Abstracts

 Methods: Two Phase 1, randomized, double-blind, placebo-controlled studies in healthy adults were conducted to determine the neuropsychological effects of ZYN002. One study was a single ascending-dose study in which 32 subjects were treated with ZYN002 50 mg (n = 6), 100 mg (n = 6), 125 mg (n = 6), 250 mg (n = 6), or placebo (n = 8). Assessments included the Trail Making Test. The other study was a seven-day multiple-dose study in which 24 subjects were treated with ZYN002 200 mg (n = 6), 250 mg (n = 6), 500 mg (n = 6), or placebo (n = 6). Assessments included the following tests: Trail Making, PASAT, DAT, ARCI, PANAS, IDAS, and CSSRS. Results: In the single-dose study, no impairment on trail making was observed. Subjects treated with 50 mg ZYN002 outperformed those receiving placebo on time to trail completion, but there were no other effects of drug condition or drug-time interactions, and there were no effects or interactions on total line length. In the multiple-dose study, scores on the PANAS positive affect subscale were similar across ZYN002 doses and reduced over time, but there were no effects on the negative affect subscale. There were mixed dose effects for the IDAS, but they appear to reflect population differences more than drug effects, and there was no interaction with time. The range of ZYN002 doses administered in these studies produced no differences in any cognitive performance measures. Conclusions: In these studies, ZYN002 doses ranging from 100 mg to 500 mg daily were not associated with cognitive impairment or feelings of euphoria. These results are significant because they represent the first human clinical study of CBD via transdermal delivery, and they distinguish treatment with ZYN002 from treatment with Cannabis or THC. Funding: This study was funded by Zynerba Pharmaceuticals Inc.