Assessment of Kratom – scientific study

Assessment of Kratom (Mitragyna Speciosa)


Executive Summary

Kratom (Mitragyna Speciosa) leaves contain a total alkaloid content from 0.5 to 1.5%, and generally, mitragynine is considered to be the major constituent. However, the content and distribution of the alkaloids varies depending on the geographical region and season and the methods of extraction also vary; these factors have contributed to a lack of standardization of the alkaloid content of extracts administered in animal studies and ingested by humans. Mitragynine has been studied most frequently for its pharmacological effects. Various in vitro and animal studies have shown that mitragynine has anaesthetic, antitussive, antinociceptive, analgesic and narcotic-like properties. Although the structure of mitragynine is different from that of morphine, pharmacological studies showed the analgesic effect of crude extracts and mitragynine are mediated by supraspinal κ, μ and δ opioid receptors, with a high selectivity for μ opioid receptors. The opioid agonistic effects of other constituents of Mitragyna speciosa have also been studied and among them, 7-hydroxymitragynine, an oxidized form of mitragynine (α-hydroxyl group at the C7 position) has shown the most potent effect. This suggests that the more potent opioid effect of the Mitragyna speciosa extract compared to mitragynine may be due to the activity of 7-hydroxymitragynine. Research also suggests that the methoxy-group on the C-9 is essential for the biological activity. When the methoxy group is replaced by a longer alkoxy-group, the biological activity is abolished.

Table 1: Alkaloid profile of Mitragyna speciosa Korth. The percentage is the estimated content in the alkaloid extracts.

7OH is one of the alkiloids that is of concern to the public this is a chart to show how much is in 10 grams of leaf. In some cases 7OH is not even detected this chart is from a scientific study.

Alkaloid Percentage Effect Reference
Mitragynine 66% Analgesic, antitussive, antidiarrheal, adrenergic, antimalarial Hooper (1907); Field (1921); Lee et al. (1967); Ponglux et al. (1994)
Paynantheine 9% Smooth muscle relaxer Ponglux et al. (1994)
Speciogynine 7% Smooth muscle relaxer Lee et al. (1967); Shellard, 1974; Shellard et al. (1978b); Ponglux et al. (1994)
7-Hydroxymitragynine 2% Analgesic, antitussive, antidiarrheal Ponglux et al. (1994)
Speciogynine 1% Weak opioid agonist Lee et al. (1967); Ponglux et al. (1994)
Mitraphylline <1% Vasodilator, antihypertensive, muscle relaxer, diuretic, antiamnesic, immunostimulant, anti-leukemic Seaton et al. (1958); Shellard, 1974; Shellard et al. (1978b); Ponglux et al. (1994)
Isomitraphylline <1% Immunostimulant, anti-leukemic Seaton et al. (1960); Shellard and Philipson (1966); Ponglux et al. (1994)
Speciophylline <1% Anti-leukemic Shellard and Philipson (1966); Beckett et al. (1966)
Rhynchophylline <1% Vasodilator, antihypertensive, calcium channel blocker, antiaggregant, anti-inflammatory, antipyretic, anti-arrhythmic, antithelmintic Seaton et al. (1960); Shellard, 1974; Shellard et al. (1978b)
Isorhynchophylline <1% Immunostimulant Seaton et al. (1958); Seaton et al. (1960); Shellard, 1974; Shellard et al. (1978b)
Ajmalicine <1% Cerebrocirculant, antiaggregant, anti-adrenergic, sedative, anticonvulsant, smooth muscle relaxer Beckett et al. (1966)
Corynantheidine <1% Opoid agonist Takayama et al. (2002)
Corynoxine A <1% Calcium channel blocker, anti-locomotive Shellard et al. (1978a)
Corynoxine B <1% Anti-locomotive Shellard et al. (1978a)
Mitrafoline <1% Hemmingway et al. (1975); Shellard et al. (1978a)
Isomitrafoline <1% Hemmingway et al. (1975); Shellard et al. (1978a)
Oxindale A <1% Shellard et al. (1978a)
Oxindole B <1% Shellard et al. (1978a)
Speciofoline <1% Analgesic, antitussive Hemmingway et al. (1975)
Isospeciofoline <1% Hemmingway et al. (1975); Shellard et al. (1978a)
Ciliaphylline <1% Analgesic, antitussive Trager et al. (1968)
Mitraciliatine <1% Lee et al. (1967)
Mitragynaline <1% Houghton et al. (1991)
Mitragynalinic acid <1% Houghton et al. (1991)
Corynantheidalinic acid <1% Houghton et al. (1991)

