This Kratom FAQ has been compiled to help people gain a better understanding of Kratom and how it can work in the body and also help debunk false myths about Kratom. Some of the Questions and subsequent answers are quite technical, so we have attempted to define some of the more important keywords for you. If you get confused, feel free to shoot us an email with further questions.
KRATOM TREES (MITRAGYNA SPECIOSA) TREES USUALLY GROW TO A HEIGHT OF 12–30 FT (3.7–9.1 M) TALL AND 15 FT (4.6 M) WIDE, ALTHOUGH SOME SPECIES CAN REACH 40–100 FT (12–30 M) IN HEIGHT.
Q: What is Kratom?
A: Kratom is a tree native to Southeast Asia in the Indochina and Malaysia floristic regions. Its botanical name is Mitragyna Speciosa [mih-tr-ah-jin-yah | spee-see-OH-sah]. Kratom is in the same family as the coffee tree Rubiaceae. The leaves of Kratom have been used as an herbal drug for centuries by peoples of Southeast Asia.
Q: What are the effects of Kratom?
A: At lower doses, it is used in folk medicine as a stimulant, reducing stress, anxiety and depression*, and at higher doses acts as a sedative for painkiller, recreational and medicinal use. Finally, Kratom is reported as being used for withdrawal treatment for opiate addiction and recovery*. For more details about this topic, please visit our kratom effects.
Q: What’s in Kratom?
A: Chemistry Make up of Kratom:
There are 40 compounds in M. speciosa leaves, including many alkaloids such as mitragynine (once thought to be the primary active constituent), mitraphylline, and 7-hydroxymitragynine (which is currently the most likely candidate for the primary active chemical in the plant). Other active chemicals in M. speciosa include raubasine (best known from Rauwolfia serpentina) and some Yohimbe alkaloids such as corynantheidine.
Mitragyna speciosa also contains at least one alkaloid (rhynchophylline) that is a calcium channel blocker and reduces NMDA-induced current. There is considerable research as to the role of NMDA receptor activity in the formation of dependence, and the symptoms of withdrawal.
Q: What are Alkaloids?
A: Alkaloids are a group of naturally occurring chemical compounds, that contain mostly basic nitrogen atoms.
Q: I hear the use of the term ANALGESIC. What does that term mean and how is it relevant to Kratom?
A: An analgesic, or painkiller, is any member of the group of drugs used to achieve analgesia — relief from pain. The word analgesic derives from Greek αν – (“without”) and άλγος – (“pain”).
There are many types of analgesic drugs from anesthesia to opiates such as oxycontin, oxycodone, Percocet, and Vicodin. It is relevant to Kratom since Kratom is considered analgesic in nature.
Q: What’s the best way to use Kratom?
A: This is mostly about personal preference. Using kratom capsules provides convenience and a tasteless/odorless experience. Using kratom powder, while more involved, generally produces quicker effects. So, it’s really up to you.
Q: Is Kratom safe?
A: When used in moderation, kratom is safe.
Q: Can you overdose on Kratom?
A: No reports from overdose on kratom alone are documented. Unlike other drugs such as Oxycontin or Vicodin which are synthetic, Kratom is unique due to the fact that if you take a dose stronger than your body needs it will expel it naturally. Taking Kratom by itself has not been found to result in overdose.
Q: Can I get sick from using too much Kratom?
A: Every pro can have a con. Here it is: Yes, it is possible to get minor hot flashes and a tummy ache. This effect will generally last 30-60 minutes. Please keep in mind, this effect only occurs if you have used more than the body needs. If this occurs, drink a cool glass of water and lay down in a dimly lit room.
Q: I have heard about Hypoventilation and it being associated with overdoses. What is Hypoventilation and can this happen with using Kratom?
A: No, Hypoventilation has not been reported to occur when you use Kratom independently, without any other substance. Read more below about hypoventilation.
Hypoventilation: In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo meaning “below”) to perform the needed gas exchange. By definition, it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis.
Causes: It can be caused by medical conditions, such as stroke affecting the brainstem, by holding one’s breath, or by drugs, typically when taken in overdose. Hypoventilation may also occur in chronic mountain sickness to conserve energy. 
Effects: As a side effect of prescription medicines or illicit recreational drugs, hypoventilation may become potentially life-threatening. Many different CNS depressant drugs such as alcohol, benzodiazepines, barbiturates, GHB, sedatives, and opiates produce respiratory depression when taken in large or excessive doses; however, this is most commonly seen as a cause of death with opiates or opioids, particularly when they are combined with sedatives such as alcohol or benzodiazepines. This has NOT however been reported as a possible side effect of using Kratom.
Q: How is Kratom said to work in the brain?
A: As of late 2011, no controlled, clinical studies have been performed on humans. Therefore, its metabolic half-life, protein binding, and elimination characteristics are all unknown within the scientific world. We do know that Kratom behaves as a μ-opioid receptor agonist, similar to opiates like morphine, although its effects differ significantly from those of opiates.Kratom does not appear to have significant adverse effects, and in particular appears NOT to cause the hypoventilation typical of other opioids.
