Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents
The conundrum of <i>Cannabis sativa</i>’s applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around th...
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/5/694 |
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| author | Leontina-Elena Filipiuc Raluca Ştefănescu Carmen Solcan Mitică Ciorpac Andrei Szilagyi Dana Cojocaru Gabriela Dumitrita Stanciu Ioana Creangă Cătălin-Cezar Caratașu Daniela-Carmen Ababei Roxana-Elena Gavrila Andrei-Daniel Timofte Silviu-Iulian Filipiuc Veronica Bild |
| author_facet | Leontina-Elena Filipiuc Raluca Ştefănescu Carmen Solcan Mitică Ciorpac Andrei Szilagyi Dana Cojocaru Gabriela Dumitrita Stanciu Ioana Creangă Cătălin-Cezar Caratașu Daniela-Carmen Ababei Roxana-Elena Gavrila Andrei-Daniel Timofte Silviu-Iulian Filipiuc Veronica Bild |
| author_sort | Leontina-Elena Filipiuc |
| collection | DOAJ |
| description | The conundrum of <i>Cannabis sativa</i>’s applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, <i>Cannabis sativa</i> L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified <i>Cannabis sativa</i> L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified <i>Cannabis sativa</i> L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain. |
| first_indexed | 2024-03-11T03:25:35Z |
| format | Article |
| id | doaj.art-87b36082a1994f7eb9d9f98d2ead84ed |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T03:25:35Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-87b36082a1994f7eb9d9f98d2ead84ed2023-11-18T02:48:35ZengMDPI AGPharmaceuticals1424-82472023-05-0116569410.3390/ph16050694Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in RodentsLeontina-Elena Filipiuc0Raluca Ştefănescu1Carmen Solcan2Mitică Ciorpac3Andrei Szilagyi4Dana Cojocaru5Gabriela Dumitrita Stanciu6Ioana Creangă7Cătălin-Cezar Caratașu8Daniela-Carmen Ababei9Roxana-Elena Gavrila10Andrei-Daniel Timofte11Silviu-Iulian Filipiuc12Veronica Bild13Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaFaculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, 700490 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaHistology Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaAdvanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, RomaniaThe conundrum of <i>Cannabis sativa</i>’s applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, <i>Cannabis sativa</i> L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified <i>Cannabis sativa</i> L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified <i>Cannabis sativa</i> L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.https://www.mdpi.com/1424-8247/16/5/694<i>Cannabis sativa</i> L.EU-GMPdelta-9-tetrahydrocannabinolcannabidiolacute oral toxicitypharmacokinetic profile |
| spellingShingle | Leontina-Elena Filipiuc Raluca Ştefănescu Carmen Solcan Mitică Ciorpac Andrei Szilagyi Dana Cojocaru Gabriela Dumitrita Stanciu Ioana Creangă Cătălin-Cezar Caratașu Daniela-Carmen Ababei Roxana-Elena Gavrila Andrei-Daniel Timofte Silviu-Iulian Filipiuc Veronica Bild Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents Pharmaceuticals <i>Cannabis sativa</i> L. EU-GMP delta-9-tetrahydrocannabinol cannabidiol acute oral toxicity pharmacokinetic profile |
| title | Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents |
| title_full | Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents |
| title_fullStr | Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents |
| title_full_unstemmed | Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents |
| title_short | Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified <i>Cannabis sativa</i> L. in Rodents |
| title_sort | acute toxicity and pharmacokinetic profile of an eu gmp certified i cannabis sativa i l in rodents |
| topic | <i>Cannabis sativa</i> L. EU-GMP delta-9-tetrahydrocannabinol cannabidiol acute oral toxicity pharmacokinetic profile |
| url | https://www.mdpi.com/1424-8247/16/5/694 |
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