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Ibogaine In The Treatment of Substance Dependence.
Abstract
Ibogaine is a psychoactive alkaloid derived from Tabernanthe iboga, a plant used in initiatory rituals in West Central Africa. Largely because of ibogaine's status as a Schedule I substance in the U.S., the development of ibogaine's use in the treatment of drug addiction took place outside conventional clinical and medical settings. This article reviews the history of ibogaine's use in the treatment of drug addiction, and discusses progress made towards, and obstacles blocking, the establishment of controlled clinical trials of ibogaine's efficacy. Preclinical research has generally supported anecdotal claims that ibogaine attenuates withdrawal symptoms and reduces drug cravings. Concerns about ibogaine's safety, as well as a dearth of solid data from human studies, have hampered progress in its development as an approved medication.This article outlines major findings from preclinical studies, discusses concerns about ibogaine's safety, and details previous and ongoing research on ibogaine's use as an anti-addictive treatment for humans.
... The maximum doses used of ibogaine in humans were between 20 and 30 mg/kg [101,102], while in preclinical studies it was 80 mg/kg [37,38,57]. For ketamine, the maximum dose used in humans was 2 mg/ kg [103][104][105][106][107][108][109], while in animals, it was 75 mg/kg [69]. In clinical studies, the routes of administration were primarily oral [104][105][106][107][108][109] and intramuscular in the case of ketamine, while for preclinical studies is intraperitoneal [103,110]. ...
... For ketamine, the maximum dose used in humans was 2 mg/ kg [103][104][105][106][107][108][109], while in animals, it was 75 mg/kg [69]. In clinical studies, the routes of administration were primarily oral [104][105][106][107][108][109] and intramuscular in the case of ketamine, while for preclinical studies is intraperitoneal [103,110]. These differences in routes are important as beyond inherent differences between species, the pharmacokinetics would change between routes. ...
... For example, studies exploring alcohol or tobacco abstainers revealed persistent effects of psilocybin-facilitated treatment that extended well beyond the acute drug action [135,136]. The findings indicated that greater mystical-type effects and more positive a high potential for abuse [107]. Ketamine, on the other hand, is more commonly recreationally used, and evidence has shown some dependence potential when it is used frequently [107,[144][145][146]. ...
The current opioid crisis has had an unprecedented public health impact. Approved medications for opioid use disorder (OUD) exist, yet their limitations indicate a need for innovative treatments. Limited preliminary clinical studies suggest specific psychedelics might aid OUD treatment, though most clinical evidence remains observational, with few controlled trials. This review aims to bridge the gap between preclinical findings and potential clinical applications, following PRISMA-ScR guidelines. Searches included MEDLINE, Embase, Scopus, and Web of Science, focusing on preclinical in vivo studies involving opioids and psychedelics in animals, excluding pain studies and those lacking control groups. Forty studies met criteria, covering both classic and non-classic psychedelics. Most studies showed that 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, and ketamine could reduce opioid self-administration, alleviate withdrawal symptoms, and change conditioned place preference. However, seven studies (two on 2,5-dimethoxy-4-methylamphetamine (DOM), three on ibogaine, one on 18-MC, and one on ketamine) showed no improvement over controls. A methodological quality assessment rated most of the studies as having unclear quality. Interestingly, most preclinical studies are limited to iboga derivatives, which were effective, but these agents may have higher cardiovascular risk than other psychedelics under-explored to date. This review strengthens support for translational studies testing psychedelics as potential innovative targets for OUD. It also suggests clinical studies need to include a broader range of agents beyond iboga derivatives but can also explore several ongoing questions in the field, such as the mechanism of action behind the potential therapeutic effect, safety profiles, doses, and frequency of administrations needed.
