Ibogaine and Bipolar Disorder

This page exists because people search for ibogaine as a treatment for bipolar disorder, and a page written as though it were one would be a service to nobody. What follows is the whole record, including the parts that cut against the warning.

What has actually been reported

The medical index lists 24 ibogaine case reports. The overwhelming majority concern the heart: long QT, torsades de pointes, arrhythmia, cardiac arrest, sudden death, forensic toxicology.

Exactly three concern a psychiatric outcome. That ratio is itself worth knowing. Ibogaine’s documented harm profile is a cardiac profile with a thin psychiatric tail.

The bipolar-relevant one is a series of three patients seen in a psychiatric emergency room, whose unregulated ibogaine use was followed by mania. Two had taken it to self-treat an addiction, one for what the authors call psycho-spiritual experimentation.

Two further psychiatric cases exist: one of ibogaine-associated psychosis in a person with schizophrenia, and one of hallucinogen persisting perception disorder following treatment for opioid dependence, reported by the Dutch academic group that ran the hospital safety studies. Both are one-page letters with no abstract published anywhere, and we could not obtain either text. We name them because the record exists; we will not describe clinical courses we have not read.

Set against those, the fourteen patients treated under continuous monitoring in a Dutch university hospital tolerated the acute psychiatric effects well, with delirium scores staying below threshold in all of them. The problems in that series were the cerebellum and the heart, not psychosis.

The exclusion, and how thin its foundation is

Two published protocols exclude bipolar disorder, and five of six substantive trial registrations do.

The 2003 treatment manual excludes active psychiatric disorders requiring treatment, naming bipolar illness among them. It is grey literature, not peer reviewed, and it is unusually candid about where its list came from: the criteria are inherited from the United States drug institute, and the manual adds that ibogaine appears to be a very safe drug in terms of psychiatric events. It even publishes internal dissent from its own contributors, who point out that excluding depressed or bipolar patients excludes a sizeable portion of the addicted population.

A 2016 provider-association guideline is stricter, and puts bipolar disorder in both its lists: absolutely excluded where the patient has been hospitalised or medicated, and separately listed as a risk factor to consider. It also excludes on family history, primarily in patients under 30.

That guideline supplies the only stated rationale anywhere in the literature: without proper therapeutic support, ibogaine may exacerbate or re-traumatise patients with some conditions. Its supporting chapter names its evidence base explicitly, and it is the same handful of cases catalogued above.

The strictest registered trial excludes bipolar I or II, primary psychotic disorder or schizophrenia, and does the same for first or second-degree family history.

And the studies people actually cite do not exclude it

The two most-cited outcome studies in the whole field state no psychiatric exclusion at all for bipolar disorder.

The veteran study in Nature Medicine excludes a history of psychotic symptoms or disorders. Bipolar disorder is not mentioned.

A study of thirty patients at two fee-for-service clinics in Baja California contains the words bipolar, psychosis, psychotic, schizophrenia, mania and contraindication zero times in its full text. Its screening as described is cardiac and metabolic only: history, ECG, electrolytes and liver function. And its own table records that nine of the thirty had a previous inpatient psychiatric hospitalisation.

A New Zealand follow-up study, in the one jurisdiction where ibogaine can lawfully be prescribed, states that providers were themselves responsible for determining medical eligibility. One patient died during treatment.

So the field says bipolar disorder is an absolute exclusion, and the field’s own published cohorts did not apply it.

The strongest argument is about your medication

This is the part that changes what someone should actually do, and it has nothing to do with mania.

The ibogaine pathway requires stopping psychiatric medication. The Nature Medicine methods document what the clinic required patients to discontinue before arrival: diuretics, CYP2D6-inhibiting drugs, serotonergic drugs, calcium-channel blockers, beta-blockers, benzodiazepines, stimulants, corticosteroids, and all psychiatric medications. Registered studies list refusal to taper off an SSRI as an exclusion in itself.

That washout has its own well-quantified hazard, and it is measured in the psychiatry literature rather than the ibogaine literature.

In 227 patients who discontinued lithium after an average of four and a half years, median time to a new episode was 3.50 months after rapid discontinuation against 10.6 months when tapered over two weeks or more. Rapid discontinuation, stopping for a medical reason, and a bipolar I diagnosis were each independently associated with illness within twelve months. An earlier study by the same group found that discontinuation increased early affective morbidity and suicidal risk, and put the point in a sentence worth keeping: discontinuing treatment is not equivalent to not treating.

