FDA Ibogaine Research Notice (2026)

Table of Contents

1. What the FDA Announced
2. What the Notice Does Not Do
3. The Background the Notice Gives: Executive Order, Guidance and Federal Funding
4. The Safety Risks the FDA Names
5. The Cardiac Science: QTc Prolongation and the Published Findings
6. Proposed Trial Design: Starting Dose and Dose Escalation
7. Inpatient Cardiac Monitoring, Medications and Discharge
8. Stopping Rules and Safety Oversight
9. Who Could Enroll and the First Study Populations
10. The Questions the FDA Is Asking
11. How and Until When the Public Can Comment
12. How the Notice Fits the FDA’s Earlier Handling of Psychedelic Research
13. Primary Documents
14. Key Research Papers
15. Connections

1. What the FDA Announced

The FDA news release, “FDA Seeks Public Input to Support Ibogaine Research,” is dated 5 October 2026. It states that the agency “today announced a request for information (RFI) describing approaches the agency is considering for the design of early-phase clinical trials of ibogaine drug products and seeking public input on those approaches.” The protocol elements it lists are dose selection and escalation, care setting, safety monitoring, eligibility criteria, stopping rules and safety oversight.

The release calls the RFI “the latest FDA action to advance” the April 2026 executive order on accelerating medical treatments for serious mental illness, “which directed agencies to accelerate research into psychedelic medicine.” That is the order’s stated aim; it is not a finding about ibogaine. The release quotes Michael Davis, M.D., Ph.D., Director of the FDA Center for Drug Evaluation and Research: “Patients facing serious conditions that have not responded to existing treatments deserve rigorous scientific investigation of promising new approaches. With ibogaine, there are important scientific questions as well as serious safety concerns. We are seeking high-quality data and input that can help inform clinical research while putting patient safety first.”

The Federal Register notice, published 6 October 2026 on pages 63563–63569 of volume 91, carries the action line “Notice; request for information; establishment of a public docket.” It is signed by Grace R. Graham, Deputy Commissioner for Policy, Legislation, and International Affairs, and names Bernard Fischer of the Center for Drug Evaluation and Research as the contact. Its summary says the FDA will use the information received “to inform whether and how these specific elements should be considered in its review of Investigational New Drug Applications (INDs) involving ibogaine.”

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2. What the Notice Does Not Do

The notice approves no trial and makes no finding that ibogaine works. In its own words it sets out “preliminary thinking” on one possible design for a first trial, and it “does not establish legally enforceable requirements or regulatory expectations, nor does it represent FDA’s final views.” The FDA states that it “has made no final determination as to the characteristics that would allow a trial of an ibogaine drug product to proceed,” that each IND must be supported by adequate scientific justification, and that “nothing in this RFI predetermines FDA’s action on any submission” — including an IND supported by federal funds.

The notice also lists five topics on which the FDA is not seeking comment, and says comments on them may not be considered:

• the safety or effectiveness of any specific ibogaine drug product, or the merits of any pending or anticipated application;
• the scheduling status of ibogaine under the Controlled Substances Act, which the notice says is handled through separate statutory processes;
• the legalization or decriminalization of psychedelic substances, or the merits of state or local programs authorizing their use (although the FDA says it welcomes input on data collected by such programs);
• religious, ceremonial or personal (non-medical) use of psychedelic substances;
• individual disputes, enforcement matters or complaints about specific practitioners or entities.

After the comment period, the notice says, the FDA “may issue new guidance or update existing guidance,” or take another action, and expects to reflect the comments in its review of protocols for federally supported and other ibogaine trials.