... Ibogaine is an indole alkaloid, isolated from the root of the Tabernanthe iboga plant, that has been used for centuries by the followers of the Bwiti religion in Central and Western Africa. As an integral part of their religious and initiation ceremonies, the Bwiti have reported its ability to abrogate thirst, hunger and fatigue as well as to induce a trancelike healing state [81]. As with LSD and psilocybin, ibogaine was experimented with throughout the 1960s in the U.S. and European psychedelic scene. ...
... Ibogaine, while an agonist for the 5HT2A receptors, is also an NMDA antagonist similar to ketamine. This action at the NMDA receptors may counteract the increase in the NMDA agonist quinolinic acid, helping to restore the glutamate imbalance and reset the HPA axis along with potentially leading to new synaptic formations and subsequent changes in learned behavior [81,98]. Moreover, ibogaine metabolizes in the body to noribogaine, an active metabolite that exhibits a strong affinity for mu opioid receptors. ...
Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote.
... Ibogaine is a naturally occurring indole alkaloid with complex neuropharmacology and strong oneirogenic ("waking dream generating") properties. Although most widely discussed as an aid to mitigating withdrawal and cravings from opioids and other drugs (1)(2)(3), ibogaine has recently garnered attention for its potential to alleviate symptoms associated with traumatic brain injury (4), neuropathic pain (5), and other neurodegenerative conditions. ...
Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by demyelination and neuronal loss. Traditional therapies often fail to halt disease progression or reverse neurological deficits. Ibogaine, a psychoactive alkaloid, has been proposed as a potential neuroregenerative agent due to its multifaceted pharmacological profile. We present two case studies of MS patients who underwent a novel ibogaine treatment, highlighting significant neuroimaging changes and clinical improvements. Patient A demonstrated substantial lesion shrinkage and decreased Apparent Diffusion Coefficient (ADC) values, suggesting remyelination and reduced inflammation. Both patients exhibited cortical and subcortical alterations, particularly in regions associated with pain and emotional processing. These findings suggest that ibogaine may promote neuroplasticity and modulate neurocircuitry involved in MS pathology.
... Ibogaine is a progressive treatment for substance dependence, traditionally used by the Bwiti tribe in Gabon, Africa as a sacrament. It has been adapted and used clinically in the treatment of substance use disorder (Brown, 2013 there is a phone upload every second Friday. If you miss the upload, you must wait another two weeks. ...
... Due to the concern about the safety of ibogaine and its toxicity, this drug was not approved by the Food and Drug Administration, and ibogaine use is illegal in several countries including the United States of America, Australia, Belgium, Denmark, France, Sweden, and Switzerland [4]. However, there are some countries with fewer legal restrictions where ibogaine is used for the treatment of opioid dependence in alternative Detoxification Centers or self-administered for recreational use [5]. We report a case of multiple episodes of cardiac arrest due to acquired long QT syndrome following the administration of ibogaine for opioid dependence. ...
Opioid dependence is a common problem, and therapeutic alternatives are scarce and ineffective. Ibogaine, illegal in several countries, has been reported as a possible therapy in alternative clinics and it is also used as a recreational drug, despite its cardiotoxic potential, including QT prolongation.
We report a case of long QT leading to multiple episodes of cardiac arrest after a single dose of ibogaine (200mg, 2.6mg/Kg) in a patient without structural heart disease. This case highlights the fact that even low doses of ibogaine can be lethal and warns us about the consequences of its use.
... Multiple open-label as well as randomized clinical trials are investigating psilocybin, ketamine, and MDMA-assisted treatment for patients who also have opioid dependence (124)(125)(126)(127)(128)(129)(130). Other psychedelic agents, such as LSD, ibogaine, kratom, and mescaline are also of interest as a potential therapeutic for OUD, for their role in reducing craving and substance use (104,(131)(132)(133)(134)(135)(136)(137)(138)(139)(140). ...
Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our increasing knowledge about the pathophysiology and existing medical treatments of OUD, it has remained a relapsing and remitting disorder for decades, with rising deaths from overdoses, rather than declining. The COVID-19 pandemic has accelerated the increase in overall substance use and interrupted access to treatment. If increased naloxone access, more buprenorphine prescribers, greater access to treatment, enhanced reimbursement, less stigma and various harm reduction strategies were effective for OUD, overdose deaths would not be at an all-time high. Different prevention and treatment approaches are needed to reverse the concerning trend in OUD. This article will review the recent trends and limitations on existing medications for OUD and briefly review novel approaches to treatment that have the potential to be more durable and effective than existing medications. The focus will be on promising interventional treatments, psychedelics, neuroimmune, neutraceutical, and electromagnetic therapies. At different phases of investigation and FDA approval, these novel approaches have the potential to not just reduce overdoses and deaths, but attenuate OUD, as well as address existing comorbid disorders.
Substance use disorders remain one of the most challenging health problems to address. Specifically, opioid dependence has caused serious public health issues in countries such as the United States and Canada over the last decade, underscoring the need for innovative and effective treatments.
Recently, mental health researchers have shown a renewed interest in psychedelic drugs. Substances such as lysergic acid diethylamide (LSD), psilocybin mushrooms, and ayahuasca have shown promising results in treating conditions including major depression and anxiety disorders. Among these, ibogaine, an alkaloid found naturally in the West African plant Tabernanthe iboga, appears particularly effective in treating substance use disorders. However, despite its widespread underground and unsupervised use, controlled trials evaluating the safety and efficacy of ibogaine are lacking, and its mechanisms of action remain largely unknown.
In this thesis, we conducted both clinical and preclinical studies on ibogaine to provide more evidence about this molecule and to expand our understanding of it. Clinically, we performed a systematic review of adverse events in humans associated with ibogaine to collect updated safety data. Subsequently, we designed a Phase II, randomized, double-blind clinical trial. In this trial, low, single doses of ibogaine (100 mg) were administered in the context of methadone detoxification. Plasma samples from the trial were analyzed using a metabolomic approach. The systematic review and clinical trial data were complemented with a narrative review, which identified all potential ibogaine targets associated with its anti-addictive effect and provided updated mechanistic literature. Preclinically, we designed a study with mice to elucidate further mechanisms of action. Following acute administration of ibogaine, brain tissue was analyzed using transcriptomic analysis to determine the expression levels of a wide array of genes.
The clinical results were highly promising. The systematic review highlighted the need for medical supervision during ibogaine treatments due to its potential to prolong the QT interval and its complex metabolism. In the clinical trial, which included 20 patients, we observed a significant decrease in both tolerance to methadone and opioid withdrawal syndrome (OWS). As a result, 17 out of 20 patients were able to halve their methadone dose over seven days without experiencing OWS symptoms and discontinue their daily methadone use for an average of 18.03 hours. No serious adverse events were reported. Results from the metabolomic analysis suggest that ibogaine can potentially reverse the effects of chronic opioid use on energy metabolism. These findings align with the multi-target profile of ibogaine identified in the narrative review. The preclinical study revealed new potential pathways associated with ibogaine's anti-addictive effects. Specifically, genes related to hormonal pathways and synaptogenesis showed increased expression after acute ibogaine administration. Additionally, gender differences were observed, with females exhibiting changes in 28 genes compared to eight in males.
This thesis provides the first evidence of ibogaine's safety and efficacy in a Phase II study and delves deeper into its mechanisms of action through a review, a preclinical study, and an analysis of human plasma samples using innovative techniques. We conclude that ibogaine represents a promising candidate for the treatment of opioid use disorders, warranting further research.
