Feasibility, safety and preliminary effects of ibogaine in patients with moderate and severe alcohol use disorder: a pilot, open-label study

Ibogaine is an atypical psychedelic that has shown preliminary promise in substance use disorders, but the clinical evidence base has mostly involved opioid dependence, with much less information for alcohol use disorder (AUD). The authors note that ibogaine can produce cardiovascular and cerebellar adverse effects, including dose-dependent QTc prolongation, bradycardia, arrhythmia, ataxia, and tremor, and that no prior studies had focused specifically on patients with AUD. Rocha and colleagues therefore set out to examine the feasibility, safety, and preliminary effects of ibogaine in people with moderate to severe AUD. The study was designed as a pilot feasibility study to generate early data on dosing, monitoring requirements, tolerability, and any initial signals of change in alcohol and other substance use.

This was a pilot, open-label, sequential dose study conducted in a tertiary-level hospital with trained staff and medical infrastructure. Nine adults aged 18-65 years with a primary diagnosis of AUD were recruited through university social media and underwent pre-screening, psychiatric assessment with the SCID-5-CV, and clinical testing including electrocardiography and laboratory analyses. Other substance use disorders were permitted, but major psychiatric or medical comorbidities, continuous medication use, and abnormal clinical findings were exclusion criteria. Ibogaine hydrochloride was given orally as capsules. The first three participants underwent a dose-finding schedule across three sessions separated by 72 hours to reduce the chance of noribogaine accumulation: participant 1 received 20/40/80 mg, participant 2 received 80/160/240 mg, and participant 3 received 240/320 mg. The remaining six participants received a single 400 mg dose. Participants were admitted 24-48 hours before dosing, remained under continuous monitoring, and received no psychotherapy before, during, or after sessions. The primary outcomes focused on safety. These included QTc interval on serial ECGs from baseline to 12 hours after dosing, blood pressure and heart rate at the same time points, laboratory tests at baseline and discharge, adverse effects, and psychiatric ratings using the UKU Side Effect Rating Scale, the Clinician-Administered Dissociative States Scale (CADSS), and the Brief Psychiatric Rating Scale (BPRS). Secondary outcomes assessed self-reported alcohol and other drug use at baseline and at 7, 14, and 21 days, plus 1 and 3 months after dosing. The study also included exploratory measures of subjective drug effects, anxiety, depressive symptoms, craving, impulsiveness, self-esteem, personality traits, and social cognition. Because the sample was very small, the analysis was descriptive.

Between January 2023 and August 2024, 388 people completed pre-screening. After multiple stages of exclusion and loss to follow-up, the final sample comprised nine participants, six men, with a mean age of 41.8 years. All had AUD, with three classified as moderate and six as severe. Eight participants also met criteria for comorbid cocaine use disorder. Five participants completed all study procedures. Regarding safety, QTc interval changes occurred in five of nine participants. Three had transient QTc shortening, and four had QTc prolongation; the most marked prolongation reached 496 ms in one participant. These changes occurred 4-12 hours after administration and were self-limiting without clinical sequelae. Blood pressure elevations were common, especially 1-4 hours after dosing, and one participant had sustained hypertensive peaks up to 180/110 mmHg that led to medical evaluation and exclusion from further dosing. Heart rate was usually within range, with one transient tachycardia and one mild bradycardia. Minor laboratory abnormalities were reported but were not clinically significant. No serious adverse events occurred. The most frequently reported symptoms were somnolence/sedation (53%), nausea (36%), anxiety (33%), and difficulty concentrating (30%), with more adverse effects at the higher doses of 240-400 mg. Some participants required lorazepam for insomnia or nicotine craving. The CADSS and BPRS indicated mild to moderate transient dissociative and psychiatric symptoms, including motor and anxiety-related changes and unusual thought content, but these did not require psychiatric intervention. For alcohol and other substance use, most participants reported reduced drinking frequency and/or quantity after the session, with some reporting abstinence or occasional use and some continuing to drink at lower levels than baseline. Several participants reported less craving and aversive responses to alcohol. Cocaine or crack use also tended to decline over follow-up, with some participants becoming abstinent and others using less frequently. Tobacco and cannabis use changed less consistently. The exploratory measures suggested reductions in depressive and anxiety symptoms among those who had such symptoms at baseline, while other exploratory domains did not show clear effects.

Rocha and colleagues interpret the study as showing that ibogaine can produce clinically relevant cardiovascular effects in people with AUD, including QTc prolongation at doses lower than those often associated with this risk in earlier work, as well as some QTc shortening that they note had not previously been described. They argue that these findings, even though they caused no clinical harm in this small sample, support the need for continuous ECG monitoring and careful individual risk assessment. The authors also note that the observed blood pressure changes add to concerns about cardiovascular safety. They suggest, cautiously, that the clustering of cardiovascular effects among Black and Brown participants could possibly relate to ethnic variation in CYP2D6 genotype, which influences ibogaine pharmacokinetics, but this is presented as a possibility rather than a conclusion. In relation to efficacy signals, the authors describe self-reported reductions in alcohol and cocaine use as encouraging but highly tentative. They explicitly state that motivation to seek ibogaine treatment and placebo effects could explain these changes, especially because several participants were lost to follow-up and the study lacked a control group and blinding. They therefore present the study primarily as feasibility and safety work rather than evidence of efficacy. The main limitations they emphasise are the very small sample size, the self-selected nature of the participants, attrition during follow-up, and the absence of a placebo-controlled double-blind design. They also stress that the level of clinical complexity needed to deliver ibogaine safely is a major barrier to scalability, implementation, and equitable access. The discussion implies that future controlled studies will be needed to define safety parameters and clarify whether ibogaine has genuine therapeutic benefit in AUD.