The frequently changing chemical nature of synthetic cannabinoid (SCB) products limits effective detection of these drugs, as new methods must be constantly developed to find new SCB species. Additionally, it complicates overdose treatment, as new SCB analogues can exhibit novel pharmacological activity, leading to unique symptomatic presentation upon intoxication. There are now more than 250 known SCB analogues, and most of these remain diagnostically cryptic in human tissues. Indeed, several new SCB analogues were identified only after causing overdose outbreaks. Suspected SCB overdoses are currently addressed through ad hoc provision of supportive care, and only followed-up by screening after clinical resolution.
Given these challenges, we propose that a single ‘theranostic’ approach allowing for both rapid presumptive diagnoses of SCB intoxication, as well as immediate therapeutic follow up to reverse overdose symptoms would be effective in improving patient outcomes. In this context, we have previously observed that antibodies can independently be used to either detect or pharmacokinetically sequester several closely-related compounds. Therefore, this work employs vaccination with sub-structurally directed ‘Markush’ SCB haptens in order to address whether antibody-mediated binding can be used to predictively detect and neutralize otherwise cryptic SCB analogues.
Overall, experiments in this project will assess whether multiplexed, sub-structurally directed cross-reactive antibodies can meaningfully expand detection of SCB analogues, and whether anti-SCB antibodies can be employed to reverse overdose symptoms, as a test of principle for the employment of this technology as predictive ‘theranostics’ for SCB overdose.