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3. The Background the Notice Gives: Executive Order, Guidance and Federal Funding

The notice places itself in a sequence of 2026 federal actions:

• Executive Order 14401 of 18 April 2026, “Accelerating Medical Treatments for Serious Mental Illness” (91 FR 21709, 22 April 2026). The notice says the order establishes a policy of accelerating innovative research models and appropriate drug approvals to help increase access to psychedelic drugs for serious mental illness, and that it “specifically notes that ibogaine compounds show potential in clinical studies” for patients whose conditions persist after standard therapy.
• Final guidance “Psychedelic Drugs: Considerations for Clinical Investigations,” issued 14 July 2026 (91 FR 43101). The ibogaine notice says it builds on this guidance and that its proposed elements are consistent with it.
• A noribogaine study. The FDA has allowed an early-phase clinical study of noribogaine hydrochloride, a derivative (and the main active metabolite) of ibogaine, to proceed under an IND as a potential treatment for alcohol use disorder.
• Federal funding. The Department of Health and Human Services, through the Advanced Research Projects Agency for Health (ARPA-H), is funding a program to collect safety and efficacy data through early-phase trials, and the National Institute on Drug Abuse (NIDA) is funding ibogaine research for opioid use disorder. The notice says the data from these programs “will be made available publicly to investigators and sponsors.”

The notice also states that the published literature suggests potential benefits of ibogaine for substance use disorders and certain psychiatric and neurologic conditions, including mood disorders, PTSD and traumatic brain injury, and in the same paragraph that “ibogaine also has serious known risks.” It describes the published literature as having “significant limitations”: studies seldom characterize the product given (dose, quality, purity and potency), and most lack participant-level data and reliable summary safety, efficacy and pharmacokinetic data.

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4. The Safety Risks the FDA Names

The notice says the FDA has identified serious safety risks with ibogaine drug products that could expose trial participants to “an unreasonable and significant risk of illness or injury” — the regulatory standard for placing a trial on clinical hold (21 CFR 312.42(b)(1)(i)). It names three:

• “prolongation of the heart rate-corrected QT (QTc) interval and the associated risk of life-threatening arrhythmia”;
• “neurotoxicity in nonclinical studies”;
• “uncertainty regarding an appropriate starting dose for humans.”

On the heart, it states that clinical data show ibogaine “commonly causes substantial QTc interval prolongation, which has been associated with life-threatening ventricular arrhythmias and death.” The commonly reported non-cardiac effects it lists are changes in perception, impaired cognition, and impaired coordination and balance (ataxia).

On the brain, it reports that published animal studies in rodent and non-rodent species found dose-dependent neurotoxicity, “ranging from tremors and ataxia at lower doses to neuronal degeneration, neuroinflammation, convulsions, and death at higher doses,” including injury to the cerebellum, the part of the brain that coordinates movement. The FDA calls defining the blood level at which brain injury would be predicted in humans “the most critical challenge,” and notes that comparing animal studies by milligram-per-kilogram dose alone can mislead, because the same dose gives very different blood levels across species and routes of administration. Whether ibogaine causes lasting neurologic or cognitive injury in people at the doses used clinically, the notice says, “has not been systematically studied.”

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5. The Cardiac Science: QTc Prolongation and the Published Findings

The QT interval is the stretch of an electrocardiogram (ECG) that covers the heart’s electrical recharging (repolarization) after each beat; QTc is that interval corrected for heart rate. The notice explains that drugs which delay repolarization lengthen the QTc and raise the risk of torsades de pointes (TdP), a life-threatening ventricular arrhythmia. After several drugs were withdrawn from the market for TdP between 1991 and 2003, the international ICH E14 guidance (October 2005) was written to evaluate this risk. Potent QTc-prolonging drugs are started in hospital and stopped if the QTc exceeds 500 milliseconds (ms), “the threshold above which the overwhelming majority of drug-induced TdP cases occur,” and 500 ms is used as a stopping criterion in drug development. A related condition, inherited long QT syndrome, is described on the site’s Long QT Syndrome page.

