The first person to analyse Kambo in a lab was an Italian pharmacologist and chemist, named Vittorio Erspamer.
Erspamer first discovered the neurotransmitter Serotonin, and was twice nominated for a Nobel Prize.
In 1986, he concluded that Phyllomedusa Bicolor - the Kambo frog - contained a fantastic chemical cocktail with potential medical applications, unequalled by any other amphibian.
Research on these chemicals found in the secretion have given rise to over 70 patents being lodged in the pharmaceutical world, primarily in the United States, according to the IAKP.
These chemicals, are in fact, very potent peptides.
What is a peptide?
Peptides are a fundamental part of nature, found in animals and humans alike. They're comprised of amino acids - the building blocks of life - just like proteins are.
The common factor that distinguishes a peptide from a protein, are the amount of amino acids that bond together. Peptides are comprised of shorter chains of amino acids. Proteins are comprised of longer chains of amino acids, roughly 50 or more.
Enzymes can break down proteins back into shorter peptides through digestion, where the body can decide whether its most beneficial to use these peptides, or excrete them.
Depending on the amino acids involved, peptides can perform many different biological functions in the body. Some perform antimicrobial, hormonal, and neuro activities, providing support to vital cellular processes and functions within the body.
It has been repeatedly pointed out that peptides found in mammalian gut and brain tissues have very frequent counterparts in amphibian skin, and vice versa, that amphibian skin peptides may offer a key for the discovery of new, analogous peptides in mammalian tissues.
The skin of the Phyllomedusa species is no exception, and carries an abundant source of peptides that show a broad spectrum of activities.
From the first Phyllomedusa peptide isolated and characterized to date, more than 200 peptides from Phyllomedusa species have had their primary structure characterized, and several of them have had their biological activities evaluated.
In 2010, it was reported that 21 peptides had been found in the Phyllomedusa Bicolor secretion. Many of these peptides are considered "bioactive", which simply means they have a specific biological function within a living organism. We also know that the Kambo secretion contains neuropeptides.
What is a neuropeptide?
Neuropeptides are peptides that influence the activity of neurons and neurological function. These particular peptides which are produced in the brain may act as neuromodulators, neurotransmitters, cotransmitters - which modify the action of neurotransmitters, or as neurohormones.
This means that these neuropeptides can contribute to a wide range of activities related to serotonin, dopamine, oxytocin, insulin, endorphins, learning, memory, analgesia, blood sugar regulation, and a host of other biological functions.
Through the isolation of Kambo's peptides, researchers have been trying to replicate the specific neurophysiological functions that these bioactive peptides produce, enhancing their capacity for clinical application in the world of medicine and pharmacology.
FOUND IN KAMBO
Several bioactive peptides and neuropeptides have been identified in the Kambo secretion thus far.
These families of peptides include Tachykinins, Bradykinins, Caeruleins, Bombesins, Sauvagine, Deltorphin, Dermaseptin, Dermatoxin, Tryptophyllins, Calcitonin and Neuropeptide Y.
While each activate potent physiological mechanisms in the body, the peptide percentage from frog-to-frog and secretion-to-secretion naturally contains variables. This may differ depending on specific regions in which the frogs are found within the Amazon, potentially leading to minor differences in predators, pathogens, diet and habitat, thus affecting peptide production within each frog.
More research is needed - and is currently being conducted - to determine both the peptide percentages and variables between different batches of Kambo secretion, and what other bioactive peptides may be awaiting discovery.
Phyllomedusin / Tachykinins Family:
Phyllomedusin acts as a neuropeptide, exciting neurons and provoking behavioural responses through the modulation of dopamine, serotonin and other neurotransmitters. It produces contraction at the smooth muscle level, affecting the stomach, intestines, pancreas, gallbladder, bowel, as well as tear ducts and salivary glands.
Being both a potent vasodilator and gastric secretagogue, it helps facilitate the purging and defecation process, and contributes to the rushing, pulsating, pounding sensations sometimes experienced during Kambo.
Phyllokinin / Bradykinins Family:
Phyllokinin induces a long lasting reduction in blood pressure, known as hypo-tension. It has been referenced as a nano-technological solution to psychiatric drugs, due to it's potential for increasing the permeability of the blood brain barrier
Phyllocaerulein / Caeruleins Family:
Phyllocaerulein is a neuropeptide that stimulates the adrenal cortex and pituitary gland. It contributes to smooth muscle contraction of the heart, vascular and gastrointestinal system; stimulating gastric acid secretions, reducing blood pressure, and contributing to the heart palpitations and abdominal discomfort felt during Kambo.
It plays a part in modulating satiety, contributes to digestive improvement, modifies sedation, and affects thermoregulation, potentially leading to profuse sweating during the experience.
This family of peptides also contributes to the reduction of nociception, which is the sensory nervous system's response to harmful stimuli. Hypothetically, this gives the nervous system a chance to reboot without the constant bombardment of stressful stimulation.
Through its powerful analgesic properties, it diminishes pain and fatigue, while increasing physical strength and resistance.
Phyllolitorin, Rohdei-Litorin, Leu8 / Bombesins Family:
These peptides of the Bombesins family have been found to be widely distributed in neural and endocrine cells. They stimulate gastric acid secretion and smooth muscle contractability.
