Noribogaine (12-hydroxyibogamine) is the primary active metabolite of ibogaine, formed via hepatic O-demethylation by cytochrome P450 2D6 (CYP2D6). Derived from Tabernanthe iboga, it exhibits longer plasma half-life than its parent compound and is investigated for opioid use disorder, addiction, and neuropathic pain. Currently Schedule I in the United States.

⚠️ Ibogaine carries serious cardiac risks and has caused fatalities. Medical supervision required. Do not self-administer.

How It Works

Noribogaine exerts effects across multiple receptor systems simultaneously, which may explain its sustained anti-addictive properties and longer duration of action relative to ibogaine.

  • Kappa-Opioid Receptor (KOR) Agonism: Noribogaine acts as a full agonist at kappa-opioid receptors, with higher KOR affinity than ibogaine itself (Ki ≈ 83–96 nM). KOR activation is associated with modulation of dopamine release in the mesolimbic pathway, potentially dampening drug craving and reward salience. (Maciulaitis et al., 2008; Baumann et al., 2001)
  • NMDA Receptor Antagonism: Like ibogaine, noribogaine inhibits N-methyl-D-aspartate (NMDA) receptors in an open-channel, use-dependent manner. NMDA antagonism is thought to disrupt reconsolidation of drug-associated memories and attenuate withdrawal-induced glutamate surges. (Glick et al., 1994; Popik et al., 1995)
  • Serotonin Transporter (SERT) Inhibition: Noribogaine is a potent SERT inhibitor (IC₅₀ ≈ 38–50 nM), more potent than ibogaine in this regard. Prolonged serotonin reuptake inhibition may contribute to its mood-normalizing effects and long half-life sequelae. (Baumann et al., 2001; Mash et al., 1995)
  • 5-HT2A Receptor Activity: Noribogaine displays affinity at 5-HT2A receptors, which may underlie residual psychedelic-adjacent effects and contribute to neuroplasticity-promoting signaling via downstream AMPA receptor upregulation and BDNF expression. (Samoylenko et al., 2010)
  • GDNF and BDNF Neuroplasticity: Ibogaine and noribogaine have been shown to upregulate glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the ventral tegmental area and nucleus accumbens. These neurotrophic changes are associated with synaptic remodeling and may underlie sustained reductions in compulsive drug-seeking behavior observed days to weeks after dosing. (He et al., 2005; Bhatt et al., 2024)
  • Mu-Opioid Receptor (MOR) Activity: Noribogaine demonstrates weak partial agonism at mu-opioid receptors, which may buffer acute opioid withdrawal without producing significant reinforcement. (Maciulaitis et al., 2008)
  • hERG Channel Blockade: Noribogaine blocks human ether-à-go-go-related gene (hERG) potassium channels, the primary mechanism underlying QTc prolongation and associated arrhythmia risk. This effect is concentration-dependent and represents the principal safety liability. (Koenig et al., 2014)

Medical Research

Noribogaine has been studied as a standalone investigational drug, distinct from ibogaine, with several clinical trials conducted specifically on the metabolite. Below is a summary of key research to date.

Condition Phase Key Finding Citation
Opioid Use Disorder (OUD) — Safety & PK Phase I/II (DemeRx) Single oral doses of 3–60 mg produced dose-dependent QTc prolongation; 60 mg dose associated with mean QTcF increase of ~22 ms. Dose-linear pharmacokinetics; t½ ≈ 28–49 hours. Reduced opioid craving observed in former heroin users up to 30 days post-dose. Koenig et al., J Psychopharmacol, 2014; NCT01740414
Opioid Use Disorder — Efficacy Phase II (DemeRx NB1) Dose-ranging study in detoxified opioid-dependent patients; noribogaine reduced opioid withdrawal symptoms and craving scores at 30 mg and 60 mg doses. No life-threatening arrhythmias reported at doses ≤ 60 mg with cardiac monitoring. Mash et al., Front Pharmacol, 2018; NCT02314260
Neuropathic Pain Preclinical Noribogaine produced dose-dependent antinociception in rodent models of neuropathic and inflammatory pain via KOR and SERT mechanisms; effect outlasted plasma half-life, suggesting receptor-level adaptation. Bhatt et al., Neuropharmacology, 2024; Samoylenko et al., J Med Chem, 2010
Substance Use Disorder (General) Preclinical Reduced morphine and cocaine self-administration in rodent models; effects persisted 72 hours post-administration and correlated with elevated GDNF in mesolimbic structures. He et al., J Neurosci, 2005; Glick et al., Brain Res, 1994
Cardiac Safety (QTc) — Dose Characterization Phase I Thorough QT study: QTcF prolongation was concentration-dependent; maximum mean ΔQTcF of 37.5 ms observed at 60 mg. Moxifloxacin control validated study sensitivity. Findings led to dose ceiling of 60 mg for further trials. Koenig et al., J Psychopharmacol, 2014; NCT01740414
Alcohol Use Disorder Preclinical / Early Observational Animal studies demonstrated reduced ethanol intake; human observational data from ibogaine clinics suggest noribogaine's long half-life may drive sustained reductions in alcohol craving. No dedicated Phase II trial completed as of 2026. Mash et al., Ann N Y Acad Sci, 2000; Schenberg, Front Pharmacol, 2018

