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Robotic Applications within Orthodontics: Changing the face area of recent Medical Proper care.
tly 1 h postuse. These results underscore the potential utility of the DRUID app for assessing acute cannabis-related psychomotor impairment. Further research is needed to explore whether the DRUID app and/or the specific psychomotor functions it assesses might serve as a tool for measuring cannabis-related driving impairment. Clinical trials registration number for the Colorado Study NCT03522103.Introduction The cannabinoid Δ9-tetrahydrocannabinolic acid (Δ9-THCA) has long been suggested in review articles and anecdotal reports to be anticonvulsant; yet, there is scant evidence supporting this notion. The objective of this study was to interrogate the anticonvulsant potential of Δ9-THCA in various seizure models-the Scn1a+/- mouse model of Dravet syndrome, the 6-Hz model of psychomotor seizures and the maximal electroshock (MES) model of generalized tonic-clonic seizures. Materials and Methods We examined the effect of acute Δ9-THCA treatment against hyperthermia-induced seizures, and subchronic treatment on spontaneous seizures and survival in the Scn1a+/- mice. We also studied the effect of acute Δ9-THCA treatment on the critical current thresholds in the 6-Hz and MES tests using outbred Swiss mice. ALKBH5 inhibitor 2 solubility dmso Highly purified Δ9-THCA was used in the studies or a mixture of Δ9-THCA and Δ9-THC. Results We observed mixed anticonvulsant and proconvulsant effects of Δ9-THCA across the seizure models. Highly pure Δ9-THCA did not affect hyperthermia-induced seizures in Scn1a+/- mice. A Δ9-THCA/Δ9-THC mixture was anticonvulsant in the 6-Hz threshold test, but purified Δ9-THCA and Δ9-THC had no effect. Conversely, both Δ9-THCA and Δ9-THC administered individually were proconvulsant in the MES threshold test but had no effect when administered as a Δ9-THCA/Δ9-THC mixture. The Δ9-THCA/Δ9-THC mixture, however, increased spontaneous seizure severity and increased mortality of Scn1a+/- mice. Discussion The anticonvulsant profile of Δ9-THCA was variable depending on the seizure model used and presence of Δ9-THC. Because of the unstable nature of Δ9-THCA, further exploration of Δ9-THCA through formal anticonvulsant drug development is problematic without stabilization. Future studies may better focus on determining the mechanisms by which combined Δ9-THCA and Δ9-THC alters seizure thresholds, as this may uncover novel targets for the control of refractory partial seizures.Introduction CBD is a major phytocannabinoid in hemp (Cannabis sativa containing less than 0.3% THC). Hemp cigarettes are a combustible form of hemp consisting of dried and smokable flowers, which represent 2% of the overall CBD market, and the market is expected to grow. Combustion and pyrolysis of organic material are associated with the production of carbonyl compounds, which are known toxicants and are associated with adverse health outcomes. Concentrations of carbonyl compounds in mainstream hemp cigarette smoke are unknown. Materials and Methods We analyzed and compared carbonyl concentrations in the mainstream smoke produced by a hemp cigarette (Brand B), a premium hemp cigarette (Brand A), Marlboro Red tobacco cigarette, and a research reference tobacco cigarette using high-performance liquid chromatography. We measured carbonyl concentrations in μg per puff and mg per cigarette. Carbonyls investigated were formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, crotonaldehyde, 2-butanone, and butyraldehyde. Significance was determined using Tukey's test. Results We observed that Brand B had significantly higher butyraldehyde than any cigarette. No significant differences were observed in crotonaldehyde concentration in the cigarettes. For the remaining carbonyls, Brand A had consistently lower concentrations in mainstream smoke than tobacco cigarettes. Hemp cigarettes emit carbonyls in a lower concentration in μg/puff than tobacco cigarettes, but the magnitude of significance generally decreases when normalized to mg/cigarette. Conclusions Smoke from hemp cigarettes contains carbonyls at biologically significant concentrations. Opportunities may exist to reduce carbonyl production in these products, and identified potential risks must be considered when balancing the harms and benefits of hemp cigarettes when used for therapeutic purposes.Introduction Cannabidiol (CBD) has antiseizure properties but no psychoactive effects. Randomized controlled trials of an oral, pharmaceutical formulation of highly purified CBD are promising; however, data regarding other formulations are sparse and anecdotal. We evaluated the effectiveness of add-on therapy with a standardized CBD-based oil in treatment-resistant epilepsy (TRE) patients. Materials and Methods An open retrospective study was carried out on patients with refractory epilepsy of different etiology. We reviewed clinical data from medical charts and caregiver's information. Participants received add-on with 24% CBD-based oil, sublingually administered, at the starting dose of 5-10 mg/[kg·day] up to the maximum dose of 50 mg/[kg·day], based on clinical efficacy. Efficacy was evaluated based on patients being seizure free or experiencing at ≥50% improvement on seizure frequency. Tolerability and suspected adverse drug reaction data were also analyzed. Results We included 37 patients (46% female) with a median age of 16.1 (range 2-54) years. Twenty-two (60%) patients suffered from epileptic encephalopathy, 9 (24%) from focal epilepsy, and 6 (16%) from generalized epilepsy. Mean follow-up duration was 68 (range 24-72) weeks. The average age at seizure onset was 3.8±2.1 years (range 7 days-21 years). The median achieved CBD-based oil dose was 4.2±11.4 (range 0.6-50) mg/[kg·day]. At 40-month follow-up, 7 (19%) patients were seizure free, 27 (73%) reported >50% improvement, 2 (5%) patients reported less then 50% improvement, and 1 patient discontinued therapy due to lack of efficacy. Weaning from concomitant antiepileptic drugs was obtained after 24 weeks from CBD introduction in 10 subjects. Mild and transitory adverse events, including somnolence or loss of appetite, occurred in nine (25%) patients. Discussion and Conclusion We showed the efficacy of a CBD-based oil formulation with few significant side effects in patients with TRE of various etiologies.
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