Trump's executive order about ibogaine should be swallowed with a lot of nitroglycerin

When it comes to the use of ibogaine to treat clinical depression, heeding the advice of pharmaceutical geniuses like podcaster Joe Rogan is probably a bad idea.

On April 18, Trump signed a so-called executive order to further the cause of medicalization of psychedelic substances. The decree is intended to accelerate the adoption of ibogaine, an extract from the root bark of the West African plant, Tabernanthe iboga.

There is a problem however: ibogaine is cardiotoxic.

In a statement published in the AP’s Newsbreak, Frederick Barrett, director of the Johns Hopkins Center for Psychedelic and Consciousness Research, had this to say:

“It’s been incredibly difficult to study ibogaine in the U.S. because of its known cardiotoxicity. If the executive order can pave the way for doing objective, scientific research with this compound, it would help us understand whether it is truly a better psychedelic therapy than others.”

Barrett’s statement, while acknowledging Trump’s order, is larded with subtext. “Objective research” does not translate into “clinical trails” nor does it suggest research on human subjects would be a good idea. It can mean biochemical studies, or research on reformulating the compound to reduce toxicity.

In a 2015 two researchers reviewed all the available literature about ibogaine on PubMed. They used the keywords: “ibogaine” and “noribogaine”. The search criteria were: “mechanism of action”, “pharmacokinetics”, “pharmacodynamics”, “neurotransmitters”, “toxicology”, “toxicity”, “cardiac”, “neurotoxic”, “human data”, “animal data”, “addiction”, “anti-addictive”, “withdrawal”, “death” and “fatalities”. Their findings were reported in Clinical Toxicology.

Their searches identified 382 unique references, of which 156 involved human data. Further research revealed 14 detailed toxicological case reports. Here’s what they found:

Twenty-seven fatalities have been reported following the ingestion of ibogaine, and pre-existing cardiovascular conditions have been implicated in the death of individuals for which post-mortem data were available. However, in this review, 8 case reports are presented which suggest that ibogaine caused ventricular tachyarrhythmias and prolongation of the QT interval in individuals without any pre-existing cardiovascular condition or family history. Noribogaine appears at least as harmful to cardiac functioning as ibogaine.

Although there was some clinical research on ibogaine conducted in the 1990s funded by the National Institutes of Health, the work was halted because of the substance’s cardiovascular toxicity.

Ibogaine’s powerful psychedelic properties remain a central component of ceremonial use in the Bwiti religion among tribal groups in West Africa, who use iboga in religious ritual. In its native form, iboga is an appetite supressant and a stimulant. Iboga has been used widely by the psychedelic underground in the US, Gabon, Cameroon, and Portugal as a treatment for drug and alcohol addiction. Those who have taken part in iboga rituals to treat substance and behavioral addictions, including cocaine, alcohol, and sexual compulsions, have reported remaining abstinent for upwards of five years.

However, the risk is high. In a 2024 case report in Cureus, doctors at an intensive care unit in Beja, Portugal, describe treating a heroin-dependent man who developed life-threatening tachycardia accompanied by cardiac arrest after participating in an underground ibogaine session. His addiction had not responded to conventional treatment. Eight days after being admitted, his heart rate was finally stablized, and he was discharged.

To date, the FDA has not approved either MDMA or psilocybin for use as legitimate medical treatments.

In order for ibogaine to become legally available prior to going through the rigorous FDA approval process, it must first go through phase I safety trials. Then, depending upon the outcomes, it could become available under the Right to Try Act (21 U.S.C. 360bbb-0a). Or, once phase II trials prove significant efficacy, it could become available under a breakthrough designation. A breakthrough designation allows a drug developer to offer a drug that has not been approved for clinical use by the FDA to a small group of patients whose clinical needs are unmet by any existing therapies.

The Right to Try Act allows individual patients to request treatment with an investigational drug that has cleared the safety phase, phase I, of the drug approval process. However, the phase I trials must prove the drug does more good than harm. Given its risk profile, ibogaine’s future as an above-board medical drug is hardly assured, scrawled executive orders notwithstanding.