Dermorphin

Origin and structure

Dermorphin was found by the group of the Italian pharmacologist Vittorio Erspamer, together with researchers from the Italian drug company Farmitalia Carlo Erba, in methanol extracts of the skin of Phyllomedusa sauvagii, a South American tree frog. Its sequence was published in 1981: Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, seven amino acids with an amide at the end. The name combines 'derm' (skin) and 'morphine'. A close relative with hydroxyproline in position 6, Hyp6-dermorphin, also occurs in frog skin.

The unusual part is the second amino acid, alanine in its mirror-image D-form. Its discoverers called a D-amino acid in a peptide from a vertebrate a surprising find, and it turned out to matter: in the first pharmacology study the D-alanine was crucial for activity, and the first four amino acids alone were enough for the full effect.

Dermorphin quickly became a template for opioid chemistry. By 1992 an Italian group had made more than 100 analogues and a Japanese group more than 20. The dried skin secretion of a related Amazonian frog, Phyllomedusa bicolor, used in the kambo ritual, also contains dermorphin-type peptides among many other active peptides.

How it works

Dermorphin binds and activates the mu-opioid receptor, the receptor through which morphine, oxycodone and fentanyl relieve pain and depress breathing. In the 1981 studies it was 39 times more potent than morphine on isolated guinea-pig gut, and the opioid blocker naloxone counteracted it. Injected into the brain ventricles of rats it gave strong, long-lasting pain relief, with a median effective dose (ED50) of about 13 to 23 picomoles per rat; morphine needed 752 to 2,170 times more, depending on the pain test. At high doses the rats became cataleptic (rigid and immobile). It also relieved pain in mice when given into a vein.

How much stronger it is than morphine therefore depends on the route, and there is no single figure for people. In the 1985 surgery trial 20 µg of dermorphin injected into the spinal fluid outlasted 500 µg of morphine given the same way, a dose 25 times smaller. In healthy volunteers an infusion into a vein raised the threshold of a spinal pain reflex, also in a person with a complete spinal cord injury, which points to an action in the spinal cord; naloxone reversed only about half of that effect. US prosecutors described it as 40 times more powerful than morphine.

In horses an injection into a vein caused a few minutes of excitation with a faster heart rate, and the peptide was cleared with a half-life of about 45 minutes (0.76 hours). According to evidence in a US criminal case, it masks pain and injuries in horses and can act as a stimulant, which is why it was given to racehorses.

Is dermorphin approved?

No. No medicine containing dermorphin has been authorised in the EU, the US or anywhere else, and none can be prescribed. After the 1985 trial it was never developed further for patients, and no later patient study has been published.

Research-grade dermorphin, the lyophilised peptide sold for laboratory use, is a chemical for in-vitro and animal research. It is not a medicine and is not intended for use in people.

• EU and the Netherlands: not authorised as a medicine. Dermorphin is not on list I or list II of the Dutch Opium Act (the version in force since 17 September 2026), so it is not a controlled drug in the Netherlands.
• US: the FDA has not approved it for use in humans or animals. In November 2017, after a nine-day federal trial in Louisiana, a veterinarian and a Nebraska compounding pharmacy were convicted of conspiracy and misbranding offences for supplying synthetic dermorphin for racehorses.
• Human sport: not on WADA's 2026 Prohibited List. WADA's 2026 Monitoring Program lists 'dermorphin (and its analogues)' among the narcotics it monitors in competition; monitored substances are not prohibited. The 2027 programme, in force from 1 January 2027, no longer includes it. According to USADA, the 2027 Prohibited List names 'peptides' in general as prohibited at all times under S0 (non-approved substances) and urges the utmost caution with peptides it does not name.
• Equestrian sport: listed as a banned substance (opioid) on the FEI's 2026 Equine Prohibited Substances List.

What the research shows

Most of the work on dermorphin is rodent pharmacology from the 1980s and 1990s. The human data come from Italy in the 1980s: short experiments with single doses, and one treatment trial in patients. None has been repeated in a modern trial, and the patient trial appeared as a three-page report in a journal supplement.

• Rats and mice (Broccardo et al. 1981): strong, long-lasting pain relief; when infused continuously into the brain, tolerance and physical dependence developed but were consistently less marked than with morphine. These comparisons come from the group that discovered it.
• Hormones in healthy volunteers (1980s): an Italian endocrinology group infused 5.5 µg/kg per minute for 30 minutes into a vein. Prolactin, growth hormone, TSH and renin activity rose and cortisol fell; pretreatment with naloxone blocked or blunted these changes. The peptide was used as a probe of opioid control of the pituitary, not as a treatment.
• Pain reflex (Sandrini et al. 1986): an infusion of 0.16 mg/kg into a vein caused a marked and long-lasting rise in the threshold of the nociceptive flexion reflex in healthy volunteers, and also in one person with a complete chronic spinal cord injury.
• Pain after surgery (Basso et al. 1985): 150 consecutive patients after elective surgery, randomised and double-blind, received 20 µg of dermorphin or 500 µg of morphine into the spinal fluid, or 30 mg of pentazocine into a muscle as routine care. Pain relief lasted a mean of 43.4 hours with dermorphin, 34.5 hours with morphine and 10.8 hours with pentazocine. Extra painkillers were needed by 22%, 58% and 88% of patients, and the hospital stay was 5.6, 6.3 and 8.7 days. Urinary retention, vomiting and headache did not differ significantly between the groups.
• Horses (Robinson et al. 2015): 10 horses received 9.3 µg/kg into a vein or a muscle. Injection into a vein brought on excitation and a faster heart rate that subsided within 5 minutes; dermorphin had already been found in post-race samples.

