Subchronic oral toxicity assessment of a cannabis extract.

Cannabidiol (CBD) is present in Cannabis Sativa L. and has been used in medicines and foods to deliver beneficial health effects. Despite this, research on CBD safety utilising modern testing methods is lacking. Therefore three separate safety experiments were performed on a CBD isolate. Sprague-Dawley rats were used to investigate prenatal development, a 14-day toxicity sighting study, and an OECD compliant 90-day subchronic oral toxicity trial, with 35-day off-dose recovery. The prenatal screening study demonstrated reduced body weights and food consumption in the highest dose group, but no substance-related changes in pregnancy rate, maternal or placental gross abnormalities, or premature deliveries. The 14-day study indicated tolerance up to 460 mg/kg bw/d of CBD isolate. Based on these findings, a 90-day repeated dose oral toxicity study was performed at doses of 0, 30, 115, 230, and 460 mg/kg bw/d of CBD, followed by a 35-day off-dose recovery period. In the 90-day study, some non-adverse organ and tissue changes were observed. With the exception of the high dose group, these fully reversed during the recovery period. Based on these findings, sub-chronic consumption of highly purified isolate results in a CBD NOAEL of 460 mg/kg bw/d for males and 230 mg/kg bw/d for females.

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures.

Exertional heat stroke (EHS) is a life-threatening medical condition involving thermoregulatory failure and is the most severe condition along a continuum of heat-related illnesses. Current EHS policy guidance principally advocates a thermoregulatory management approach, despite growing recognition that gastrointestinal (GI) microbial translocation contributes to disease pathophysiology. Contemporary research has focused to understand the relevance of GI barrier integrity and strategies to maintain it during periods of exertional-heat stress. GI barrier integrity can be assessed non-invasively using a variety of in vivo techniques, including active inert mixed-weight molecular probe recovery tests and passive biomarkers indicative of GI structural integrity loss or microbial translocation. Strenuous exercise is strongly characterised to disrupt GI barrier integrity, and aspects of this response correlate with the corresponding magnitude of thermal strain. The aetiology of GI barrier integrity loss following exertional-heat stress is poorly understood, though may directly relate to localised hyperthermia, splanchnic hypoperfusion-mediated ischemic injury, and neuroendocrine-immune alterations. Nutritional countermeasures to maintain GI barrier integrity following exertional-heat stress provide a promising approach to mitigate EHS. The focus of this review is to evaluate: (1) the GI paradigm of exertional heat stroke; (2) techniques to assess GI barrier integrity; (3) typical GI barrier integrity responses to exertional-heat stress; (4) the aetiology of GI barrier integrity loss following exertional-heat stress; and (5) nutritional countermeasures to maintain GI barrier integrity in response to exertional-heat stress.