Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users

Abstract Background Differences in cannabinoid metabolism and patient responses can arise even with equivalent doses and formulations. Genetic polymorphisms in genes responsible for cannabinoid metabolism and medications that alter CYP450 pathways responsible for metabolism of cannabinoids may accou...

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Main Authors: Jessica A. Wright, Linda Huang, Basant E. Katamesh, Siddhant Yadav, Abhinav Singla, Ann Vincent
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Cannabis Research
Subjects:
Online Access:https://doi.org/10.1186/s42238-024-00256-6
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author Jessica A. Wright
Linda Huang
Basant E. Katamesh
Siddhant Yadav
Abhinav Singla
Ann Vincent
author_facet Jessica A. Wright
Linda Huang
Basant E. Katamesh
Siddhant Yadav
Abhinav Singla
Ann Vincent
author_sort Jessica A. Wright
collection DOAJ
description Abstract Background Differences in cannabinoid metabolism and patient responses can arise even with equivalent doses and formulations. Genetic polymorphisms in genes responsible for cannabinoid metabolism and medications that alter CYP450 pathways responsible for metabolism of cannabinoids may account for some of this variability. Materials and methods A retrospective chart review was conducted on a cohort of unselected patients who had previously completed pharmacogenomic testing and reported oral cannabis use, as defined as “oral” or “by mouth” route of administration. The objective was to identify atypical variants and medications in this cohort and formulate a hypothesis on how these variables influence the metabolism of Tetrahydrocannabinol (THC) and Cannabidiol (CBD). Results Oral cannabis use was confirmed in 71 patients, with an average age of 68.5 years, and primarily white women. Of the 71 patients, 10 had no atypical variants; 31 had atypical variants in CYP2C9; 37 had atypical variants in CYP2C19; 6 had atypical variants in CYP3A4; and 15 had atypical variants in CYP3A5. Of the 71 patients, 5 were taking medications that could interact with THC, and 8 were taking medications that could interact with CBD. Conclusion The results this study reveal the spectrum of hypothesized alterations in THC and CBD metabolism due to atypical genetic variants and medications. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, clinicians should remain aware of the possibility that atypical variants and medications may impact patients’ responses to THC and CBD.
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spelling doaj-art-21bb48518e204792aed0da38213c9bdb2025-01-05T12:44:53ZengBMCJournal of Cannabis Research2522-57822025-01-01711810.1186/s42238-024-00256-6Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis usersJessica A. Wright0Linda Huang1Basant E. Katamesh2Siddhant Yadav3Abhinav Singla4Ann Vincent5Pharmacy Services, Mayo Clinic College of Medicine and SciencePharmacy Services, Mayo Clinic College of Medicine and ScienceDivision of General Internal Medicine, Mayo Clinic College of Medicine and ScienceDivision of General Internal Medicine, Mayo Clinic College of Medicine and ScienceDivision of General Internal Medicine, Mayo Clinic College of Medicine and ScienceDivision of General Internal Medicine, Mayo Clinic College of Medicine and ScienceAbstract Background Differences in cannabinoid metabolism and patient responses can arise even with equivalent doses and formulations. Genetic polymorphisms in genes responsible for cannabinoid metabolism and medications that alter CYP450 pathways responsible for metabolism of cannabinoids may account for some of this variability. Materials and methods A retrospective chart review was conducted on a cohort of unselected patients who had previously completed pharmacogenomic testing and reported oral cannabis use, as defined as “oral” or “by mouth” route of administration. The objective was to identify atypical variants and medications in this cohort and formulate a hypothesis on how these variables influence the metabolism of Tetrahydrocannabinol (THC) and Cannabidiol (CBD). Results Oral cannabis use was confirmed in 71 patients, with an average age of 68.5 years, and primarily white women. Of the 71 patients, 10 had no atypical variants; 31 had atypical variants in CYP2C9; 37 had atypical variants in CYP2C19; 6 had atypical variants in CYP3A4; and 15 had atypical variants in CYP3A5. Of the 71 patients, 5 were taking medications that could interact with THC, and 8 were taking medications that could interact with CBD. Conclusion The results this study reveal the spectrum of hypothesized alterations in THC and CBD metabolism due to atypical genetic variants and medications. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, clinicians should remain aware of the possibility that atypical variants and medications may impact patients’ responses to THC and CBD.https://doi.org/10.1186/s42238-024-00256-6PharmacogenomicsPotential drug-gene interactionsCBDTHCCYP450 enzymePharmacology
spellingShingle Jessica A. Wright
Linda Huang
Basant E. Katamesh
Siddhant Yadav
Abhinav Singla
Ann Vincent
Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
Journal of Cannabis Research
Pharmacogenomics
Potential drug-gene interactions
CBD
THC
CYP450 enzyme
Pharmacology
title Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
title_full Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
title_fullStr Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
title_full_unstemmed Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
title_short Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
title_sort hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users
topic Pharmacogenomics
Potential drug-gene interactions
CBD
THC
CYP450 enzyme
Pharmacology
url https://doi.org/10.1186/s42238-024-00256-6
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