Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies

<b>Background/Objectives</b>: Diabetes mellitus is a growing global health concern, driving the exploration of new therapies like cannabidiol (CBD), which shows potential in improving insulin sensitivity and glycemic control, though its effects on glucose metabolism remain unclear. This...

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Main Authors: Elena Rafailovska, Elona Xhemaili, Zorica Naumovska, Olga Gigopulu, Biljana Miova, Ljubica Suturkova, Gjoshe Stefkov
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/4/446
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author Elena Rafailovska
Elona Xhemaili
Zorica Naumovska
Olga Gigopulu
Biljana Miova
Ljubica Suturkova
Gjoshe Stefkov
author_facet Elena Rafailovska
Elona Xhemaili
Zorica Naumovska
Olga Gigopulu
Biljana Miova
Ljubica Suturkova
Gjoshe Stefkov
author_sort Elena Rafailovska
collection DOAJ
description <b>Background/Objectives</b>: Diabetes mellitus is a growing global health concern, driving the exploration of new therapies like cannabidiol (CBD), which shows potential in improving insulin sensitivity and glycemic control, though its effects on glucose metabolism remain unclear. This study evaluates CBD’s dose-dependent effects on glycemia, insulin, and hepatic carbohydrate metabolism in diabetic rats. <b>Methods</b>: The Oral Glucose Tolerance Test (OGTT) was performed in healthy rats to compare intragastric vs. intraperitoneal CBD (0.5, 5, 50 mg/kg). Diabetic rats were treated with intragastric CBD (25, 50, 100 mg/kg) or metformin (70 mg/kg) for 8 days. Blood glucose, insulin, lipid profiles, and key carbohydrate-metabolizing enzymes were analyzed. <b>Results</b>: In the OGTT, intragastric CBD reduced glycemic AUC, with 50 mg/kg showing the strongest effect, while intraperitoneal CBD had no impact. In diabetic rats, metformin and 25 mg/kg CBD lowered blood glucose, but only CBD increased insulin. The 50 mg/kg dose caused the greatest glucose reduction and moderate insulin rise, while 100 mg/kg had no effect. At 25 mg/kg, CBD inhibited glucose-6-phosphatase and increased glucose-6-phosphate. The 50 mg/kg dose further suppressed gluconeogenic enzymes, reduced glycogen phosphorylase and liver glucose, and enhanced glucose-6-phosphate, showing the strongest metabolic effects. The 100 mg/kg dose increased hexokinase but had weaker metabolic effects. Metformin improved glucose utilization and glycogen storage. CBD at 25 and 50 mg/kg reduced triacylglycerols and increased HDL, while 100 mg/kg had no effect. <b>Conclusions:</b> This study provides strong evidence of CBD’s antidiabetic potential, especially at 50 mg/kg, particularly through its modulation of glucose metabolism and tendency to regulate insulin levels.
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spelling doaj-art-2d7f3fc0a9a44e879af9dd0d96d8edb62025-08-20T02:28:18ZengMDPI AGPharmaceuticals1424-82472025-03-0118444610.3390/ph18040446Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical StudiesElena Rafailovska0Elona Xhemaili1Zorica Naumovska2Olga Gigopulu3Biljana Miova4Ljubica Suturkova5Gjoshe Stefkov6Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 3, 1000 Skopje, North MacedoniaDepartment of Pharmacy, Faculty of Medical Sciences, University of Tetovo, Ilinden bb, 1200 Tetovo, North MacedoniaFaculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North MacedoniaFaculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North MacedoniaInstitute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 3, 1000 Skopje, North MacedoniaFaculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North MacedoniaFaculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia<b>Background/Objectives</b>: Diabetes mellitus is a growing global health concern, driving the exploration of new therapies like cannabidiol (CBD), which shows potential in improving insulin sensitivity and glycemic control, though its effects on glucose metabolism remain unclear. This study evaluates CBD’s dose-dependent effects on glycemia, insulin, and hepatic carbohydrate metabolism in diabetic rats. <b>Methods</b>: The Oral Glucose Tolerance Test (OGTT) was performed in healthy rats to compare intragastric vs. intraperitoneal CBD (0.5, 5, 50 mg/kg). Diabetic rats were treated with intragastric CBD (25, 50, 100 mg/kg) or metformin (70 mg/kg) for 8 days. Blood glucose, insulin, lipid profiles, and key carbohydrate-metabolizing enzymes were analyzed. <b>Results</b>: In the OGTT, intragastric CBD reduced glycemic AUC, with 50 mg/kg showing the strongest effect, while intraperitoneal CBD had no impact. In diabetic rats, metformin and 25 mg/kg CBD lowered blood glucose, but only CBD increased insulin. The 50 mg/kg dose caused the greatest glucose reduction and moderate insulin rise, while 100 mg/kg had no effect. At 25 mg/kg, CBD inhibited glucose-6-phosphatase and increased glucose-6-phosphate. The 50 mg/kg dose further suppressed gluconeogenic enzymes, reduced glycogen phosphorylase and liver glucose, and enhanced glucose-6-phosphate, showing the strongest metabolic effects. The 100 mg/kg dose increased hexokinase but had weaker metabolic effects. Metformin improved glucose utilization and glycogen storage. CBD at 25 and 50 mg/kg reduced triacylglycerols and increased HDL, while 100 mg/kg had no effect. <b>Conclusions:</b> This study provides strong evidence of CBD’s antidiabetic potential, especially at 50 mg/kg, particularly through its modulation of glucose metabolism and tendency to regulate insulin levels.https://www.mdpi.com/1424-8247/18/4/446cannabidioldiabetes mellitusinsulin sensitivityhepatic carbohydrate metabolismlaboratory animalsOGTT
spellingShingle Elena Rafailovska
Elona Xhemaili
Zorica Naumovska
Olga Gigopulu
Biljana Miova
Ljubica Suturkova
Gjoshe Stefkov
Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
Pharmaceuticals
cannabidiol
diabetes mellitus
insulin sensitivity
hepatic carbohydrate metabolism
laboratory animals
OGTT
title Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
title_full Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
title_fullStr Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
title_full_unstemmed Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
title_short Unlocking the Antidiabetic Potential of CBD: In Vivo Preclinical Studies
title_sort unlocking the antidiabetic potential of cbd in vivo preclinical studies
topic cannabidiol
diabetes mellitus
insulin sensitivity
hepatic carbohydrate metabolism
laboratory animals
OGTT
url https://www.mdpi.com/1424-8247/18/4/446
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