Explore studies of cognitive enhancement.
Hippocampal dynorphins and enkephalins regulate synaptic transmission efficiency at granule cell synapses, with opioid levels changing dramatically under different physiological and pathological conditions.
Morris, B J; Johnston, H M · Review
Proenkephalin-derived peptides increase hippocampal excitability via mu/delta receptors, while prodynorphin-derived peptides decrease it via kappa receptors, providing opposing regulation of memory circuits.
Simmons, M L; Chavkin, C · Review
Selank selectively enhanced conditioned avoidance learning and memory in rats with initially low learning ability while minimally affecting normal learners, demonstrating deficit-correcting rather than general cognitive enhancement.
Kozlovskii, I I; Danchev, N D · Animal Study
Semax upregulated BDNF mRNA and TrkB receptor expression in the rat hippocampus, providing the neurotrophic molecular mechanism for its documented cognitive enhancement and neuroprotective effects — BDNF is the brain's primary growth and survival factor.
Dolotov, Oleg V; Karpenko, Ekaterina A; Inozemtseva, Lyudmila S; Seredenina, Tamara S; Levitskaya, Natalia G; Rozyczka, Joanna; Dubynina, Elena V; Novosadova, Ekaterina V; Andreeva, Lyudmila A; Alfeeva, Lyudmila Yu; Kamensky, Andrey A; Grivennikov, Igor A; Myasoedov, Nikolay F; Engele, Jürgen · Animal Study
Semax (ACTH 4-10 analog) showed specific binding to rat brain tissue and increased brain-derived neurotrophic factor (BDNF) protein levels, confirming receptor-mediated neurotrophin enhancement as the mechanism for its nootropic and neuroprotective activities.
Dolotov, Oleg V; Karpenko, Ekaterina A; Seredenina, Tamara S; Inozemtseva, Lyudmila S; Levitskaya, Natalia G; Zolotarev, Yuriy A; Kamensky, Andrey A; Grivennikov, Igor A; Engele, Juergen; Myasoedov, Nikolay F · Animal Study
Intranasal oxytocin significantly improved performance on the Reading the Mind in the Eyes test in healthy men, demonstrating enhanced social cognition and emotional theory of mind — a distinct cognitive effect beyond anxiety reduction.
Domes, Gregor; Heinrichs, Markus; Michel, Andre; Berger, Christoph; Herpertz, Sabine C · RCT
Noopept (proline-containing dipeptide) restored spatial memory in brain-lesioned rats and increased hippocampal BDNF immunoreactivity, establishing BDNF upregulation as the neurotrophic mechanism for Noopept's cognitive-enhancing and neuroprotective activities.
Ostrovskaya, Rita U; Gruden, Marina A; Bobkova, Natalya A; Sewell, Robert D E; Gudasheva, Tatyana A; Samokhin, Alexander N; Seredinin, Sergey B; Noppe, Wim; Sherstnev, Vladimir V; Morozova-Roche, Ludmilla A · Animal Study
Intranasal oxytocin in healthy men increased trust behavior AND prevented trust adaptation (trust reduction) after betrayal in a social investment game, shaping the neural circuitry of both trust formation and trust resilience — with implications for social anxiety and autism.
Baumgartner, Thomas; Heinrichs, Markus; Vonlanthen, Aline; Fischbacher, Urs; Fehr, Ernst · RCT
Intranasal davunetide (NAP peptide) did not significantly improve cognitive test scores (MCCB) versus placebo in 63 people with schizophrenia over 12 weeks. However, it did significantly improve functional capacity — the ability to perform real-world tasks — as measured by the UPSA (p = 0.048). The 5 mg dose showed stronger effects than 30 mg, with effect sizes of d = 0.74 for functional capacity and d = 0.34 for cognition. The peptide was well tolerated with no significant side effects. The authors estimated 45–50 subjects per group would be needed to detect significant cognitive effects in future trials.
Javitt, Daniel C; Buchanan, Robert W; Keefe, Richard S E; Kern, Robert; McMahon, Robert P; Green, Michael F; Lieberman, Jeffrey; Goff, Donald C; Csernansky, John G; McEvoy, Joseph P; Jarskog, Fred; Seidman, Larry J; Gold, James M; Kimhy, David; Nolan, Karen S; Barch, Deanna S; Ball, M Patricia; Robinson, James; Marder, Stephen R · Randomized Controlled Trial
DA4-JC improved cognition, enhanced hippocampal synaptic function, normalized mitochondria via PINK1-Parkin pathway, and reduced both amyloid and p-tau pathology in APP/PS1/Tau transgenic mice.
Cai, Hong-Yan; Yang, Dan; Qiao, Jing; Yang, Jun-Ting; Wang, Zhao-Jun; Wu, Mei-Na; Qi, Jin-Shun; Hölscher, Christian · Animal
Preclinical evidence supports GLP-1 receptor agonists as potential cognitive enhancers, with activity in brain regions involved in learning and memory, though clinical evidence in schizophrenia is still needed.
Flintoff, Jonathan; Kesby, James P; Siskind, Dan; Burne, Thomas Hj · Review