Introduction

Nearly three million Americans are struggling with addiction to prescription painkillers such as opioids and opiates. This epidemic has had a massive societal and economic impact. Moreover, opioids and their synthetic variations (opiates) caused nearly 80,411 deaths in 2021. Between the years 1999 to 2020, the CDC estimates that 932,000 people died due to opioid abuse or accidental overdose.^(1, 2, 3)

Opioid addiction is a serious and often debilitating affliction that can be extremely difficult to overcome. A study published by the National Library of Medicine, titled A Comparative Study of Factors Associated with Relapse in Alcohol Dependence and Opioid Dependence, indicated that up to 91% of individuals with opioid addiction will relapse within one year of receiving treatment. Thankfully, a new option may exist in the fight against opioid addiction: the psychedelic compound ibogaine.⁽⁴⁾

What is Ibogaine?

Ibogaine is a psychedelic compound that has dissociative qualities. It is found in the Tabernanthe iboga shrub native to West Africa, and is known for its potential as a treatment for substance use disorders. In fact, it has been the subject of addiction research since as early as 1985. Its history stretches much further back, however: ibogane has been used for hundreds of years (that we know of) for both spiritual and medicinal purposes.

Ibogaine has notably been used by the Bantu people of Gabon, who are thought to be the original practitioners of the Bwiti religion. As part of their religious practices, the Bantu participate in a ceremony known as the nlem myore or “one heart” ceremony. This event is used as a way for the community to come together in a state of spiritual bliss and is accompanied by music, dancing, and food. Participants may take ibogaine to enter deep states of trance where they may experience interaction with religious figures. The Nganga people also use iboga for medicinal and psychiatric purposes, such as treating depression, anxiety, and schizoid disorders.⁽⁵⁾

What are Opioids and How Do They Work?

Opioids are a broad class of pain-relieving drugs designed to interrupt the signal between the body’s nervous system and the brain. Essentially, these medications dampen the body’s ability to feel pain — a major benefit for people suffering from chronic illness or severe injuries. But the downside to these potentially life-changing drugs is that they are highly addictive and come with risky withdrawal symptoms when it’s time to cut down on dosage, or quit taking the medication entirely.^(6, 7)

There were more than 191 million opioid prescriptions handed out in 2020 alone. Given that number, and the intense withdrawal symptoms that could prevent people from leaving opioids behind when the time is right, researchers are motivated to find therapeutic options to help mitigate the side effects of opioid withdrawal and support individuals in their efforts to live healthier, drug-free lives.⁽⁸⁾

The People and Purpose Behind the Oral Ibogaine Study

The study Ibogaine to Determine Maximum Tolerated Dose (MTD) or Treat-to-Target Dose (TTD) for the Evaluation of Efficacy and Safety is Phase I of a clinical trial with a current estimated completion date of August 2023. 

Clinical trial sponsors DemeRx, Inc. partnered with several collaborators, including MAC Clinical Research, ERT: Clinical Trial Technology Solutions, and Hammersmith Medicines Research, to assess the safety and efficacy of a potential opioid withdrawal medication. The two-stage clinical trial aims to understand ibogaine’s impact on withdrawal symptoms, focusing expressly on patients seeking medically supervised detox.⁽⁹⁾

DemeRx was particularly well-suited for this study, as they’ve spent countless research hours exploring ibogaine’s ability to reduce the severity of drug cravings and manage withdrawal in a medical setting. This is a timely and important topic, as opioid use is at epidemic levels, and withdrawal following opioid dependency can actually be life-threatening.⁽¹⁰⁾

In an ideal world, withdrawal medications like ibogaine could be used as part of a comprehensive opioid detox program at medical facilities. DemeRx hopes to demonstrate that ibogaine treatment can:

Opioid Use Disorder and Withdrawal

Opioid use disorder (OUD) is defined as the chronic use of opioids resulting in distress or impairment. This is not a case of using prescription medication to find relief from cancer pain or a car accident injury, but rather misusing or overusing the medication to the point of dependency and/or addiction.⁽¹¹⁾

People living with opioid dependence may experience the following withdrawal symptoms when they stop taking the drug:

Suddenly ceasing the use of opioids without medical supervision can result in opioid withdrawal syndrome (OWS), a life-threatening condition. Supervised medical detox is critical for patients’ well-being and offers a source of support when withdrawal symptoms become unbearably uncomfortable.^(11, 12)

But what if there was an easier way for those struggling with opioid use disorder to essentially wean themselves off this highly addictive drug without experiencing the side effects of withdrawal that often lead to relapse?

