Peptide Cycling Guide: On/Off Protocols Explained
Your body is not a machine that responds the same way to the same input forever. Give it the same stimulus long enough and it adapts, downregulates, and eventually stops responding. This is true for exercise, for caffeine, and for peptides.
Your body is not a machine that responds the same way to the same input forever. Give it the same stimulus long enough and it adapts, downregulates, and eventually stops responding. This is true for exercise, for caffeine, and for peptides.
Peptide cycling --- the practice of alternating periods of use ("on") with periods of rest ("off") --- exists to prevent that adaptation. By giving your receptors periodic breaks, you maintain their sensitivity and keep the peptide working effectively over the long term. Without cycling, some peptides gradually lose their punch. Others may carry unknown risks from indefinite continuous use.
But cycling isn't one-size-fits-all. Growth hormone peptides cycle differently than healing peptides. Nootropic peptides follow a different rhythm than immune modulators. The wrong cycling protocol can undermine your results just as easily as the right one can protect them.
This guide breaks down the science behind peptide cycling, covers specific protocols by peptide category, and gives you practical frameworks for building your own cycling schedule.
Table of Contents
- Why Cycling Matters: The Science of Receptor Sensitivity
- Key Cycling Concepts
- Growth Hormone Peptides
- Healing and Repair Peptides
- GLP-1 Agonists and Metabolic Peptides
- Nootropic Peptides
- Immune-Modulating Peptides
- Other Peptides: PT-141, Melanotan, DSIP
- Common Cycling Frameworks
- Master Cycling Reference Table
- How to Build Your Own Cycling Protocol
- Monitoring During Cycles
- The Bottom Line
- References
Why Cycling Matters: The Science of Receptor Sensitivity
Every peptide works by binding to specific receptors on your cells. When a receptor is activated continuously without rest, several things can happen.
Receptor Downregulation
The cell reduces the number of receptors on its surface. Fewer receptors means less signal from the same dose. This is why your third cup of coffee doesn't hit like the first one did six months ago --- your adenosine receptors adapted.
Growth hormone secretagogue receptors (GHS-R1a) are particularly susceptible to this effect. Continuous stimulation by GHRP-type peptides can blunt the pituitary's GH release over time.
Tachyphylaxis
Rapid tolerance development where the same dose produces progressively weaker effects. Some signaling pathways become desensitized within days of continuous stimulation. Taking periodic breaks allows the signaling cascade to reset.
Feedback Loop Disruption
Peptides that stimulate hormonal pathways can suppress the body's own production through negative feedback. Growth hormone peptides, for example, raise GH and IGF-1 levels, which then signal the hypothalamus to reduce its own stimulatory output. Extended breaks allow natural production to recover.
Unknown Long-Term Risks
Most peptide studies span weeks to months, not years. Indefinite continuous use pushes beyond the available safety data. Cycling provides built-in rest periods that reduce cumulative exposure and lower the theoretical risk of undiscovered long-term effects.
Key Cycling Concepts
Before diving into specific protocols, understand these terms.
On-Cycle
The active period when you're using the peptide. Length varies from 2 weeks to 16 weeks depending on the compound.
Off-Cycle
The rest period. No peptide use (of that specific compound). Off periods allow receptor resensitization, restore natural hormonal axes, and provide a physiological reset.
Weekly Schedule
Within an on-cycle, many protocols use a 5-on/2-off weekly pattern (Monday through Friday, weekends off). This provides micro-breaks that may help maintain sensitivity without fully interrupting the therapeutic effect.
Loading Phase
Some protocols start with higher frequency dosing (daily injections for 1--2 weeks) to build tissue concentration, then transition to a maintenance schedule.
Maintenance Phase
Reduced frequency or dosing after initial effects are established. Often 3--5 days per week at a lower dose.
Stacking
Using multiple peptides simultaneously, sometimes with staggered cycling to avoid running all compounds on and off at the same time.