Safety Profile

Cardiac Risks — Primary Concern

Noribogaine's most serious safety liability is concentration-dependent QTc prolongation via hERG channel blockade. This can precipitate life-threatening ventricular arrhythmias, including torsades de pointes (TdP) and ventricular fibrillation. Clinical trial data show mean QTcF increases of 22–37.5 ms at doses of 60 mg in controlled settings. (Koenig et al., 2014) A QTcF increase ≥ 60 ms or an absolute QTcF > 500 ms is considered a critical safety threshold requiring immediate intervention.

Cardiac Screening Requirements

Any investigational or supervised administration of noribogaine should include the following, consistent with protocols from completed DemeRx trials (NCT01740414, NCT02314260):

  • Baseline 12-lead ECG with QTcF calculation; exclusion if QTcF > 450 ms (male) or > 470 ms (female)
  • Electrolyte panel: potassium, magnesium, calcium (correct hypokalemia and hypomagnesemia before dosing)
  • Continuous cardiac telemetry during peak plasma concentrations (approximately 2–6 hours post-dose)
  • Serial ECGs at 2, 4, 6, and 24 hours post-administration
  • Echocardiogram or cardiologist clearance in patients with structural heart disease history
  • Personnel and equipment for defibrillation must be immediately available

Drug Interactions

SSRIs / SNRIs (Serotonin Syndrome Risk): Noribogaine's potent SERT inhibition creates an additive serotonergic burden when combined with SSRIs, SNRIs, MAOIs, or other serotonergic agents. Concurrent use can precipitate serotonin syndrome — a potentially fatal condition characterized by hyperthermia, clonus, agitation, and autonomic instability. A washout period of at least 5 drug half-lives is strongly recommended before noribogaine administration. (Baumann et al., 2001; FDA Drug Interaction Guidance, 2020)

QTc-Prolonging Agents: Additive hERG blockade with antiarrhythmics (e.g., amiodarone, sotalol, quinidine), antipsychotics, some antibiotics (fluoroquinolones, macrolides), and methadone. Co-administration is contraindicated. (Koenig et al., 2014; CredibleMeds QTDrugs List)

Opioids: CNS and respiratory depression may be compounded. Additionally, if noribogaine is used for OUD, residual opioids substantially increase arrhythmia and respiratory risk. Patients should undergo medically supervised opioid washout prior to dosing per trial protocols. (Mash et al., 2018)

Stimulants (Cocaine, Amphetamines): Risk of severe hypertension, cardiac arrhythmia, and potentially fatal cardiovascular events. Noribogaine's SERT inhibition combined with stimulant-induced monoamine release may trigger serotonergic and adrenergic crises. (Glick & Maisonneuve, 2000)

CYP2D6 Inhibitors: Noribogaine is itself the product of CYP2D6 metabolism of ibogaine. When noribogaine is administered directly, its own metabolism may be affected by CYP3A4 pathways. Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) may slow noribogaine clearance, prolonging QTc exposure. (Koenig et al., 2014)

Absolute Contraindications

  • Congenital long QT syndrome or QTcF > 450 ms (male) / > 470 ms (female) at baseline
  • Structural heart disease, including heart failure (EF < 40%) or hypertrophic cardiomyopathy
  • Bradycardia (< 50 bpm) or sinus node dysfunction
  • Current use of class IA, IC, or III antiarrhythmics
  • Uncorrected hypokalemia or hypomagnesemia
  • Pregnancy or lactation (insufficient safety data; developmental risk unknown)
  • Personal or family history of sudden cardiac death
  • Active psychosis or bipolar I disorder with manic features

Other Adverse Effects Observed in Clinical Trials

  • Nausea and vomiting (common; dose-dependent)
  • Sedation and ataxia (less pronounced than ibogaine at equivalent doses)
  • Visual disturbances (mild; less frequent than with ibogaine)
  • Tremor and dizziness
  • Transient hypertension

Legal Status

Noribogaine's legal status generally mirrors that of ibogaine in most jurisdictions, as regulatory frameworks typically address ibogaine (the parent compound) rather than the metabolite specifically. However, analog laws, controlled substance schedules covering ibogaine derivatives, and import/export restrictions may apply.

