Side-by-side · Research reference

DermorphinvsTesofensine

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

BPhase 3AUTO-DRAFTED10/40 cited

Dermorphin

Opioid Peptide · μ-Receptor Agonist · Research Only

~30×Morphine potency

μ-selectiveReceptor typeNegri 1992

D-Ala²Unique featureAmiche 1998

Research only · ICV / SC (animal models)

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

Dermorphin

Tesofensine

Primary target

μ-opioid receptors (central and peripheral)Negri 1992 Steel 2014

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

μ-receptor activation → G-protein coupling → adenylyl cyclase inhibition → neuronal hyperpolarization

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

Potent analgesia, reduced nociceptive signaling, opioid-mediated CNS and peripheral effects

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

N/A — exogenous opioid agonist

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Origin

Phyllomedusa sauvagei and P. bicolor frog skin — gene-encoded with natural D-amino acid incorporationAmiche 1998 Mignogna 1992

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

Site-directed antibodies produced for detection and purificationCucumel 1996

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02Dosage Protocols

Parameter

Dermorphin

Tesofensine

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

Phase 2b + ongoing Phase 3Astrup 2008

Human toxicity

Kambô ritual (P. bicolor skin) — violent emesis, vasodilation, fluid shifts, ADH dysregulationTran 2025

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Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Frequency

—

Once daily, morning

Lower / starter dose

—

0.125 mg / day

Duration

—

24 weeks per studied cycle

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

Half-life

—

~9 days (very long)

04Side Effects & Safety

Parameter

Dermorphin

Tesofensine

Opioid effects

Respiratory depression, sedation, euphoria, tolerance, dependence risk

—

CNS effects

Analgesia (high-affinity sites), catalepsy (low-affinity sites)Negri 1992

—

Kambô ritual toxicity

Violent emesis, vasodilation, profound fluid shifts, hyponatremia, ADH dysregulation, brain death (case report)Tran 2025

—

Peripheral effects

GI motility inhibition (ileum > vas deferens in vitro)Negri 1992

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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

—

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Pregnancy / OB

—

Contraindicated

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

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

Dermorphin

·Any context outside approved animal research protocols
·CNS depressant co-administration

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

Dermorphin

Tesofensine

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.

Oral capsule (investigational; not commercial).

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.

Swallow whole with water, morning only.

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

Morning to mitigate insomnia. Do not dose evening.

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

Room temp ≤25 °C, dry place.

5. Caveat

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Monitor BP + HR + mood. Avoid stimulants + MAOIs.