Cognitive flexibility

Every compound in the sci-wiki that affects cognitive flexibility; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

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Nootropic

MK-0777

MK-0777 was a Merck compound built to be a benzodiazepine-like drug without the sedation; it selectively potentiated GABA-A receptors carrying the alpha2 or alpha3 subunit instead of hitting alpha1 (the subunit responsible for benzodiazepine sedation and abuse liability). The idea came out of University of Pittsburgh postmortem work showing that GABA neurotransmission onto pyramidal cells in the schizophrenic prefrontal cortex is weakened, which was proposed as a root cause of the working-memory deficits in the disease. A small 2008 open-label-adjacent proof-of-concept trial in chronic schizophrenia patients found real improvements on working-memory tasks and increased frontal gamma power, which made a fair bit of noise in the field. A larger, properly randomized follow-up then failed to replicate the benefit, and Merck quietly let the program lapse; it never advanced past early Phase II.

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Nootropic

Tabernanthalog

Tabernanthalog (TBG) is a synthetic analogue of the plant alkaloid ibogaine, engineered to be water-soluble and, according to its developers, non-hallucinogenic and less toxic than the parent compound. It was created in the laboratory of David Olson at the University of California, Davis, as an example of a psychoplastogen, a molecule meant to promote the rewiring of brain circuits. In rodent studies it has shown antidepressant-like effects and has reduced alcohol- and drug-seeking behavior without triggering the responses that signal a psychedelic experience.

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