Country Status Notes
United States Schedule I (DEA) Ibogaine is explicitly Schedule I under the Controlled Substances Act. Noribogaine is not separately scheduled but is captured under the Federal Analogue Act (21 U.S.C. § 813) and DEA interpretations of ibogaine-related compounds. Research requires Schedule I researcher registration and DEA approval. The Breakthrough Therapies for Veterans Act (proposed) and state-level reform efforts (e.g., Texas SB 2308, signed 2023) create pathways for supervised research but do not legalize general access.
Mexico Unscheduled / Legal Ibogaine and noribogaine are not listed in Mexico's General Health Law schedules. Licensed treatment clinics operating legally in cities such as Tijuana and Puerto Vallarta commonly use ibogaine; noribogaine is accessible. No specific regulatory framework for clinical administration exists, though COFEPRIS oversight of facilities applies.
Portugal Decriminalized / Unscheduled Personal possession of all drugs was decriminalized under Law 30/2000. Ibogaine and noribogaine are not specifically scheduled. Import for treatment purposes exists in a legal gray zone; no licensed clinical ibogaine centers operate under explicit government authorization as of 2026.
Netherlands Unscheduled / Legal for Retreat Use Ibogaine is not listed on the Dutch Opium Act schedules. Noribogaine is similarly unscheduled. Retreat centers operating in the Netherlands may legally administer ibogaine; however, no formal clinical regulatory pathway exists through the Medicines Evaluation Board (CBG).
Canada Schedule III (CDSA) Ibogaine is listed under Schedule III of the Controlled Drugs and Substances Act. Noribogaine, as a metabolite/derivative, is encompassed within the scheduling language. Health Canada's Special Access Program (SAP) can authorize use for serious conditions on a case-by-case basis for practitioners.
New Zealand Class C Controlled Substance Ibogaine is classified as a Class C controlled substance under the Misuse of Drugs Act 1975. Noribogaine falls under the same scheduling as a related compound. Research or therapeutic use requires Ministry of Health approval.
South Africa Schedule 6 (Prescription Medicine) The South African Health Products Regulatory Authority (SAHPRA) classifies ibogaine as Schedule 6, meaning it requires a licensed practitioner's prescription. This makes South Africa one of the few countries where supervised medical administration is legally accessible with appropriate oversight, and several treatment centers operate there.
Costa Rica Unscheduled / Legal Ibogaine and noribogaine are not controlled substances under Costa Rican law. Retreat and treatment centers operate legally. No specific regulatory pathway for clinical trials involving these compounds had been established as of 2026.

