7-Hydroxymitragynine

7-Hydroxymitragynine (7-OH) is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as kratom.^[2] It was first described in 1994^[3] and is a human metabolite metabolized from mitragynine present in the Mitragyna speciosa. 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater efficacy.^[4]

7-Hydroxymitragynine

Clinical data
Other names	7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1]
Routes of administration	By mouth; inhalation
Drug class	Opioid
ATC code	None
Legal status
Legal status	BR: Class F1 (Prohibited narcotics) US: Unscheduled
Pharmacokinetic data
Metabolites	Mitragynine pseudoindoxyl
Identifiers
IUPAC name Methyl (2E)-2-[(2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate
CAS Number	174418-82-7 N
PubChem CID	44301524
ChemSpider	23152144 Y
UNII	2T3TWA75R0
ChEMBL	ChEMBL61630 Y
CompTox Dashboard (EPA)	DTXSID20903988
Chemical and physical data
Formula	C23H30N2O5
Molar mass	414.502 g·mol−1
3D model (JSmol)	Interactive image Interactive image
SMILES CC[C@@H]1CN2CC[C@@]3(O)C(=Nc4cccc(OC)c34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC CC[C@@H]1CN2CC[C@@]3(O)C(=NC4=CC=CC(OC)=C34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC
InChI InChI=1S/C23H30N2O5/c1-5-14-12-25-10-9-23(27)20-17(7-6-8-19(20)29-3)24-21(23)18(25)11-15(14)16(13-28-2)22(26)30-4/h6-8,13-15,18,27H,5,9-12H2,1-4H3/b16-13+/t14-,15+,18+,23+/m1/s1 Y Key:RYENLSMHLCNXJT-CYXFISRXSA-N Y

7-Hydroxymitragynine (7-OH), a metabolite of the psychoactive botanical kratom, exhibits significantly higher binding affinity to mu-opioid receptors (MOR) than morphine, with estimates ranging from 14 to 22 times greater potency. Although kratom's primary alkaloid, mitragynine, is associated with lower abuse potential and moderate safety, 7-OH demonstrates opioid-like effects and can substitute for morphine in a dose-dependent manner, raising concerns about its potential for physical dependence and addiction.^[5]

Pharmacology

7-Hydroxymitragynine, like mitragynine, appears to be a mixed opioid receptor agonist/antagonist, with recent research indicating that it acts as a partial agonist at μ-opioid receptors and as a competitive antagonist at δ- and κ-opioid receptors.^[6][7] 7-OH does not appear to activate the β-arrestin pathway, distinguishing it from traditional opiate & opioid chemicals.^[6] It shares this trait with mitragynine.

Synthesis

In natural kratom leaves, 7-Hydroxymitragynine is only present in small amounts from 0.6%-0.7% on average. Therefore, extracting 7-OH in high concentrations directly from natural kratom leave is not feasible due to the natural yield being too low. This means that all high-concentration 7-OH products must be produced via synthesis. The most common methods usually involve modifying mitragynine, the most abundant alkaloid in kratom, to artificially increase 7-OH concentration via oxidation reactions.