As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by 18 F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.metabolism | thermogenesis | respiratory quotient | norepinephrine | white adipose tissue B rown adipose tissue (BAT) is a type of fat that consumes calories to generate heat. Multiple recent studies have shown that adult humans have functional BAT that can be activated in response to cold exposure in a process called nonshivering thermogenesis (1-4). In both small and large population studies (1, 2, 4, 5), there is an inverse correlation between BAT activity and obesity, suggesting that activating BAT, through pharmacological, environmental, or potentially nutritional interventions, could become a therapeutic means to treat obesity and diabetes. Indeed, human BAT energy expenditure may be a critical counterbalance to the weight gain and metabolic dysregulation caused by excess energy storage in white adipose tissue.Human BAT has a high density of both nerves and blood vessels (6), providing two general approaches to activate BAT. Based on studies in rodents, it is known that the sensation of cold by the skin and body core sends signals via peripheral neurons to the spinal cord and then up to the preoptic area of the hypothalamus for processing. From the hypothalamus, some signals go to the cerebral cortex for conscious thermal perception and localization, and others go to premotor neurons in the rostral raphe pallidus of the brainstem, projecting to neurons of the peripheral sympathetic nervous system (SNS) (reviewed in ref. 7). Ultimately, postganglionic SNS nerves release norepinephrine to activate BAT via induction of uncoupling protein-1, the tissue-specific protein that allows BAT to generate heat by uncoupling aerobic respiration from the generation of ATP.Because the endogenous pathways by cold exposure are complex and indirect, an attractive alternative for stimulation of BAT has been the use of pharmacological agents. As norepinephrine itself has too many adverse effects on the ...

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Purpose of review To examine the spectrum of emergency department presentations associated with cannabis use or misuse that are currently seen in the pediatric population. Recent findings There is a growing concern that pediatric emergency department visits related to cannabis are on the rise, especially given rapidly changing legislation on cannabis and its broad availability in certain areas. These concerns are substantiated in the current literature, as the evidence mounts for an array of emergency department presentations of intentional or accidental cannabis use. The range of presentations documented in the recent literature spans gastrointestinal, psychiatric and cardiorespiratory effects, in addition to traumatic injuries and accidental ingestions by younger children. Complications of chronic cannabis use, such as ‘cannabis hyperemesis syndrome’, depression, psychosis or cognitive impairment, are now recognized outcomes and even more are likely to emerge. Summary An array of cannabis-related symptoms is possible from acute use or exposure. Common presentations include acute intoxication, hyperemesis, depression and acute physical injuries from impaired psychomotor function. Uncommon presentations include cardiorespiratory effects, and a range of symptoms in young children that include hyperkinesis and coma. Clinical vigilance is needed to suspect and clinically diagnose cannabis exposure in the emergency department.