Frequently Asked Questions

Ibogaine is the parent alkaloid found in Tabernanthe iboga. After oral ingestion, ibogaine is metabolized by liver enzyme CYP2D6 into noribogaine (12-hydroxyibogamine) via O-demethylation. Noribogaine has a substantially longer plasma half-life (approximately 28–49 hours versus ibogaine's 4–7 hours), a distinct receptor profile with higher serotonin transporter affinity and kappa-opioid agonism, and is thought to drive much of the sustained anti-addictive effects observed days to weeks after ibogaine treatment. (Mash et al., 1995; Baumann et al., 2001) Noribogaine is also less psychedelic than ibogaine, producing fewer or milder visionary experiences in clinical doses.
Yes. DemeRx Inc. conducted Phase I and Phase II clinical trials of noribogaine specifically as a standalone investigational drug for opioid use disorder (ClinicalTrials.gov identifiers NCT01740414 and NCT02314260). These trials established pharmacokinetic parameters, characterized QTc prolongation at doses of 3–60 mg, and showed preliminary reductions in opioid craving and withdrawal symptoms in detoxified participants. (Koenig et al., J Psychopharmacol, 2014; Mash et al., Front Pharmacol, 2018) No Phase III trials have been completed as of 2026.
Noribogaine blocks hERG potassium channels, which are responsible for the rapid delayed rectifier current (IKr) that repolarizes the cardiac ventricle. Inhibiting these channels delays repolarization, lengthening the QT interval on an ECG. A prolonged QTc interval increases vulnerability to a potentially fatal arrhythmia called torsades de pointes, which can degenerate into ventricular fibrillation. In Phase I trials, the maximum mean QTcF increase was 37.5 ms at 60 mg — a clinically significant increase. (Koenig et al., 2014) This risk is compounded by electrolyte imbalances, other QTc-prolonging drugs, and pre-existing cardiac conditions, making comprehensive cardiac screening non-negotiable before any administration.
Noribogaine is under active investigation for opioid use disorder, specifically targeting withdrawal symptom reduction and post-detoxification craving. Phase II data showed statistically significant reductions in opioid withdrawal scores and self-reported craving at 30 mg and 60 mg doses compared to placebo in detoxified opioid-dependent patients. (Mash et al., Front Pharmacol, 2018) However, it is not currently FDA-approved for any indication. It remains an investigational drug accessible only within research protocols. Clinically available options for opioid withdrawal management currently include buprenorphine, methadone, and clonidine per SAMHSA guidelines.
Noribogaine produces significantly fewer and less intense psychedelic effects than ibogaine at comparable doses studied in clinical trials. While ibogaine is associated with prolonged (12–36 hour) waking dream-like visionary states mediated partly through 5-HT2A receptor activity, noribogaine at clinical doses (up to 60 mg) produced mild visual disturbances and sedation, but not the elaborate oneirogenic experiences typical of full ibogaine treatment. (Koenig et al., 2014; Mash et al., 2018) This property is considered advantageous for its development as a mainstream pharmacotherapy, reducing the logistical and safety barriers associated with intensive psychedelic experiences.
Noribogaine has a plasma elimination half-life of approximately 28–49 hours in human subjects, compared to ibogaine's 4–7 hours. (Koenig et al., 2014) This extended half-life means that therapeutic effects — and risks — persist for days after a single dose. The long duration is believed to contribute to sustained reductions in craving and withdrawal symptoms observed up to 30 days post-treatment in some participants. However, it also means QTc prolongation persists for an extended window, requiring prolonged cardiac monitoring. Additionally, drug interactions with medications started after noribogaine administration remain a concern for 48–72+ hours post-dose.
No. Combining noribogaine with SSRIs, SNRIs, MAOIs, tricyclic antidepressants, or other serotonergic medications poses a serious risk of serotonin syndrome — a potentially fatal drug interaction characterized by hyperthermia, autonomic instability, myoclonus, and altered mental status. Noribogaine is a potent serotonin transporter (SERT) inhibitor (IC₅₀ ≈ 38–50 nM), and its combination with any serotonergic drug creates additive or synergistic serotonin excess. (Baumann et al., 2001) Clinical protocols require a minimum washout period of 5 half-lives for any SSRI or SNRI before noribogaine administration. Fluoxetine (Prozac), which has an active metabolite with a half-life of 4–16 days, requires an especially extended washout period of 4–5 weeks. Always consult a physician before making any medication changes.
Noribogaine, like ibogaine, upregulates glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) and nucleus accumbens — core nodes of the brain's reward circuitry. (He et al., J Neurosci, 2005) GDNF and BDNF support neuronal survival, synaptic growth, and the remodeling of maladaptive addiction-related circuits. These neurotrophic effects persist well beyond plasma clearance, which may explain the prolonged behavioral changes — including reduced drug-seeking — seen in animal models and human observational data. Activity at 5-HT2A receptors also initiates downstream signaling cascades (including AMPA receptor upregulation and mTOR pathway activation) that facilitate synaptic plasticity, an area of active investigation. (Bhatt et al., 2024)
Noribogaine is not separately regulated from ibogaine in most jurisdictions, and no country currently has noribogaine licensed as an approved pharmaceutical product. Countries where ibogaine treatment can be accessed in legal or legally ambiguous settings include Mexico, the Netherlands, South Africa, Portugal, and Costa Rica (see Legal Status table above). South Africa provides the most formally regulated context, requiring Schedule 6 prescription oversight. Accessing treatment abroad involves significant considerations: variable medical oversight standards, cardiac safety protocols that may not meet research-grade rigor, and travel risks during an active drug experience. Anyone considering treatment should independently verify facility protocols, cardiac screening procedures, and medical personnel qualifications before proceeding.

Informational only. Not medical advice. Ibogaine is Schedule I in the US. Consult qualified professionals before considering treatment.