Taken from Hassan et al. 2013


  • Analgesic / Behavioral Activities: Study on analgesic and behavioral activities of the methanol and alkaloid extracts of Mitragyna speciosa showed it possessed analgesic activity which partly acted at opioid receptors in the supraspinal opioid system. It produced no significant prolongation of latency in nociceptive response.
  • Sedating Effects: Study results suggest that mitragynine possess sedative properties acting on the CNS of rats. The methanol and alkaloid extracts produced no significant changes in locomotor activity.
  • Anti-Diarrheal: Study showed methanolic extracts of leaves caused a dose-dependent protection against castor-oil induced diarrhea in rats and also inhibited intestinal transit. The anti-diarrheal effect was not antagonized by naloxone. The effect may occur via pathways in addition to the action on opioid receptors.
  • Antinociceptive / Anti-Inflammatory: (1) Study in rodents suggests the presence of potent antinociceptive and anti-inflammatory principles in the methanol extract, with significant dose-dependent activity in all nociceptive models and dose dependent suppression of carrageenan-induced paw edema.
(2) Study showed the antinociceptive effect of mitragynine was less potent than the crude extract of Mitragyna speciosa, suggesting that one or more minor constituents of Mitragyna speciosa may have a very potent antinociceptive effect.
  • Neuromuscular Blockade: Study investigated the effects of mitragynine and a methanolic extract of kratom leaves on neuromuscular junction and compound nerve action potential. The ME and mitragynine blocked nerve conduction, amplitude and duration of compound nerve action potential. Muscle contraction was greater with extract. The dominant effect of the K extract was at the neuromuscular junction and not at the skeletal muscle or somatic nerve.
  • Alcohol Withdrawal Benefit / Antidepressant Effect: Administration of the aqueous extract of Mitragyna speciosa at dose of 300 mg/K significantly inhibited ethanol-induced withdrawal behaviors such as rearing, displacement and head weaving. It also showed antidepressant activity without affecting spontaneous motor activity.


Mitragyna speciosa

Mitragyna speciosa (Kratom), is a large tree native to Thailand and Malaysia, growing to 50-100 feet (16-33m) in height. It is botanically related to the Corynanthe, Cinchona and Uncaria genii and shares some similar biochemistry. Other species in the Mitragyna genus are used medicinally in Africa.


Kratom is well established like coffee as a plant in its native region, and there is some increasing use elsewhere in the world. The leaves are usually made into a tea, although they are sometimes also chewed or extracted into water and then evaporated into a tar that can be swallowed. Kratom is not smoked.


Over 25 alkaloids have been isolated from kratom including mitragynine, once thought to be the primary active as it is the most abundant alkaloid in the plant, and 7-hydroxymitragynine, which is currently the most likely candidate for the primary active chemical in the plant. Although structurally related to yohimbine and tryptamines, its pharmacology is quite different and it seems to act in some ways similarly to opiates, although it seems to also have some stimulant properties similar to yohimbine. Kratom also contains alkaloids found in uña de gato (Uncaria tomentosa) which are powerful immune system enhancers and blood pressure decreasers, as well as epicatechin, a powerful antioxidant found in dark chocolate and closely related to the ECGC that gives green tea its beneficial effects.


Most of the identified alkaloids are yohimbe-type indoles and oxindoles. The most abundant alkaloids consist of three indoles and two oxindoles. The three indoles are mitragynine, paynanthine, and speciogynine – the first two of which appear to be unique to this species. The two oxindoles are mitraphylline and speciofoline. Other alkaloids present include other indoles and oxindoles such as ajmalicine, akuammigine, corynanthedine, mitraversine, rhynchophylline, speciociliatine (also unique to kratom) and stipulatine. Working with Malay plants, Houghton and Said found new types of indole alkaloids (mitragynaline, corynantheidaline, mitragynalinic acid, and corynantheidalinic acid), in very young leaves. Those alkaloids were reported as having an unusual skeleton, having a carbon function at the C14 position (compared with previously known monoterpenoid indoles), but Takayama et al. later revised the structure of mitragynaline and corynantheidaline, showing that there was no substitution on the 14 position. Other active chemicals in kratom include raubasine (best known from Rauwolfia serpentina) and some yohimbe alkakoids such as corynantheidine.