Growth Hormone Peptides
Growth hormone secretagogues are the peptide category where cycling is most clearly supported by physiological reasoning. These compounds stimulate the pituitary gland to release more GH, and the pituitary can become less responsive to that stimulation over time.
CJC-1295/Ipamorelin
The most commonly prescribed GH peptide stack. CJC-1295 is a GHRH analog that extends the GH release window, while ipamorelin is a selective GHRP that triggers discrete GH pulses.
Standard cycling protocol:
| Parameter | Details |
|---|---|
| On-cycle length | 12--16 weeks |
| Off-cycle length | 4--6 weeks |
| Weekly schedule | 5 days on, 2 days off |
| Daily dosing | 2--3 times per day (AM, post-workout, pre-bed) |
| Typical dose | CJC-1295: 100--300 mcg per injection; Ipamorelin: 100--300 mcg per injection |
The pre-bed dose is particularly valuable because it synergizes with the natural GH pulse that occurs during deep sleep. The 5-on/2-off weekly schedule provides micro-recovery windows that help maintain pituitary sensitivity.
Some practitioners prescribe continuous use for patients with documented GH deficiency, monitoring IGF-1 levels every 3--6 months to adjust dosing. But for most optimization-oriented users, cycling remains the standard approach.
CJC-1295 with DAC (Drug Affinity Complex)
The DAC modification extends the half-life to approximately 6--8 days, making this a once-weekly injection. Because the compound provides sustained GHRH stimulation between doses, the case for cycling is arguably stronger.
Cycling protocol:
- On-cycle: 8--12 weeks
- Off-cycle: 4 weeks
- Dosing: 1--2 mg once weekly
Sermorelin
An older GHRH analog with a shorter half-life, sermorelin was one of the first prescribed GH peptides.
Cycling protocol:
- On-cycle: 3--6 months
- Off-cycle: 1--2 months
- Dosing: 200--500 mcg nightly (subcutaneous)
- Weekly schedule: Daily or 5-on/2-off
GHRP-2 and GHRP-6
Older growth hormone releasing peptides with less selectivity than ipamorelin. They stimulate GH release more aggressively but also increase cortisol and prolactin to a greater degree.
Cycling protocol:
- On-cycle: 8--12 weeks
- Off-cycle: 4 weeks
- Weekly schedule: 5 days on, 2 days off
- Dosing: 100--300 mcg per injection, 2--3 times daily
MK-677 (Ibutamoren)
Technically not a peptide but a small molecule GH secretagogue often discussed alongside GH peptides. It has a long half-life and is taken orally once daily.
Cycling protocol:
- On-cycle: 8--12 weeks
- Off-cycle: 4--8 weeks
- Some protocols extend to 6 months on / 2 months off
- Monitor fasting glucose closely --- MK-677 can increase insulin resistance
Key Monitoring for GH Peptides
During any GH peptide cycle, monitor:
- IGF-1 levels every 4--8 weeks (target the upper third of the age-appropriate reference range)
- Fasting glucose and HbA1c (GH antagonizes insulin)
- Joint symptoms (elevated GH can cause water retention and joint stiffness)
Healing and Repair Peptides
Healing peptides present a different cycling question. Unlike GH secretagogues --- where you're stimulating a hormonal axis that can downregulate --- healing peptides work through tissue repair mechanisms that may not develop tolerance in the same way.
BPC-157
BPC-157 is a 15-amino-acid peptide derived from human gastric juice. Over 100 animal studies demonstrate effects on tendon, muscle, ligament, and gut tissue repair.
