A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery.

INTRODUCTION: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). METHODS: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min-30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). RESULTS: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22-3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0-t]) of 7.74 h × ng/mL (90% CI 5.03-10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50-2.68) and AUC0-t of 10.4 h × ng/mL (90% CI 7.03-13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. CONCLUSION: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.

Left hemispheric cortical watershed infarcts triggered by carotid sinus self-massage.

A 69-year-old man was presented to our emergency department with acute onset of hemianopsia, aphasia and dizziness. He reported that while he was sitting in front of his computer at home, he had performed a bilateral self-massage of his carotid arteries when suddenly the symptoms occurred. A neurological examination revealed a hemianopsia with a visual field loss on the right side. In addition, a mild aphasic syndrome with agraphia and a word-finding disorder (National Institutes of Health Stroke Scale (NIHSS): 3 points) was diagnosed. The initial brain CT scan with CT angiography showed neither an intracerebral haemorrhage nor a cerebral infarction. Also, no occlusion or any signs of artery dissection or a flow relevant stenosis of the brain supplying arteries were found. After excluding other contraindications, an intravenous thrombolysis with weight-adapted alteplase was performed. The symptoms of the patient significantly improved in the short-term follow-up. Three days after admission no neurological deficits remained. The MRI of the brain revealed multifocal, small, left hemispherical strokes in the middle cerebral artery territory. In general, watershed infarcts after carotid sinus self-massage follow a rare ischaemic stroke mechanism. This case emphasises the importance of a detailed anamnestic evaluation to determine the aetiological classification of ischaemic stroke as well as educating patients' (poststroke) behaviour.

Olfactory and Gustatory Function After Bariatric Surgery.

BACKGROUND: Neither hormone levels nor malabsorption alone fully explains the distinct weight loss after bariatric surgery in morbidly obese patients. Postoperatively, patients regularly report a change in the sense of taste and the development of food aversions. Hedonic and sensory components like olfactory and gustatory stimuli significantly affect appetite and flavour. METHODS: We prospectively analysed the orthonasal olfactory and gustatory function with psychophysical testing in 44 patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or adjustable gastric banding (AGB) and in 23 healthy controls. RESULTS: About 22.7 % of morbidly obese patients were hyposmic, showing significantly lower threshold-discrimination-identification (TDI) scores (p = 0.009) with decreased discrimination and identification ability. In addition, 22.7 % of patients were tested to be limited in gustatory function, with significantly lower taste strip test (TST) scores (p = 0.003). Six months after surgery, olfactory and gustatory function was not different when compared to healthy controls. CONCLUSIONS: Due to obesity, patients frequently show impaired olfactory and gustatory function. Six months after laparoscopic bariatric surgery, both chemosensory functions improve. The TDI test is an appropriate tool to measure olfactory function in obese patients.