GB-115 vs PE-22-28
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Ranquilon, N-phenylacetyl-L-prolylglycine ethyl ester
GB-115 is a synthetic dipeptide anxiolytic developed in Russia, chemically the amide of N-phenylhexanoyl-glycyl-L-tryptophan and described as a retro-analogue of cholecystokinin-4. Rather than acting like a benzodiazepine, it blocks cholecystokinin receptors, a different anti-anxiety route. It has been studied in animals and in a small pilot human study, but it is not an approved or widely available medication.
Also: PE22-28, Spadin Analog
PE-22-28 is a seven-amino-acid peptide that blocks a potassium channel in the brain called TREK-1, the same target tied to depression. It is a shortened, more potent and more stable version of spadin, a natural fragment cut from the sortilin propeptide, and it was built to act like a fast antidepressant. All evidence is from rodents. There are no human clinical trials.
Key Comparison Insights
- Both peptides belong to the Cognitive category, suggesting similar primary applications.
- GB-115 has stronger research evidence (Human Trials) compared to PE-22-28 (Animal Studies).
Detailed Comparison
| Attribute | GB-115 | PE-22-28 |
|---|---|---|
| Category | Cognitive | Cognitive |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | Cholecystokinin (CCK) is a peptide that acts as a neurotransmitter in the brain, and activating its CCK-2 (also called CCK-B) and CCK-1 receptors tends to trigger anxiety and panic-like states. GB-115 works as an antagonist at these cholecystokinin receptors, meaning it occupies the receptor and blocks CCK from setting off that anxiety signaling. In animal work it specifically prevented anxiety provoked by CCK-4, which shares a pharmacological target with GB-115. This CCK-blocking mechanism is the proposed explanation for its calming effect, and it is distinct from the GABA system that classic sedatives act on. | PE-22-28 inhibits TREK-1, a two-pore-domain potassium channel that normally lets potassium leak out of neurons and quiets them down. Block that leak and serotonin-producing neurons in mood-related regions become easier to fire, which is the proposed antidepressant mechanism. This is the same pathway implicated in why TREK-1 knockout mice show a depression-resistant phenotype. Compared to the parent peptide spadin, PE-22-28 binds TREK-1 far more tightly and survives much longer in the body, which is why it was developed. Whether TREK-1 blockade translates into a real antidepressant effect in people remains unproven. |
| Common Dosing | 6 mg daily (2 mg three times daily) 2-3 times daily (morning, afternoon, evening) | 100-300 mcg intranasal or subcutaneous Once daily |
| Administration | Oral tablets or sublingual | Intranasal or subcutaneous injection |
| Typical Duration | 21+ days in clinical trials, effects noted by day 7 | Research protocols vary, often 2-4 weeks |
| Best Time to Take | Morning and throughout the day | Morning |
Possible Side Effects May vary by individual |
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| Research Summary | The research record is real but thin and almost entirely from a single Russian group. In rodent studies (rats, BALB/c and C57Bl/6 mice), GB-115 reduced anxiety induced by CCK-4 and by yohimbine, with effects that varied by mouse strain, and it stayed effective after long-term dosing without producing tolerance or a withdrawal syndrome when stopped. Preclinical safety work has also been published. The only human data comes from a small pilot clinical study of 25 patients with generalized anxiety disorder given 6 mg daily for 21 days, where anxiety scores on the Hamilton scale fell substantially and fatigue scores improved. Importantly, that study was a single-arm pilot with no placebo or control group, so it cannot prove the drug caused the improvement. There are no large randomized controlled trials, no Western regulatory approval, and the evidence base remains preliminary. | The core data come from a single 2017 paper by Djillani and colleagues in Frontiers in Pharmacology, which screened shortened spadin analogs and found PE-22-28 to be the standout: dramatically stronger TREK-1 inhibition, longer in vivo stability, and antidepressant-like behavior in mice using standard tests like the forced swim and novelty-suppressed feeding paradigms. The same line of work reported that short treatment courses increased hippocampal neurogenesis in rodents, which the authors framed as a possible mechanism for faster mood effects than conventional SSRIs. The broader TREK-1 and spadin story traces back to Mazella et al. in 2010, who first described spadin as a natural antidepressant-type TREK-1 blocker. Importantly, every result is preclinical and in animals. There are no completed or published human efficacy or safety trials of PE-22-28, and it is not an approved drug anywhere. Claims that it treats depression, anxiety, or cognitive decline in people go well beyond what the evidence supports. |
Frequently Asked Questions: GB-115 vs PE-22-28
What is the difference between GB-115 and PE-22-28?
GB-115 is a cognitive peptide that gb-115 is a synthetic dipeptide anxiolytic developed in russia, chemically the amide of n-phenylhexanoyl-glycyl-l-tryptophan and described as a retro-analogue of cholecystokinin-4. rather than acting like a benzodiazepine, it blocks cholecystokinin receptors, a different anti-anxiety route. it has been studied in animals and in a small pilot human study, but it is not an approved or widely available medication. PE-22-28 is a cognitive peptide that pe-22-28 is a seven-amino-acid peptide that blocks a potassium channel in the brain called trek-1, the same target tied to depression. it is a shortened, more potent and more stable version of spadin, a natural fragment cut from the sortilin propeptide, and it was built to act like a fast antidepressant. all evidence is from rodents. there are no human clinical trials. The main differences lie in their mechanisms of action and clinical applications.
Which is better, GB-115 or PE-22-28?
Neither is universally "better" - the choice depends on your specific goals. GB-115 is typically used for cognitive purposes, while PE-22-28 is used for cognitive. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can GB-115 and PE-22-28 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using GB-115 and PE-22-28 together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.