More important is the research on 7-hydroxymitragynine (or mitragynine hydroxyindolenine), which is a naturally occurring minor alkaloid (around 2% of total alkaloids) first mentioned in a paper published in 1994. In a series of papers beginning in 2001, it has also been shown to be highly selective for mu receptors and is more potent by weight than morphine. Eventually, it occurred to the researchers that given the low potency of mitragynine, even though it is the most abundant alkaloid in the plant it cannot account for the effects of kratom. Bioassays indicated that mitragynine was a much weaker anti-nociceptive than kratom extracts. Starting with crude extracts of kratom and moving then to five isolated alkaloids, it was found that 7-hydroxymitragynine is the most likely candidate for the chief agent of kratom’s activity. Given that nearly all the chemical studies of kratom have been done on the assumption that mitragynine was the most important alkaloid, and that nearly all pharmacological research prior to the late 1990s was done on mitragynine or crude plant material, this discovery likely means that much of what is believed about kratom will need to be revised.


Kratom’s pharmacology shares some elements of the activity of other substances including opiates and yohimbine. The comparison to opiates is sometimes emphasized by persons and businesses who are selling it, though this is frequently exaggerated. A good analogy might be comparing kava to benzodiazepines. For example, the analgesic and sedative activity of kratom is much lower than with narcotics. Kratom also does not produce such extreme constipation as opiates. Kratom also has a yohimbe-like stimulant activity, and uncaria-like immunostimulant activity. Its effects are reported to be relatively short-lived, typically fading after two to four hours or less.


Kratom contains many active alkaloidal chemicals. These include:


Ajmalicine (Raubasine), a cerebrocirculant, antiaggregant, anti-adrenergic (at alpha-1), sedative, anticonvulsant, smooth muscle relaxer;

Corynantheidine, an opioid antagonist;

Corynoxeine, a calcium channel blocker;

Corynoxine A and B, Dopamine mediating anti-locomotives;

(-)-Epicatechin, an antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti-inflammatory, anti-leukemic, antimutagenic, antiperoxidant, antiviral, cancer preventative, alpha-amylase inhibitor;

9-Hydroxycorynantheidine, a partial opioid agonist;

7-Hydroxymitragynine, an analgesic, antitussive, antidiarrheal, primary psychoactive in kratom; NOTE THE LOW AMOUNT PRESENT IN THE LEAF. Some leaf if does not appear at all.

Isomitraphylline, an immunostimulant, anti-leukemic;

Isopteropodine, an immunostimulant;

Mitragynine, an analgesic, antitussive, antidiarrheal, adrenergic, antimalarial, possible psychedelic (5-HT2A) antagonist;

Mitraphylline, a vasodilator, antihypertensive, muscle relaxer, diuretic, anti-amnesic, possible immunostimulant;

Paynantheine, a smooth muscle relaxer;

Rhynchophylline, a vasodilator, antihypertensive, calcium channel blocker, antiaggregant, anti-inflammatory, antipyretic, anti-arrhythmic, antithelmintic;

Speciociliatine, a weak opioid agonist;

Speciogynine, a smooth muscle relaxer;

Speciophylline, An anti-leukemic; and

Tetrahydroalstonine, a hypoglycemic, anti-adrenergic (at alpha-2).


Medicinal Benefits and Health Effects:


Pain: Kratom, like other mu-opiate receptor agonists is useful in the treatment of moderate to severe pain especially in chronic situations such as back pain. The increasing popularity of Kratom as a substitute for pharmaceutical opiates is due to a reduced risk of physical dependence and the relative ease of acquisition and legality of possession. Anecdotal evidence also indicates that side effects associated with narcotic pain medications, though present with Kratom, are not as severe.


Diarrhea: Kratom has been used in Thailand traditionally to treat diarrhea and studies in rats have shown it to be as effective as Loperimide (Immodium AD) especially for the treatment of severe diarrhea (Chittrakarn, 2007).


Like other opiate medicines, Kratom may exhibit cough-suppressant characteristics. Little is known about this particular use of Kratom other than personal experiences.


Some of the compounds found in Kratom have been shown to have antioxidant properties and therefore are considered to be of significant health benefit in the same way as Green Tea. Additionally, consumption of Kratom can help add fiber to the digestive tract which is useful in mitigating the constipation that some experience with Kratom.

At lower doses Kratom is known to act as a stimulant. Reported effects include:


* More Energy

* Feeling More Social

* Alert & Sharper Mind

* Increased Sexuality


At larger doses Kratom is known to act as a pain reliever and give a euphoric sensation. Reported effects include:


* Feeling Calm

* Less Emotional Stress

* Numbing Physical Pain