Mitragyna speciosa: Balancing Potential Medical Benefits and Abuse

Abstract

, also known as kratom, has the potential meet the need for pain medications that lack the addictiveness and overdose risk of classical opioid analgesics, such as morphine. This need is urgent because opioid addiction and overdose deaths have risen throughout diverse segments of U.S. society. Some opioid addicts have found relief in kratom preparations. The use of kratom as an analgesic has been validated by historical accounts and contemporary pharmacological research. Although kratom is a promising source of analgesic candidates, it is a euphoriant with potential for both abuse and addiction. However, kratom appears to be less addictive and to have milder withdrawal symptoms than opioid drugs. Thus, there is a need to balance the potential medical benefits and abuse of .

Comparative Pharmacokinetics of Mitragynine after Oral Administration of Mitragyna speciosa (Kratom) Leaf Extracts in Rats

“…In functional assays utilizing opioid transfected cell lines, it was demonstrated that mitragynine activates µ-opioid receptors selectively through G-protein signaling, without stimulating β-arrestin-2. Owing to this biased G-protein opioid activity, mitragynine produces antinociception through µ-opioid receptors (EC 50 , 203 ± 13 nM) without recruiting β-arrestin-2 proteins and their putative associated side effects (e.g., respiratory depression, constipation, physical dependence, and tolerance), unlike morphine and β-endorphin [10,11]. Mitragynine inhibits forskolin-stimulated 3′,5′-cyclic adenosine monophosphate (cAMP) formation along with the blocking of opioid receptor-mediated neuronal Ca 2+ release on the cellular level [12,13].…”

Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays

“…Although mitragynine has been potentially developed as a candidate for opioid substitution and opioid withdrawal syndrome treatment, the high chance of abuse due to the sedative and euphoric effects cannot be neglected. Hence, a balance between the medical benefits and the potential to cause addictiveness as well as the overdose risk need to be investigated intensively [25].…”

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine

“…In 2017, >130 individuals died every day in the United States due to opioid overdose and, in 2016, nearly 12 million individuals claimed to have misused prescription opioid pain‐killers in the previous year . Mitragynine ( 85 , Scheme ), an indole alkaloid found in Kratom ( Mitragyna speciose korth ), is a mu‐opioid agonist that has received attention as a safe alternative to traditional opiates (e.g., morphine) and as a replacement therapy for opiate dependence . In addition, iboga root extracts were found to alleviate opiate withdrawal symptoms, which has initiated work to use iboga as a treatment for addiction .…”

“…[86] Mitragynine (85, Scheme 8), an indole alkaloid found in Kratom (Mitragyna spe-ciose korth), is am u-opioid agonist that hasr eceived attention as as afea lternative to traditional opiates (e.g.,m orphine) and as ar eplacement therapy for opiate dependence. [91][92][93][94][95][96] In addition, iboga root extracts were found to alleviateo piate withdrawals ymptoms, [97,98] whichh as initiated work to use iboga as at reatment for addiction. [99] Ibogaine (99,S cheme 9) is the active pharmacological substance of the iboga root and shares tryptophan/isoprenoid biosynthetic origins with all other monoterpenoid indole alkaloids.…”

“…[4,[69][70][71][72][73][99][100][101][102][103][104] Tryptophan (91) an extensive series of biosynthetic transformations to the aldehyde-containing intermediate secologanin (93). [4] Tryptamine and secologanin undergo as tereoselective Pictet-Spengler reactionc atalyzed by strictosidines ynthase to form the key biosynthetic intermediate strictosidine (95). [4,6,69] Once formed, strictosidine undergoes divergentb iosynthetic pathways involvings pecific modeso fc yclization,o xidation and skeletal rearrangements to generatei ndole alkaloids with unique and complexm olecular architectures (Scheme 9a nd 10).…”