The Hunter Williams Podcast

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https://hunterwilliamshealth.com/links

PE-22-28 is one of those peptides almost nobody is talking about, and I think that's a shame. In this episode I walk you through what it is, how it works, and why I'd put it in the antidepressant category before I'd call it a true nootropic.

I get into the background as an optimized analogue of spadin, the TREK-1 channel inhibition that drives the effect, and the downstream impact on BDNF, synaptogenesis, and neuroinflammation. I also cover the part most people care about: the rapid antidepressant onset, usually around four days, versus the three to four weeks you wait on a typical SSRI.

From there I share the dosing protocol I've been using on myself, including a four-on, three-off cycle to keep tolerance low, plus what I've noticed in terms of mood, mental energy, and the lack of any real come-down or withdrawal.

I'm not saying this is a cure for depression. Depression is multifaceted and deserves a multifaceted approach. But if you need something to help get you out of the hole and back into the habits that actually move the needle, PE-22-28 is worth knowing about.

Hunter and Taylor are back for another deep dive Reader Mailbag. Real questions, real answers, no shortcuts.

This week: traveling with peptides and TRT through customs, fixing glutathione injection pain, melanatan 1 vs 2 and skin cancer risk, severe female insomnia and perimenopause sleep protocols, retatrutide plateaus and GLP-1 desensitization, and how to actually build a peptide stack using the bleeding neck framework.

Whether you're new to peptides or deep in your optimization journey this one has something for everyone.

Submit your questions for the next episode at the link below.

For research and entertainment purposes only.

👇 EVERYTHING IN ONE PLACEhttps://hunterwilliamshealth.com/links

👇 ALL MY LINKS IN ONE PLACE
https://hunterwilliamshealth.com/links

GLP-1s like retatrutide are the kings of fat loss. No argument there. But what do you actually do when you're cycling off, when GLP-1s aren't on the table, or when you want to stack something alongside your GLP-1 so you don't have to escalate the dose?

In this video I rank 20 non-GLP-1 fat loss compounds from F-tier to S-tier. Most are peptides. A few are small molecules. Some I use all the time. Some I would never touch.
I cover the mechanisms, the dosing protocols I actually run, the side effects I've personally experienced, and where each one fits in a real fat loss program. You'll get my honest take on adipotide, AOD-9604, sermorelin, setmelanotide, tesofensine, SS-31, cagrilintide, IGF-1 LR3, cardarine, CJC/ipamorelin, MOTS-c, 5-amino-1MQ, BAM15, SLU-PP-332, ATX-304, mirabegron, albuterol, HGH, and tesamorelin.
Hormones and lifestyle come first. Always. But once those are dialed in, these are the tools worth knowing about.
If you want my peptide cheat sheet and links to everything I use, check the description 
below. And if you want to ask me questions directly, come hang out in the Axion Collective.

All links here: https://hunterwilliamshealth.com/links

👇 ALL MY LINKS IN ONE PLACE
https://hunterwilliamshealth.com/links

Low-dose naltrexone is one of my favorite compounds out there, and in this updated 2026 episode I'm breaking down why it deserves a spot in your protocol. I cover the four mechanisms that make LDN work: the endorphin rebound, the OGF/OGFR axis, TLR4 antagonism, and broad anti-inflammatory signaling. Then I get into where LDN actually shines clinically. Autoimmune conditions like Hashimoto's and Crohn's. Chronic pain and fibromyalgia. Depression. PCOS and fertility. Even skin issues like acne, which I've personally dealt with for years.
But the part I'm most excited about is how LDN stacks with hormones and peptides. I walk through why it pairs so well with TRT, estrogen, and thyroid optimization, and then I get into specific peptide combos including BPC-157, TB-500, thymosin alpha-1, KPV, SS-31, and GLP-1 agonists. I also share why LDN might let you stay at lower GLP-1 doses for longer.
I cover dosing, titration, side effects, and my own experience cycling versus staying on continuously. If you're already optimizing with peptides and hormones, LDN might be that last five to ten percent that makes everything else work better.
00:00 – Intro and why LDN deserves an updated episode
02:22 – Why LDN belongs in your protocol (40-year safety record, broad benefits)
03:44 – The history of LDN and Dr. Bernard Bihari's HIV discovery
05:42 – The four mechanisms of action explained
06:30 – The OGF/OGFR axis and cancer applications
07:30 – TLR4 antagonism and the immune benefits
09:24 – Where LDN shines: autoimmune, pain, gut, depression, PCOS, skin
13:14 – Dosing, titration, and timing (night vs morning)
15:06 – Side effects, contraindications, and safety
16:14 – LDN and hormone replacement therapy synergy
18:34 – LDN for men on TRT, sexual function, and cortisol
20:48 – LDN stacked with peptides (BPC-157, TB-500, KPV, SS-31, GLP-1s, TA-1)
28:38 – My personal take on cycling vs daily use
30:16 – Closing thoughts

Timestamps