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Analytical and Pharmacological Challenges in Cannabis Research
21 February 2018 (online)
The millennial history of the use of cannabis as crop, medicinal and recreational plant reads like a novel in which the most recent chapter is dedicated to the current worldwide transformation of Cannabis sativa L. flos into a modern evidence-based botanical drug. Although Δ9-tetrahydrocannabinol (Δ9-THC) (dronabinol) is an approved monosubstance that can be prescribed to treat anorexia in AIDS patients and nausea during chemotherapy, muscle spasms and certain forms of chronic pain, Sativex® (Nabiximols®) is the only standardized cannabis extract approved to reduce symptoms in Multiple Sclerosis. Despite a lack of clinical trials for most of the indications in which cannabis is used medically, cannabis products are increasingly demanded by patients. Like a molecular fountain, cannabis pours bioactive cannabinoids into the toolbox of pharmacologists, as illustrated by the recent pharma enterprise to develop cannabidiol (CBD) and cannabidiverin (CBDV) to treat certain forms of epilepsy. While it is recognized that the major psychoactive cannabinoid Δ9-THC and the major non-psychoactive cannabinoid CBD, which occur in different ratios in distinct cannabis chemotypes, are of pharmaceutical relevance; minor cannabinoids, acid precursors and terpenes are believed to also play a role in the action of the diverse botanical formulations of medicinal cannabis. Importantly, increasing evidence suggests that CBD, though rather poorly bioavailable to the brain, can decrease the adverse effects of Δ9-THC by acting as a negative allosteric CB1 receptor modulator. Thus, in addition to the different worldwide and regional legal situations, numerous analytical and pharmacological questions arise. The aim of this Planta Medica special issues is to increase the awareness in the natural product research community regarding challenges in cannabinoid analytics and pharmacology, both of which are fundamental for the urgently required standardization of medical cannabis. Clearly, standardization in the context of cannabis implies improved pharmacological and clinical insights regarding the different forms of administration and chemotypes employed. Intriguingly, less than 2% of the published papers on cannabis currently deal with analytics. Here, a state of the art LC-MS/MS method as well as an UV-MS method were developed and validated for quantitative determination of major and minor cannabinoids of pharmacological relevance in different C. sativa samples including medicinal chemovars. Moreover, a gas-chromatography with flame ionization detector (GC-FID) method was developed and validated for the versatile qualitative and quantitative analysis of acid and neutral cannabinoids in C. sativa extracts. The method involves trimethyl silyl derivatization of the extracts. Another study analyzed C. sativa olive oil preparations for medical applications as they are used in Italian pharmacies. A different study demonstrates that the products of supercritical CO2 extraction may have a significantly different chemical fingerprint from that of cannabis flower. These results highlight the need for more complete characterization of cannabis products beyond cannabinoid content. In a pharmacological study morphine addicted mice displayed robust place preference that was attenuated by 10 mg/kg CBD. The finding that cannabidiol blocks opioid reward in mice suggests that this compound may be useful in addiction treatment settings. A rather provocative study attempts to classify different terpenes in cannabis chemovars in light of their alleged pharmacological actions, largely based on anecdotal clinical data. Nevertheless, this paper shows that there is an urgent need to better study the clinical actions of the different complex cannabis botanical drugs that seem to have distinct pharmacological effects beyond their differing CBD and Δ9-THC content. Moreover, one review summarizes the current efforts and perspectives on the biotechnological cannabinoid production in plants, thus complementing the issues focus on multicomponent mixtures. All the papers presented in this special issue underline diverse aspects of the current cannabis research and should inspire researchers to engage in the interdisciplinary nature of this field. Cannabis is a prototype phytopharmakon with numerous therapeutic promises in need of analytical, pharmacological and clinical confirmation (i.e. evidence). The guest Editor thanks all the authors for their valuable contributions in this special cannabis issue, all the reviewers for their work in the evaluation of the manuscripts and the editor in chief and the editorial staff of Planta Medica.