Quantitative Profiling of Terpenes and Pesticides in Medicinal Cannabis Matrices and Biological Fluids for Standardization and Forensic Toxicological Assessment

Abstract

Natural plant concentrates have been used for many decades in folk medicine, however in recent times, cannabis-derived therapeutics have re-emerged in the pharmaceutical industry due to their purported ability to help treat a vast range of pathologies [30, 35, 36]. Legislation around the use of cannabis in traditional medicine vs. its legal status as a drug of abuse for recreation is a hot topic of debate limiting its acceptance in modern medicine. With the current outcome of the Cannabis referendum and continued push towards legalizing recreational use of cannabis in New Zealand, the efficacy, safety and traceability of emerging cannabis products needs to be rigorously investigated. Aside from testing for safety and potency, there is pharmaceutical and forensic interest in the detection and quantitation of terpenes, pesticides, and mycotoxins in the different varieties of cannabis plant grown for medicinal use. In this research gas chromatography and liquid chromatography tandem mass spectrometry methodology were developed to profile terpene and pesticide content in fourteen cannabis plant variants and twelve cannabis-derived products. The terpene fingerprint of cannabis plant variants was extremely diverse, whereby variants could easily be distinguished when assessing terpene profiles. Some varieties were dominated by a single terpene whilst others showed general sesquiterpene or monoterpene prevalence. β-Myrcene and βcaryophyllene typically dominated varieties, also being quantitated at the highest level in twelve plants. The same distribution of terpenes was observed in cannabis-derived therapeutics, however the degree of terpene diversity fluctuated across different matrix types (oil, spray, semi-solid fats). β-Caryophyllene, β-myrcene, α-pinene and α-bisabolol were quantitated at the highest levels within the products. Investigation into the application of terpenes as biomarkers of cannabis use in human blood produced results that suggested this was a plausible proposition. Ten of the most bioactive terpenes were identified in the blood of cannabis users at levels much greater than in an individual who had not used cannabis. Pesticide assessment across the cannabis varieties included in this research determined pyrethrins I, pyrethrins II and spiromesifen to be present. The facile methodology developed shows credible viability to establish the terpene profile and detect pesticides for analysis in raw cannabis plant material and plant derived products. Furthermore, the methods showed suitability for analysis of terpenes in blood samples, which can find application as biomarkers for cannabis use.