Beta-Endorphin

The native 31-residue opioid peptide cleaved from pro-opiomelanocortin in the pituitary and hypothalamus, a mu- and delta-opioid receptor agonist studied by intravenous, intrathecal and epidural routes in small human series around 1980 and never developed into an approved product.

Also referenced as: beta-Endorphin (1-31), beta-Lipotropin (61-91), beta-LPH (61-91), Lipotropin C-fragment, beta-EP, beta-Endorphin acetate

Also appears in: Hormone

COA Public product evidence No certificate records are bound to a tracked Beta-Endorphin product page A record counts here only when a vendor publishes a certificate against one of its own tracked Beta-Endorphin product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is Beta-Endorphin?

Beta-endorphin is a native 31-amino-acid opioid peptide produced by cleavage of pro-opiomelanocortin (POMC), the same precursor that yields corticotropin (ACTH), alpha-MSH and beta-lipotropin. In the 267-residue human POMC preproprotein it occupies residues 237 to 267, which is also the C-terminal segment (residues 61 to 91) of beta-lipotropin, hence the older names “lipotropin C-fragment” and beta-LPH (61-91). The human sequence is Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu; its first five residues are met-enkephalin, the opioid “message” motif shared with leu-enkephalin, while the remaining 26 residues confer much higher receptor affinity and metabolic stability than the pentapeptide alone. PubChem lists the human peptide as C158H251N39O46S with a molecular weight of 3,465 Da.

The peptide was isolated in 1976 from camel pituitary extracts by Li and Chung, who determined its structure, showed it to be identical to the C-terminal 31 residues of ovine beta-lipotropin, and found that it carried significant opiate activity but very low lipotropic activity (Li and Chung, Proceedings of the National Academy of Sciences, 1976;73(4):1145–1148). The precursor relationship was settled when the bovine corticotropin–beta-lipotropin precursor cDNA was sequenced, revealing a single protein whose component peptides are separated by pairs of lysine and arginine residues (Nakanishi et al., Nature, 1979;278(5703):423–427). Beta-endorphin is synthesized and released by the pituitary, by POMC neurons of the hypothalamus and brainstem, and by immune cells. It has never been developed into an approved medicine anywhere, and synthetic human beta-endorphin exists today as a research reagent.

How it works

• Agonist at mu- and delta-opioid receptors. Beta-endorphin binds the brain opiate receptor with high affinity, a property first demonstrated for the lipotropin C-fragment in the same year it was isolated (Bradbury et al., Nature, 1976;260(5554):793–795). Profiling of the cloned kappa, delta and mu receptors with opioid drugs and endogenous peptides noted that opioid agents with abuse potential share high mu-receptor affinity (Raynor et al., Molecular Pharmacology, 1994;45(2):330–334). A comparison of 22 endogenous opioid peptides found that nearly all activate all three receptor types, that many show biased signaling, and that the shorter processed forms of beta-endorphin, long assumed inactive, signal robustly in cells and brain slices (Gomes et al., Proceedings of the National Academy of Sciences, 2020;117(21):11820–11828).
• Potent central analgesic that is blocked by naloxone. Injected directly into the brain, beta-endorphin was 18 to 33 times more potent than morphine on a molar basis in tail-flick, hot-plate and writhing tests in mice and the wet-shake test in rats, and the effect was blocked by naloxone (Loh et al., Proceedings of the National Academy of Sciences, 1976;73(8):2895–2898). Mice engineered to lack beta-endorphin while retaining the rest of POMC respond normally to morphine but lose the naloxone-reversible analgesia produced by mild swim stress, the clearest genetic evidence that the peptide mediates endogenous, stress-triggered pain inhibition (Rubinstein et al., Proceedings of the National Academy of Sciences, 1996;93(9):3995–4000).
• Peripheral and immune actions. Immune cells infiltrating inflamed tissue carry increased amounts of opioid peptides, and opioid receptors are present on the peripheral terminals of sensory neurons; antibodies against the peptides or receptors, or immunosuppression with cyclosporine, block the local antinociception produced by cold-water swim stress in rats with hind-paw inflammation (Stein et al., Proceedings of the National Academy of Sciences, 1990;87(15):5935–5939).
• Energy balance and exercise-related opioid release. Male mice selectively lacking beta-endorphin, with intact melanocortin signaling, become hyperphagic and obese, implying the peptide is required for normal feeding regulation (Appleyard et al., Endocrinology, 2003;144(5):1753–1760). In humans, PET imaging in 10 athletes showed reduced opioid receptor availability in prefrontal and limbic regions after two hours of endurance running, inversely correlated with euphoria ratings (Boecker et al., Cerebral Cortex, 2008;18(11):2523–2531), and a mu-receptor study in 22 men found decreased binding after high-intensity interval training but not after moderate exercise (Saanijoki et al., Neuropsychopharmacology, 2018;43(2):246–254); such studies measure receptor occupancy, not beta-endorphin specifically.