Researching a New Approach to Medication-Assisted Withdrawal

This study was predicated on previously published data suggesting ibogaine is an effective therapeutic intervention for substance use disorders. That data indicated a correlation between ibogaine therapy and decreased withdrawal symptoms. The medication also showed a potentially positive impact on patients with depressive psychological symptoms. In other words, researchers think ibogaine treatment might work, and hopefully, it’ll work better than the existing options.⁽¹³⁾

Currently, treatment for opioid use disorder in the United States is limited to opioid replacement therapy using methadone or buprenorphine. Naltrexone is also used to prevent relapse. These drug abuse treatments have had some success, but they also come with problems. Patients often become reliant on the opioid substitute, and in some cases, as with methadone, the medication therapy isn’t a substitute at all but rather another type of opioid.⁽⁹⁾

Ibogaine To Treat Opioid Addiction Study Methodology 

The study was open to healthy volunteers between the ages of 18 and 55. The initial phase was an open-label study (where participants know which drug they’re taking) with 110 participants. After reviewing data from the original cohort, an additional six subjects were added, bringing the total number of participants to 116. 

In this randomized clinical trial, participants were randomly assigned to either the placebo or the drug being tested. In Phase I, patients were given an initial dose of the placebo on day one and a dose of ibogaine on day two. They were given a single ascending dose of ibogaine to evaluate their maximum tolerated dose (MTD) or their treat-to-target dose (TTD).

In Phase II, patients did not have control over whether they were taking the placebo or ibogaine. Participants in Phase I were healthy volunteers who engaged in recreational opioid use. Participants in Phase II were opioid-dependent patients seeking medically assisted detox. 

In addition to age parameters, the criteria for participants to be considered healthy and eligible for the Ibogaine study were as follows:

To be considered healthy volunteers for Ibogaine treatment, study participants had to be free of previous or current cardiovascular disease, including:

Participants in Phases I and II of the study were also subject to a mental health assessment. Candidates were disqualified if they had an immediate or a first or second-degree family history of:

Finally, study participants submitted to testing and questionnaires around the following parameters:

In Phase I of the study, healthy volunteers provided negative urine tests for use of the following drugs within seven days of dosing:

In Phase II of the study, opioid-dependent participants provided negative blood and urine tests for the following substances within seven days of dosing:

Framework: How the Ibogaine Study Was Built and Run

All participants underwent the described mandatory testing before the ibogaine study began. Data from baseline assessments were completed the day before the study began to assess heart rate variability in normal circumstances, and in response to physical changes/movements. Following the baseline evaluations, all subjects took the placebo on day one and a dose of ibogaine on day two. Treatment for participants in Phase I continued at one of four ascending ibogaine dose levels: three, six, nine, or 12 mg.⁽⁹⁾

In Phase II, opioid-dependent patients were randomized to receive ibogaine or a placebo as a single dose. The placebo was presented in an identical capsule as the ibogaine. From day two to six, patients completed a 10-item questionnaire to assess the severity of their opioid withdrawal symptoms. This questionnaire provided a Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) average score for each participant. Higher scores indicate more severe symptoms. 

Subjects also received scores based on the Visual Analog Scale for Efficacy (VAS-E) from day two to six and on day 30 to assess the severity of their cravings and Clinical Global Impression – Improvement (CGI-I) ratings on day two to six to compare the subject’s condition to their baseline numbers. 

On days six and 30, the Hamilton Depression Rating Scale (HAM-D) score was used to evaluate the level of depression participants experienced. 

Ibogaine to Treat Opioid Addiction Study Results

While no results are available yet (the trial is still in progress), this study represents one of the most exciting trials for new addiction treatments in decades. Assuming the clinical trial results align with those of past, more limited studies, it could mean that ibogaine treatment represents a real and potent option to aid in the fight against opioid and opiate abuse — possibly saving thousands, if not hundreds of thousands of lives. Preliminary results are expected to be published in August of 2023, with more comprehensive trial results anticipated in October of 2023. 

The potential is exciting for addiction specialists and laypeople with a vested interest in opioid use disorders and withdrawal issues. Continued research into the potential efficacy of psychedelics like Ibogaine and others such as psilocybin, MDMA, and LSD is vital if we are to find new treatments for some of the most debilitating mental health conditions currently affecting nearly 53 million Americans. However, this sort of research isn’t only important because of its potential to generate new medications. Psychedelic use has also been linked to increased mental wellness, creativity, and spirituality. Potentially helping Americans to not only have better mental health, but to also live overall happier, more fulfilling lives.⁽¹⁴⁾

Sources

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