Detoxification from methadone using low, repeated, and increasing doses of ibogaine : A case report

CLARE WILKINS, RAFAEL G. DOS SANTOS, JORDI SOLÁ, MARC AIXALÁ, PEP CURA, ESTEFANÍA MORENO, MIGUEL ÁNGEL ALCÁZAR-CÓRCOLES, JAIME E. C. HALLAK and JOSÉ CARLOS BOUSO

Journal of Psychedelic Studies,  2017, 1, (1), pp. 29–34

DOI: 10.1556/2054.01.2017.005

 

Background and aims : Ibogaine is a natural alkaloid that has been used in the last decades as an adjuvant for the treatment of opiate withdrawal. Despite the beneficial results suggested by animal studies and case series, there is a lack of clinical trials to assess the safety and efficacy of ibogaine. Moreover, the majority of reports described cases of heroin-dependent individuals, with and without concomitant use of methadone, using high doses of ibogaine. Therefore, it is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT).

Methods : Case report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogaine over a 6-week period.

Results : The patient successfully eliminated her withdrawals from methadone with ibogaine. Each administration of ibogaine attenuated the withdrawal symptoms for several hours, and reduced the tolerance to methadone until all signs of withdrawal symptoms disappeared at the end of the treatment. No serious adverse effects were observed, and at no point did the QTc measures reach clinically significant scores. Twelve months after the treatment, she was no longer on MMT.

Conclusions : To our knowledge, this is the first case report describing an ibogaine treatment using low and cumulative doses in a person on MMT. Although preliminary, this case suggests that low and cumulative doses of ibogaine may reduce withdrawal symptoms in patients undergoing MMT.

Keywords : ibogaine, methadone, opioid substitution treatments (OST), methadone maintenance treatments (MMT), methadone detoxification, drug addiction

INTRODUCTION

Opioid misuse is increasing alarmingly in both the EU and North America. According to the US Centers for Disease Control and Prevention, “since 1999, the number of overdose deaths involving opioids (including prescription opioid pain relievers and heroin) nearly quadrupled. From 2000 to 2014 nearly half a million people died from drug overdoses. 78 Americans die every day from an opioid overdose” (Centers for Disease Control and Prevention, 2016). Since the problem has repeatedly been described as an “epidemic,” a drug abuse and treatment bill has recently been signed into US law after passing through the House and Senate (Spangler, 2016). Simultaneously, in the EU, and according to the 2016 European Drug Report, “Europe’s opioids problem remains a central issue in the 2016 analysis, reflecting the significant impact these drugs still have on mortality and morbidity. We see now an increasingly complex relationship between use of heroin and synthetic opioids, accompanied by a worrying increase in overall estimates of opioid-related deaths” (European Monitoring Centre for Drugs and Drug Addiction [EMCDDA], 2016).

The new epidemic of opioid overdoses is not only related to heroin misuse, as it has been in the past, but also to a high prevalence of the misuse of prescription opioids, including methadone (Substance Abuse and Mental Health Services Administration [SAMHSA], 2016). The Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence of the World Health Organization (WHO) state that there are two strategies to treat opioid use disorders: (a) to progressively reduce the dose and (b) to begin an opioid substitution treatment (OST), generally using methadone or buprenorphine (WHO, 2009). According to those guidelines, opioid withdrawal (rather than maintenance treatment) results in poor outcomes over the long term (WHO, 2009). Although an OST is a successful approach to reduce opioid misuse and crime, it tends to become a perpetual treatment, and it has been shown that those stabilized on high doses in methadone maintenance treatments (MMT) have more medical, cognitive, and emotional problems and a decreased quality of life than people who terminated MMT (Pedrero-Pérez & MethaQoL, 2016). It is clear that novel pharmacological treatments that are effective in ceasing opioid misuse are necessary.

Ibogaine is the principal alkaloid in Tabernanthe iboga, an African plant used in ethnomedicine in traditional communities (Alper, 2001). In 1956, a Ciba Pharmaceuticals patent was acquired for its properties to reduce tolerance to morphine (United States Patent Office, 1957). In the 1960s, Howard Lotsof serendipitously discovered the anti-withdrawal properties of ibogaine (Alper, 2001). Ibogaine has demonstrated efficacy in attenuating opioid withdrawal in animal models (Belgers et al., 2016), but the evidence in humans is scarce (Brown, 2013). Globally, approximately 70–100 private clinics and practitioners offer treatments with ibogaine, and in New Zealand and South Africa, ibogaine is listed as a prescription medication (Ibogaine Legal Status, 2016). The typical doses used for treating substance use disorders are between 15 and 20 mg/kg (Brown, 2013) in a single administration. High doses of ibogaine may induce bradycardia and prolong the QTc interval (Litjens & Brunt, 2016; Meisner, Wilcox, & Richards, 2016), which can be life-threatening. Indeed, ibogaine administration has been associated with
several fatalities (>25 cases), which appear to involve increases in cardiac arrhythmias, previous cardiovascular diseases, and use of opiates/opioids or other drugs during the acute effects of ibogaine (Litjens & Brunt, 2016; Meisner et al., 2016).

In a recent clinical trial with noribogaine (Glue, Cape, Tunnicliff, Lockhart, Lam, Hung, et al., 2016), the main metabolite of ibogaine and a possible candidate for explaining its anti-addictive properties (Mash et al., 1998), this compound was administered to people on MMT who were switched to morphine. No significant reduction in withdrawal symptoms was observed after the administration of 60, 120, and 180 mg [the 180 mg dose of noribogaine is equivalent in noribogaine plasma concentration to a 286 mg dose of ibogaine (Glue, Cape, Tunnicliff, Lockhart, Lam, Gray, et al., 2016)] but was observed a concentration-dependent increase in QTc. The authors of that study speculated that the dose of noribogaine administered probably was too low, and repeated dosing would be necessary to achieve a reduction in withdrawal symptoms. A recent report establishes the safe dose to be administered in an ibogaine treatment in 0.87 mg/kg that is far from the 15–20 mg/kg doses (Schep, Slaughter, Galea, & Newcombe,
2016).

We present here the case of a successful detoxification from long-term methadone dependence using low, repeated, and increasing doses of ibogaine.

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2054.01.2017.005