Why cycling matters — receptor desensitization isn't a myth
41 posts
Saw another "I ran X daily for 14 months, it stopped working, why?" post. Making this thread to link to in the future.
Chronic agonism at most receptors leads to downregulation. This is true for GPCRs (most melanocortin peptides, GLP-1 receptors, opioid receptors) and for growth factor pathways (insulin, IGF-1 downstream).
Consequences:
- Tolerance — same dose, less effect over time.
- Dependence at the receptor level — pulling the drug is rougher than if you'd cycled.
- Some chronic downregulation persists past the washout in some systems.
Cycling isn't superstition, it's respect for biology. Specific guidelines vary by peptide:
- GH peptides: 8 on / 4 off or 12 on / 6 off.
- Melanocortin (PT-141, MT-2): use, don't daily.
- Epithalon, TA-1: pulsed course 2x/year.
- BPC-157, TB-500: targeted to injury, stop when healed.
- Cog peptides (Semax/Selank): weekend washouts at minimum.
Skip cycles at your own metabolic/receptor peril.
10 Replies
46 posts
Linking this in the beginner FAQ.
- Sermorelin · 200 mcg · 5x/wk AM · sub-Q
- BPC-157 · 250 mcg · 2x/day · sub-Q
94 posts
The chronic downregulation persisting past washout is the one that scares me. It's one thing to get tolerant, another to permanently alter a setpoint.
- CJC-1295 no DAC · 100 mcg · pre-bed · sub-Q
- Ipamorelin · 200 mcg · pre-bed · sub-Q
- BPC-157 · 250 mcg · 2x/day · sub-Q
205 posts
Biggest offender in my observation is MT-2 (melanotan II). People run it daily for tanning for months, then experience significant appetite and libido issues when they stop. Receptor-level downstream effects are real.
- CJC-1295 no DAC · 100 mcg · pre-bed · sub-Q
- Ipamorelin · 200 mcg · pre-bed · sub-Q
- BPC-157 · 500 mcg · 2x/day · sub-Q
115 posts
Good post overall. One nit: "some chronic downregulation persists" is species- and receptor-specific and not universally true. Some systems recover fully, others don't. Don't want to catastrophize but also agree the caution is warranted.
16 posts
I'd add: taper off, don't hard stop. Especially with GH peptides. Abrupt cessation after a long run can produce a rougher rebound than if you step down over 1-2 weeks.
10 posts
And on the other side: loading phases aren't usually warranted except for specific healing protocols. People do 4-week loading because it "feels safer" when it's just unnecessary cost.
46 posts
Best cycling framework I've used: think of peptides like caffeine. Acceptable daily for a while, better with rest days, worse if you never stop.
25 posts
18 posts
The metaphor I use with newer people: your receptors are staff, they're willing to work overtime for a while, then they get surly. Schedule their days off before they schedule them for you.
16 posts