Letter from the WHO

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Jim:

The WHO report speaks for itself (Page 7):

“The  Committee  considered  information  regarding  the  traditional  use  and  investigation  into  possible  medical applications of kratom.

The  Committee  concluded  that  there  is  insufficient  evidence  to  recommend  a critical  review  of  kratom.  With respect to mitragynine and 7-hydroxymitragynine, the Committee, except for one member, also concluded that there is insufficient evidence to recommend a critical review at this time.

Recommendation: The Committee recommended that kratom, mitragynine and 7-hydroxymitragynine be kept under surveillance by the WHO Secretariat. ”

 

A great victory for kratom consumers, for science, and for the truth!

Best regards,

Mac Haddow, Senior Fellow on Public Policy

ECDD Report Dec 2021

 

Kratom, mitragynine, 7hydroxymitragynine
Substance identification

Kratom is the common term for Mitragyna speciosa, a tree native to Southeast Asia. Kratom use is almost
exclusively oral, typically by chewing the leaves, ingesting powdered leaf, or drinking a kratom infusion or
decoction, or by ingesting powdered leaf as a capsule or pill or dissolved in a beverage. Other forms such as
extracts and resins are also used.

Several alkaloids have been detected in kratom plants. The main known psychoactive components of kratom are
mitragynine and 7hydroxymitragynine, both of which are found in the leaves of Mitragyna speciosa. Mitragynine

E/CN.7/2021/CRP.12

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is the most abundant alkaloid in kratom. Whilst 7hydroxymitragynine is a minor alkaloid, it is also a metabolite
of mitragynine.

WHO review history

Kratom has been under ECDD surveillance since 2020 due to a country level report indicating the potential for
abuse, dependence, and harm to public health from mitragynine and 7hydroxymitragynine, and a report from
an international organization regarding documented fatalities associated with kratom use. A prereview on
kratom, mitragynine, and 7hydroxymitragynine was initiated following consideration of these reports.

Similarity to known substances and effects on central nervous system

Mitragynine and 7hydroxymitragynine are partial agonists at the muopioid receptor. Human studies
demonstrate the analgesic effects of kratom, while kratom extract, mitragynine and 7hydroxymitragynine have
been shown to be antinociceptive in animal models. The antinociceptive effects are reversed by an opioid
antagonist.

Mitragynine also binds to adrenergic receptors, serotonergic and dopamine receptors. Although there is limited
information regarding its effects at these receptors, kratom extracts and mitragynine have been reported in
animal studies to have a variety of nonopioidlike behavioural effects, including antidepressant and
antipsychotic effects.

Reported adverse effects as a result of kratom intoxication have included neuropsychiatric (agitation, confusion,
sedation, hallucinations, tremor, seizure, coma), cardiovascular (tachycardia, hypertension), gastrointestinal
(abdominal pain, nausea, vomiting) and respiratory (respiratory depression) symptoms. A number of cases of
kratomassociated liver toxicity have been documented.

Dependence potential

In animal models, repeated dosing with mitragynine produced dependence, evidenced by naloxoneprecipitated
withdrawal. The withdrawal syndrome from kratom appears to be less severe than withdrawal from morphine.

In humans, opioidlike withdrawal symptoms have been reported following cessation of kratom use. Limited
epidemiological evidence indicates that withdrawal is usually mild. There are a small number of cases of neonatal
opioid withdrawal symptoms in neonates born to mothers who used kratom regularly.

Actual abuse and/or evidence of likelihood of abuse

Animal studies with kratom extracts have not shown abuse liability in one animal model. Mitragynine and
7hydroxymitragynine have effects indicative of abuse liability in some animal models but not in others.
Mitragynine is not selfadministered by animals, while 7hydroxymitragynine has been shown to be
selfadministered, supporting a likely abuse liability.

Kratom can produce serious toxicity in people who use highdoses, but the number of cases is probably low as a
proportion of the total number of people who use kratom. Although mitragynine has been analytically confirmed
in a number of deaths, almost all involve use of other substances, so the degree to which kratom use has been
a contributory factor to fatalities is unclear.

Kratom and mitragynine have been associated with cases of driving under the influence, but their role in driving
impairment could not be established in most instances.

Multiple countries across various regions r
eport nonmedical use of kratom. Seizures of kratom and related
products have been reported in several countries.