Psilocybin as a tool for enhancing cognitive flexibility”

Posttraumatic stress disorder (PTSD) is an anxiety disorder in which an individual’s ability to function is impaired by emotional responses to memories of a traumatic event. It is typically a chronic illness associated with high rates of psychiatric and medical comorbidity, disability, suffering, drug abuse, and suicide. However despite the high incidence of PTSD, current therapies provide limited effectiveness, with many people being unresponsive to treatment. Suggestions for effective treatments for PTSD include a hypothetical drug that would be capable of enhancing divergent thinking, a cognitive process used to generate as many innovative ideas as possible. A recent study from our lab showed that psychedelics significantly increased divergent thinking after drug intake. Furthermore, imaging studies have shown that the classic psychedelic, psilocybin, promotes a de-synchronization in the default mode network that is suggested to result in cognitive flexibility and enhanced creative thinking. Taken together these studies suggest that psilocybin can enhance divergent thinking, which may provide therapeutic potential in facilitating goal directed over habitual behaviour. Principal demonstrations showing that psilocybin facilitates cognitive flexibility would be very relevant for future support of clinical applications of psilocybin assisted therapy in PTSD patients, and may provide therapeutic potential for patients whom current options are not effective.

The study will assess drug-induced change in performance in divergent thinking and goal-directed behaviour when comparing psilocybin to placebo, before and after an induction of stress. Additional study parameters include frontal-subcortical connectivity alterations and neurotransmission of glutamate and GABA between treatment conditions, as well as subjective questionnaires, pharmacokinetics, and cortisol.

Measurements will take place up until 360 minutes after drug intake on testing day one. Testing day two includes up to 2.5 hours of follow up measurements.

psilocybin (.17 mg/kg) bodyweight or placebo;
Maastricht acute stress test or placebo