GB-115 vs Orexin B
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: Hypocretin-2, Hcrt-2
Orexin B (hypocretin-2) is the sister peptide of orexin A. Both are cut from the same precursor protein in the hypothalamus and both help regulate wakefulness and appetite. Orexin B is a 28-amino-acid linear peptide that mostly acts through the OX2R receptor, the receptor most tied to narcolepsy. The catch for anyone hoping to use it: it falls apart fast in the blood, barely reaches the brain from the bloodstream, and has never been given to humans in a published study.
Key Comparison Insights
- Both peptides belong to the Cognitive category, suggesting similar primary applications.
- GB-115 has stronger research evidence (Human Trials) compared to Orexin B (Preclinical).
Detailed Comparison
| Attribute | GB-115 | Orexin B |
|---|---|---|
| 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. | Orexin B binds OX2R about as strongly as orexin A does, but binds OX1R roughly 20 times more weakly, so it behaves as a relatively OX2R-preferring signal. OX2R is the receptor that matters most for staying awake and keeping REM sleep in its place: a broken OX2R gene causes inherited narcolepsy in dogs, and the newest approved narcolepsy drug is an OX2R agonist. Structurally, orexin B is a linear chain without the two disulfide bridges that make orexin A more stable. A 1999 mouse study found that injected orexin B was rapidly degraded in blood and none reached the brain intact, while orexin A crossed easily. That is the main reason human research has focused on orexin A. |
| Common Dosing | 6 mg daily (2 mg three times daily) 2-3 times daily (morning, afternoon, evening) | No established human dose Not established |
| Administration | Oral tablets or sublingual | Intracerebroventricular or local injection in animal studies |
| Typical Duration | 21+ days in clinical trials, effects noted by day 7 | Acute single-dose animal experiments |
| Best Time to Take | Morning and throughout the day | Not established |
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. | Orexin B has been studied for almost 30 years, but almost entirely as a research tool in animals and tissue. The 1998 discovery paper in Cell (Sakurai and colleagues) showed both orexins increased food intake when injected into rat brains. Work since then has mapped its role in arousal, feeding, and more recently pain: 2026 mouse research found orexin B acting at OX2R could trigger migraine-like headache pain in male but not female mice. We could not find any published study giving orexin B to humans, by nose or by injection, and no registered clinical trials. If you want the orexin story with actual human data, see orexin A. Orexin B on its own is a preclinical compound with a real biological role and no tested human use. |
Frequently Asked Questions: GB-115 vs Orexin B
What is the difference between GB-115 and Orexin B?
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. Orexin B is a cognitive peptide that orexin b (hypocretin-2) is the sister peptide of orexin a. both are cut from the same precursor protein in the hypothalamus and both help regulate wakefulness and appetite. orexin b is a 28-amino-acid linear peptide that mostly acts through the ox2r receptor, the receptor most tied to narcolepsy. the catch for anyone hoping to use it: it falls apart fast in the blood, barely reaches the brain from the bloodstream, and has never been given to humans in a published study. The main differences lie in their mechanisms of action and clinical applications.
Which is better, GB-115 or Orexin B?
Neither is universally "better" - the choice depends on your specific goals. GB-115 is typically used for cognitive purposes, while Orexin B is used for cognitive. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can GB-115 and Orexin B be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using GB-115 and Orexin B 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.