The FDA stated early this February that kratom has “opioid properties” and is “associated” with 44 deaths. With that Commissioner Gottlieb also stated that his agency developed a computational model to identify the possibility of abuse of designer street drugs for which there is little pharmacological data. Using this model the FDA scientists analyzed the 25 most common compounds in kratom and concluded that 22 of them share the most structural similarities with opioid painkillers such as morphine derivatives.

It seems the FDA is very concerned with substances having “opioid properties”, but it appears that very common substances possess similar characteristics, yet they are not being demonized like the herb kratom. For instance it was discovered some time ago in a study titled “Coffee contains potent opiate receptor binding activity”1 that, “Opiate receptor-active peptide fragments (exorphins) have been identified recently in casein and gluten hydrolysates, and morphine has been found in bovine and human milk.” This leads to another study titled “Opioids in milk”2. This study stated that, “In various studies, the milk has been screened for the presence of free or precursor-bound opioids.” Even Black Cohosh, a very common herb, has central opioid activity and has been documented in a study titled “Black Cohosh has Central Opioid Activity in Postmenopausal Women: Evidence from Naloxone Blockade and PET Neuroimaging Studies”3. A very surprising one is ginger. In a study titled, “Ginger prevents morphine-induced addictive behaviors in conditioned place preference test in rats”4. The data in this study indicated that ginger extract has a potential anti-addictive property against chronic usage of morphine. These facts about coffee, milk, ginger, and black cohosh have been known for sometime and yet they remain. The fact is, just because there is opioid activity for an herb or milk does not mean it is identical to dangerous substances that are responsible for the deaths of millions of Americans like Fentanyl and other highly addictive pharmaceutical painkillers.

Dr. Andrew Kruegel, PhD, Pharmacologist and researcher at Columbia University stated, “Research suggests the [7-OH and Mitragynine] result in different effects than traditionally abused opioids, appearing only to be partial agonists of the mu opioid receptor. They activate what is called the “G” protein pathway but not a separate opioid pathway associated with constipation and respiratory depression, a primary cause of overdose deaths.” Numerous researchers have stated this that kratom is different for a lot of reasons but mainly it will not depress the respiratory system, which is what is always found in pharmaceutical opiate painkiller, induced deaths.

The FDA has stated that kratom has been “Associated” with 44 deaths. The Botancial Education Alliance had leading toxicologist William R. Sawyer, Ph.D., D-ABFM conduct a full toxicological review of 30 associated deaths when the DEA was attempting to schedule the plant. Dr. Sawyer found no deaths solely attributed to kratom in the TOXNET data network, and determined there was insufficient toxicological evidence to support Schedule I classification. Since then the FDA has added 14 new associated deaths, and reports revealed that the majority of the deceased had other harmful drugs in their system that could have potentially caused respiratory depression. One teenager in the FDA kratom associated deaths died from hanging himself while testing positive for prescription drug abuse, another man with over nine different substances in his system fell out of a window and refused medical treatment before passing, then another gentlemen passed from complications due to deep vein thrombosis while taking 5 different prescription medications. In one listed kratom related death the individual died by homicide with a gunshot wound to the chest, and another nine deaths occurred in Sweden from a concoction of synthetic opioids mixed with other substances alongside kratom. After viewing the list of associated deaths it is clear that kratom is not the sole cause of death.

It has been noted that, “High kratom doses have not been reported to cause lethality in the toxicological literature; respiratory depression deaths have not been demonstrated with kratom and the pharmacological mechanisms of action of kratom are protective against respiratory depression as compared to that of opiates.” In fact it was scientifically determined that the lethal dose of Kratom is 1:233, which proves that Kratom is safer than caffeine 1:84, nicotine 1:21, acetaminophen 1:34, and is virtually impossible to overdose on. Kratom and its constituents have shown no acute toxicity5 , displays powerful antioxidant and antibacterial properties6 , assists with drug and alcohol withdrawal symptoms7 , contains several oxindole alkaloids, which have exhibited potent immunomodulation properties, and even contains constituents that have exhibited anti-cancer properties.8 Not to diverge from kratom but to put things into perspective, energy drinks like Monster, Red Bull, and 5-Hour energy have 34 direct deaths related to them including the death of a 16 year old girl Lanna Hamman of AZ. These can be found the in FDA’s adverse events reporting system where kratom has zero direct deaths to its name.