The cycling debate:
The peptide community is genuinely split on whether BPC-157 needs cycling. Here's the case for each side:
Arguments for cycling (4--8 weeks on, 2--4 weeks off):
- Most animal studies used finite treatment periods (typically 2--4 weeks)
- BPC-157 promotes angiogenesis (new blood vessel formation) --- prolonged use theoretically risks overstimulating this pathway
- Cycling gives you natural assessment windows to evaluate progress
Arguments against cycling (continuous use for chronic conditions):
- BPC-157 operates more as a repair agent than a receptor stimulant
- No strong evidence of desensitization to its regenerative effects
- Chronic conditions (ongoing tendinopathy, persistent gut inflammation) may require sustained support
Practical recommendation:
| Use Case | Protocol |
|---|---|
| Acute injury (strain, tear, post-surgery) | 4--6 weeks continuous daily use, then reassess |
| Chronic condition (tendinopathy, gut issues) | 8--12 weeks on, 4 weeks off, repeat as needed |
| Maintenance after recovery | 200--250 mcg daily, 3--4 days per week |
| Typical dose | 250--500 mcg daily (often split into 2 doses) |
TB-500 (Thymosin Beta-4 Fragment)
TB-500 promotes tissue repair through cell migration and differentiation. It's often stacked with BPC-157 for injury recovery.
Cycling protocol:
- Loading phase: 2--2.5 mg twice weekly for 4--6 weeks
- Maintenance: 2 mg once weekly for 4--6 additional weeks
- Off-cycle: 2--4 weeks
- Total typical cycle: 8--12 weeks
BPC-157 + TB-500 Stack
The combination is popular for accelerated injury recovery. A typical stacked protocol:
- Weeks 1--2 (Loading): Both peptides daily. BPC-157: 250--500 mcg/day. TB-500: 2--2.5 mg twice weekly.
- Weeks 3--8 (Maintenance): BPC-157: 250 mcg daily, 5-on/2-off. TB-500: 2 mg once weekly.
- Weeks 9--12: Taper to BPC-157 only, 3--4 days per week.
- Weeks 13--16: Off-cycle. Reassess.
GHK-Cu
A copper-containing tripeptide involved in wound healing, collagen synthesis, and tissue remodeling. Available both as an injectable and topical.
Cycling protocol:
- On-cycle: 4--8 weeks
- Off-cycle: 2--4 weeks
- Injectable dose: 1--2 mg daily
- Topical use often does not require cycling
GLP-1 Agonists and Metabolic Peptides
GLP-1 receptor agonists like semaglutide operate differently than most peptides discussed in cycling contexts. These are prescribed as chronic medications, often without planned off-cycles, because the conditions they treat (type 2 diabetes, obesity) are chronic.
Do GLP-1 Agonists Need Cycling?
The short answer: not in the traditional cycling sense. Clinical trials like the STEP program studied semaglutide for 68+ continuous weeks. The SELECT cardiovascular outcomes trial ran for over 3 years of continuous use.
However, two practical considerations apply:
Weight regain after discontinuation: The STEP 1 Extension study showed that participants regained approximately two-thirds of their lost weight within one year of stopping semaglutide. This is not a cycling concern --- it's a discontinuation concern. It suggests these medications may need long-term use for sustained benefit.
Dose titration as a form of cycling: Most GLP-1 protocols involve gradual dose escalation (starting at 0.25 mg weekly for semaglutide, increasing to 1.0--2.4 mg over 16+ weeks). Some practitioners use temporary dose reductions or brief pauses to manage side effects, which functions as informal micro-cycling.
AOD-9604
A growth hormone fragment studied for fat loss without the metabolic effects of full GH. Limited human data.
Cycling protocol (from clinical practice):
- On-cycle: 8--12 weeks
- Off-cycle: 4 weeks
- Dose: 300 mcg daily (typically morning, fasted)
Nootropic Peptides
Cognitive-enhancing peptides generally follow shorter cycling patterns because their mechanisms involve neurotransmitter modulation, which can lead to tolerance.
Semax
A synthetic seven-amino-acid peptide derived from ACTH, Semax rapidly upregulates Brain-Derived Neurotrophic Factor (BDNF) in the hippocampus. It's approved in Russia as a neuroprotective agent.
Cycling protocol:
| Parameter | Details |
|---|---|
| On-cycle length | 6--8 weeks |
| Off-cycle length | 2--4 weeks |
| Starting dose | 300 mcg daily (intranasal) |
| Target dose | 600--800 mcg daily by weeks 5--8 |
| Titration | Increase by 100--200 mcg every 1--2 weeks |
| Administration | Intranasal spray, 1--2 times daily |
Semax is recommended for pulsed use to maintain brain sensitivity. Running it continuously without breaks may blunt the BDNF response over time.