Q: What is a μ- Opioid Receptor (MOR) and why is it important to talk about?
(see reference Section 2 for notations)
A: μ-(pronounced MU) opioid receptors are the receptors in your brain associated with pain. Kratom is said to be an agonist of these receptors; theory suggests it activates the receptors and aids the body to block the reception of pain signals, similar in nature to an opiate but without the negatives. We feel individuals should be knowledgeable about the theories on how kratom interacts with the brain and body in order to be fully cognizant of what is going on when using kratom and to combat the myths about Kratom use. So, read below!
Active and inactive μ-opioid receptors. The μ-opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide or (MOP) receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ (mu) refers to morphine.
SUBQUESTION: Wait a minute, this is complicated….What’s an Agonist?
A: An agonist is a chemical that binds to some receptor of a cell within the body and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance. So, an agonist causes an action, and an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.
TYPES of μ Receptors :
Three variants of the μ opioid receptor are well-characterized, though reverse-transcriptase PCR has identified up to 10 total splice variants in humans (we have complicated brains eh?).
- μ1 –More is known about the μ1 opioid receptor than is known about the other types.
- μ2 –TRIMU 5 is a selective agonist of the μ2 receptor.
- μ3 –In 2003, a μ3 variant was described, which was responsive to opiate alkaloids but not opioid peptides.
Q: Where are these receptors located?
A: In layman’s terms, they are within the brain and in the spinal cord.
Here’s the technical science behind them:
They can exist either presynaptically or postsynaptically depending upon cell types.
The μ-receptors exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord (specifically the substantia gelatinosa of Rolando). Other areas where μ-receptors have been located include the external plexiform layer of the olfactory bulb, the nucleus accumbens, in several layers of the cerebral cortex and in some of the nuclei of the amygdala, as well as the nucleus of the solitary tract.
μ receptors are also found in the intestinal tract. This causes constipation, a major side effect of μ agonists, due to inhibition of peristaltic action.
Q: Ok, I think I understand a bit more about all of this. Now, what about Activating all of this?
A: MOR can mediate acute changes in neuronal excitability via “disinhibition” of presynaptic release of GABA (see works from “Charles Chavkin, PhD.;”. and “Roger Nicoll, M.D.;”. ). Activation of the MOR leads to different effects on dendritic spines depending upon the agonist and may be an example of functional selectivity at the μ receptor.
Activation of the μ receptor by an agonist causes analgesia, sedation, slightly reduced blood pressure, itching(with certain agonists like morphine), euphoria, decreased respiration (again, no fear of HYPOVENTILATION using Kratom!), miosis (constricted pupils) and decreased bowel motility. Some of these effects, such as analgesia, sedation, euphoria and decreased respiration, tend to lessen with continued use as tolerance develops.
We hope the Kratom FAQ section has helped you learn more about this special herb.
- Zhorov BS, Ananthanarayanan VS (March 2000). “Homology models of mu-opioid receptor with organic and inorganic cations at conserved aspartates in the second and third transmembrane domains”. Arch. Biochem. Biophys. 375 (1): 31–49. doi:10.1006/abbi.1999.1529. PMID 10683246.
- Dortch-Carnes J, Russell K (2007). “Morphine-stimulated nitric oxide release in rabbit aqueous humor”. Exp. Eye Res. 84 (1): 185–90. doi:10.1016/j.exer.2006.09.014. PMC 1766947. PMID 17094965.
- Pan L, Xu J, Yu R, Xu MM, Pan YX, Pasternak GW (2005). “Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm”. Neuroscience. 133 (1): 209–20. doi:10.1016/j.neuroscience.2004.12.033. PMID 15893644.
- Eisenberg RM (1994). “TRIMU-5, a μ2-opioid receptor agonist, stimulates the hypothalamo-pituitary-adrenal axis”. Pharmacol. Biochem. Behav. 47 (4): 943–6. doi:10.1016/0091-3057(94)90300-X. PMID 8029266.
- Cadet P, Mantione KJ, Stefano GB (2003). “Molecular identification and functional expression of μ3, a novel alternatively spliced variant of the human μ opiate receptor gene”. J. Immunol. 170 (10): 5118–23. PMID 12734358.
- Stefano GB (2004). “Endogenous morphine: a role in wellness medicine”. Med. Sci. Monit. 10 (6): ED5. PMID 15173675.
- Liao D, Lin H, Law PY, Loh HH (February 2005). “Mu-opioid receptors modulate the stability of dendritic spines”. Proc. Natl. Acad. Sci. U.S.A. 102 (5): 1725–30. Bibcode:2005PNAS..102.1725L. doi:10.1073/pnas.0406797102. JSTOR 3374498. PMC 545084. PMID 15659552.