Integrative Addiction and Recovery is a book discussing the epidemic of addiction that is consuming our friends, family, and community nationwide. In 2016, there were 64,000 drug overdoses, and addiction became the top cause of accidental death in America in 2015. We are in a crisis and in need of a robust and integrated solution. We begin with the definition of addiction, neurobiology of addiction, and the epidemiology of varying substances of abuse and treatment guidelines. Section II reviews different types of addiction such as food, alcohol, sedative-hypnotics, cannabis, stimulants (such as cocaine and methamphetamine), opiates (including prescription and illicit opiates), and tobacco, and evidence-based approaches for their treatment using psychotherapy, pharmacotherapy, as well as holistic treatments including acupuncture, nutraceuticals, exercise, yoga, and meditation. We also have chapters on behavioral addictions and hallucinogens. Section III reviews co-occurring disorders and their evidence-based integrative treatment and also overviews the holistic therapeutic techniques such as acupuncture and TCM, Ayurveda, homeopathy, nutrition, nutraceuticals, art and aroma therapy, and equine therapy as tools for recovery. We have unique chapters on shamanism and ibogaine, as well as spirituality and group support (12 steps included). The final section deals with challenges facing recovery such as trauma, acute/chronic pain, and post acute withdrawal. Integrative Addiction and Recovery is an innovative and progressive textbook, navigating this complex disease with the most comprehensive approach.
Ibogaine, the principle psychoactive alkaloid from the plant Tabernanthe Iboga, native to West African rainforest and sacramentally ingested in local syncretic ritual-religious practice is increasingly being sought and used for the treatment of substance dependence-predominantly in underground or poorly regulated treatment settings due to its legally outlawed status in much of the Global North (although this is slowly changing with some high income countries starting to legislate for its medical use). While research corroborates a direct empirical effect on craving and withdrawal states, many addicts attest to the importance of ibogaine-induced visionary-experience on subsequent recovery. While not a classical hallucinogen-psychedelic such claims link to the wider revival of the first-wave of hallucinogen-psychedelic research, including for the treatment of substance misuse, from the 1960s and early 70s before the prohibition of research indefinitely forestalled their use in the wake of both clinical safety and wider sociocultural concerns-until the so called "psychedelic renaissance" of the last decade; despite prior promise of therapeutic efficacy. As such this revival also represents the resurrection of ontological, epistemological and therapeutic dilemmas around the use of such agents that must be addressed in order to ensure robust research validity and the maximisation of safety and efficacy in both clinical and ritual contexts (recognising the convergence of the clinical and ritual-spiritual for this unique class of psychoactive-agents). This extended essay seeks to explore these dimensions, through interdisciplinary review and reflective commentary providing some tentative resolutions of the tensions and dilemmas involved and suggested directions for further research.
Research proposal to MAPS (www.maps.org) Principal Investiigator V. Mojeiko, MAPS, Protocol Number: I-OA3
Introduction Ibogaine is a naturally occurring psychoactive indole alkaloid derived from the roots of the rainforest shrub Tabernanthe iboga.Ibogaine is used by indigenous peoples of Western Africa in low doses to combat fatigue, hunger, and thirst, and in higher doses as a sacrament in religious rituals (Goutarel et al., 1991). The use of ibogaine for the treatment of drug dependence was based on anecdotal reports by groups of self-treating addicts that the drug blocked opiate withdrawal and reduced craving for opiates, cocaine, and other illicit drugs for extended time periods (Shepard, 1994; Alper et al., 1999). Preclinical studies supported these early claims and provided proof-of-concept in animal models (Dzoljic et al., 1988; Glick et al., 1992). Addiction is a behavioral pattern of drug abuse characterized by compulsive use, loss of behavioral control, and a high tendency to relapse. An integrated medical, psychosocial, and spiritual treatment is often needed to achieve recovery in addicted patients. Ibogaine is a unique pharmacotherapy for the treatment of substance abuse disorders because it fosters a life change or may work as a transition-based therapy similar to the goals set in the 12-step fellowship programs. While ibogaine's effects on behavior are complex, the beneficial actions of the drug on withdrawal symptoms and cravings are because of an interaction of the active metabolite noribogaine with neurotransmitters in the brain reward and addiction circuit.
