E-Thesis 634 views 347 downloads
Investigating the response of Lumbriculus variegatus to cannabidiol and endocannabinoids / Julanta Carriere
Swansea University Author: Julanta Carriere
Abstract
The endocannabinoid system (ECS) plays a crucial role in maintaining biological balance, encompassing G protein-coupled receptors, endogenous ligands, and catabolic enzymes. This system is targeted by endogenous cannabinoids such as anandamide (AEA), 2-arachidonoyglycerol (2-AG), and Δ9-tetrahydroca...
| Published: |
Swansea, Wales, UK
2025
|
|---|---|
| Institution: | Swansea University |
| Degree level: | Master of Research |
| Degree name: | MSc by Research |
| Supervisor: | Wallace, Lisa ; Seeley, Aidan ; Davies, Nia |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa68917 |
| Abstract: |
The endocannabinoid system (ECS) plays a crucial role in maintaining biological balance, encompassing G protein-coupled receptors, endogenous ligands, and catabolic enzymes. This system is targeted by endogenous cannabinoids such as anandamide (AEA), 2-arachidonoyglycerol (2-AG), and Δ9-tetrahydrocannabinol (THC), the psychoactive constituent of the cannabis plant. Cannabidiol (CBD), which isn’t a component in the ECS, is a compound found in cannabis and has a proposed 56 molecular targets. CBD is non-psychoactive and complex in its mechanisms and only interacts with ECS receptors in the presence of THC. Utilising the freshwater invertebrate Lumbriculus variegatus as a novel in vivo model, we investigate endogenous cannabinoids, along with AEA combined with the fatty acid amide hydrolase (FAAH) inhibitor URB 597, and CBD. Our objectives were to analyse cannabinoid-like receptor proteins in vertebrates and invertebrates, determining the lethal dose for 50% of the population, assessing behavioural effects post-CBD and endocannabinoid exposure, and developing novel methodologies for drug absorption analysis. The conservation of endocannabinoid proteins in other animals suggest they have an essential role across different species. Our study reveals stereotypical movement is significantly reduced with exposure to ≥10 µM 2-AG, ≥10 µM AEA, and ≥10 µM AEA concentrations ± URB 597 (250 µM). Notably, combining AEA and URB 597 results in further movement reduction post-rescue period compared to AEA alone (≥5 µM vs. ≥10 µM). This study also shows CBD is toxic to L. variegatus at concentrations of ≥30 µM. Through GC-MS, we found CBD was undetectable at concentrations below 10 µM, which implies there is a minimum concentration threshold for CBD to be detected through GC-MS. Additionally saw CBD significantly alters stereotypical movement in L. variegatus at concentrations of ≥5 µM. We show L. variegatus could potentially serve as an invaluable model for understanding cannabinoid interactions, facilitating drug design, and highlighting environmental impacts from cannabinoid exposure. |
|---|---|
| Item Description: |
ORCiD identifier: https://orcid.org/0009-0006-7446-6956 |
| Keywords: |
Cannabidiol, endocannabinoid system, Lumbriculus variegatus, pharmacology, ecotoxicology |
| College: |
Faculty of Medicine, Health and Life Sciences |