The FDA also stated that after analyzing 25 of the most common compounds in kratom, also known as alkaloids, that 22 of the 25 bind strongly to opioid receptors in the brain. This could not be further from the truth. Contrary to popular belief kratom has years if not decades of clinical research, NIH funded studies, and other thorough scientific data behind it. Its alkaloids were analyzed and in the detailed list below you’ll see several of its naturally occurring compounds that do not bind directly to opioid receptors. To name a few there is Isorhyncophylline that stimulates the immune system, Isomitraphylline that is also an immunostimulant and anti- leukemic, and Epicatechin that is a antioxidant, anti-aggregant, anti-bacterial and an anti- diabetic while also being found commonly in chocolate. That is only 3 of the 25 available compounds in kratom that do not strongly bind to opioid receptors with plenty more in the list below.

NIH studies, leading universities such as Columbia, Duke, Ole Miss, and other researchers around the world have sought to understand nature by conducting clinical studies on mice, rats, and even humans to obtain concrete data so that humanity as a whole may have the strongest understanding of these natural substances whether green tea, St. Johns wort, or ginger. These studies are the cornerstone for a higher learning and understanding of natural substances. So the new computational model the FDA used in this instance seems inconclusive and does not relate the real life relationship between kratom as a plant and humans. It merely tells us it has a partial relationship to opioid receptors that the studies above confirm milk and coffee do as well. We applaud the FDA’s effort to gain further understanding of this herb via its computational model for the sake of protecting the American public, but this limited computational analysis and the years worth of available science on the herb kratom do not add up.

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1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546775/

2. https://www.ncbi.nlm.nih.gov/pubmed/1764604

3. https://www.ncbi.nlm.nih.gov/pubmed/6296693

4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137441/

5. S.N. Harizala, b, c, , S.M. Mansorb, , J. Hasnanc, J.K.J. Tharakana and J. Abdullaha Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Centre for Drug Research, Universiti Sains Malaysia Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia 2010

6. Evaluation of Antioxidant and Antibacterial Activities of Aqueous, Methanolic and Alkaloid Extracts from Mitragyna Speciosa (Rubiaceae Family) Leaves. Suhanya Parthasarathy,Juzaili Bin Azizi, Surash Ramanathan, , Sabariah Ismail, Sreenivasan Sasidharan, Mohd Ikram Mohd. Said and Sharif Mahsufi Mansor.

Universiti Sains Malaysia, Penang, Malaysia Institute for Research in Molecular Medicine, Malaysia Universiti Kebangsaan Malaysia Selangor, Malaysia 2009

7. Fitoterapia Volume 78, Issue 3, April 2007, Pages 182–185

8. García Prado, E., et al. “Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines.” Phytomedicine. 2007; 14(4):280–4.

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LIST OF KRATOM ALKALOIDS AND THEIR INDIVIDUAL QUALITIES:

Tetrahydroalstonine: Hypoglycemic, anti-adrenergic. Speciophylline: Indole alkaloid. Anti-leukemic.

Speciogynine: Smooth muscle relaxer.

Rhynchophylline: Vasodilator, antihypertensive, calcium channel blocker, antiaggregant, anti- inflammatory, antipyretic, anti-arrhythmic, antithelmintic.

Paynantheine: Indole alkaloid. Smooth muscle relaxer.

Mitraphylline: Oxindole alkaloid. Vasodilator, antihypertensive, muscle relaxer, diuretic, antiamnesic, anti-leukemic, possible immunostimulant.

Mitragynine: Indole alkaloid. Analgesic, antitussive, antidiarrheal, adrenergic, antimalarial.

Isorhynchophylline: Immunostimulant

Isomitraphylline: Immunostimulant, anti-leukemic.

Epicatechin: Antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti- inflammatory, anti-leukemic, antimutagenic, antiperoxidant, antiviral, potential cancer preventative, alpha-amylase inhibitor. Also found in dark chocolate.

Corynantheidine: μ -opioid antagonist, also found in Yohimbe. Ciliaphylline: antitussive, analgesic.

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