טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentDaniel Ben-Eliezer
SubjectThe Effect of Stress, Anxiety and Anxiolytic Drugs on
Cognitive Performance and Decision Making Among
Healthy Adults
DepartmentDepartment of Industrial Engineering and Management
Supervisor Full Professor Yechiam Eldad


Abstract

Benzodiazepines are very common anxiolytic drugs, causing inhibition of neuronal activity by binding to GABA receptors, thus having some adverse effect on several cognitive domains such as attention and working memory. Anxiety and stress also have adverse effects on cognitive performance, especially in moderate or high levels. Therefore, both anxiety and its common cure impair cognition. Hypericum perforatum, considered an antidepressant and anti-anxiety herbal compound, affects multiple neurotransmitters levels (including 5-HT, dopamine and GABA) in a non-competitive synergistic manner. Pre-clinical meta-analysis based on 13 studies not only show no effect of cognitive impairment, but even enhance cognition among rodents: both intact and stressed rodents showed increased cognitive performance under H. perforatum, as compared to a placebo. Following these results, we conducted a randomized double-blind clinical trial including 82 healthy adults participants (aged 19 to 35, 41% females) who attended two counter-balanced sessions: with a 250 or 500 mg single dose of Remotiv (drug including H. perforatum extract), and with a placebo. In both sessions, following a baseline psychological battery measuring mainly stress and anxiety, participants were administered either H. perforatum or placebo. Sixty minutes later they underwent a computerized cognitive battery measuring mainly working memory and attention. Results show better recalling performance for 250 mg Remotiv (vs. placebo) in the digit span and operation span tasks, and less omission rates in a go / no-go task. However, the 500 mg Remotiv slightly impaired performance in these tasks. The anxiolytic effect of H. perforatum was minimal, and no interaction between stress or anxiety and the drug on cognitive performance was found. Regarding healthy adults, a single small dosage H. perforatum seems to have some benefit regarding several cognitive domains, regardless of the presence of anxiety or stress levels. However, the limited acute anxiolytic effect does not allow H. perforatum to substitute benzodiazepines as a non cognitive-impairing acute anxiolytic agent. Additional analysis focusing on the mere relations between anxiety and cognitive performance, conducted only on a placebo condition, showed a clear U-shaped relation between anxiety and arousal, and attention and WM.