GB-115 vs ARA-290
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: Cibinetide, ARA 290
ARA-290 (cibinetide) is a synthetic 11-amino-acid peptide carved from the tissue-protective region of erythropoietin (EPO), engineered to calm inflammation and repair nerves without thickening the blood the way EPO does. It has been tested in real Phase 2 human trials, mainly for sarcoidosis-related small fiber neuropathy and diabetic neuropathy, and holds FDA orphan drug status, but it was never approved and development largely stalled. So: genuine clinical data, promising signals, no finish line.
Key Comparison Insights
- Both peptides belong to the Cognitive category, suggesting similar primary applications.
Detailed Comparison
| Attribute | GB-115 | ARA-290 |
|---|---|---|
| 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. | EPO does two jobs - it tells bone marrow to make red blood cells, and separately it protects and repairs injured tissue. ARA-290 was designed to trigger only the second job. It selectively activates the innate repair receptor (IRR), a heteroreceptor that pairs the EPO receptor with the CD131 beta-common chain and shows up at sites of injury and inflammation. By switching on this receptor, the peptide dampens inflammatory signaling and reduces cell death while leaving red blood cell production alone, which sidesteps EPO's clotting and cardiovascular risks. Some research also links its pain-relieving effect to modulation of the TRPV1 channel where the immune system and nociception intersect. |
| Common Dosing | 6 mg daily (2 mg three times daily) 2-3 times daily (morning, afternoon, evening) | 4 mg daily Once daily |
| Administration | Oral tablets or sublingual | Subcutaneous injection |
| Typical Duration | 21+ days in clinical trials, effects noted by day 7 | 28-day courses in trials |
| Best Time to Take | Morning and throughout the day | Consistent daily timing |
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. | ARA-290 has more real human data than most peptides in this category. A 2015 phase 2 trial published in Molecular Medicine (Brines et al., registered as NTR3858) found that ARA-290 improved hemoglobin A1c and lipid profile and significantly improved PainDetect neuropathic symptom scores in type 2 diabetes patients, with increased corneal nerve fiber density in those with small fiber neuropathy. In sarcoidosis-associated small fiber neuropathy, controlled studies reported increased corneal nerve fiber area and more regenerating (GAP-43-positive) skin nerve fibers, though in at least one dose-ranging trial pain did not clearly separate from placebo - an honest caveat worth keeping. Tolerability in these small, early-phase studies has been favorable, with no signal of EPO-style blood thickening. That said, the trials are small and early, ARA-290 holds FDA orphan drug status for sarcoidosis neuropathy but is not approved, and the program stalled around 2020. Net: real clinical evidence pointing in a hopeful direction, but not yet proven enough to be a standard treatment. |
Frequently Asked Questions: GB-115 vs ARA-290
What is the difference between GB-115 and ARA-290?
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. ARA-290 is a cognitive peptide that ara-290 (cibinetide) is a synthetic 11-amino-acid peptide carved from the tissue-protective region of erythropoietin (epo), engineered to calm inflammation and repair nerves without thickening the blood the way epo does. it has been tested in real phase 2 human trials, mainly for sarcoidosis-related small fiber neuropathy and diabetic neuropathy, and holds fda orphan drug status, but it was never approved and development largely stalled. so: genuine clinical data, promising signals, no finish line. The main differences lie in their mechanisms of action and clinical applications.
Which is better, GB-115 or ARA-290?
Neither is universally "better" - the choice depends on your specific goals. GB-115 is typically used for cognitive purposes, while ARA-290 is used for cognitive. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can GB-115 and ARA-290 be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using GB-115 and ARA-290 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.