Mitragyna speciosa (Korth.) Havil., better known as kratom, is a tropical tree indigenous of Thailand, Borneo, Malaysia, Myanmar, Sumatra, New Guinea, and the Philippines [1]. The genus Mitragyna comprises ten species with four occurring in Africa (M. inermis, M. ledermannii, M. rubrostipulata and M. stipulosa) and six in South and South-East Asia, between India and New Guinea (M. speciosa, M. tubulosa, M. rotundifolia, M. parvifolia, M. hirsuta and M. diversifolia). The species M. speciosa was first described by the Dutch botanist Pieter Willem Korthals in 1839 (M. speciosa (Korth.)) [2] and eventually given its final name and classification in 1897 by George Darby Haviland (M. speciosa (Korth.) Havil.) [3].

From a botanical point of view, the kratom tree has dark glossy green and elliptical petiolate leaves, which present 12–17 pairs of veins [1]. The latter are generally used to distinguish three kinds of kratom: red veined kratom, green veined kratom and a third kind with two small teeth-like formations next to the apex of the leaf [4]. The green-vein type is also reported in the literature as white-vein kratom [5]. The colour of the veins affects the potency of the product ascribing a higher effect to the green-vein kratom [5]. On the other hand, other studies report the vein colour also as a sign of the leaf age with the red-vein type being younger and more potent than the green-vein type [6].

In the last 150 years kratom use has been documented in Southeast Asia and reported to give both a stimulant effect to stave off fatigue by chewing fresh leaves and an analgesic and relaxing effect by brewing the leaves into a tea [7]. It is also used to manage opium withdrawal, as well as an antispasmodic, muscle-relaxant, and antidiarrheal agent [8]. From a legal point of view, the use of kratom is prohibited in Malaysia under the Poisons Act of 1952 and Thailand lifted the ban on the use, production, and possession of kratom in 2018 for medicinal purposes, although its use remains widely spread in local communities [9,10]. Over the years, kratom has been regulated as a legal herbal product under US FDA and DEA policies, although a few US states have banned the local sale and possession of kratom [11]. The DEA tried to ban kratom by instituting an emergency scheduling of its active ingredients in 2016 [12] but had to withdraw its notice of intent as it caused a strong adverse public reaction [13]. In 2021 the WHO started a pre-review process of kratom, which ended up with the recommendation that even though the contribution of kratom use to the reported kratom-related fatalities is unclear, the scientific data was not sufficient to recommend a critical review, thus it should be taken under surveillance due to the opioid-like activity of some of its constituents [14]. Even though there is insufficient evidence on both therapeutic and abuse potential [14], at present kratom remains a self-medication in some countries, but a much wider diffusion is expected in the next years [15]. As the interest in kratom has increased in the last ten years, not only for therapeutic purposes but also as a recreational drug, the scientific research, especially in Thailand and Malaysia, has made great progresses [16]. Consequently, the number of publications concerning several aspects of this herbal drug has exponentially grown, especially in the last five years in which it has even tripled (Scopus results for “kratom”).

The aim of this review is to collect all the scientific contributions to the chemical analysis of kratom and its bioactive constituents and to highlight the tricky aspects and challenges especially of kratom alkaloids analysis. To the best of the authors’ knowledge, no other review has been published on this topic since analytical research on kratom started. The pharmacological properties of kratom will not be reviewed in the present work as they are beyond the scope and the literature teems with this type of contributions.