Treating drug dependence with the aid of ibogaine: A retrospective study

Schenberg and colleagues situate their work within the larger public‑health problem of substance use disorders, noting that effective pharmacological treatments remain limited for many types of dependence, particularly psychostimulant dependence. They outline ibogaine as a naturally occurring alkaloid with long‑lasting psychoactive effects that has been proposed, on the basis of case reports, animal studies and an informal medical subculture, to reduce craving and drug self‑administration for opioids and other substances. The introduction highlights safety concerns reported in uncontrolled settings, especially reports of fatalities possibly linked to QT interval prolongation and comorbid medical conditions, and emphasises that evidence for ibogaine in treating stimulants such as cocaine and crack is scarce despite promising preclinical data. This study set out to assess the safety and therapeutic outcomes of a physician‑supervised ibogaine programme practised in Brazil for dependence on non‑opioid substances. Using a retrospective design, the investigators aimed to describe adverse events, abstinence and relapse patterns after one or more ibogaine HCl administrations combined with psychotherapy in a residential treatment context, and to evaluate whether medically supervised administration could avoid the complications reported from underground use.

The researchers conducted a retrospective evaluation of patient records and follow‑up interviews from a private residential clinic in Curitiba, Brazil, that provided cognitive behavioural therapy (CBT) and arranged physician‑administered ibogaine HCl sessions in a private hospital. Data came from 75 patients treated between 2001 and the time of data collection; information sources included clinic records, the treating physician's records, and 5–20 minute telephone interviews with patients or close relatives. The clinic reported DSM‑IV criteria were used to establish substance dependence, although the investigators note that dependence criteria and some drug use data were not confirmed with structured instruments. Inclusion into the ibogaine programme required routine clinical laboratory tests showing general good health, absence of psychiatric comorbidity (as stated), strong motivation to remain abstinent, and agreement to pre‑ and post‑treatment psychotherapy with family support. Exclusion criteria included pregnancy, recent surgery, uncontrolled hypertension or diabetes, cardiac arrhythmias, renal or hepatic insufficiency, and neurodegenerative disorders. The clinic initially required 30 days' abstinence prior to administration, later extended to 60 days to reduce pharmacological interactions. Ibogaine HCl (imported powder) was dosed individually, typically given as 17 mg/kg with adjustments by weight and incremental supplemental doses of 100–200 mg if the response was judged weak; a total of 20 mg/kg was not exceeded. Domperidone 20 mg was given 30–45 minutes beforehand to reduce nausea. Administration occurred in hospital rooms in the morning, with the physician present and vital signs checked regularly; acute effects lasted roughly 10 hours and patients remained overnight. Decisions about repeat ibogaine sessions were made jointly by patient, family and therapeutic team, usually when cravings, lapses or reintegration problems persisted. Outcome data included self‑reported abstinence, lapses (brief return to use) and relapses (complete return to use); abstinence was defined as no drug use except brief lapses. Statistical analyses used SPSS 17.0; parametric tests included Student's t‑test, non‑parametric tests included Mann–Whitney U, Friedman and Wilcoxon tests with Bonferroni correction where appropriate, and categorical associations were assessed with Pearson Chi‑square. Significance was set at p < 0.05. Ethical approval was obtained from Universidade Federal de São Paulo and patient consent for interviews was recorded at the start of each telephone contact.

