Kratom

Kratom (Mitragyna speciosa Korth.; Rubiaceae) is a tropical evergreen tree belonging to the coffee family. The plant is indigenous to Southeast Asia (particularly Thailand, Malaysia and Indonesia), and Papua New Guinea, and is cultivated in many other countries. Kratom has a long history of traditional use in treating chronic pain and diarrhoea, for increasing stamina and energy, and as a substitute for opium, or in opium withdrawal. The leaves are the part used medicinally and as a recreational substance due to the presence of constituents with psychoactive and opioid-like activity.

In New Zealand, kratom is classified as a prescription medicine and its use in herbal remedies (as described in section 2 of the Medicines Act 1981) is prohibited. Kratom has no authorised indication in New Zealand and it is not permitted in dietary supplement products.

Kratom [English]; biak, biak-biak, ketom, kutum [Malaysia] and others.

Kratom is usually ingested orally, although smoking leaves has also been described. Traditionally, chewing on fresh leaves was common. Leaves were also brewed in water to prepare a tea or decoction. In Southeast Asia, kratom is still used and prepared in these ways.

Contemporary commercial kratom products typically contain dried, crushed or powdered leaf material formulated as pastes, capsules, tablets and teabags, or sold in powder form. Some users mix powdered kratom into food or drinks. The active constituents of kratom are also available added to liquids used in electronic cigarettes (‘vapes’).

Commercial material may be described as being white (or white-vein), green (green-vein), or red (red-vein); the different colours correspond to the age of the plant (white – young plant; red – mature plant) and are associated with different alkaloid content. The different ‘colours’ are claimed to have different properties: for example, white kratom is marketed as improving concentration, green as ‘energising’, and red as calming. In addition, different ‘strains’ of kratom are available, usually relating to the region in which the material was grown.

Different kratom products are marketed for enhancing concentration, to increase energy and productivity, for their calming/relaxing properties, and for treating pain and diarrhoea, among other claims. Kratom is also believed to produce a euphoric effect and is used as a recreational substance, as an aid in the treatment and management of opioid addiction and withdrawal.

Kratom contains over 40 alkaloid compounds; the major alkaloids present are mitragynine and 7-hydroxymitragynine (7-HMG). Both compounds are partial agonists at mu opioid receptors, and antagonists at delta and kappa opioid receptors. These biphasic (ie having dual properties) alkaloids are the main constituents responsible for kratom’s central nervous system effects: kratom is reported to produce ‘cocaine-like’ stimulant effects when used at lower doses, and ‘morphine-like’ sedative effects at higher doses.

Mitragynine, 7-HMG, and kratom leaf extracts have shown a range of pharmacological activities in preclinical studies, particularly opioid-like effects, including analgesia, reduced gastrointestinal motility, and suppression of opioid withdrawal symptoms.

There has been very little clinical research conducted for kratom. A recent systematic review identified 18 clinical studies, but only one randomised, double-blind, placebo-controlled trial. This small study, involving 26 chronic users of kratom in Malaysia, found that kratom leaf extract, prepared as a decoction, increased pain tolerance an hour after use.

Comprehensive investigation of the clinical safety profile of kratom and its important constituents when used in medicinal and recreational contexts is required.

Preclinical studies have demonstrated kratom’s potential for causing dependence and toxicity. In humans, dependence and withdrawal symptoms have been described following chronic use of kratom. High doses of kratom can cause agitation, hypertension, respiratory depression and other effects. Overdoses are possible and fatalities have occurred; many such cases involve use of kratom with other substances.

Isolated case reports of adverse reactions associated with use of kratom include seizures, circulatory shock, intracerebral haemorrhage and ventricular fibrillation; causality has not necessarily been established in these cases. An observational study involving kratom users (n = 100) and control participants (n = 100) found no difference in the prevalence of electrocardiogram abnormalities between the two groups.

Use of kratom has been associated with acute liver injury in rare cases, including one case of an hepatic reaction following kratom use reported to the Centre for Adverse Reactions Monitoring (CARM) in New Zealand. In these cases, typically, symptoms of hepatotoxicity (fatigue, nausea, pruritis, dark urine, jaundice) began within 3 weeks (range 1–8) of commencing regular use of oral preparations of kratom. The pattern of liver injury was usually cholestatic or mixed. Cessation of kratom usually resulted in recovery within 1 month.

Poor-quality kratom material has also been associated with adverse effects. In the USA, around 200 cases of Salmonella infection, over 50 of which required hospitalisation, were associated with ingestion of contaminated kratom material originating from multiple sources. Some kratom products have a high content of toxic heavy metals, such as lead.

Mitragynine inhibits some cytochrome P450 liver enzymes and enhances the activity of others in vitro. The potential for interactions between kratom and drugs metabolised by these CYP enzymes needs to be explored. Concomitant use of kratom with other sedatives, hypnotics, and alcohol can increase the risk of central nervous system depression.

Data sharing is not applicable as no new data were generated or analysed for this article.

JB is a co-author/co-editor of books on scientific aspects of herbal medicines and receives/has received royalties from Pharmaceutical Press, Elsevier, and SpringerNature/MacMillan Education.

This research did not receive any specific funding.