Most clinical studies ofCannabistoday focus on the contents of two phytocannabinoids: (-)-Δ⁹-trans-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD), regardless of the fact that the plant contains over 100 additional phytocannabinoids whose therapeutic effects and interplay have not yet been fully elucidated. This narrow view of a complexCannabisplant is insufficient to comprehend the medicinal and pharmacological effects of the whole plant. In this study we suggest a new ESI-LC/MS/MS approach to identify phytocannabinoids from 10 different subclasses, and comprehensively profile the identified compounds in diverse medicalCannabisplants. Overall, 94 phytocannabinoids were identified and used for profiling 36 of the most commonly usedCannabisplants prescribed to patients in Israel. In order to demonstrate the importance of comprehensive phytocannabinoid analysis before and throughout medicalCannabisclinical trials, treatments, or experiments, we evaluated the anticonvulsant effects of several equally high-CBDCannabisextracts (50% w/w). We found that despite the similarity in CBD contents, not allCannabisextracts produced the same effects. This study’s approach for phytocannabinoid profiling can enable researchers and physicians to analyze the effects of specificCannabiscompositions and is therefore critical when performing biological, medical and pharmacological-based research usingCannabis.

Cannabis or its derivatives are widely used by patients with cancer to help with cancer symptoms and treatment side effects. However, cannabis has potent immunomodulatory properties. To determine if cannabis consumption during immunotherapy affects therapy outcomes, we conducted a prospective observatory study including 102 (68 immunotherapy and 34 immunotherapy plus cannabis) consecutive patients with advanced cancers who initiated immunotherapy. Cannabis consumption correlated with a significant decrease in time to tumor progression and overall survival. On the other hand, the use of cannabis reduced therapy-related immune-related adverse events. We also tested the possibility that cannabis may affect the immune system or the tumor microenvironment through the alteration of the endocannabinoid system. We analyzed a panel of serum endocannabinoids (eCBs) and eCB-like lipids, measuring their levels before and after immunotherapy in both groups. Levels of serum eCBs and eCB-like lipids, before immunotherapy, showed no significant differences between cannabis users to nonusers. Nevertheless, the levels of four eCB and eCB-like compounds were associated with patients’ overall survival time. Collectively, cannabis consumption has considerable immunomodulatory effects, and its use among cancer patients needs to be carefully considered due to its potential effects on the immune system, especially during treatment with immunotherapy.

Oncotarget | https://doi.org/10.18632/oncotarget.26983 Liran Baram, Ella Peled, Paula Berman, Ben Yellin, Elazar Besser, Maya Benami, Igal Louria-Hayon, Gil M. Lewitus, David Meiri

The therapeutic effect of Cannabis largely depends on the content of its pharmacologically active secondary metabolites, mainly phytocannabinoids, flavonoids, and terpenoids. Recent studies suggest there are therapeutic effects of specific terpenoids as well as synergistic effects with other active compounds in the plant. Although Cannabis contains an overwhelming milieu of terpenoids, only a limited number are currently reported and used for metabolic analysis of Cannabis chemovars. In this study, we report the development and validation of a method for simultaneous quantification of 93 terpenoids in Cannabis air-dried inflorescences and extracts. This method employs the full evaporation technique via a static headspace sampler, followed by gas chromatography–mass spectrometry (SHS-GC/MS/MS). In the validation process, spiked terpenoids were quantified with acceptable repeatability, reproducibility, sensitivity, and accuracy. Three medical Cannabis chemovars were used to study the effect of sample preparation and extraction methods on terpenoid profiles. This method was further applied for studying the terpenoid profiles of 16 different chemovars acquired at different dates. Our results demonstrate that sample preparation methods may significantly impact the chemical fingerprint compared to the nontreated Cannabis. This emphasizes the importance of performing SHS extraction in order to study the natural terpenoid contents of chemovars. We also concluded that most inflorescences expressed relatively unique terpenoid profiles for the most pronounced terpenoids, even when sampled at different dates, although absolute concentrations may vary due to aging. The suggested method offers an ideal tool for terpenoid profiling of Cannabis and sets the scene for more comprehensive works in the future.

1H low field nuclear magnetic resonance (LF-NMR) relaxometry has been suggested as a tool to distinguish between different molecular ensembles in complex systems with differential segmental or whole molecular motion and/or different morphologies. In biodiesel applications the molecular structure versus liquid-phase packing morphologies of fatty acid methyl esters (FAMEs) influences physico-chemical characteristics of the fuel, including flow properties, operability during cold weather, blending, and more. Still, their liquid morphological structures have scarcely been studied. It was therefore the objective of this work to explore the potential of this technology for characterizing the molecular organization of FAMEs in the liquid phase. This was accomplished by using a combination of supporting advanced technologies. We show that pure oleic acid (OA) and methyl oleate (MO) standards exhibited both similarities and differences in the 1H LF-NMR relaxation times (T2s) and peak areas, for a range of temperatures. Based on X-ray measurements, both molecules were found to possess a liquid crystal-like order, although a larger fluidity was found for MO, because as the temperature is increased, MO molecules separate both longitudinally and transversely from one another. In addition, both molecules exhibited a preferred direction of diffusion based on the apparent hydrodynamic radius. The close molecular packing arrangement and interactions were found to affect the translational and segmental motions of the molecules, as a result of dimerization of the head group in OA as opposed to weaker polar interactions in MO. A comprehensive model for the liquid crystal-like arrangement of FAMEs in the liquid phase is suggested. The differences in translational and segmental motions of the molecules were rationalized by the differences in the 1H LF-NMR T2 distributions of OA and MO, which was further supported by 13C high field (HF)-NMR spectra and 1H HF-NMR relaxation. The proposed assignment allows for material characterization based on parameters that contribute to properties in applications such as biodiesel fuels.