Sigma A Peptides: the trouble with adding it all up
I distrust a total assembled from enzyme activity, rat behavior and brain growth factors. The individual findings are more interesting.
Plasma enkephalin breakdown
In a 2001 experiment with human plasma, Selank slowed the breakdown of enkephalins, the body's own opioid peptides involved in stress regulation. The reported IC50 was approximately 15 micromolar: the concentration that cut the measured enzyme activity by half. The experiment happened outside the body. Its result was about preserving a molecule already present.
That is an appealingly specific piece of biology. I hadn't expected enzyme inhibition to be such a useful clue. The paper proposes a mechanism for anxiety relief, and the distance between that proposal and an anxious person's experience is exactly where my curiosity starts.
GABA, anxiety and BDNF
Sigma brings a sum to mind. Add a GABA-binding result in rat brain membranes reviewed in 2018, add less anxiety in a small Russian patient study, add BDNF expression in a rat hippocampus, and a reassuring overall picture begins to form. The appeal is obvious. Each finding gives the next one somewhere to land.
Here I start disputing the arithmetic. An enzyme assay, a symptom outcome and a brain-tissue measurement answer different questions. I give the patient study weight for its reported anxiety outcome; the plasma work earns its place by suggesting how an effect might arise. Combining them into a score would throw away the distinction that makes either useful.
Semax neurotrophin measurements
Semax makes the problem wonderfully concrete. In male Wistar rats, its effects on neurotrophin gene expression varied by brain region: NGF and BDNF mRNA rose in the hippocampus, BDNF mRNA rose in the brainstem and cerebellum, and NGF mRNA fell in the frontal cortex. Neurotrophins help support neurons; mRNA is the message a cell uses to make a protein.
I think the decrease deserves as much space as the increases. A phrase such as more growth-factor activity flattens a spatially varied response into a single direction. The Semax page follows those regions, then turns to the very different circumstances of brain and spinal-cord injury.
Selank and Semax
Selank has anxiety trials and proposed GABA and enkephalin mechanisms; Semax has a substantial animal literature on neurotrophins and injury. The unevenness draws me back: where results reinforce one another, where the measurement changes, and where a familiar reputation runs ahead of a trial.
The comparison sets the actual endpoints beside each other. The questions page deals with the reports of calm, clarity and disappointment that circulate around both compounds. Those accounts are anecdotal rather than clinical evidence. Neither compound has FDA or EMA approval, and their long-term effects in healthy people remain poorly characterized.
Selank studies
An enzyme assay, GABA-related experiments and the patient result that carries the most clinical weight here.
Follow Selank →Semax by brain region
A close look at where the neurotrophin measurements rose, where one fell, and what injury studies measured instead.
Follow Semax →