Selank
A synthetic analog of the tuftsin peptide, Selank modulates GABA-A receptors and balances serotonin/norepinephrine activity. Approved in Russia as an anxiolytic. Unlike benzodiazepines, it doesn't cause cognitive impairment, amnesia, or dependence.
Cycling protocol:
| Parameter | Details |
|---|---|
| On-cycle length | 2--4 weeks |
| Off-cycle length | 2--4 weeks (matched duration) |
| Dose | 250--750 mcg daily |
| Administration | Intranasal, 1--3 times daily |
| Typical annual schedule | One month on, one month off (6 cycles per year) |
Cycling off periodically helps you assess whether the anxiolytic effects persist without continued use --- many users report sustained benefits for days to weeks after stopping.
Dihexa
An extremely potent cognitive peptide studied for its effects on hepatocyte growth factor (HGF) signaling. Very limited data. Typically administered at microgram-level doses.
Cycling protocol (conservative):
- On-cycle: 2--4 weeks
- Off-cycle: 4+ weeks
- Very low doses (0.5--5 mg, oral or intranasal)
- Due to limited safety data, shorter cycles with longer breaks are prudent
PE-22-28
An emerging nootropic peptide with limited research. Practitioners who use it typically follow:
- On-cycle: 4--6 weeks
- Off-cycle: 2--4 weeks
- Dose: Varies by formulation and route
Immune-Modulating Peptides
Thymosin Alpha-1
An immune-modulating peptide approved in over 30 countries for hepatitis B and used as an immune system support. It modulates dendritic cells, T-helper cells, and natural killer cell activity.
Cycling protocol:
- On-cycle: 4--5 weeks
- Off-cycle: 6--8 weeks
- Frequency: 2--3 cycles per year
- Dose: 1.6 mg subcutaneous, 2--3 times weekly
- Common timing: Before cold/flu season, during recovery from illness, or during periods of high stress
KPV (Alpha-MSH Fragment)
An anti-inflammatory tripeptide fragment used for gut inflammation and immune modulation.
Cycling protocol:
- On-cycle: 4--8 weeks
- Off-cycle: 2--4 weeks
- Dose: 200--500 mcg daily (oral capsule or subcutaneous)
- Often used in conjunction with BPC-157 for GI applications
LL-37
An antimicrobial peptide with immune defense and wound healing properties.
Cycling protocol:
- On-cycle: 4--6 weeks
- Off-cycle: 4--8 weeks
- Dose: 50--100 mcg subcutaneous, 2--3 times weekly
- Short cycles with longer breaks due to limited long-term safety data
Other Peptides: PT-141, Melanotan, DSIP
PT-141 (Bremelanotide)
FDA-approved as Vyleesi for female hypoactive sexual desire disorder. PT-141 activates melanocortin receptors and doesn't require traditional cycling because it's used on-demand.
Use pattern:
- 1.75 mg subcutaneous, 45 minutes before anticipated sexual activity
- No more than 1 dose per 24 hours
- No more than 8 doses per month (per FDA labeling)
- No cycling needed --- this is an as-needed medication
Melanotan II
A tanning and libido peptide that activates MC1R and MC4R receptors.
Cycling protocol (from community protocols --- not FDA-approved):
- Loading phase: 0.25--0.5 mg daily for 2--4 weeks
- Maintenance: 0.5 mg 1--2 times weekly
- Cycle length: 8--12 weeks on, 4--8 weeks off
- Nausea is common at initiation and typically resolves
DSIP (Delta Sleep-Inducing Peptide)
A neuropeptide involved in sleep regulation.
Cycling protocol:
- On-cycle: 2--4 weeks
- Off-cycle: 2--4 weeks
- Dose: 100--300 mcg before bed
- Short cycles recommended to avoid dependency on exogenous sleep signaling
Common Cycling Frameworks
Three general approaches cover most situations.
