Shortcomings of Current Medication-Assisted Treatments in Addressing the Complex Neuropathology of Opioid Use Disorder and Evaluating Ibogaine (12-Methoxyibogamine) as a Viable Alternative Therapy

Abstract

The opioid epidemic is a growing public health concern in the United States (Volkow & Blanco, 2020). Methadone, buprenorphine, and naltrexone are the three most common pharmacologic treatments that are currently used in addition to psychotherapy to treat opioid use disorder (OUD) (Volkow et al., 2014). Although these treatments have been shown to be somewhat effective in reducing opioid use while patients are in treatment (Krupitsky et al., 2011; Sordo et al., 2017) the seemingly high levels of drop-out (Klimas et al., 2021; Sofuoglu et al., 2018; Zhang et al., 2013) and large propensity for relapse following discharge from these programs (Dole & Joseph,1978) warrants their reevaluation. The rising number of opioid-related deaths in recent years (U.S. Department of Health and Human Services, 2023) likewise calls for an exploration of other treatment modalities that may be more effective in achieving lasting sobriety among opioid abusers. The psychedelic substance ibogaine may be one such pharmacological treatment that shows promise as an alternative treatment for OUD (Alper, 2001; Brown, 2013). Although banned in the United States and therefore insufficiently tested in controlled clinical trials (Brown, 2013), anecdotal claims from those receiving ibogaine treatment in other countries suggest that it can successfully prevent withdrawal symptoms, reduce drug cravings, and produce introspective visions that offer the user insights into the psychological sources of their addiction (Lotsof & Alexander, 2001; Schenberg et al., 2017; Sheppard, 1994). The purpose of the current thesis is to synthesize the scholarly conversations around the three main medication-assisted therapies for opioid addiction and the preliminary evidence for ibogaine to argue that ibogaine shows legitimate promise in filling the shortcomings of the treatment modalities currently used for OUD patients in the United States. Bearing in mind the complex neuropathology of opioid addiction, I argue that ibogaine appears superior to methadone, buprenorphine, and naltrexone in that it (1) seems to reverse, rather than mask, the abnormal neural signaling caused by repeated opioid abuse, (2) simultaneously addresses the physical neuroadaptations and underlying psychological components of addiction, and (3) appears to be efficacious in treating polysubstance abuse. Based on the investigation done here, ibogaine looks to be a viable and urgently-needed treatment option for OUD that is worthy of further consideration for FDA approval.