Early detection of cannabinoids in biological samples based on their affinity interaction with the growth hormone secretagogue receptor

George Madalin Danila; Mihaela Puiu; Lucian-Gabriel Zamfir; Camelia Bala

doi:10.1016/j.talanta.2021.122905

Early detection of cannabinoids in biological samples based on their affinity interaction with the growth hormone secretagogue receptor

Talanta. 2022 Jan 15:237:122905. doi: 10.1016/j.talanta.2021.122905. Epub 2021 Sep 29.

Authors

George Madalin Danila¹, Mihaela Puiu², Lucian-Gabriel Zamfir³, Camelia Bala⁴

Affiliations

¹ Laboratory for Quality Control and Process Monitoring, University of Bucharest, 030018, Bucharest, Romania; Romanian Doping Control Laboratory, 022103, Bucharest, Romania.
² Laboratory for Quality Control and Process Monitoring, University of Bucharest, 030018, Bucharest, Romania.
³ Laboratory for Quality Control and Process Monitoring, University of Bucharest, 030018, Bucharest, Romania; ICUB, University of Bucharest, 050107, Bucharest, Romania.
⁴ Laboratory for Quality Control and Process Monitoring, University of Bucharest, 030018, Bucharest, Romania; Department of Analytical Chemistry, University of Bucharest, 030018, Bucharest, Romania. Electronic address: camelia.bala@chimie.unibuc.ro.

PMID: 34736642
DOI: 10.1016/j.talanta.2021.122905

Abstract

Herein we report on the early detection of cannabinoids in urine samples according to their affinity profiles in competitive assays with labelled ghrelin (GHR). We have demonstrated for the first time that cannabidiol (CBD) and 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) act as extracellular ligands for the growth hormone secretagogue receptor (GHS-R1a), strongly promoting the binding of ghrelin (GHR), the endogenous ligand of GHS-R1a. The affinity profiles of CBD and carboxy-THC are significantly different from the profiles of synthetic GHR mimetics such as CJC-1295 or [D-Arg¹-D-Phe⁵-D-Trp^7,9-Leu¹¹]-Substance P peptides, which are the most common interferents; the cannabinoids promoted the GHR/GHS-R1a interaction, while the ghrelin mimetics acted rather as competitive inhibitors. The analysis of 1:4 diluted urine samples proved that the proposed method displays good linearity and sensitivity in the range of 5-30 ng/mL for both CBD and carboxy-THC, whereas GHR mimetics display no interference at concentrations up to 100 ng/mL. The results were validated by comparison with the gas chromatography tandem mass spectrometry reference method. CBD may exert the same promoting effect on the interaction of GHS-R1a with other GHR mimetics listed as performance-enhancing substances.

Keywords: Affinity profile; Cannabidiol; Carboxy-THC; Early detection; Growth hormone secretagogue receptor; Performance-enhancing drugs.

MeSH terms

Cannabidiol* / analysis
Cannabinoids* / analysis
Dronabinol / analysis
Gas Chromatography-Mass Spectrometry
Receptors, Ghrelin

Substances

Cannabinoids
Receptors, Ghrelin
Cannabidiol
Dronabinol