Subjective effectiveness of ibogaine treatment for problematic opioid consumption : Short- and long-term outcomes and current psychological functioning, Alan K. Davis et al., 2017

Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning

ALAN K. DAVIS, JOSEPH P. BARSUGLIA, MARLEY WINDHAM-HERMAN, MARTA LYNCH and MARTIN POLANCO

Journal of Psychedelic Studies, 2017, 1, (2), pp. 65–73

DOI: 10.1556/2054.01.2017.009

 

Background and aims : Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. Therefore, this study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning.

Methods : Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Results : Most participants (72%) had used opioids for at least 4 years and 69% reported daily use. Most (80%) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25%) reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54%) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41% of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48% reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective wellbeing and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

Conclusion : The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.

Keywords : ibogaine, heroin, prescription opioids, outcomes, effectiveness

INTRODUCTION

Opioid addiction has developed into a substantial contributor to global disease burden and is one of the largest public health epidemics in the United States (U.S.) and Europe (Degenhardt et al., 2014). Twelve percent of all people with a substance use disorder are addicted to opioids (SAMHSA, 2015) and rates are greater among vulnerable populations, such as U.S. military veterans (Samoylenko et al., 2010) and chronic pain patients (Sehgal, Manchikanti, & Smith, 2012). Moreover, drug overdose is now the primary cause of accidental death in the U.S., with approximately 78 Americans dying every day from an opioid overdose (Center for Disease Control and Prevention, 2016).

Opioid maintenance therapies (OMT) are the current mainline intervention in the U.S. and although there is a broad literature base on their efficacy, these treatments require long-term use and monitoring with potentially hazardous iatrogenic effects (Andersen, Olaussen, Ripel, & Mørland, 2011; Tennant, 2013; Upadhyay et al., 2010). Further, OMT demonstrate mixed efficacy (Ling & Compton, 2005; Nielsen et al., 2016; Veilleux, Colvin, Anderson, York, & Heinz, 2010) as a high percentage of individuals often relapse during or shortly after tapering off of opioid replacements (Stotts, Dodrill, & Kosten, 2009; Weiss et al., 2011). One way to address these problems is to provide access to a single-dose medication that could interrupt/reduce withdrawal and craving for opioids and provide important psychotherapeutic effects to the patient (e.g., insight, motivation to change), thus allowing the opioid user to address the environmental and behavioral problems associated with their consumption of opioids. An example of such a treatment is the use of ibogaine as an opioid detoxification treatment.

Ibogaine history and evidence for use as a treatment for opioid addiction

Ibogaine is a naturally occurring alkaloid, obtained from the root bark of the African shrub Tabernanthe iboga, and is also produced through semi-synthesis of voacangine from the African tropical tree Voacanga africana. Iboga was historically used as a medicinal and ceremonial agent in indigenous cultures in West Central Africa to treat fatigue, physical maladies, and as a sacrament in initiation rituals and rites of passage (Fernandez, 1982; Goutarel, Gollnhofer, & Sillans, 1993). The subjective effects of ibogaine are described with several classifications, as a psychedelic, a dissociative, and most precisely as oneirophrenic, or a substance that invokes a dream state without loss of consciousness (Goutarel et al., 1993).

Ibogaine was initially marketed in France in the 1930s as a medical product called Lamberene and was used to treat depression, fatigue, and infectious diseases (Goutarel et al., 1993). In the early 1960s, Howard Lotsof identified ibogaine as effective in ameliorating withdrawal and craving from his own heroin addiction (Alper, Beal, & Kaplan, 2001). Since the substance was added to the Controlled Substance Act in 1970, several Phase I/Phase II human clinical trials were developed but were not completed. In 1993, the US FDA granted approval to Dr. Deborah Mash at the University of Miami for a dose-escalation study, which was subsequently suspended in 1995 due to lack of grant support (Alper et al., 2001; Brown, 2013). In 1993–1994, The National Institute on Drug Abuse (NIDA) developed a Phase I investigation to evaluate pharmacokinetic and safety data in a fixed dosage study for cocaine dependence, but they decided not to fund the implementation of the protocol (Alper, 2001; Alper et al., 2001). In two Phase I studies, low doses of noribogaine (the active metabolite of ibogaine, which has a distinct pharmacological profile) was well tolerated (Glue et al., 2015) and showed a trend toward reduction in opioid withdrawal ratings (Glue et al., 2016).

In clinical settings, a typical flood dose ibogaine experience (15–20 mg/kg) results in a session lasting 12–36 hrs and is segmented into different experiential phases or stages. The initial acute phase begins within the first 1–3 hrs and typically consists of vivid waking dreams, which last for 4–8 hrs and are intensified in a dark environment and with the eyes closed. The second phase is evaluative and has an onset between 8 and 20 hrs after initial dosing during which visual imagery diminishes and individuals often report increased levels of intuition, personal insight, and reflection. During the initial two phases, unpleasant effects can include auditory buzzing (tinnitus-like noise), auditory hypersensitivity, ataxia, dissociation, visual tracers, nausea, and vomiting. The final residual phase has an onset 12–24 hrs after the initial dosing and can last from 24 to 72 hrs depending on dosage and metabolic factors. During this last phase, individuals often report reduced need for sleep and feelings of mental clarity and calmness (Alper & Lotsof, 2007).

Despite the legal restrictions on ibogaine in the U.S. and internationally, several clinical outcome studies have been conducted. For example, in a 1999 case series, 33 individuals were treated for opioid detoxification in the U.S. and the Netherlands (Alper, Lotsof, Frenken, Luciano, & Bastiaans, 1999). Relief of withdrawal symptoms was rapid – within 1–3 hrs of administration. Full resolution of opioid withdrawal symptoms was achieved within 34 hrs. Participants did not exhibit drug-seeking behavior within 24 hrs, which was sustained for 72 hrs following treatment in 75% of patients. In another study, Mash et al. (2001) conducted an open-label prospective evaluation of ibogaine in St. Kitts, West Indies with 32 patients diagnosed with a severe opioid use disorder (OUD). Physician ratings indicated the resolution of withdrawal signs and symptoms at 2, 24, and 36 hrs following ibogaine administration. Selfreports of withdrawal symptoms were also significantly reduced from pre-ibogaine ratings. These results suggested ibogaine was an effective treatment for opiate withdrawal. Furthermore, scores of depression and opioid cravings remained reduced 1 month following treatment.

Yet another study (Bastiaans, 2004) evaluated the longterm effects of ibogaine treatment on drug use and on the long-term medical, psychological, social, and legal outcomes among a sample comprised primarily of opioid users (87%) using a web-based survey. After long-term follow-up in this group, 24% (5 out of 21) quit using all substances with an average drug-free period of 24 months following treatment. An additional 33% of the sample continued to use their primary substance but decreased the amount used. Secondary analyses indicated approximately 60% of subjects reported an improvement in their medical condition, 88% reported improvement in relationships with significant others, 92% reported improvement in anxiety, and 100% reported improvement in depression.

Although these observational and outcome studies on ibogaine suggest that it is an effective compound for treating OUDs because it rapidly mitigates withdrawal symptoms and cravings (Alper et al., 1999; Bastiaans, 2004; Mash et al., 2001), the small sample sizes of these studies combined with the limited long-term evidence for effectiveness restrict our understanding of the benefits of this medicine. Therefore, the current observational study aimed to address this key question by evaluating whether ibogaine treatment was associated with short- and long-term opioid usereduction and abstinence (up to 3 years posttreatment), and current psychological functioning among a larger sample of patients who received treatment for problematic opioid use from 2012 to 2015 at a treatment facility in Mexico.

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