Psilocybin as a tool for enhancing cognitive flexibility

The study will assess drug-induced change in performance in divergent thinking and goal-directed behaviour when comparing psilocybin to placebo, before and after 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.

Topic Creativity
Compound Psilocybin
Status Planned
Results Published No
Start date 01 May 2017
End date 01 May 2020
Chance of happening 100%
Phase Phase I
Design Open
Type Interventional
Generation First
Participants 60
Sex All
Age 18- 40
Therapy No

Trial Details

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.

NCT Number

Sponsors & Collaborators

Maastricht University
Maastricht University is host to the psychopharmacology department (Psychopharmacology in Maastricht) where various researchers are investigating the effects of psychedelics.

Papers

The unique neural signature of your trip: Functional connectome fingerprints of subjective psilocybin experience
This re-analysis (n=48) of a double-blind study on the effects of psilocybin (12mg, n=21) finds that function connectomes (FCs) become more idiosyncratic, especially in the default-mode network (DMN). Looking specifically at the DMN, the researchers find reduced within-DMN activity and more connectivity with attentional systems.

Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study
This double-blind placebo-controlled paper (n=60) explores the effects psilocybin (12mg/70kg) has on a range of inflammatory markers associated with stress-related psychiatric disorders. Blood samples, MRI and questionnaires were used to assess different aspects of the immune response. Psilocybin immediately reduced levels of the inflammation-inducing TNF-α while other markers were unchanged. After seven days, TNF-α returned to baseline while levels of IL-6 and CRP were reduced in the psilocybin group, which were associated with more persisting positive mood and social effects.

Spontaneous and deliberate creative cognition during and after psilocybin exposure
This double-blind, placebo-controlled, between-subjects study (n=60) investigated the effects of psilocybin (11.9 mg/70kg) on creativity in healthy participants, with respect to acute and persisting changes in convergent and divergent thinking in relation to restructuralization of Default Mode Network (DMN) connectivity. Although subjects felt more insightful under the acute psychedelic state, their ability to generate ideas and associations in a goal-directed manner was impaired. However, 7 days after psilocybin administration, participants generated a higher quantity of novel ideas for uses of an everyday object. Decreased integrity of the DMN under the acute state was the strongest predictor of subjective insightfulness, acute decrease in scores of originality, and a long-term increase in the generation of novel ideas.

Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin
This brain imaging study (n=60) with psilocybin (12mg/70kg) investigated the changes in glutamate levels in various brain areas and found that lower levels in hippocampal glutamate were correlated with positively experienced ego dissolution. Higher levels of medial prefrontal cortical glutamate correlated with negatively experienced ego dissolution.

Data attribution

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