I've been researching nootropic/anxiolytic peptides and keep coming back to two Russian-developed peptides: Selank and Semax. Both have been approved and used clinically in Russia for years but are largely unknown in Western medicine.

I'm dealing with generalized anxiety that's been exacerbated since starting tirzepatide (the appetite suppression is great but I've noticed increased baseline anxiety — anyone else?). Looking for something with a better side effect profile than SSRIs or benzos.

Can anyone with experience compare these two? Mechanisms, subjective effects, practical differences?

Great question, and yes — increased anxiety on GLP-1 RAs is reported, though the mechanism isn't fully clear. Likely related to altered gut-brain axis signaling and possibly changes in blood sugar dynamics.

Here's a comparison of the two peptides:

Selank (TP-7 / Thr-Lys-Pro-Arg-Pro-Gly-Pro):

• Synthetic analog of the immunomodulatory peptide tuftsin
• Primary mechanism: modulation of GABAergic neurotransmission, with effects on BDNF expression and monoamine metabolism
• Key study: Zozulya et al. (2008, PMID: 18577369) — demonstrated anxiolytic effects comparable to medazepam in GAD patients in a clinical trial
• Also shown to modulate IL-6 and influence enkephalin metabolism (Seredenin et al., 2013)
• Approved in Russia as an anxiolytic (trade name: Selank nasal spray)

Semax (Met-Glu-His-Phe-Pro-Gly-Pro):

• Synthetic analog of ACTH(4-10), the fragment of adrenocorticotropic hormone responsible for nootropic effects
• Primary mechanism: BDNF upregulation, modulation of dopaminergic and serotonergic systems, neurotrophic effects
• Key study: Eremin et al. (2004, PMID: 15341466) — showed improved cognitive function and reduced anxiety in patients with cognitive impairment
• Stronger nootropic profile than Selank; approved in Russia for stroke recovery and cognitive enhancement

TL;DR: Selank is the more anxiolytic-focused peptide. Semax is more of a cognitive enhancer with secondary anxiolytic effects. For your stated goal of managing anxiety, Selank is probably the better starting point.

I've used both extensively. Here's my subjective comparison:

Selank feels like a calm clarity descending about 15-20 minutes after intranasal dosing. Anxiety just... quiets down. Not sedating, not euphoric, just a reduction in the mental noise. The effect is subtle the first few times — it's not going to hit you like a benzo would. But after a week of consistent use, I noticed a real baseline shift. I was less reactive to stressors, slept better, and felt more emotionally regulated.

Semax is more stimulating. Better focus, faster word recall, more motivation to tackle difficult tasks. Think of it as somewhere between a strong coffee and a low-dose Adderall, but smoother and without the jitteriness. The anxiolytic effect is there but secondary — if pure anxiety relief is your goal, Selank wins.

I currently use Selank daily (300 mcg intranasal, morning) and Semax situationally (600 mcg intranasal before demanding cognitive tasks). They stack well together without any issues I've noticed.

That's really helpful. A few follow-ups:

1. Is intranasal the only viable route? I'm already doing subQ injections for tirze so another pin wouldn't bother me.
2. Any tolerance buildup with daily Selank use?
3. Interactions with GLP-1 RAs specifically?

1. Intranasal is the standard route and how it's used clinically in Russia. The nasal mucosa provides good bioavailability for these small peptides and gets them close to the CNS via the olfactory pathway. SubQ would work systemically but the onset is different and there's less direct CNS penetration. Stick with intranasal — it's what the clinical data is based on.

2. Tolerance is a good question. The Russian clinical data suggests Selank doesn't produce tolerance or dependence with continuous use up to 3 months, which aligns with its mechanism — it's not directly agonizing receptors the way benzos do. It's modulating the GABAergic system more indirectly. Anecdotally, I haven't heard of tolerance being an issue, and the Russian prescribing information doesn't list it as a concern. That said, some people cycle 4 weeks on / 1 week off out of general prudence.

3. No known interactions with GLP-1 RAs. These act through completely different systems. Selank's GABAergic / enkephalinergic mechanism doesn't overlap with GLP-1 receptor signaling. I'd call it very low risk for interaction, though of course there's no study specifically examining the combination.