Nootropic Peptides and Behavioral Health: What Is Semax?
A Russian peptide with neurotrophic benefits
Hello and welcome, new subscribers!
Before this week’s essay, I think it’s probably time I reintroduce myself and tell you a little more about the work I’m doing here at Peptide Partners Corner.
I’m a journalist with a variety of special interests. Some of those interests most pertinent to this Substack include the changing face of healthcare, longevity, biotechnology, the (un)predictability of human behavior, and rapid growth sectors that engage all four of these things in some way. This is why I’ve felt particularly drawn to writing about the recent peptide boom, and why I go by the nom de plume Peptide Reporter on Substack.
As they currently exist within (and without) regulatory, healthcare, and DIY/biohacking spaces, peptides are compounds whose growing popularity point to broader trends in how we’ve begun to think about health, medical care, and personal autonomy post-COVID.
Fifty years ago, getting sick or injured often meant little more than a visit to a doctor who might prescribe a round of antibiotics or set your broken bone. Now, things have changed. We’re on the other side of a global pandemic. We’ve witnessed an ever-widening wealth gap, several polarizing presidential terms, the rapid proliferation of telehealth companies and online wellness influencers, and growing public distrust in regulatory agencies like the FDA. For many, Big Pharma and Silicon Valley have fallen under suspicion as well.
This means that getting sick or injured looks different from how it did 50 years ago. Gaps in insurance, staggering medical bills, patients who are dissatisfied with their doctors and doctors feeling hamstrung by a healthcare system that only lets them see their patients for 15 minutes. Nowadays, we’re lucky if we don’t walk away from an ER visit with a staggering bill – never mind finding an in-network specialist who can see us within the next three months. (This is assuming, of course, that we actually have medical insurance in the first place.)
Given our challenging present, it’s not surprise that the advent of peptide therapies is being met with a great deal of enthusiasm. And much of this enthusiasm is merited: peptides are amino acid chains whose biological (or bio-identical) makeup harnesses the human body’s ability to heal itself with compounds intrinsic to it. But peptides are still a relatively new medical intervention, and even newer on the consumer market. There’s much to be learned about them, and we in the journalistic ecosphere are absorbing new information about them all the time.
Which brings me to the final two points I’d like to make in this re-introduction:
I am a journalist, not a medical or scientific professional. This means that, while I and my editorial team do our very best to keep the information we share on the Peptide Partners Corner Substack as up-to-date and rigorously fact-checked as possible, there is always the possibility that new or updated empirical information will become available, or readers with specialized knowledge we lack will know something we don’t. This is an epistemic pattern that’s quite literally built into the nature of scientific discovery (just ask the great philosopher of science Thomas Kuhn), so instead of fighting it and expecting our team to have all the answers at any given point in time, why not join us? If you’re a scientist, science journalist, medical professional, biotech researcher, or layperson with a special interest in peptides and you see a gap in our coverage, consider sending us an essay pitch or a tip: rf@peptide.partners.
We are AI realists at Peptide Partners Corner. This means that, while we acknowledge that AI can be a powerful research/organizational tool and “thought partner” for writers in, say, planning the structure of an essay or testing out a thesis, I am taking this opportunity to state plainly that I do not publish LLM writing on this site. All essays with the Peptide Reporter byline or written by guest essayists were 100% written and fact-checked by human beings. We go through this process every week, with very few exceptions. You may feel compelled to debate the authorship of our essays in the comments – trust me, I understand what a slap in the face it feels like to think you’ve recognized a trace of Claude or ChatGPT syntax in an essay by a human author you were otherwise enjoying – but it will be to no avail. At that point, you’d probably be better off asking yourself what aspect of the essay’s content – not its voice – felt lacking in the first place. And then send us a pitch! Or if you’d rather, leave us a tip via email: rf@peptide.partners.1
And now that you know me a bit better, let’s dive back into our investigation of peptides and behavioral health, shall we?
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What Is Semax?
Semax is one of multiple peptides developed by Cold War-era Russian scientists targeting the enhancement of human cognitive performance under stress. Others – including Selank – will be the topic of next week’s essay.
Two weeks ago, we broached the possibility that Semax and Selank will gain popularity among millennials otherwise skeptical of the peptide boom and celebrity Ozempic use. Burgeoning curiosity about these compounds within the online-and-anxious communities appear to foretell this trend:
But given that GLP-1s may have significant mental health benefits in their own right – new evidence of this is emerging all the time – what makes compounds like Semax and Selank so different? The answer lies in how they act on the brain.
Semax’s Origins and Design
Semax was first developed in the 1980s as a treatment for ischemic stroke, a life-threatening medical emergency that requires immediate triage to prevent permanent brain damage. Semax is a synthetic analog of a fragment of adrenocorticotropic hormone (ACTH), specifically ACTH(4-10), modified with a Proline-Glycine-Proline (PGP) tail. A technical mouthful, in other words. So here’s what that means in layperson’s terms:
ACTH is a “chemical messenger” produced by the pituitary gland, which is located at the base of the brain. ACTH’s primary function is to inform the adrenal glands – located on top of the kidneys – to produce and release cortisol.