Dermorphin in horse racing

The best-documented use of dermorphin outside the laboratory is the doping of racehorses. According to the US Department of Justice, from November 2010 to December 2012 a compounding pharmacy in Omaha, Nebraska, obtained synthetic dermorphin from a California chemical company, repackaged it, labelled it 'D-Peptide' and sold it to veterinarians; a veterinarian in Lake Charles, Louisiana, filled syringes with it for racehorse trainers. Evidence at the trial showed that it masks pain and pre-existing injuries and, depending on the dose, acts as a stimulant in horses.

After a nine-day trial that ended on 7 November 2017, both were convicted. In February 2018 the veterinarian was sentenced to 15 months in prison and a $10,000 fine, and the pharmacy to a $200,000 fine and five years of corporate probation. The charges were conspiracy and offences involving adulterated or misbranded drugs. In international equestrian sport the FEI lists dermorphin as a banned substance.

Side effects and what is not known

The side-effect data come almost entirely from the spinal injections in surgical patients. In open pilot work before the 1985 trial (number of patients not reported), about half of the patients given spinal dermorphin had nausea or vomiting, persistent in 10%; naloxone relieved the vomiting but also ended the pain relief, and pretreatment with the anti-sickness drug domperidone brought nausea and vomiting below 20%. In the trial itself urinary retention occurred in 26% with dermorphin, 30% with morphine and 18% in the control group, and nausea and vomiting in 22%, 18% and 14%, as summarised in a 2018 review.

Much is simply unknown. The human data cover single doses only, so addiction and repeated dosing were never studied in people; the published reports give no data on breathing depression, and the rat data on milder tolerance and dependence than morphine come from one group. As a potent mu-opioid agonist it belongs to the drug class that causes breathing depression and dependence.

Frequently asked questions

Is dermorphin legal in the Netherlands?

Dermorphin is not on the lists of the Dutch Opium Act, so it is not a controlled drug in the Netherlands. It is not an authorised medicine either, here or anywhere else, so it cannot be prescribed. What is sold is research material for laboratory use, not for use in people.

Is dermorphin banned in sport?

Not for human athletes in 2026: it is not on WADA's Prohibited List. WADA's 2026 Monitoring Program lists dermorphin and its analogues among the narcotics it monitors in competition, which is not a ban, and the 2027 programme no longer includes them. From 1 January 2027 the Prohibited List names 'peptides' in general under S0 (non-approved substances), and USADA advises the utmost caution with any peptide the list does not name. Horse sport is different: the FEI lists dermorphin as a banned substance, and in US racing it led to criminal convictions.

How much stronger than morphine is dermorphin?

It depends on how it is given. Injected into the brain of rats it was 752 to 2,170 times more potent than morphine, and on isolated guinea-pig gut 39 times. In the only treatment trial in patients, 20 µg in the spinal fluid gave longer pain relief than 500 µg of morphine given the same way. US prosecutors called it 40 times more powerful than morphine, but there is no reliable potency figure for people.

Has dermorphin been tested in humans?

Only in the 1980s, in Italy. Small groups of healthy volunteers received a single infusion to study its effects on hormones and on a pain reflex, and one randomised, double-blind trial in 150 surgical patients compared a single spinal injection with spinal morphine and with pentazocine. Dermorphin gave the longest pain relief, but the trial was never repeated and no later patient study has been published.

What does dermorphin have to do with kambo?

Kambo is the dried skin secretion of a related Amazonian frog, Phyllomedusa bicolor, that is applied to small fresh burns in a ritual. It contains dermorphin-type peptides, but also many other active peptides, so the strong reactions people describe, such as vomiting, a racing heart and facial swelling, cannot be attributed to dermorphin alone. Dermorphin itself was first isolated from a different frog, Phyllomedusa sauvagii.

Why was dermorphin given to racehorses?

Because it masks pain and existing injuries and, depending on the dose, acts as a stimulant in horses, as the evidence in the 2017 US trial showed. In a study in 10 horses, an injection into a vein caused a few minutes of excitation with a faster heart rate. Supplying it for racehorses between 2010 and 2012 led to the conviction of a Louisiana veterinarian and a Nebraska pharmacy.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.