Research status

Discovery era, 1976 to 1979. Within 1976, Li and Chung isolated the 31-residue peptide from camel pituitaries and determined its structure (Proceedings of the National Academy of Sciences, 1976;73(4):1145–1148), Bradbury and colleagues showed the high affinity of the lipotropin C-fragment for brain opiate receptors (Nature, 1976;260(5554):793–795), and Loh and colleagues established its central analgesic potency in rodents (Proceedings of the National Academy of Sciences, 1976;73(8):2895–2898). In six chronic-pain patients, stimulation of the periaqueductal gray raised immunoreactive beta-endorphin in ventricular fluid by 50 to 300% in three patients with pain of peripheral origin, whereas internal-capsule stimulation in three patients with deafferentation dysesthesia did not, evidence that the human peptide is released in vivo during naloxone-reversible pain relief (Hosobuchi et al., Science, 1979;203(4377):279–281). Pituitary endorphins were also found to be stored partly as biologically inactive alpha-N-acetylated forms (Smyth et al., Nature, 1979;279(5710):252–254).

Intravenous studies in cancer pain and psychiatry. Foley and colleagues gave 5 or 10 mg of synthetic human beta-endorphin intravenously to three patients with cancer pain and administered it intracerebroventricularly to one. The mean plasma terminal half-life was 37 minutes, the volume of distribution 178 mL/kg and metabolic clearance 3.2 mL/min/kg; in cerebrospinal fluid after intraventricular dosing the half-life was 93 minutes. Prolactin rose rapidly by both routes at doses below those needed for analgesia, growth hormone fell only after intraventricular dosing, and analgesia appeared after 7.5 mg given intraventricularly (Foley et al., Proceedings of the National Academy of Sciences, 1979;76(10):5377–5381). An early report described behavioral changes in schizophrenic and depressed patients given beta-endorphin (Kline et al., Archives of General Psychiatry, 1977;34(9):1111–1113). Two controlled studies followed. In a double-blind, placebo-controlled crossover of 10 depressed and 8 schizophrenic inpatients, depressed patients improved significantly 2 to 4 hours after infusion, the schizophrenic group did not change overall although 6 of 8 worsened, and no effects were seen during the infusions themselves or on later days (Gerner et al., Archives of General Psychiatry, 1980;37(6):642–647). In a second double-blind study, 4 to 15 mg intravenously in 6 schizophrenic and 4 depressed patients produced no significant behavioral difference from placebo in either subgroup, while 10 mg produced neuroendocrine effects comparable to 5 mg of intravenous methadone in one patient and large rises in circulating opioid activity in two others (Pickar et al., American Journal of Psychiatry, 1981;138(2):160–166).