Two separate drug interactions

Through the liver. Ibogaine is cleared almost entirely by one enzyme, CYP2D6, and its activity varies several-fold between people on genetic grounds. In fourteen genotyped patients, clearance rose by about thirty litres per hour for each point of activity score from a baseline near zero, and QT prolongation tracked ibogaine concentration.

Several psychiatric drugs inhibit that enzyme, according to their own approved labels: fluoxetine, described as a potent inhibitor; paroxetine, whose inhibition is irreversible and therefore outlasts the last dose; bupropion, whose inhibition is carried by long-lived metabolites; duloxetine, moderate; and sertraline. Escitalopram raised a test drug’s exposure by 100%.

The best direct evidence is a study of 21 healthy volunteers pretreated with paroxetine or placebo. Exposure to ibogaine and its metabolite was roughly twice as high after paroxetine. The dose used was 20 mg, a fraction of a treatment dose, and there was no cardiac endpoint, so this is proof that a common antidepressant doubles exposure and not a cardiac measurement. No source establishes how long a washout would be needed.

Three drugs commonly asked about are not CYP2D6 issues. Lamotrigine is cleared by glucuronidation, valproate almost entirely by other routes, and carbamazepine induces a set of enzymes that does not include CYP2D6. No source establishes any pharmacokinetic interaction between carbamazepine and ibogaine.

Through the QT interval. This is the mechanism that kills. Several psychiatric drugs lengthen it in their own right. Citalopram’s label carries explicit dose-dependent warnings, torsades and sudden death, and instructs avoidance in patients taking other QT-prolonging drugs. Haloperidol’s carries the sentence most directly transferable here: avoid concomitant use with drugs that may increase the risk of QT prolongation, and cases have been reported even in the absence of predisposing factors. Ziprasidone’s label states it has a greater capacity to prolong the interval than several other antipsychotics.

Ibogaine and the heart sets out what that combination means.

Lithium is a different shape of problem

Lithium is not metabolised by any cytochrome enzyme; the word does not appear in its label. And at therapeutic levels it shows no QT signal: a study of lithium augmentation found no significant change in heart rate, QTc, PQ or QRS.

At toxic levels it is another matter. In a cohort of 1,136 patients with 112 intoxication episodes, QT prolongation occurred in 24% of episodes, and in 54% of those the QTc exceeded 500 milliseconds. The label itself lists prolonged QT under toxicity rather than among routine effects.

The case that points the other way

Honesty requires this section, and its details matter more than its headline.

A woman of 47 with a twenty-year history of bipolar II and a severe depressive episode took two 4 mg capsules twice daily for sixty days. Depression, anxiety and hopelessness scores fell steadily, by 90%, 56% and 100% at ninety days. No manic switch was evident at any point.

Four things bound it.

It is one person, open, unblinded, and self-referred to a private clinic. The dose is 16 mg a day, described by the authors as about one per cent of a full conventional dose, so it is not evidence about the treatment people search for; anyone reading this and booking a flood dose is not reading about the same intervention. The patient decided to taper off her mood stabilisers and her antidepressant on her own, which is confounded with the outcome and is itself the hazard described above. And follow-up was ninety days, while relapse after mood-stabiliser discontinuation has a median latency measured in months.

The one author disclosure is that a co-author is a medical consultant for a pharmaceutical company.

For context rather than evidence: a study of fifteen people with bipolar II given a single dose of psilocybin under intensive supervision, with psychotropics stopped at least two weeks beforehand, found large antidepressant effects and no significant change in mania ratings. That is a different drug in a monitored trial, and it demonstrates that the medication washout is standard practice in this field rather than an ibogaine peculiarity.

What this page concludes

Not that ibogaine causes mania. Three cases in people without the diagnosis cannot carry that, and the authors did not claim it.

What the record supports is narrower and more useful. Nobody has studied this. The exclusion that every protocol applies rests on those same few cases and is stated without a reason in almost every document that applies it. The one positive report is a microdose in a patient who stopped her own medication. And the route to treatment requires abandoning a medication regime in a way that psychiatry has measured and found to carry a median relapse at three and a half months.

If you are on lithium, on an anticonvulsant mood stabiliser, or on an antidepressant, the interaction questions on this page are ones to put to the person who prescribes them, before anything else. Who should not take ibogaine sets out the rest of the contraindications.