REVIEW OF: Knuijver T et al, Addiction 2022;117(1):118–128

STUDY TYPE: Open-label observational study

Ibogaine is a psychedelic drug, derived from the bark of the iboga tree, that has been used over the years as a potential treatment for opioid use disorder (OUD). However, there are significant safety concerns, with numerous deaths reported due to cardiac arrhythmia and arrest, possibly driven by QT prolongation. Ibogaine is illegal in the US and is classified as a Schedule I drug. In a new study, researchers sought to better understand ibogaine’s potential adverse effects in order to determine whether it has a place in the future of OUD treatment.

Researchers recruited 14 subjects in remission from OUD, taking either methadone (n=12) or buprenorphine (n=2), who wanted detoxification and abstinence from all opioid medications. Twelve of the participants were men, and all participants were between the ages of 20 and 40. None had cardiac or liver disease, psychosis, or depression. Subjects were first converted from methadone or buprenorphine to morphine (because methadone prolongs the QT interval). After eight days, morphine was stopped. Patients were given ibogaine four hours later at a dose of 10 mg/kg, which is on the low side of the dosage range used in other studies. Over the next 12 hours, researchers periodically obtained vital signs and ECGs, and assessed for ataxia, delirium, and withdrawal symptoms using the Clinical Opiate Withdrawal Scale (COWS).

The primary outcome measure was change in QTc from baseline. There was large variability between subjects, but all had some degree of QT prolongation. The median increase was 102 msec over baseline, with half having a QTc above 500 msec. Six subjects still had an elevated QTc 24 hours after receiving ibogaine. Those whose QTc was >500 msec received magnesium infusions, and none of the subjects developed torsades de pointes.

Of the other outcomes, all subjects experienced varying levels of ataxia peaking between two and six hours after administration, which fully resolved within 48 hours. Half met criteria for bradycardia (heart rate <60) within the first 12 hours. Four developed mild delirium symptoms, such as wakeful dreaming and spatial disorientation, which lasted no more than a few hours. COWS scores remained low in all participants, though three of them requested to be restarted on morphine due to a subjective feeling of treatment failure.

The authors concluded that routine use of ibogaine in patients with OUD cannot be justified given its potent QT-prolonging effects. They noted that half of the subjects developed a QTc >500 msec, which is associated with an 11-fold increased risk of adverse cardiovascular events in patients presenting with drug overdose. They also noted that ibogaine metabolism is highly dependent on CYP2D6, so its cardiotoxicity could be higher in patients who are poor metabolizers or are taking 2D6 inhibitors, further limiting its clinical utility.

CARLAT TAKE

Any potential clinical utility of ibogaine is outweighed by its potent ­QT-prolonging effects. Stick to methadone and buprenorphine, both of which are well-established treatments with a firm evidence base.