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Articles for Kratom

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish


With drawal syndrome consists of a set of physical and psychological symptoms that a rise when people abruptly stop sabusing a substance that they have abused before or if the amount of substance they used to abstain decreases.

The Opioids Most Commonly Involved in the withdrawal syndrome are: morphine, meperidine, codeine, oxycodone, tramadol, hydromorphone and heroin, whether they are used the rapeutically (for example, in the treatment of chronicpain) orifthey are used as substances of abuse (heroin)

All These Substances Have in common that they act on opioid receptors; Many of them are used in medicine, mainly because of their potentanal gesic effect, but they have a great potential for great potential for abuse due to their psychoactive properties.

Our body is always in search of homeostasis. Thus, when it receives in a very continuous way the same substance, a series of mechanisms that aim to return to the previous state are triggered. Thatis, keep working withoutt the consumption of the drug affect it.

Therefore, if the substanceis removed, the homeostasis reached is broken and the unpleasant symptoms of thewithdrawal syndrome appear.

Clinical Manifestations

The clinic Pictures similar withallopioids, and includes three phases:

Initialphase: there is the presence of rhinorrhea, epiphora lacrimation, yawning, anxiety and sweating; Generally, it appears within 8-12 hours after the last dose of the opioid.

Intermediatephase: occurs when the with drawal syndrome reaches its greatest intensity. It ischaracterized by mydriasis, piloerection, myalgias, arthralgias, muscular contractures, bonepain, diaphoresis, tachycardia, hypertension, tremor, irritability, motor agitation, anorexia and insomnia.

Late phase: pares thesias, fever, colicky abdominal pain, nausea, vomits, diarrhea and hyperglycemia, and spontaneous orgasms orejaculations may appear.

The Desire To Avoid and escape the aversive symptoms of abstinence can lead undesirable to the search for opiates, which causes a relapse. Therefore, a majorgoal in the treatment of addiction to relieve these verity of opioid withdrawal symptoms.

A series of experiment was carried out to investigate the effect of mitragynine on anxiety behavior, cortisol level and the expression of genes related to the stress pathway in zebrafish in phase of morphine withdrawal.

The Researchers Deciphered The Zebrafish Genome, a "modelorganism" commonly used in laboratories to study human diseases.

This Genome Is The Largest Deciphered so far with, 26,000 genes encoded, and was sequenced so accurately that we can actually makedirectcomparisonsbetween human genes and zebrafish genes. Its DNA isvery similar tothat of men, 70% of human genes have a homolog in zebrafish and in the genes associated with human pathologies, the proportion resisto 84%

Their embryos, being transparent, make it possible to see the effects of the drugs inside their organs. Thereis no problem whenit comes to dyeing their viscera and their rapid development give th epossibility of study innumerous diseases induced in a same generation and identifythe causes.

Cortisol is a hormone produced by interrenal cells in fish (in mammals it is produced in the adrenal glands), which under normal cconditions plays a very important role in processes of metabolism, growth, energy regulation and hydromineral balance. Under stress conditions, cortisol is part of the body's primary response, so it is used as one of the most important physiological stress markers in fish. Under normal conditions, vertebrates present daily rhythms of cortisol secretion, with production maximums at the beginning of the activity phase.

A major obstacle in the treatment of drugaddictionisthe severity of the opioid withdrawal syndrome, which can cause an unwanted relapse.Mitragynine Is The Main Alkaloid Compound Found in the leaves of Mitragyna Speciosa Popularly known as kratom, a plant widely used by opiateaddicted to mitigate the harshness of drug abstinence.

A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, it was first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.



Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish
Beng-Siang Khor,1 MohdFadzly Amar Jamil,1 MohamadIlham Adenan,1,2 and Alexander Chong Shu-Chien1,3,*
RamaniRamchandran, Editor



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