- Liu X-Y, Liu Z-C, Sun Y-G, Ross M, K S, Tsai F-F, Li Q-F, Jeffry J, Kim J-Y, Loh HH, Chen Z-F. “Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids”. Cell 147 (2): 447–458. doi:10.1016/j.cell.2011.08.043. PMC 3197217. PMID 22000021. Lay summary – Washington University in St. Louis Press Release.
- Martini L, Whistler JL (October 2007). “The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence”. Current Opinion in Neurobiology 17 (5): 556–64. doi:10.1016/j.conb.2007.10.004. PMID 18068348.
- Zuo Z (September 2005). “The role of opioid receptor internalization and beta-arrestins in the development of opioid tolerance”. Anesthesia and Analgesia 101 (3): 728–34, table of contents. doi:10.1213/01.ANE.0000160588.32007.AD. PMID 16115983.
- Marie N, Aguila B, Allouche S (November 2006). “Tracking the opioid receptors on the way of desensitization”. Cellular Signalling 18 (11): 1815–33. doi:10.1016/j.cellsig.2006.03.015. PMID 16750901.
- DuPen A, Shen D, Ersek M (September 2007). “Mechanisms of opioid-induced tolerance and hyperalgesia”. Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses 8 (3): 113–21. doi:10.1016/j.pmn.2007.02.004. PMID 17723928.
- Garzón J, Rodríguez-Muñoz M, Sánchez-Blázquez P (May 2005). “Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter”. Neuropharmacology 48 (6): 853–68. doi:10.1016/j.neuropharm.2005.01.004. PMID 15829256.
- Hooks SB, Martemyanov K, Zachariou V (January 2008). “A role of RGS proteins in drug addiction”. Biochemical Pharmacology 75 (1): 76–84. doi:10.1016/j.bcp.2007.07.045. PMID 17880927.
- Sirohi S, Dighe SV, Walker EA, Yoburn BC (November 2008). “The analgesic efficacy of fentanyl: relationship to tolerance and mu-opioid receptor regulation”. Pharmacology, Biochemistry, and Behavior 91 (1): 115–20. doi:10.1016/j.pbb.2008.06.019. PMC 2597555. PMID 18640146.
- Lopez-Gimenez JF, Vilaró MT, Milligan G (November 2008). “Morphine desensitization, internalization, and down-regulation of the mu opioid receptor is facilitated by serotonin 5-hydroxytryptamine2A receptor coactivation”. Molecular Pharmacology 74 (5): 1278–91. doi:10.1124/mol.108.048272. PMID 18703670.
- Kraus J (2009). “Regulation of mu-opioid receptors by cytokines”. Frontiers in Bioscience (Scholar Edition) 1: 164–70. PMID 19482692.
- García-Fuster MJ, Ramos-Miguel A, Rivero G, La Harpe R, Meana JJ, García-Sevilla JA (November 2008). “Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers”. Neuroscience 157 (1): 105–19. doi:10.1016/j.neuroscience.2008.09.002. PMID 18834930.
- Ueda H, Ueda M (2009). “Mechanisms underlying morphine analgesic tolerance and dependence”. Frontiers in Bioscience 14: 5260–72. doi:10.2741/3596. PMID 19482614.
REFERENCE SECTION 2:
**1. **“hypoventilation” at Dorland’s Medical Dictionary
**2. **Zubieta-Calleja, GR; Paulev, PE; Zubieta-Calleja, L; Zubieta-Calleja, N; Zubieta-Castillo, G (September 2006). “Hypoventilation in chronic mountain sickness: a mechanism to preserve energy.”. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society. 57 Suppl 4: 425–30. PMID 17072073. Cite uses deprecated parameters (help)
**3. **Harper,D. (2001). “Online Etymology Dictionary: Analgesia”. Retrieved December 3, 2012.
5. Ward J, Rosenbaum C, Hernon C, McCurdy CR, Boyer EW (December 2011). “Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy?”. CNS Drugs25 (12): 999–1007. doi:10.2165/11596830-000000000-00000. PMID 22133323. **6. ** Adkins, Jessica E.; Edward W. Boyer, Christopher R. McCurdy (2011-05-01). “Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity.”. Current Topics in Medicinal Chemistry **10. ****^**Chittrakarn, S; Keawpradub, N; Sawangjaroen, K; Kansenalak, S; Janchawee, B (2010). “The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.)”. Journal of Ethnopharmacology 129 (3): 344–349. doi:10.1016/j.jep.2010.03.035. PMID 20371282.
**11. **Prozialeck, WC; Jivan, JK; Andurkar, SV (2012). “Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic, and opioid-like effects”. The Journal of the American Osteopathic Association 112 (12): 792–799. PMID 23212430.
**12. **Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D et al. (2002). “Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands”. J Med Chem 45 (9): 1949–1956. doi:10.1021/jm010576e. PMID 11960505.
**13. **Microgram Bulletin – Department of Justice
**14. **Hendrickson, JB, Sims JJ. Mitragyna alkaloids – The structure of stipulatine. Tetrahedron Letters 1963;14:959-963