The notice adds a point specific to ibogaine: the 500 ms rule exists mainly to stop further doses of drugs taken every day, while ibogaine is usually given once or occasionally. Because TdP occurs in a minority of people whose QTc exceeds 500 ms and can be terminated with drug infusions, cardioversion or temporary pacing, the FDA writes that it is “conceivable” that repeat exposure could still have a favorable benefit–risk balance in an intensively monitored setting. Its preliminary view is that a first trial would give a single dose, and that the data could inform whether repeat dosing could be studied. As a monitoring model it cites ibutilide, an approved antiarrhythmic that causes TdP in about 1.7 percent of patients and requires continuous ECG monitoring for at least 4 hours; ibogaine, with an active metabolite, “likely would require more prolonged monitoring.”

The notice’s reference list includes the published studies below, each checked on PubMed for this page:

• Deaths after ingestion (Alper 2012). A review of 19 known fatalities between 1990 and 2008 outside West Central Africa found deaths occurring 1.5 to 76 hours after ingestion. In 12 of the 14 cases with adequate postmortem data, pre-existing medical conditions — mainly cardiovascular disease — and/or other substances explained or contributed to the death.
• The prospective Dutch study (Knuijver 2022). Fourteen people with opioid use disorder received a single 10 mg/kg dose of ibogaine hydrochloride under hospital monitoring. The mean maximum QTcF prolongation was 95 ms (range 29–146); half the participants exceeded a QTc of 500 ms; in 6 of 14 the QTc stayed above 450 ms for more than 24 hours. No torsades de pointes occurred, and all participants had severe transient ataxia. The FDA notice cites this study for the ataxia finding.
• Pharmacokinetics in the same patients (Knuijver 2024). How fast ibogaine was cleared depended strongly on the CYP2D6 gene, and the QTc and cerebellar effects tracked blood levels of ibogaine itself rather than noribogaine.
• Systematic review of adverse events (Ona 2022). Across 18 studies published 2015–2020, QTc prolongation was the most common acute adverse event; the authors called for phase I trials using standardized products.
• Cardiovascular review (Brunt 2026). Case reports of torsades occur at doses described as therapeutic and in people without prior heart disease, with CYP2D6 variability among the factors discussed.

The notice also records that ibogaine’s link with QTc prolongation and TdP “was identified after the Advisory Committee met in 1993,” so that committee never addressed this risk (see section 12).

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6. Proposed Trial Design: Starting Dose and Dose Escalation

The design the FDA describes is an initial, open-label trial in which small groups of participants each receive a single dose, with the dose rising from one group to the next. Its main goals, as the notice lists them, would be to measure how the body handles ibogaine and noribogaine (pharmacokinetics and pharmacodynamics), how both affect the heart, how well participants tolerate them, and whether the monitoring plan works.

• Starting dose: “an initial dose justified by the published literature and not exceeding 10 mg/kg.” The notice states that published clinical reports describe doses of 5 to 20 mg/kg, and that these doses “lack adequate safety margins based on available nonclinical data.”
• Escalation: sequential dose-ascending groups, participants within each group dosed one at a time, with any increase for the next group considered after review by a safety review committee (SRC), a data and safety monitoring board (DSMB) and the FDA.
• Genotyping: CYP2D6 is the main enzyme converting ibogaine to noribogaine, so participants could be genotyped and only fast and intermediate metabolizers included, with doses adjusted if needed.
• Magnesium pretreatment: sponsors could study whether pretreatment, such as intravenous magnesium, reduces the size of the QTc prolongation. (Background on the mineral is on the Magnesium page; the notice frames this only as a question to study.)
• Product quality: the ibogaine used “must be well characterized, with a certificate of analysis” and the chemistry, manufacturing and controls information required under 21 CFR 312.23(a)(7).

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7. Inpatient Cardiac Monitoring, Medications and Discharge

Care setting. In the designs the FDA is contemplating, the setting would be an inpatient unit equipped to manage a life-threatening arrhythmia, which the notice says would likely include continuous heart-rhythm monitoring, a physician-led team trained in advanced cardiac life support, a defibrillator at the bedside, drugs to treat TdP, emergency cardiac pacing and ventilator support.

Heart monitoring. A recording before dosing (for example 24 hours) would establish each participant’s baseline rhythm. Continuous monitoring would begin at dosing and end when there are no abnormal rhythms and the QTc has returned to near its pre-dose value, “which could be as long as 36 hours.”

