Cannabidiol (CBD) has substantial therapeutic potential, but its development as an effective drug by the pharmaceutical industry is hindered by intrinsic characteristics such as low bioavailability, low water solubility, and variable pharmacokinetic profiles. Importantly, lack of patentability of the drug substance also limits the likelihood of an expensive, full development programme in anything other than orphan indications. Potential avenues to overcome these issues with CBD include self-emulsifying drug delivery systems, improved crystal formulations and other solid-state delivery formulations, which are mostly in the pre-clinical or early clinical stages of development. This review identifies issues compromising current delivery of solid-state CBD, and how advanced pharmaceutical development strategies can enable CBD to realise the full potential as a successful therapeutic agent.

Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD −2.0; 95% CI −2.38, −1.61; p < 0.00001) and permanent (SMD −1.54; 95% CI −2.38, −1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD −1.63; 95% CI −1.97, −1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4–9/10); Egger’s test suggested publication bias ( p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.

<b><i>Introduction:</i></b> Cannabidiol (CBD) can be isolated from <i>Cannabis sativa</i> L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources. <b><i>Methods:</i></b> Six purified samples of CBD were obtained, 4 of these were natural and 2 synthetic. The anticancer effects of CBD were assessed in a human ovarian cancer cell line (SKOV-3 cells). The neuroprotective effects of CBD were assessed in human pericytes in a model of stroke (oxygen glucose deprivation [OGD]). The ability of CBD to restore inflammation-induced intestinal permeability was assessed in differentiated human Caco-2 cells (a model of enterocytes). <b><i>Results:</i></b> (1) In proliferating and confluent SKOV-3 cells, all CBD samples similarly reduced resazurin metabolism as a marker of cell viability in a concentration-dependent manner (<i>p</i> &#x3c; 0.001). (2) In pericytes exposed to OGD, all CBD samples similarly reduced cellular damage (measured by lactate dehydrogenase) at 24 h by 31–48% and reduced inflammation (measured by IL-6 secretion) by 30–53%. Attenuation of IL-6 was inhibited by 5HT_1A receptor antagonism for all CBD sources. (3) In differentiated Caco-2 cells exposed to inflammation (TNFα and IFNγ, 10 ng/mL for 24 h), each CBD sample increased the speed of recovery of epithelial permeability compared to control (<i>p</i> &#x3c; 0.05–0.001), which was inhibited by a CB₁ receptor antagonist. <b><i>Conclusion:</i></b> Our results suggest that there is no pharmacological difference in vitro in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD. The purity and reliability of CBD samples, as well as the ultimate pharmaceutical preparation, should all be considered above the starting source of CBD in the development of new CBD medicines.