title: From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction.
abstract: Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
authors.affiliation: Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
authors.forename: Zurina
authors.initials: Z
authors.lastname: Hassan
authors.forename: Mustapha
authors.initials: M
authors.lastname: Muzaimi
authors.forename: Visweswaran
authors.initials: V
authors.lastname: Navaratnam
authors.forename: Nurul H M
authors.initials: NH
authors.lastname: Yusoff
authors.forename: Farah W
authors.initials: FW
authors.lastname: Suhaimi
authors.forename: Rajakumar
authors.initials: R
authors.lastname: Vadivelu
authors.forename: Balasingam K
authors.initials: BK
authors.lastname: Vicknasingam
authors.forename: Davide
authors.initials: D
authors.lastname: Amato
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.forename: Nurul I W
authors.initials: NI
authors.lastname: Ismail
authors.forename: Nanthini
authors.initials: N
authors.lastname: Jayabalan
authors.forename: Ammar I
authors.initials: AI
authors.lastname: Hazim
authors.forename: Sharif M
authors.initials: SM
authors.lastname: Mansor
authors.forename: Christian P
authors.initials: CP
authors.lastname: Müller
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001210:Asia, Southeastern; D016739:Behavior, Addictive / Q000523:psychology*; D002490:Central Nervous System / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D032065:Mitragyna / Q000009:adverse effects* / Q000737:chemistry; D015394:Molecular Structure; D010936:Plant Extracts / Q000009:adverse effects; D046948:Secologanin Tryptamine Alkaloids / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D012651:Self Medication / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D010936:Plant Extracts; D046948:Secologanin Tryptamine Alkaloids; C001801:mitragynine