Seventy‑five patients (67 male, 8 female) who underwent a total of 134 ibogaine HCl sessions were included. Contact sources were 55 telephone interviews, six in‑person interviews, and third‑party reports for 14 individuals. The sample was largely poly‑substance using: 72% reported lifetime use of multiple substances (alcohol, cannabis, cocaine and crack). Reported lifetime use prevalences were 64% for alcohol, 81% for cannabis, 83% for snorted cocaine, 68% for crack and 15% for tobacco; only one patient reported prior opioid use. Patients had substantial prior treatment histories, with only six (8%) reporting no previous drug‑treatment attempts. Regarding ibogaine exposure, all patients had at least one session; 44% had two sessions, 19% three, 7% four, 3% five, and a single patient underwent nine sessions. Mean intervals between sessions varied widely (for example, first–second interval mean 245.3 days, range 31–979). Dosing commonly targeted 17 mg/kg but recorded mean first‑session doses differed by sex: men 14.81 ± 1.61 mg/kg (n = 67) and women 12.03 ± 0.85 mg/kg (n = 8), a statistically significant difference (U = 19.0, p < 0.001). Subsequent male session mean doses were reported (second 13.75 ± 2.10 mg/kg; third 13.34 ± 2.28 mg/kg), with few females undergoing repeat sessions. Abstinence and relapse outcomes were heterogeneous. All eight women were reported abstinent at follow‑up, with two reporting a relapse after the initial session and then remaining abstinent after a second session. Among men, 48 (72%) stated they were abstinent at contact, but 10 of these were concurrently in other treatment programmes; excluding those 10, 38 men (57% of men) achieved abstinence without other treatments. After the first ibogaine session, 22 male patients (29% of the full sample) recovered without further relapse, whereas 53 (71%) relapsed; relapse rates changed across subsequent sessions (after second session 55% relapsed, after third session 43% relapsed, etc.). A significant association between gender and relapse after the first session was reported, with men relapsing more often than women (Chi‑square = 9.009; p = 0.007). Duration of abstinence was assessed in subsets: 66 patients had calculable post‑treatment abstinence periods and 41 provided data on days abstinent immediately before the first ibogaine session. Median days of abstinence before the first session were 60; after the first session the median was 165 days (≈5.5 months) and after all sessions combined the median was 252 days (≈8.4 months). These differences were statistically significant (Friedman Chi‑square = 23.471; p < 0.001). The authors also report that in a subgroup of men who experienced a single relapse, the abstinence duration after the relapse until contact was significantly longer than the period between the most recent ibogaine session and the relapse (median 520 days vs median 120 days; Z = -3.385; p < 0.001). Safety data indicated no fatalities, no reported cardiac arrhythmias or persistent ataxia, and no serious adverse events among the 75 patients. Common acute adverse effects during the ibogaine experience included nausea, vomiting, ataxia, tremors, headache and episode(s) of mental confusion; these were described as transient and occurring during the acute 10‑hour period. Four patients (5%) complained about aspects of the psychotherapeutic care or residential activities. Electrocardiogram (ECG) results prior to administration were available for only 36 patients (48%) in the extracted dataset.

Schenberg and colleagues interpret their findings as indicating that physician‑supervised administration of ibogaine HCl, combined with psychotherapy and a mandated pre‑treatment abstinence period, was not associated with fatalities or serious cardiac complications in this retrospective sample. They stress that the controlled dosing (7.5–20 mg/kg), use of pharmaceutical‑grade ibogaine HCl rather than unregulated preparations, and the largely non‑opioid history of the cohort may have contributed to the absence of severe adverse outcomes. The authors note that previously reported fatalities often involved non‑pharmaceutical preparations or occurred in underground settings without medical supervision, and that comorbid medical conditions may have contributed to those cases. With respect to efficacy, the investigators highlight that both single and multiple ibogaine sessions were associated with substantially longer median abstinence periods than the required pre‑treatment abstinence (median 5.5 months after the first session and 8.4 months after all sessions combined), and that repeat sessions appeared to extend abstinence further. They caution, however, that comparison with psychotherapy alone or with pharmacological trials is tentative given methodological differences. The authors explicitly acknowledge major limitations: the retrospective design, reliance on unstructured self‑report or reports from relatives for lapse/relapse and abstinence data, incomplete ECG records, and the selection bias introduced by requiring patients to achieve 30–60 days' abstinence before treatment. They emphasise these limitations preclude causal inference and that only a randomised double‑blind trial could establish efficacy definitively. The discussion points to practical implications and future research directions proposed by the authors: routine ECG monitoring to address QT‑prolongation risk, systematic assessment of secondary outcomes such as self‑efficacy, psychosocial functioning, craving and quality of life, and comparative studies against other psychedelic agents or pharmacotherapies. The authors conclude that, despite limitations, their data constitute the first formal clinical report suggesting ibogaine has therapeutic potential for stimulant and other non‑opiate drug dependence when administered in a safe, medical setting.