Cannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC) are the two best known and most extensively studied phytocannabinoids within Cannabis sativa. An increasing number of preclinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major Phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimised and validated a method for the simultaneous quantification of CBD, THC and their major Phase I metabolites 6‐hydroxy‐CBD (6‐OH‐CBD), 7‐hydroxy‐CBD (7‐OH‐CBD), 7‐carboxy‐CBD (7‐COOH‐CBD), 11‐hydroxy‐tetrahydrocannabinol (11‐OH‐THC) and 11‐carboxy‐tetrahydrocannabinol (11‐COOH‐THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive and can be carried out in high‐throughput 96‐well formats, ideal for larger scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. The application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open‐label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.

Research shows that various types of stem cells (SCs) have the ability to rebuild damaged heart tissue. The TIME and Late TIME human trials shed light on the optimum timing of SC therapy administration after myocardial damage. The FOCUS study failed to show a substantial positive effect of bone marrow-derived mononuclear cells in patients suffering from ischemic heart failure; however, some completed human trials do show promise, with improvement in cardiac function. Recent clinical trials have identified a subset of marrow cells that was able to stimulate endogenous adult cardiac SCs where cardiac SCs administration showed promise in the SCIPIO trial. This review addresses some of the lessons learned from clinical trials with SC therapy in ischemic heart failure.