Block Cycling
Long on-periods followed by defined off-periods. Best for compounds with slower onset and sustained effects.
Pattern: 8--16 weeks on, 4--6 weeks off
Best for: GH peptides, long-term healing protocols, metabolic peptides
Pulse Cycling
Short bursts of use with equal or longer rest periods. Best for potent compounds where receptor sensitivity is a concern.
Pattern: 2--4 weeks on, 2--4 weeks off
Best for: Nootropic peptides, immune modulators, compounds with limited safety data
Continuous with Micro-Breaks
Daily use within a 5-on/2-off weekly pattern within a longer block cycle. The weekend breaks provide mini-recovery periods.
Pattern: 5 days on, 2 days off, within a 12--16 week block
Best for: GH peptides, BPC-157 during active healing, any peptide where consistent tissue levels matter
Master Cycling Reference Table
| Peptide | Category | Typical On-Cycle | Off-Cycle | Weekly Pattern | Key Monitoring |
|---|---|---|---|---|---|
| CJC-1295/Ipamorelin | GH Secretagogue | 12--16 weeks | 4--6 weeks | 5 on / 2 off | IGF-1, fasting glucose |
| Sermorelin | GH Secretagogue | 3--6 months | 1--2 months | Daily or 5/2 | IGF-1, sleep quality |
| MK-677 | GH Secretagogue (oral) | 8--12 weeks | 4--8 weeks | Daily | Glucose, insulin, IGF-1 |
| BPC-157 (acute) | Healing | 4--6 weeks | 2--4 weeks | Daily | Symptom tracking |
| BPC-157 (chronic) | Healing | 8--12 weeks | 4 weeks | 5 on / 2 off | Symptom tracking, imaging |
| TB-500 | Healing | 8--12 weeks | 2--4 weeks | 2--3x/week | Symptom tracking |
| GHK-Cu | Regenerative | 4--8 weeks | 2--4 weeks | Daily | Skin/tissue assessment |
| Semaglutide | GLP-1 Agonist | Continuous | N/A (chronic use) | Weekly | HbA1c, weight, GI symptoms |
| Semax | Nootropic | 6--8 weeks | 2--4 weeks | Daily | Cognitive assessment |
| Selank | Nootropic | 2--4 weeks | 2--4 weeks | Daily | Anxiety/mood tracking |
| Thymosin Alpha-1 | Immune | 4--5 weeks | 6--8 weeks | 2--3x/week | CBC, immune markers |
| PT-141 | Sexual Health | On-demand | N/A | Max 8 doses/month | Blood pressure |
| DSIP | Sleep | 2--4 weeks | 2--4 weeks | Nightly | Sleep quality tracking |
How to Build Your Own Cycling Protocol
Step 1: Identify Your Goal
Are you treating an acute injury, optimizing long-term hormone levels, or doing a time-limited cognitive enhancement protocol? The goal determines the framework.
Step 2: Match the Framework
- Acute injury recovery --- Block cycling with front-loaded doses
- Hormonal optimization --- Block cycling with 5/2 weekly schedule
- Cognitive enhancement --- Pulse cycling with equal on/off periods
- Immune support --- Seasonal pulse cycling (2--3 times per year)
Step 3: Set Your Monitoring Schedule
Decide what you'll track before you start. This might include blood work (IGF-1, metabolic panel, CBC), subjective markers (sleep quality, energy, pain levels), or performance metrics (strength, body composition, cognitive tests).
Step 4: Plan Transitions Between Cycles
When running multiple peptides, stagger your off-cycles so you're not stopping everything at once. For example, if you're using CJC-1295/Ipamorelin alongside BPC-157 for an injury:
- Weeks 1--12: Both compounds active
- Weeks 13--16: Stop CJC-1295/Ipamorelin, continue BPC-157 if still healing
- Weeks 17--20: Off everything
- Week 21: Reassess and decide on next cycle
Step 5: Work With a Provider
This guide gives you a framework, but cycling protocols should be supervised by a physician experienced in peptide therapy. Individual factors --- your age, health status, lab values, response patterns, and specific medical conditions --- all influence the optimal protocol.
