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Detection of Cannabinoids for Anti-Doping and Clinical purposes

Cannabis is commonly used for recreational or medicinal purposes. While there are more than one hundred different compounds in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-known, researched, and consumed. Over the last decade synthetic cannabinoids (SCs) have emerged (e.g., FUB-APINACA, MFUBINAC, and AMB-FUBINACA) as a worrying alternative to the natural form.

This research has three main tenets.

  1. The World Anti-Doping Agency (WADA) Prohibited List has included natural as well as SC that mimic the effect of tetrahydrocannabinol (THC) under Section 8 Cannabinoid categories with CBD being the only exception. Analysis of SC is challenging since they exist with various structural motifs and the physicochemical diversity. It is further complicated by the formation of multiple metabolites (often pharmacologically active) which have not been fully characterised or understood. This limits availability of certified reference material (CRM) that are commonly used in an analytical setting to help with identification and quantification. Identification and detection therefore require analytical instrumentation capable of detecting very low (nanogram and in some cases picogram) concentrations where parent compounds are targeted.
  2. Hyphenated chromatography (GC-MS, HRMS) and other techniques (NMR) have been used by King’s Forensics to provide structural identification and characterisation of these complicated compounds. The analytical detection of new compounds is challenging as it is pivotal to know details of the metabolites formed after consumption. These compounds are mostly excreted in urine as metabolites, which can in turn be used as markers of previous use. Both King’s Forensics and Dresden University have independently been investigating synthetic cannabinoids and will work together to explore marker metabolites by using in vitro biotransformation with liver microsomes, cell lines enable the combined investigation of phase I and phase II metabolism. We will pool resources to identify long-term metabolites of several synthetic cannabinoids. Both groups will use biomarker metabolites to screen athletes for these compounds.
  3. In addition, methods will be developed for the detection of THC, CBD, and their metabolites as well as endocannabinoids, AEA and 2-AG in biological fluids. This will enable clinical colleagues to study predictors of psychotic response among cannabis users as well as the usefulness of medicinal cannabis and/ CBD to alleviate the symptoms of Parkinson’s and Alzheimer’s disease.

Investigators

Dr Erika Castrignano 

Principal Analyst

Dr Marta Di-Forti

Senior Clinical Fellow

Dr Latha Velayudhan

Senior Lecturer

Dr Sagnik Bhattacharyya 

Professor

Dr Annekathrin Keiler

Post doctoral research, Institute of Doping Analysis & Sports Biochemistry (IDAS)

Dr Detlef Thieme

Lab Director, IDAS Dresdner, Germany

Dr Oliver Zierau

Professor, Institute for Zoology

PhD Students

Abraham Ali

PhD Student
Orapan Apirakkan

PhD Student

Aims

To investigate the feasibility of detecting a range of cannabinoids, endocannabinoids and synthetic cannabinoids in biological samples using LC-MS/MS.

Methods

Hyphenated chromatography-mass spectrometry

Trials Design

Laboratory method development and analysis

Summary of Findings

TBC

Impact

The development of methodology to detect cannabinoids, new synthetic analogues, endocannabinoids, and their metabolic breakdown products in biological fluids will improve our understanding of the use and misuse of these compounds. Regulations surrounding the use of illicit substances or medicinal products containing THC, synthetic analogues or CDB are wide ranging and differ by jurisdiction. This research will support ongoing work that seeks to improve information regarding the effects of these compounds on health, performance, and disease state.

Project status: Ongoing

Principal Investigators

Funding

Funding Body: King’s Health Partners Clinical Trials Office

Amount: £35,000

Period: January 2021 - January 2026

Keywords

ANTI-DOPINGCANNABINOIDS