymon Hryhorowicz1, Michal Walczak2, Oliwia Zakerska-Banaszak2

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Pharmacogenetics can explain the therapeutic and side effects of medical cannabis. Gene variations influence how the body processes cannabinoids, paving the way for personalized medicine and cannabinoid drug therapy.

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Area of Science:

  • Pharmacogenetics
  • Molecular Biology
  • Medical Science

Background:

  • The therapeutic applications of medical marijuana and cannabinoid drugs are expanding, despite ongoing controversy.
  • While promising for conditions like glioma and epilepsy, understanding cannabinoid efficacy and side effects remains limited.
  • Cannabinoid pharmacogenetics offers a potential pathway to address these knowledge gaps.

Purpose of the Study:

  • To explore the role of pharmacogenetics in understanding medical cannabis and cannabinoid drug effects.
  • To identify candidate genes involved in cannabinoid transport, action, and metabolism.
  • To organize current knowledge for personalized cannabinoid therapy.

Main Methods:

  • Reviewing scientific literature on cannabinoid pharmacogenetics.
  • Identifying genes associated with cannabinoid receptors (CNR1, CNR2, TRPV1, GPR55).
  • Examining genes involved in transport (ABCB1, ABCG2, SLC6A) and metabolism (CYP450 family, COMT, FAAH, COX2, ABHDs, MAPK14).

Main Results:

  • Candidate genes for cannabinoid effects include those for receptors, transporters, and metabolic enzymes.
  • Variations in these genes are hypothesized to influence both therapeutic benefits and adverse effects.
  • This framework supports the concept of individualized medicine in cannabinoid therapy.

Conclusions:

  • Pharmacogenetics is crucial for elucidating the mechanisms behind medical cannabis efficacy and side effects.
  • Identifying genetic markers can guide personalized cannabinoid drug selection and dosing.
  • This approach advances the development of individualized medicine for cannabinoid-based treatments.