Bombesins also seem to be involved in the regulation of a number of CNS and PNS functions, such as thermoregulation, glucoregulation, behaviour, satiety, circadian rhythm, sensory nerve transmission, energy homeostasis, motility, immunological functions, effects in the respiratory and urogenital system, the secretion of numerous hormones and neurotransmitters, as well as prolactin and growth hormone release.
Dermorphin / Sauvagine Family:
Dermorphin induces potent opiate-like activity with its high selectivity for mu-type opioid receptors. These class of peptides are many times more potent than endogenous beta-endorphin.
The duration and potency of Dermorphins analgesic properties have shown to exceed those of morphine, while suggesting that this peptide class is also less likely than morphine to produce tolerance, dependence and opiate side effects.
In a study involving guinea pigs and mice, Dermorphin was respectively 57, 294, 18 and 39 times more potent than Met-enkephalin, Leu-enkephalin, beta-endorphin, and morphine, on ileum opiate receptors of guinea pigs.
On vas deferens receptors of mice, Dermorphin was about as potent as the enkephalins and 40 times more potent than morphine.
Sauvagine functions like a hormone, interacting with the pituitary-adrenal axis and corticotropin-releasing receptors, which are involved in cortisol, stress, anxiety, depression, and addictive behaviours. It also holds properties that affect smooth muscle contraction of the colon and urinary bladder, alongside tachycardia and a reduction in blood pressure.
Deltorphin / Deltorphin Family:
Deltorphins could be considered amongst the most powerful pain killing substances ever discovered, with the highest binding affinity and selectivity to delta opioid receptors of any natural compound. Two Deltorphin peptides have been discovered in the secretion of Phyllomedusa Bicolor so far.
Alongside Dermorphin, this peptide is many times more potent than our endogenous beta-endorphins.
Dermaseptin, Adenoregulin, Plasticin, Phylloseptin, Phylloxin / Dermaseptin Family:
The Dermaspetin family of peptides are known for their potent and lethal antimicrobial activity against bacteria, fungi, yeasts, protozoa, and viruses - including both HSV-1 and HIV-1.
These peptides have shown destructive action against filamentous fungi responsible for debilitating infections which can accompany immuno-deficiency syndrome and the use of immuno-suppressive agents.
Research conducted at both the University of Paris and Queens University in Belfast, have shown that Dermaseptin peptides are also effective in killing certain types of cancer cells; inhibiting the growth of these tumor cells whilst also being cytotoxic towards the same cells.
While Dermaseptins and their analogues hold powerful activity in disintegrating harmful cells with their antimicrobial and anticancer mechanisms, research has shown that there is zero (to minimal - only in extremely high levels) damage or toxicity to mammalian cells.
It seems that Adenoregulin receptors also hold potential for the targeted treatment of depression, stroke and cognitive decline, caused by Alzheimers and Parkinsons disease.
Dermatoxin / Dermatoxins Family:
Two dermatoxins were identified in the skin secretions of Phyllomedusa Bicolor. Similar to Dermaseptin with it's antibacterial activity, Dermatoxin proved to be bactericidal towards mollicutes (wall-less eubacteria) and Gram-positive eubacteria, and also, though to a lesser extent, towards Gram-negative eubacteria.
Measurement of the bacterial membrane potential revealed that Dermatoxin's primary target is the plasma membrane. It's mechanism of cell-killing is based upon the alteration of membrane permeability.
Tryptophyllin / Tryptophyllins Family:
Tryptophyllins are neuropeptides which are said to be opening up new perspectives within neuroscience. This family of peptides hold antimicrobial properties, with suggestions that this peptide could inhibit the growth of the microorganisms Staphylococcus aureus, Escherichia coli and Candida albicans.
In studies it was shown that tryptophyllins had an anti-proliferative effect on three different human prostate cancer cell lines. With the inhibition of this proliferation in prostate cancer cells - and lack of undesirable side effects - this peptide may have potential in cardiovascular, inflammatory and anticancer therapy
Calcitonin Gene-Related Peptides / Calcitonin Family:
Calcitonin gene related peptide is a highly potent vasodilator, thought to play a role in cardiovascular homeostatis and nociception. There is mounting evidence to suggest that this neuropeptide may be beneficial in preventing the development of hypertension and cardiovascular pathologies associated with hypertension.
Calcitonin possesses protective mechanisms important for wound healing, whlie preliminary research shows interesting potential for conditions such as arthritis, skin conditions, diabetes, and obesity.
Skin Peptide Tyrosine-Tyrosine (SPYY) / Neuropeptide Y Family:
Skin Peptide Tyrosine-Tyrosine (SPYY) holds potent antibiotic activity against strains of bacteria, fungi and protozoa.
Researched showed that SPYY exhibited a 94% similarity with Peptide Tyrosine-Tyrosine (PYY), found within the frog Rana Ridibunda, and 85% similarity with human Peptide Tyrosine-Tyrosine (PYY), both of which are related peptides in the Neuropeptide Y Family.
Related peptides that belong to the Neuropeptide Y family seem to integrate a variety of important regulatory functions, such as sympathetic vascular control, central regulation of endocrine and autonomic function, food intake, circadian rhythm, histamine release from isolated mast cells, and increase of intracellular Ca2 in many cell types.