Chemical transformation of cannabidiol into psychotropic cannabinoids under acidic reaction conditions: Identification of transformed products by GC-MS.

Recently, cannabidiol (CBD), one of the major components of the Cannabis species, has been a focus in the cannabis industry due to its various pharmacological effects. Interestingly, CBD can be converted into several psychoactive cannabinoids, such as 9-tetrahydrocannabinol (Δ9-THC) and its structural isomers, under acidic reaction conditions. In this study, chemical transformation of CBD in ethanol solution was conducted with variation in pH at 2.0, 3.5, and 5.0 by addition of 0.1 M hydrochloric acid (HCl). These resulting solutions were derivatized with trimethylsilyl (TMS) reagent and analyzed using GC/MS-scan mode. Time profiles of CBD degradation and transformation of products were examined according to variations in pH and temperature. Several transformed products produced after the acidic reaction of CBD were identified by matching retention times and mass spectra to authentic standards. Regarding the identification of products without authentic standards, the EI-mass spectra of such cannabinoid-OTMS derivatives were interpreted according to structural class, suggesting mass fragmentation pathways. From the GC/MS data, Δ9-THC, CBC, and ethoxy-hexahydrocannabinol (HHC) analogs were shown to be major components, and THC isomers (Δ8- and Δ10-THCs) and 9-hydroxy-HHC were observed as minor components. Using time profile data, the acidity of the reaction solution was an important factor in degradation of CBD. Degradation of CBD and formation of THC rarely occurred at pH 5.0, even at 70 °C with a long process time of 24 h. In contrast, degradation of CBD occurred readily at pH 3.5 and 30 °C over a short process time and was further accelerated by lowering pH, increasing temperature, and lengthening the process time. Based on profile data and identified transformed products, formation pathways from the degradation of CBD under acidic reaction conditions are suggested. Among the transformed products, seven components are known to have psychoactive effects. Thus, industrial CBD manufacturing processes in food and cosmetic products should be carefully controlled. These results will provide important guidelines on the control of manufacturing processes, storage, fermentation processes, and new regulation in industrial applications of CBD.

Effects of topiramate on language functions in newly diagnosed pediatric epileptic patients.

BACKGROUND: The aim of this study was to characterize the effects of topiramate on language functions in newly diagnosed pediatric epileptic patients. METHODS: Thirty-eight newly diagnosed epileptic patients were assessed using standard language tests. Data were collected before and after beginning topiramate during which time a monotherapy treatment regimen was maintained. Language tests included the Test of Language Problem Solving Abilities, a Korean version of the Peabody Picture Vocabulary Test. We used language tests in the Korean version because all the patients were spoken Korean exclusively in their families. RESULTS: All the language parameters of Test of Language Problem Solving Abilities worsened after initiation of topiramate (determine cause, 13.2 ± 4.8 to 11.2 ± 4.3; problem solving, 14.8 ± 6.0 to 12.8 ± 5.0; predicting, 9.8 ± 3.6 to 8.8 ± 4.6). Patients given topiramate exhibited a shortened mean length of utterance in words during response (determine cause, 4.8 ± 0.9 to 4.3 ± 0.7; making inference, 4.5 ± 0.8 to 4.1 ± 1.1; predicting, 5.2 ± 1.0 to 4.7 ± 0.6; P < 0.05), provided ambiguous answers during the testing, exhibited difficulty in selecting appropriate words, took more time to provide answers, and used incorrect grammar. However, there were no statistically significant changes in the receptive language of patients after taking topiramate (95.4 ± 20.4 to 100.8 ± 19.1). CONCLUSIONS: Our data suggest that topiramate may have negative effects on problem-solving abilities in children. We recommend performing language tests should be considered in children being treated with topiramate.