Intrathecal and epidural series, 1980 to 1986. The best-known human data come from Oyama’s anesthesiology group in Japan, working with synthetic human beta-endorphin. A single intrathecal injection of 3 mg produced profound analgesia in all 14 patients with intractable pain from disseminated cancer, with a mean duration of relief of 33.4 hours (range 22.5 to 73.5 hours) and no respiratory depression, hypotension, hypothermia or catatonia (Oyama et al., Lancet, 1980;1(8160):122–124). In 14 women given intrathecal beta-endorphin at delivery, analgesia was rapid and prolonged, uterine contractions continued, the women remained fully conscious, respiration and circulation were unchanged and infant Apgar scores were excellent; the authors argued that the intrathecal route was necessary because the peptide does not cross the blood-brain barrier, which would also keep it out of the fetal brain (Oyama et al., American Journal of Obstetrics and Gynecology, 1980;137(5):613–616). Epidural administration of 3 mg to 10 cancer patients relieved pain with a mean onset of 24 minutes and a mean duration of 19 hours, slower and shorter than the intrathecal route (Oyama et al., Canadian Anaesthetists’ Society Journal, 1982;29(1):24–26). In 8 cancer patients, large intrathecal doses did not change plasma ACTH, cortisol or growth hormone but raised prolactin (Oyama et al., Acta Endocrinologica, 1982;99(1):9–13). Japanese-language case reports extended the approach to continuous intrathecal infusion in cancer patients (Jin et al., Masui, 1986;35(1):148–151). These were small series of 8 to 14 patients from a single group, and no sponsor took the peptide into formal development.

No registered development program. Drugs@FDA holds no application for beta-endorphin, and as of November 2026 ClinicalTrials.gov lists no study in which beta-endorphin is the administered product; the registry entries that mention the peptide measure its circulating levels as a biomarker. Research since the 1990s has used beta-endorphin as a tool and a biomarker rather than a drug; a 2020 review surveys its roles in stress, behavior, neuroinflammation and brain energy metabolism (Pilozzi et al., International Journal of Molecular Sciences, 2020;22(1):338).

Common dosage forms

• No pharmaceutical presentation. Beta-endorphin has never been formulated as an approved or compounded medicine in any country.
• Clinical-study material, 1977 to 1986. Synthetic human beta-endorphin was prepared in academic peptide-chemistry laboratories as a sterile solution supplied for individual research protocols, and it was never commercialized.
• Research reagent. Synthetic human beta-endorphin (1-31), usually as the acetate or trifluoroacetate salt, is supplied as a lyophilized powder in microgram-to-milligram vials for in vitro receptor, immunoassay and neuroscience work.

Key considerations

• Regulatory status. The Research Market status reflects the absence of any FDA application, approved product or registered US development program for beta-endorphin. No approved beta-endorphin product has been identified in any other jurisdiction either, and the DailyMed listings that name it are unapproved homeopathic sprays and drops in which it is one of many diluted ingredients.
• Human evidence is small, old and largely uncontrolled. The published human series between 1977 and 1986 enrolled 4 to 18 patients each, most of them open series, and the two double-blind psychiatric studies disagreed on whether the peptide had any behavioral effect. The intrathecal cancer-pain and obstetric results were striking but came from a single group and were never carried into controlled comparisons with established intrathecal opioids.
• It is a potent mu-opioid agonist with the class’s hazards. The pharmacology that makes beta-endorphin analgesic also predicts respiratory depression, sedation, nausea, prolactin elevation and dependence liability; the absence of respiratory depression in the intrathecal series reflects small numbers and single doses, not a demonstrated safety margin. Its analgesia was naloxone-reversible in animals, and intravenous dosing in humans produced opiate-like neuroendocrine effects.
• Route and stability govern what it can do. A plasma half-life of about 37 minutes, rapid proteolysis and poor passage across the blood-brain barrier mean that peripheral administration mainly produces endocrine effects such as prolactin release, while central analgesia in the human studies required intrathecal, epidural or intraventricular delivery. Circulating beta-endorphin measured in exercise or stress studies is largely of pituitary origin and is not a direct index of brain opioid activity.
• Naming and fragments. Beta-endorphin, beta-endorphin (1-31), beta-lipotropin (61-91) and lipotropin C-fragment denote the same human peptide. Shorter processing products such as beta-endorphin (1-27) have receptor activity of their own, N-acetylated forms are biologically inactive, and met-enkephalin shares only the N-terminal motif, so results for one should not be assumed to apply to another.