Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective
<b>Background</b>: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. <b>Methods</b>: This study evaluates the subacute toxic effects and pharmacokinetics of 4...
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2024-10-01
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| author | Elkhatim Hassan Abdelgadir Jihad Al-Qudsi Elham S. Abu-Nukhaa Dimah A. Alsidrani |
| author_facet | Elkhatim Hassan Abdelgadir Jihad Al-Qudsi Elham S. Abu-Nukhaa Dimah A. Alsidrani |
| author_sort | Elkhatim Hassan Abdelgadir |
| collection | DOAJ |
| description | <b>Background</b>: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. <b>Methods</b>: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. <b>Results</b>: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (<i>p</i> < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. <b>Conclusions</b>: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart. |
| format | Article |
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| institution | Kabale University |
| issn | 2673-9879 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Future Pharmacology |
| spelling | doaj-art-eca0155a1a3e4a44a112e2f3d6d2fa202024-12-27T14:27:25ZengMDPI AGFuture Pharmacology2673-98792024-10-014467669910.3390/futurepharmacol4040036Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological PerspectiveElkhatim Hassan Abdelgadir0Jihad Al-Qudsi1Elham S. Abu-Nukhaa2Dimah A. Alsidrani3Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh 14812, Saudi ArabiaDepartment of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh 14812, Saudi ArabiaDepartment of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh 14812, Saudi ArabiaDepartment of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh 14812, Saudi Arabia<b>Background</b>: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. <b>Methods</b>: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. <b>Results</b>: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (<i>p</i> < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. <b>Conclusions</b>: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart.https://www.mdpi.com/2673-9879/4/4/364F-MDMB-BUTINACA toxicitysynthetic cannabinoid pharmacokineticsrat model drug studyGC–MS/MS analysishematological and biochemical changeshistopathological examination |
| spellingShingle | Elkhatim Hassan Abdelgadir Jihad Al-Qudsi Elham S. Abu-Nukhaa Dimah A. Alsidrani Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective Future Pharmacology 4F-MDMB-BUTINACA toxicity synthetic cannabinoid pharmacokinetics rat model drug study GC–MS/MS analysis hematological and biochemical changes histopathological examination |
| title | Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective |
| title_full | Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective |
| title_fullStr | Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective |
| title_full_unstemmed | Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective |
| title_short | Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective |
| title_sort | subacute toxicity and pharmacokinetic evaluation of the synthetic cannabinoid 4f mdmb butinaca in rats a forensic and toxicological perspective |
| topic | 4F-MDMB-BUTINACA toxicity synthetic cannabinoid pharmacokinetics rat model drug study GC–MS/MS analysis hematological and biochemical changes histopathological examination |
| url | https://www.mdpi.com/2673-9879/4/4/36 |
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