Semax's Effects: A Breakdown Of The Research

Written by Johnathon Anderson, Ph.D., a research scientist specializing in regenerative medicine and serving as an Associate Professor at the University of California Davis School of Medicine 

What is Semax?

Semax peptide is a unique fragment derived from adrenocorticotropic hormone (ACTH), specifically from its 4-7 segment. (1) ACTH is secreted by corticotroph cells in the pituitary gland. It’s secreted in several intermittent pulses throughout the day into the bloodstream and body. Just like cortisol, levels of adrenocorticotropic hormone are typically high in the morning when we wake up and lower throughout the day.

Does Semax Research Indicate Regulation of Neurotransmitters?

A groundbreaking study revealed that Semax stimulates the release of dopamine and brain-derived neurotrophic factor (BDNF). (2) Dopamine is a neurotransmitter often referred to as the brain’s ‘feel-good’ chemical, while BDNF promotes the growth and survival of neurons. Imagine dopamine as the spark that lights up your motivation and mood, while BDNF nurtures and strengthens your brain’s pathways, enhancing your cognitive resilience.

Semax Learning Research

In one preclinical study, Semax induced noticeable improvements in learning abilities and significantly reduced anxiety-driven behaviors. (3) Not only did the rats become more adept learners, but their anxiety levels dropped, allowing them to navigate challenges with greater ease and focus. Remarkably, when exposed to Semax, the negative cognitive effects typically induced by SSRIs (Selective Serotonin Reuptake Inhibitors) seemed to be mitigated. (3)

Research on Semax and Anxiety

Semax was shown to reduce anxiety stemming from neonatal maternal deprivation, a condition that often leaves lasting emotional scars. (4) Semax appeared to stabilize the brain’s response to anxiety, helping to repair and rebalance emotional well-being. (4)

Semax and Brain Damage

In a study involving 30 stroke patients, Semax treatment led to a noticeable improvement in both general cerebral function and motor deficits. (5) Patients showed marked progress, regaining cognitive sharpness and motor control that had been previously impaired by the stroke, offering hope for renewed independence and a better quality of life.

Semax and Memory

Semax significantly enhanced memory and attention in patients. (6) Patients experienced improvements in their ability to concentrate and recall details, allowing for clearer and more precise thinking. This cognitive boost not only sharpened their mental performance but also improved their overall sense of clarity and productivity.

Semax and Other Brain Research

In an fMRI study, Semax was found to boost the activity of the default mode network (DMN), the brain’s ‘resting state’ system that governs introspective thinking and self-awareness. (7) Picture the DMN as the brain’s internal GPS, guiding you through complex thoughts and social interactions when you're not actively focused on a task. This increased activity is particularly intriguing because the DMN is also involved in higher-order social cognition—such as the ability to understand and attribute mental states to others. (8) By enhancing the DMN, Semax may help improve both reflective thinking and social awareness, potentially creating a more attuned and cognitively agile mind.

In a rodent study, nerve growth factor (NGF) gene expression in the hippocampus increased as quickly as 20 minutes after Semax administration, showing its rapid impact on brain health. (9) A large body of research demonstrates that NGF noticeably promotes axonal regeneration and increases electrophysiological parameters in the central nervous systems and behavioral recovery following peripheral nerve injury.

References

1. Kolomin, T et al. “A New Generation of Drugs: Synthetic Peptides based on Natural Regulatory peptides” Neuroscience & Medicine, 2013, 223-252. Published Online December 2013. http://dx.doi.org/10.4236/nm.2013.44035

2. Medvedeva, EV et al. “The peptide Semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis.” BMC Genomics 15, 228 (2014). https://doi.org/10.1186/1471-2164-15-228

3. Nataliya YU, et al. “Semax, synthetic ACTH(4–10) analogue, attenuates behavioral and neurochemical alterations following early-life fluvoxamine exposure in white rats” Neuropeptides, Volume 86, 2021, 102114, ISSN 0143-4179. https://doi.org/10.1016/j.npep.2020.102114

4. Volodina MA, et al. “Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats.” Bull Exp Biol Med. 2012 Mar;152(5):560-3 PMID: 22803132. https://pubmed.ncbi.nlm.nih.gov/22803132/

5. Gusev EI, et al. “Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study”. 1997;97(6):26-34. PMID: 11517472. https://pubmed.ncbi.nlm.nih.gov/11517472/

6. Asmarin IP, el at. A nootropic adrenocorticotropin analog 4-10-semax. 1997 Mar-Apr;47(2):420-30. PMID: 9173745 https://pubmed.ncbi.nlm.nih.gov/9173745/

7. Lebedeva, IS et al. “Effects of Semax on the Default Mode Network of the Brain” Bull Exp Biol Med 2018 Sep;165(5):653-656, PMID: 30225715 https://link.springer.com/article/10.1007/s10517-018-4234-3

8. Mars, RB et al. “On the relationship between the “default mode network” and the “social brain” Front Hum Neurosci. 2012; 6:189 PMID: 22737119 https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2012.00189/full

9. Agapova, TI, et al. “Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex” Mol Gen Mikrobiol Virusol 2008:(3):28-32 https://pubmed.ncbi.nlm.nih.gov/18756821/

10. Ivanov, AV, et al. “Influence of ACTG4-7-PGP (Semax) on Morphofunctional State of Hepatocytes in Chronic Emotional and Painful Stress” Bull Exp Biol Med 2017 May;163(1):105-108 PMID: 28577097 https://link.springer.com/article/10.1007/s10517-017-3748-4