If you need help finding a qualified provider, see our guide on how to choose a peptide therapy clinic or learn how to discuss peptides with your doctor.
Monitoring During Cycles
Blood Work Schedule
| Timing | What to Test |
|---|---|
| Baseline (before starting) | Complete metabolic panel, CBC, IGF-1, fasting insulin, HbA1c, thyroid panel, hormone panel |
| Mid-cycle (4--8 weeks in) | IGF-1, fasting glucose, any peptide-specific markers |
| End of on-cycle | Full panel repeat |
| End of off-cycle | IGF-1 and hormone panel (to confirm natural levels recovering) |
Subjective Tracking
Keep a simple daily log of:
- Sleep quality (1--10 scale)
- Energy levels (1--10 scale)
- Recovery from exercise
- Any side effects (injection site reactions, water retention, GI symptoms)
- Specific symptoms related to your treatment goal
This data helps your provider optimize your next cycle's length, dose, and frequency.
The Bottom Line
Peptide cycling isn't arbitrary. It's a strategy grounded in receptor biology, hormonal feedback, and the practical reality that most peptide safety data comes from time-limited studies, not decades of continuous use.
The core principle is simple: stimulate, rest, reassess. Give the peptide time to work, give your body time to recover, and give yourself time to evaluate whether the protocol is producing the results you want.
Growth hormone peptides benefit most from structured cycling --- 12--16 weeks on, 4--6 weeks off, with 5-on/2-off weekly micro-breaks. Healing peptides may not need strict cycling for acute injuries but benefit from periodic breaks during chronic use. Nootropic peptides work best in short pulses with matched rest periods. Immune peptides are typically cycled seasonally.
Whatever protocol you choose, monitor your response, track your labs, and work with a qualified provider who can adjust the plan based on your individual data. Cycling is the framework. Your body's response is the guide.
References
- Balanced Aesthetics. "Peptide Therapy and Cycling Protocols." https://balancedaestheticsmedspa.com/peptide-cycling-why-smart-scheduling-matters-more-than-you-think/
- SeekPeptides. "Peptide Cycle Planning Guide: Protocols, Timing, and Transitions." https://www.seekpeptides.com/blog/articles/peptide-cycle-planning-guide
- Functional Weight Loss Blog. "Peptide Cycling Protocols: A Clinical Framework for Mitigating Tolerance and Maximizing Long-Term Therapeutic Outcomes." https://blog.thefunctionalweightloss.com/post/pharmacists-peptide-cycling-protocols
- Nootropicos Peru. "Peptide Cycling: Physiological Necessity or Persistent Myth?" https://www.nootropicosperu.shop/en/blogs/peptidos/ciclar-peptidos-necesidad-fisiologica-o-mito-persistente
- Alpha Rejuvenation. "BPC-157 Dosage Guide 2025." https://alpha-rejuvenation.com/peptide-dosing/bpc-157-dosage-guide-2025/
- Oath Peptides. "How Long Should a BPC-157 Cycle Last?" https://oathpeptides.com/2025/12/16/how-long-should-a-bpc-157-cycle-last/
- Innerbody. "Selank Peptide: Benefits, Safety & Buying Advice [2026]." https://www.innerbody.com/selank-peptide
- Peptide Initiative. "Selank Dosing Protocols." https://peptideinitiative.com/peptides/legacy/selank/protocol-dosing/dosing-protocols
- Alpha Rejuvenation. "Semax: The Brain Performance Peptide." https://alpha-rejuvenation.com/peptides/semax-brain-performance/
- iPharm Pharmacy. "The Definitive Clinical Guide to Nootropic Peptide Stacking for Peak Executive Performance." https://www.ipharmapharmacy.com/clinical-guide-nootropic-peptide-stacking-executive-performance-3/