Iboga Alkaloid Encyclopedia · Active Metabolite

Noribogaine

Ibogaine's active O-demethylated metabolite — long half-life, lower QT signal, mu-opioid partial agonist.

Noribogaine (12-hydroxyibogamine) is the primary active metabolite of ibogaine, formed in vivo by hepatic CYP2D6 O-demethylation. Its plasma half-life substantially exceeds that of ibogaine and accounts for the long tail of post-flood-dose effects observed clinically.

Pharmacologically, noribogaine has a cleaner mu-opioid partial-agonist profile than parent ibogaine and a smaller hERG/QT signal in vitro, which is why some research programs have explored noribogaine alone as a development candidate for opioid use disorder.

CYP2D6 poor metabolizers convert ibogaine to noribogaine more slowly, which has dosing implications. CYP2D6 ultra-rapid metabolizers convert it faster and may experience a different time course. Pharmacogenomic screening is part of the MindScape eligibility workup where indicated.

• Mu-opioid receptor: partial agonist (cleaner profile than parent ibogaine).
• Kappa-opioid receptor: partial agonist activity reported.
• Serotonin transporter (SERT): inhibition reported — contributes to mood-elevating tail.
• hERG / QT: lower in vitro signal than parent ibogaine.

• Glue P, et al. (2016). Clinical Pharmacology in Drug Development, 5(6), 460-468.
• Mash DC, et al. (1995). Annals of the New York Academy of Sciences, 844, 274-292.
• Alper KR, et al. (2008). Annals of the New York Academy of Sciences, 1139, 369-377.

Citation list is illustrative. Where peer-reviewed data is thin or absent, MindScape's pharmacology summary draws on textbook references (Alper 2001 — The Alkaloids: Chemistry and Biology, vol. 56) and is hedged accordingly.

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