Orexin-A

Human Research

Orexin-A (Hypocretin-1)

A hypothalamic neuropeptide involved in wakefulness, appetite, and energy homeostasis. Deficiency causes narcolepsy. Researched for sleep disorders, cognitive enhancement, and metabolic effects.

Nasal sprayIVSleepCognitive EnhancementMetabolic Health

Dose

Research doses vary widely based on administration route and research goal, commonly ranging from 10-100 mcg for nasal administration in some contexts, and 0.1-1.0 mg/kg for intravenous administration in animal models.

Route

Nasal spray, IV

Cycle

Acute administration in most research protocols; longer-term studies are less common and highly variable.

Storage

Store at -20°C to -80°C

What is Orexin-A?

Orexin-A, also known as Hypocretin-1, is a neuropeptide produced primarily by neurons in the lateral hypothalamus. It plays a crucial role in regulating sleep-wake cycles, promoting wakefulness and suppressing REM sleep. Beyond sleep regulation, Orexin-A is involved in appetite control, energy balance, reward seeking, and cognitive functions. Deficiency in orexin signaling, particularly Orexin-A, is a primary cause of narcolepsy type 1. Research explores its potential as a therapeutic agent for narcolepsy, a cognitive enhancer, and a modulator for metabolic disorders.

Key Benefits

Wakefulness promotion
Cognitive performance improvement
Appetite regulation
Narcolepsy research
Energy homeostasis

Mechanism of Action

Orexin-1 and Orexin-2 receptor agonist
Promotes norepinephrine, serotonin, dopamine release
Stabilizes sleep-wake transitions

Best For

Wakefulness research
Narcolepsy research
Sleep disorder research
Cognitive research

Body Systems

Nervous SystemMetabolicEndocrine

🐾 Griffin Says...

Orexin deficiency is literally what causes narcolepsy - people with narcolepsy have lost their orexin-producing neurons. Research into orexin supplementation is directly relevant to one of the most debilitating sleep disorders. Also interesting as a wakefulness promoter.

Molecular Information

Molecular weight

3563.8 g/mol

Length

Type

Peptide

Amino acid sequence

Pyr-Pro-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu-NH2

Pyr denotes pyroglutamic acid; Cys residues form two disulfide bonds (Cys6-Cys12 and Cys7-Cys14).

Pharmacokinetics

Time to peak

Minutes (nasal/IV)

Half-life

1.5 h

Time to clear

Within hours

DoseEstimated plasma concentration9 h

Vast literature, often cited from early human and animal studies (e.g., Narcolepsy Network, scientific reviews)

Research Indications

Narcolepsy Type 1 Research
Widely researched for its role in the pathophysiology of narcolepsy type 1 due to orexin deficiency. Studies investigate its potential to restore wakefulness and reduce cataplexy.
Sleep-Wake Cycle Regulation
Explored for its ability to promote wakefulness and stabilize sleep-wake transitions in various models of sleep disruption.

Research Protocols

Goal	Dose	Frequency	Route
Acute Wakefulness Promotion (Nasal)	10-50 µg	Single dose or as needed (e.g., once daily)	Intranasal
Acute Wakefulness Promotion (Intravenous)	0.1-1.0 µg/kg	Single infusion	Intravenous (IV)
Narcolepsy Model Studies	10-100 µg/day	Daily	Intranasal or subcutaneous (SC) in animal models
Cognitive Performance Enhancement	10-30 µg	Prior to cognitive task or as needed	Intranasal
Metabolic Regulation Studies	Varied (e.g., 20-50 µg)	Daily or multiple times per week	Intranasal or subcutaneous (SC)

Timing of administration is crucial for sleep-wake cycle modulation. For acute wakefulness, administration is typically prior to desired wake period. For chronic conditions, regular administration schedules are explored.

Peptide Interactions

CNS Depressants (e.g., sedatives, hypnotics)
Orexin-A promotes wakefulness, which could counteract the effects of CNS depressants. Combined use may lead to unpredictable effects on alertness.
Use Caution
Stimulants (e.g., modafinil, caffeine)
Both Orexin-A and stimulants increase alertness. Co-administration could potentially lead to excessive CNS stimulation, increased heart rate, or anxiety. Research should monitor for synergistic but potentially overstimulating effects.
Monitor Combination
Antihistamines (sedating types)
Sedating antihistamines induce drowsiness, which may oppose the wake-promoting effects of Orexin-A. Effects might be mitigated or unpredictable.
Use Caution
Alcohol
Alcohol is a CNS depressant that can disrupt sleep architecture and impair cognitive function. Combining with Orexin-A is likely to result in opposing effects and could lead to unpredictable physiological responses.
Avoid
Cannabinoids (e.g., THC, CBD)
Cannabinoids can have diverse effects on sleep and arousal. Their interaction with the orexin system is complex and may vary depending on the specific cannabinoid and dosage. Close monitoring is advised.
Monitor Combination

How to Reconstitute

1Carefully remove the cap from the lyophilized peptide vial.
2Swab the rubber stopper with an alcohol wipe and allow to air dry.
3Using a sterile syringe, draw the appropriate amount of bacteriostatic water for injection (BWFI) as per desired concentration.
4Slowly inject the BWFI into the vial, aiming the stream against the side of the glass to avoid direct contact with the peptide powder.
5Gently swirl the vial to dissolve the peptide. Do not shake vigorously, as this can denature the peptide.
6Once dissolved, the solution should be clear. If not, allow more time or gentle swirling. Do not use if particulate matter is present.

Orexin-A is sensitive to degradation and requires careful handling. Reconstitution should be performed using sterile, bacteriostatic water for injection.

What to Expect

Week 1-2: Initial observations may include increased alertness or changes in sleep architecture, particularly in research models of narcolepsy. Acute cognitive effects might be noted shortly after administration.
Week 3-4: Continued administration might show more consistent effects on wakefulness and potentially some stabilization of sleep-wake cycles. Metabolic changes, if any, may begin to be observed.
Week 5-8: Sustained research could explore long-term effects on cognitive performance, mood, and energy regulation. Metabolic parameters might show more definitive trends in chronic administration studies.

Side Effects & Safety

Effect	Frequency	Severity
Limited safety data in humans	Unknown	Unknown
Potential cardiovascular stimulation	Theoretical	Mild

Quick Start Guide

Typical doseResearch doses vary widely based on administration route and research goal, commonly ranging from 10-100 mcg for nasal administration in some contexts, and 0.1-1.0 mg/kg for intravenous administration in animal models.

FrequencyAs needed (Nasal), Infusion (IV)

TimingDependent on the research objective, e.g., prior to a task for cognitive enhancement studies or at specific times in sleep-wake cycle research.

SitesIntravenous (IV) administration is commonly discussed in research, though other routes like intranasal are also explored.

Cycle lengthAcute administration in most research protocols; longer-term studies are less common and highly variable.

Storage (lyophilized)Store at -20°C to -80°C

Storage (reconstituted)Store at 4°C for short term (days) or -20°C to -80°C for long term (weeks/months)

Time to effectsImmediate to rapid onset for wakefulness promotion, longer-term effects for metabolic regulation may require sustained or repeated administration.

🐾 Griffin's Research Scorecard

Research Strength

Human Data

Animal Data

Long-Term Data

Beginner Friendly

Storage Difficulty

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Peptides discussed here are for research purposes only. Nothing on this page is medical advice. Always consult a qualified professional before making health decisions.