The overall objective of this proposal, A Functional Cell Based Assay for Synthetic Cannabinoids, is to develop a flexible and inexpensive screening assay that can detect all synthetic cannabinoids (SCs). Identification of SC abuse remains difficult for clinicians and law enforcement due to the rapid evolution of SC compounds. There are over 200 SCs known to exist though the most comprehensive clinical assay can only detect 43 of these drugs. In fact, more than 90% of SCs identified in patients seen in the University of Colorado Emergency Department are not detectable through the clinically available assay. High performance liquid chromatography- mass spectrometry methods are far more sensitive, though lack of reference standards, lack of availability, and cost remain a limitation of this drug detection method for the vast majority of clinical and law enforcement applications. New inexpensive drug screens able to detect rapidly evolving SC compounds are necessary. In this proposal, we employ an innovative strategy to detect new synthetic cannabinoids (SCs) through detection of activation of the cannabinoid receptor (CB1). The priorities are to create an assay that (a) will rapidly and cheaply detect binding and/or activation of CB1, (b) will distinguish between THC-level binding/activation and SC-level binding/activation, (c) can be integrated as a pre-screen prior to mass spectrometry confirmation. To achieve these priorities, we will develop and assess three independent detection systems of CB1 agonism via membrane potential change (Aim 1), cAMP production (Aim 2), and receptor conformational change (Aim 3). When completed, this receptor based-strategy can be used for detection of other new psychoactive substances, such as synthetic opioids, and can be optimized for rapid bedside screening of a large number of patients. Since avoidance of detection is a major reason SCs are chosen by users, increased screening will decrease use of these drugs. This technique is a solution for clinical and law enforcement detection of all new psychoactive substances.

R21DA048350

2020-09-15

2022-09-14