Staffing and mental-health monitoring. At least two staff members would watch each participant during the acute effects, one of them a licensed mental health professional (drawn from the July 2026 psychedelics guidance). Participants would be assessed for adverse events that may include ataxia, seizures, suicidal thoughts, psychosis and other psychiatric symptoms, and cognitive testing at baseline and at intervals through 12 months after dosing could help separate short-term from lasting effects on thinking.

Medications. Before dosing, participants would stop medicines that prolong the QTc, slow the heart rate, interact with CYP2D6 or raise serotonin levels. The notice’s examples include opioid agonist medications (methadone, buprenorphine), antipsychotics, antiemetics and selective serotonin reuptake inhibitors (paroxetine, sertraline). Low blood potassium, calcium or magnesium would be corrected before dosing.

Discharge. Participants would stay in the telemetry-monitored unit for an appropriate time, for example at least 36 hours after dosing, and leave after meeting predetermined criteria, for example a 48-hour 12-lead ECG without QTc prolongation, escorted home by a trusted adult after the physician approves discharge.

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8. Stopping Rules and Safety Oversight

In the scenario the FDA is considering, dosing would be paused for review by the SRC, the DSMB and the FDA if any of the following occurred:

1. a participant has a sustained ventricular arrhythmia or a seizure;
2. a participant’s QTc prolongation above 500 ms persists more than two days;
3. a participant develops new suicidal thoughts or behavior after the acute effects wear off, or lasting perceptual disturbances;
4. a death or serious adverse event possibly related to ibogaine occurs;
5. two or more participants in a group have severe adverse events.

For oversight, the notice describes an SRC that includes a cardiologist, and an independent DSMB with a cardiologist, a neurologist, a psychiatrist and a biostatistician. In trials enrolling people with opioid use disorder, both bodies would include an addiction medicine physician. The FDA could also ask to review trial data, for example after an event that meets a stopping rule or before dose escalation in a group.

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9. Who Could Enroll and the First Study Populations

Potential participants could be adults aged 18 to 55 who have stopped psychiatric medications. The likely exclusions the notice lists are: structural heart disease, a baseline QTcF of 430 ms or more, or abnormal heart rate or blood pressure; a personal or family history of arrhythmia or sudden cardiac death; a history of seizures, psychosis or bipolar disorder; recent suicidal thoughts or behavior; a neurodegenerative or balance disorder; significant liver or kidney impairment; and pregnancy or breastfeeding.

HHS is prioritizing two initial populations for federally supported research, adults with opioid use disorder and adults with PTSD, in which the notice says “the seriousness of the condition and the limits of available therapy may justify the known risks of ibogaine in a closely monitored early-phase trial.” The example definitions it gives are:

• PTSD: moderate-to-severe PTSD for at least 6 months that has not responded to at least one adequate course of a selective serotonin reuptake inhibitor and one full course of PTSD-focused psychotherapy, with at least 12 months since the most recent course. (See PTSD.)
• Opioid use disorder: moderate or severe OUD in people who want to stop using opioids and have not achieved sustained remission in recent years despite adequate treatment with an FDA-approved medication for OUD, including opioid agonist treatment, and multiple treatment attempts (outpatient, residential, inpatient). (See Addiction and Opioid Overdose.)

The notice also asks how informed consent can convey ibogaine’s “serious, potentially life-threatening risks,” and says the investigator’s brochure would need to summarize the clinical and nonclinical data behind the protocol’s population, dosing and monitoring choices.