When the pituitary gland releases ACTH, it’s typically in response to a stress trigger (illness, trauma, etc.) Cortisol is a steroid hormone that regulates the body’s fight-or-flight stress response by reducing inflammation, slowing or pausing digestion, and raising blood pressure. While this helps the stressed-out system in the short term, it can have deleterious effects on the body in the long term.
Semax is a synthetic – i.e. bioidentical as opposed to endogenous/biological – analog of ACTH. The “PGP tail” is a short amino chain that protects Semax from degrading in the body, allowing it to extend its biological activities.
So what are the biological activities of this synthetic ACTH analog? Semax has positive cognitive effects that are neurotrophic, a word which describes a class of substances and biological factors that “support the growth, differentiation, and survival of neurons.” Semax’s neurotrophic effects aren’t the benefit of a single, direct action but of what researchers have described as a “beneficial neurotrophic cascade” resulting from the modulation of a variety of important neural pathways. Here’s what that neurotrophic cascade looks like:
Semax increases the presence of brain-derived neurotrophic factor (BDNF), a vital protein commonly described as “brain fertilizer.” BDNF promotes the survival and growth of new neurons in maturing young brains, and ensures the ongoing survival and function of existing neurons in the adult brain. BDNF helps with neuronal “pruning” and facilitates memory and learning.
Semax increases the presence of nerve-growth factor (NGF), another vital protein crucial for the survival and maintenance of neurons in both the peripheral and central nervous systems. NGF drives pain perception, which is why “anti-NGF” medications like monoclonal antibodies are sometimes used to treat chronic pain and osteoarthritis. It also aids in cholinergic neuron survival, which is why neurodegenerative conditions like Alzheimer’s are associated with low levels of NGF.
While BDNF and NGF aren’t the only neurotrophic factors, they are probably the most critical ones. They both play important roles in neurogenesis (the birth of new neurons), synaptogenesis (the formation of new synapses), and long-term potentiation (the molecular basis of learning and memory). By boosting the levels of these essential proteins, Semax effectively provides the brain with the raw materials it needs to repair itself and build stronger, more resilient neural networks.
It’s not difficult to see how these effects would be highly beneficial for a stroke patient. An ischemic stroke does serious damage to neurons by starving them of oxygen (hypoxia) when it disrupts blood flow to the brain; millions of neurons can die as a result of one dangerous “ischemic cascade.” And in addition to the neurotrophic effects of enhanced BDNF and NGF, Semax has also been shown to inhibit the synthesis of nitric oxide, a molecule that can be highly neurotoxic in the high concentrations produced during a stroke. It also improves the trophic supply of the brain, enhancing blood flow and nutrient delivery to damaged areas. This combination of effects helps limit the extent of neuronal damage following a stroke and promotes functional recovery during the rehabilitation period.
Damage halted, neurotrophic repair initiated! There’s no question that Semax can treat patients who’ve suffered neuronal damage from stroke. But what about the compound’s application for non-stroke patients?
Semax: the Nootropic Peptide
When administered intranasally, Semax can function as a “nootropic” or cognitively enhancing compound in individuals seeking to improve their focus, memory, and mental clarity. Semax’s neurotrophic properties foster neuroplasticity in the human brain, otherwise known as the nervous system’s ability to “change its activity in response to extrinsic or intrinsic stimuli by reorganizing its structure, function, or connections.”
Neuroplasticity comes in two major forms: functional plasticity (the brain’s ability to offload certain functions from a damaged area to undamaged ones) and structural plasticity (the brain’s ability to change its physical form in response to changes in environment or new information). The neuroplastic brain is also a highly resilient and adaptive brain. The same neurotrophic factors that allow it to grow new neurons, pave new pathways, and recover from injuries faster also allow it to store new information and adapt its structure to the needs of its environment with ease.
All that said, Semax and nootropic peptides like it are still off-label treatments for mental health disorders in otherwise healthy American patients. While it is possible to get a prescription for Semax through telehealth providers – as Hannah Bronfman did via Hone Health – it is important to understand that the corpus of scientific knowledge about this peptide’s effectiveness in treating diagnosable mental health disorders like anxiety and ADHD – not to mention mention other issues like Traumatic Brain Injury – is still being built.
As you learn more about the history, benefits, and side effects of Semax, I suggest (as always) that you proceed with cautious optimism.
Further reading:
What is the mechanism of Semax?
Effects of Semax on the Default Mode Network of the Brain
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Really interesting post. I started Semax a couple of weeks ago and, as someone with ADHD, I’ve been pleasantly surprised by the effect on mental clarity and focus. It’s still early days, but for me it feels less like stimulation and more like a reduction in cognitive friction. I’ve found it easier to prioritise, stay on task, and maintain momentum. I’d be interested to see more research emerge in this area, particularly around neurodivergent populations.