When I first heard about the peptides “semax” and “selank,” it was from a family friend who simply said:
“Since I started snorting these peptides, my mood has been the best it’s been in decades!”
Naturally, I was a little concerned.
Hearing those words for the first time, they sounded like party drugs.
And when a family friend discloses that they’ve been snorting [insert unknown compound here] and feeling on top of the world, that’s bound to raise a yellow flag.
However, my concern turned to curiosity when I learned what these compounds actually were, and once I tried them myself.
When I did — in the middle of an absolutely maddening homeowner nightmare — I noticed an abrupt shift toward calm and equanimity. I'll tell you that story shortly.
But first, let's review the science.
These peptides were first studied in Russia and are now used for certain medical indications, including stroke, as well as now recreationally to reduce anxiety and to improve focus and mental clarity.
So today, we’re going to move beyond the sketchy names that sound either like party drugs (or—in the case of semax—some strange manosphere supplement aimed at maximizing sperm quality), and explore a scientific story grounded in some fascinating biology.
What is Semax?
Semax is, at its core, a fragment of the hormone adrenocorticotropic hormone (ACTH).
This is a hormone normally released by the pituitary gland that signals the adrenal glands to release hormones like cortisol.
At first, this might seem concerning because you could logically conclude:
“Okay, now you’re taking something that’s just going to spike cortisol, and that can’t be good.”
But importantly, the ACTH fragment that serves as the basis for semax excludes the portion of the parent hormone that actually stimulates cortisol release.
The remainder of the ACTH molecule—including the semax fragment—appears to retain a number of brain-boosting, nootropic effects associated with improvements in learning and increases in certain brain growth factors, but without acting as a stress hormone.
So, although its origins lie within the stress-response axis, it does not stimulate the release of cortisol.
Semax also includes an additional synthetic modification: a “protective tail” made of three amino acids (proline-glycine-proline) attached to one end.
The purpose of this protective tail is to inhibit enzymes that would otherwise rapidly break down the molecule. This allows semax to survive long enough to be transported to the brain.
But how does semax work in the brain?
Semax Mechanisms of Action
While its exact molecular targets aren’t fully understood, there are data suggesting that semax increases levels of brain-derived neurotrophic factor (BDNF), which is often described as fertilizer for brain cells.
It may also increase related factors that support neurogenesis and cognitive preservation, such as nerve growth factor (NGF), particularly in brain regions involved in higher-order thinking, like the cortex, and memory formation, like the hippocampus.
If you want the simple version, you can think of semax as a signal that turns up the volume on the brain’s own repair and plasticity programs.
In addition, although the mechanisms are not fully worked out, semax appears to influence dopamine and serotonin systems, which would fit with the reported benefits for mood, motivation, and anxiety reduction.
But mechanistic speculation will only get us so far.
What do the human data show?
In the rest of this letter for StayCurious Metabolism Premium members, we’ll dive into:
What the data show, especially the human data
Semax’s peptide sibling, selank:
How is it different?
How do they work together?
Real-world benefits
How to learn more and access appropriate clinical guidance
If you’re passionate about metabolic health—particularly brain health and mental health—now is as good a time as any to join StayCurious Metabolism. Find out why so many members call it the best and most practical investment they’ve ever made in their health and education.