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10. The Questions the FDA Is Asking

The FDA invites comment on every element above, asking commenters to name the element, say whether it should stay, change or be dropped, and give the supporting data or clinical experience. It lists specific questions in four areas, which the press release summarizes the same way:

1. General study design. Which study populations have a strong enough potential for benefit to justify the known risks? In opioid use disorder trials, how should opioid agonist medicines be stopped before dosing — setting, duration, and measures against the risks of lost opioid tolerance?
2. Dose selection and escalation. Is a maximum of 10 mg/kg, reached through small stepwise groups, appropriate for finding a minimum active dose and an approximate maximum tolerated dose? Should dosing be based on total body weight, lean body weight or a target blood exposure? What animal data can link blood levels to no-adverse-effect levels; what neurotoxicity threshold appears across species after single and repeated doses; what role noribogaine plays; and how can clinical assessments, cognitive testing, brain imaging or lab tests be combined with animal findings to detect neurotoxicity?
3. Safety. For the heart: what care setting (for example intensive care or hospital telemetry) is needed; how QTc prolongation is managed once the full dose is given; how to measure the effect of magnesium or other pretreatment; what pre-dose QTc cut-off (for example above 430 ms) best limits the share of people exceeding 500 ms; and which enrollment criteria best reduce arrhythmia risk, given known TdP risk factors including low potassium, calcium or magnesium, slow heart rate, structural heart disease, other QTc-prolonging drugs, a history suggesting congenital long QT syndrome, and groups with known susceptibility, including women. For the nervous system: what assessments capture acute neurologic and cognitive risk, and how long follow-up must last to characterize lasting effects.
4. Ethics and oversight. What consent information ensures participants understand the risks; what DSMBs and institutional review boards need to weigh; and what would make data from treatment settings outside the United States useful, including individual-level pharmacokinetic, ECG and product information.

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11. How and Until When the Public Can Comment

• Deadline: Friday 20 November 2026, 45 days after publication. The electronic system accepts comments until 11:59 p.m. Eastern Time that day; mailed or hand-delivered comments count as timely if received on or before that date. The notice and the press release both state that late comments will not be considered.
• Electronic: through the Federal eRulemaking Portal at regulations.gov, Docket No. FDA-2026-N-10429 (the docket’s comment page is listed under Primary Documents below). Electronic comments and attachments are posted to the docket unchanged and are public, including any name or contact details placed in the body of the comment.
• Paper: Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Every submission must carry the docket number and the notice title. Confidential information can be submitted only on paper, as two copies, one marked “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION” and one redacted for public posting.
• Reading the docket: received comments are viewable on regulations.gov under the same docket number, or at the Dockets Management Staff office between 9 a.m. and 4 p.m., Monday to Friday.

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12. How the Notice Fits the FDA’s Earlier Handling of Psychedelic Research

1993: the first ibogaine review. The notice recalls that in 1993 the FDA convened its Drug Abuse Advisory Committee to discuss an ibogaine IND for cocaine dependence, focused on whether enough safety data existed to test ibogaine in human volunteers (58 FR 38773, 20 July 1993). The discussion centered on finding a meaningful window between effective and toxic doses; members raised the neurotoxicity data, the difficulty of describing risks well enough for informed consent, the need for more preclinical data, and the large unmet need for cocaine use disorder treatment. The FDA writes that those questions “remain relevant today,” and that the heart-rhythm risk now at the center of its proposal was identified only after that meeting.

2017–2019: Breakthrough Therapy designations. A separate FDA notice of 14 July 2026 (91 FR 43095) records that the agency granted Breakthrough Therapy designation to MDMA for PTSD (2017) and to psilocybin for treatment-resistant depression (2018) and major depressive disorder (2019). That notice states that such designation is not an FDA determination of safety or effectiveness and is no substitute for approval.

2023: draft psychedelics guidance. On 26 June 2023 the FDA published the draft guidance “Psychedelic Drugs: Considerations for Clinical Investigations” (88 FR 41407, Docket No. FDA-2023-D-1987), describing the trial-design challenges these compounds present.

