Side-by-side · Research reference
DermorphinvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED20/47 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
Dermorphin
Opioid Peptide · μ-Receptor Agonist · Research Only
Research only · ICV / SC (animal models)
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Dermorphin
PE 22-28
Primary target
μ-opioid receptors (central and peripheral)Negri 1992Steel 2014
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
μ-receptor activation → G-protein coupling → adenylyl cyclase inhibition → neuronal hyperpolarization
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Potent analgesia, reduced nociceptive signaling, opioid-mediated CNS and peripheral effects
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
N/A — exogenous opioid agonist
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Phyllomedusa sauvagei and P. bicolor frog skin — gene-encoded with natural D-amino acid incorporationAmiche 1998Mignogna 1992
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
Site-directed antibodies produced for detection and purificationCucumel 1996
Not reported in animal studies
02Dosage Protocols
Parameter
Dermorphin
PE 22-28
Legal status
Controlled substance in many jurisdictions · Research only
Not approved for human use.
—
Animal research (ICV)
Low nanomolar to picomolar range
Intracerebroventricular administration in rodent models.
—
Detection limit (doping)
5 pg/mL in equine plasma/urineSteel 2014
High-throughput LC-MS/MS screen developed for racing industry.
—
Duration of action
10–120 minutes (dose-dependent, intrathecal)
—
Evidence basis
Animal studies · In vitro assays
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Human toxicity
Kambô ritual (P. bicolor skin) — violent emesis, vasodilation, fluid shifts, ADH dysregulationTran 2025
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Frequency
—
Once daily
Sustained antidepressant effect over 7+ days.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
04Side Effects & Safety
Parameter
Dermorphin
PE 22-28
Opioid effects
Respiratory depression, sedation, euphoria, tolerance, dependence risk
—
Kambô ritual toxicity
Violent emesis, vasodilation, profound fluid shifts, hyponatremia, ADH dysregulation, brain death (case report)Tran 2025
—
Receptor selectivity caveat
Two μ-receptor subtypes — differential behavioral effects (analgesia vs. catalepsy)Negri 1992
—
Proteolytic stability
Tyr³-Pro⁶ bond relatively unstable; endogenous enzymes may produce tetrapeptide fragmentsCucumel 1996
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
Dermorphin
- ·Human use — not approved by any regulatory authority
- ·Controlled substance status — possession illegal in many jurisdictions
- ·Known opioid hypersensitivity or respiratory compromise
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Dermorphin
- ·Any context outside approved animal research protocols
- ·CNS depressant co-administration
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Dermorphin
PE 22-28
1. Legal and ethical framework
Dermorphin is a controlled substance in many jurisdictions and is not approved for human use. Possession, synthesis, or distribution may be illegal. Use is restricted to licensed research settings under institutional review.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Animal research protocols
In rodent models, intracerebroventricular (ICV) or intrathecal injection is used at nanomolar to picomolar concentrations. Subcutaneous administration also documented. All protocols require IACUC approval.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Analytical detection
High-throughput LC-MS/MS screens developed for anti-doping programs detect dermorphin and 17 related peptides in equine and human urine/plasma at limits as low as 5 pg/mL.Steel 2014
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Kambô ritual (traditional use)
Application of Phyllomedusa bicolor skin secretions to superficial burns. Not recommended — associated with severe toxicity including violent emesis, hyponatremia, and documented case of brain death.Tran 2025
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.