A review mapped out how 13 synthetic cannabinoids are metabolized and their potential for dangerous drug interactions
A comprehensive review described the metabolic pathways of 13 prevalent synthetic cannabinoids, identifying which drug-metabolizing enzymes (CYPs, UGTs, carboxylesterases) process them and documenting their potential to inhibit these enzymes, creating risk for drug-drug interactions.
Quick Facts
What This Study Found
Researchers reviewed the metabolism of 13 prevalent synthetic cannabinoids, mapping which cytochrome P450 (CYP) enzymes, UDP-glucuronosyltransferases (UGTs), and carboxylesterases are responsible for breaking them down.
Synthetic cannabinoids are substrates of multiple drug-metabolizing enzymes, meaning these enzymes process and eliminate them from the body.
Critically, synthetic cannabinoids also inhibit CYP and UGT enzymes. This means they can interfere with the metabolism of other drugs taken concurrently, potentially causing dangerous increases in blood levels of co-administered medications.
The review emphasized the urgency of understanding these interactions given the rise in synthetic cannabinoid poisonings and the likelihood that users are taking multiple substances simultaneously.
Key Numbers
13 synthetic cannabinoids reviewed. Multiple CYP enzymes, UGTs, and carboxylesterases identified as metabolizing enzymes. Inhibitory effects on CYP and UGT activities documented for predicting drug-drug interactions.
How They Did This
Comprehensive review of published literature on metabolic pathways of 13 prevalent synthetic cannabinoids. Covered CYP enzyme characterization, UGT involvement, and inhibition studies.
Why This Research Matters
Synthetic cannabinoid users frequently use other drugs simultaneously, and emergency departments are seeing increasing poisoning cases. Understanding which enzymes process these substances and which other drugs might interact is essential for toxicology and emergency medicine.
The Bigger Picture
As new synthetic cannabinoids are continuously developed to evade scheduling, understanding their metabolic profiles helps forensic labs identify them in biological samples and helps clinicians anticipate drug interactions in overdose situations.
What This Study Doesn't Tell Us
Review of existing literature, which is incomplete for many newer synthetic cannabinoids. In vitro enzyme studies may not perfectly predict in vivo drug interactions. The rapid emergence of new compounds means the review is inherently incomplete.
Questions This Raises
- ?Which clinically significant drug-drug interactions are most likely with synthetic cannabinoids?
- ?Can metabolic profiling help predict toxicity of novel synthetic cannabinoids before they appear in clinical settings?
Trust & Context
- Key Stat:
- Synthetic cannabinoids both use and block the same enzymes that metabolize other drugs
- Evidence Grade:
- Moderate. Comprehensive review of metabolic data with clinical relevance, though limited by gaps in primary research for newer compounds.
- Study Age:
- Published in 2018. New synthetic cannabinoids have continued to emerge, requiring ongoing metabolic characterization.
- Original Title:
- Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes.
- Published In:
- Archives of pharmacal research, 41(7), 691-710 (2018)
- Authors:
- Kong, Tae Yeon, Kim, Ju-Hyun, Kim, Dong Kyun, Lee, Hye Suk
- Database ID:
- RTHC-01723
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
Why are drug interactions with synthetic cannabinoids dangerous?
When synthetic cannabinoids block the enzymes that break down other drugs, blood levels of those other drugs can rise to toxic levels. This is especially dangerous because synthetic cannabinoid users often take multiple substances, and emergency physicians may not know what drugs are involved.
How are synthetic cannabinoids different from natural cannabis?
Synthetic cannabinoids are lab-made chemicals sprayed onto plant material. They bind cannabinoid receptors much more potently than THC, often as full agonists rather than partial agonists. Their metabolism and drug interaction profiles can be very different from natural cannabis compounds.
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Cite This Study
https://rethinkthc.com/research/RTHC-01723APA
Kong, Tae Yeon; Kim, Ju-Hyun; Kim, Dong Kyun; Lee, Hye Suk. (2018). Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes.. Archives of pharmacal research, 41(7), 691-710. https://doi.org/10.1007/s12272-018-1055-x
MLA
Kong, Tae Yeon, et al. "Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes.." Archives of pharmacal research, 2018. https://doi.org/10.1007/s12272-018-1055-x
RethinkTHC
RethinkTHC Research Database. "Synthetic cannabinoids are substrates and inhibitors of mult..." RTHC-01723. Retrieved from https://rethinkthc.com/research/kong-2018-synthetic-cannabinoids-are-substrates
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.