2026: a run of actions. According to the July 2026 hearing notice, in April 2026 the FDA issued national priority vouchers (designed to shorten review times) to sponsors studying psilocybin for treatment-resistant and major depression and methylone for PTSD, again stating that a voucher is not a determination of safety or effectiveness. Executive Order 14401 followed on 18 April 2026. On 14 July 2026 the FDA finalized the psychedelics guidance (91 FR 43101), saying it had considered the docket comments on the 2023 draft and made “a few revisions” for clarity, and the same day announced a public hearing on the potential future therapeutic use of psychedelic drugs in supervised and supportive settings, scheduled for 14 September 2026 with comments accepted until 5 October 2026 (Docket No. FDA-2026-N-7542). The ibogaine RFI was announced on 5 October, the day that hearing docket closed.

Read together, the documents show the ibogaine notice taking the general psychedelics guidance and applying it to one compound with a specific, documented cardiac hazard: where the guidance gives broad considerations, the RFI sets out a candidate starting dose ceiling, a hospital monitoring setting, numeric stopping rules and named first populations, and asks for data on each before any guidance is issued.

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13. Primary Documents

1. U.S. Food and Drug Administration (2026). FDA Seeks Public Input to Support Ibogaine Research. FDA News Release, 5 October 2026 — fda.gov press announcement (fda.gov, Newsroom → Press Announcements)
2. Food and Drug Administration, HHS (2026). Design and Safety Considerations for Clinical Trials Involving Ibogaine Drug Products; Request for Information. Federal Register 91:63563–63569, 6 October 2026. Docket No. FDA-2026-N-10429 — FR Doc. 2026-20427 (official PDF, govinfo.gov)
3. Public docket FDA-2026-N-10429, comment page — regulations.gov FDA-2026-N-10429-0001
4. Food and Drug Administration, HHS (2026). Psychedelic Drugs: Considerations for Clinical Investigations; Guidance for Industry; Availability. Federal Register 91:43101, 14 July 2026 — FR Doc. 2026-14158
5. Food and Drug Administration, HHS (2026). Considerations for Potential Future Therapeutic Use of Psychedelic Drugs; Public Hearing; Request for Comments. Federal Register 91:43095, 14 July 2026 — FR Doc. 2026-14155
6. Food and Drug Administration, HHS (2023). Psychedelic Drugs: Considerations for Clinical Investigations; Draft Guidance for Industry; Availability. Federal Register 88:41407, 26 June 2023 — FR Doc. 2023-13428

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Key Research Papers

1. Alper KR, Stajić M, Gill JR (2012). Fatalities temporally associated with the ingestion of ibogaine. Journal of Forensic Sciences 57(2):398-412 — PubMed PMID: 22268458
2. Knuijver T, Schellekens A, Belgers M, Donders R, van Oosteren T, Kramers K, Verkes R (2022). Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study. Addiction 117(1):118-128 — PubMed PMID: 33620733
3. Knuijver T, ter Heine R, Schellekens AFA, et al. (2024). The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients. Journal of Psychopharmacology 38(5):481-488 — PubMed PMID: 38519421
4. Ona G, Rocha JM, Bouso JC, Hallak JEC, Borràs T, Colomina MT, dos Santos RG (2022). The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020). Psychopharmacology 239(6):1977-1987 — PubMed PMID: 34406452
5. Brunt TM (2026). Rare but relevant: Ibogaine and cardiovascular complications — prolonged QT interval and ventricular arrhythmias. Addiction 121(6):1616-1621 — PubMed PMID: 41560340

All five papers appear in the reference list of the Federal Register notice (section IV).

PubMed Topic Searches

1. PubMed: ibogaine QT prolongation
2. PubMed: ibogaine torsades de pointes
3. PubMed: ibogaine, CYP2D6 and noribogaine
4. PubMed: ibogaine neurotoxicity and the cerebellum
5. PubMed: ibogaine and opioid use disorder

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Connections

• FDA and Regulation
• FDA Final Guidance on Psychedelic Drug Trials (2026)
• Ibogaine: History, Pharmacology and Safety
• Medicines and Oils
• News, 11 October 2026
• News
• Long QT Syndrome
• PTSD
• Addiction
• Opioid Overdose
• Magnesium
• Crape Jasmine Alkaloids: Pharmacology and Toxicity
• Albert Hofmann

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