A number of medication trials at major U.S. research universities are now, once more, legally exploring psychedelics' vast potential for treating various physical and psychological problems. These studies have been approved based on a medical model that considers psychedelics' effects as primarily biochemical, but some are also addressing wider humanistic and transpersonal implications for research and praxis. These studies may challenge the prevailing medical model of psychopathology that not only reduces humans to just their biology but also has led to widespread medical treatments through formularies that predominantly constrict, rather than enhance, human potential. Psychedelics offer great potential as tools for researching elusive areas within humanistic and transpersonal psychology, as well as powerful ways to facilitate humanistic and transpersonal growth.
In the 20th century, while billions of dollars have been spent to treat addictive diseases, the search for effective medication continues. The mainstay of such treatments includes therapy and counseling, AA and NA, different kinds of rehabilitation programs, drug maintenance programs, and pharmacotherapy. The ef-ficacy of all these suggested methods of addiction treat-ment is not enough, however, and still there is a need for new effective medications. The use of hallucino-gens in the treatment of addictions could be one prom-ising approach (Halpern, 1996). Many addiction studies in the 1950's and 1960's (Grinspoon and Bakalar, 1979), suggested that hallu-cinogen-assisted (psychedelic) psychotherapy might be an efficient treatment, but different methodologies made it difficult to generalize across studies. In the 1970's Savage and McCabe (1973) showed that LSD-assisted psychotherapy had a positive effect on the outcome of treatment of heroin addicts: 25% of the subjects treated with LSD remained abstinent from opiates for one year as opposed to only 5% of the con-trol group of conventional weekly group psycho-therapy. these substances had essentially come to an end in America because of controversy associated with their non-medical use (Halpern, 1996). Later in the 1980's and 1990's both animal studies and anecdotal human reports suggested anti-craving properties of another hallucinogen--ibogaine ("Endabuse") (Lotsof, 1995; Mash, 1998). However, further human research with ibogaine is needed to dem-onstrate its antiaddictive properties as well as safety. Ketamine is a drug for general anesthesia, but in subanesthetic doses it induces a profound psychedelic (hallucinogenic) experience (Bowdle et al., 1998). Ketamine has several advantages over other halluci-nogens as an adjunct to psychotherapy in the treat-ment of addictions: it is safe, short-acting, and, most importantly, it is not a scheduled drug like other hallu-cinogens. Our previous studies showed that ketamine-assisted psychotherapy is an effective method for al-coholism treatment (Krupitsky and Grinenko, 1997). Also, ketamine could have anti-craving properties because of its influence on the NMDA receptor, simi-lar to other NMDA receptor ligands-acamprosate and ibogaine (Mash et al., 1998; Sass et al., 1996). All these factors led us to study the efficacy of ketamine-assisted psychotherapy for heroin dependence.
Ibogaine is a naturally occurring psychoactive indole alkaloid that is used to treat substance-related disorders in a global medical subculture, and is of interest as an ethnopharmacological prototype for experimental investigation and possible rational pharmaceutical development. The subculture is also significant for risks due to the lack of clinical and pharmaceutical standards. This study describes the ibogaine medical subculture and presents quantitative data regarding treatment and the purpose for which individuals have taken ibogaine.
All identified ibogaine "scenes" (defined as a provider in an associated setting) apart from the Bwiti religion in Africa were studied with intensive interviewing, review of the grey literature including the Internet, and the systematic collection of quantitative data.
Analysis of ethnographic data yielded a typology of ibogaine scenes, "medical model", "lay provider/treatment guide", "activist/self-help", and "religious/spiritual". An estimated 3414 individuals had taken ibogaine as of February 2006, a fourfold increase relative to 5 years earlier, with 68% of the total having taken it for the treatment of a substance-related disorder, and 53% specifically for opioid withdrawal.
Opioid withdrawal is the most common reason for which individuals took ibogaine. The focus on opioid withdrawal in the ibogaine subculture distinguishes ibogaine from other agents commonly termed "psychedelics", and is consistent with experimental research and case series evidence indicating a significant pharmacologically mediated effect of ibogaine in opioid withdrawal.