Ibogaine

The United States is entering its fourth decade of the opioid epidemic with no clear end in sight. At the center of the epidemic is an increase in opioid use disorder (OUD), a complex condition encompassing physical addiction, psychological comorbidities, and socioeconomic and legal travails associated with the misuse and abuse of opioids. Existing behavioral and medication-assisted therapies show limited efficacy as they are hampered by lack of access, strict regimens, and failure to fully address the non-pharmacological aspects of the disease...

There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a "classic" serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin's potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted...

Natural psychedelic compounds are emerging as potential novel therapeutics in psychiatry. This review will discuss how natural psychedelics exert their neurobiological therapeutic effects, and how different neurotransmission systems mediate the effects of these compounds. Further, current therapeutic strategies for depression, and novel mechanism of action of natural psychedelics in the treatment of depression will be discussed. In this review, our focus will be on N, N-dimethyltryptamine (DMT), reversible type A monoamine oxidase inhibitors, mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, ibogaine, muscimol extracted from Amanita spp...

BACKGROUND: Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance...

Tabernaemontana arborea (Apocynaceae) is a Mexican tree species known to contain ibogan type alkaloids. This study was aimed to determine central nervous system-related activities of an alkaloid extract obtained from the root bark of T. arborea. A gas chromatography-mass spectrometry (GC-MS) analysis was performed to describe the alkaloid profile of extract. A wide dosing range (0.1 to 56.2 mg/kg) of this extract was evaluated in different murine models. Electrical brain activity was examined by electroencephalography (EEG)...

BACKGROUND: The potential use of psychedelic drugs as therapeutics for neuropsychiatric disorders has been limited by their hallucinogenic properties. To overcome this limitation, we developed and characterized tabernanthalog (TBG), a novel analogue of the indole alkaloids ibogaine and 5-methoxy- N,N -dimethyltryptamine with reduced cardiac arrhythmogenic risk and a lack of classical psychedelic drugs-induced sensory alterations. We previously demonstrated that TBG has therapeutic efficacy in a preclinical model of opioid use disorder (OUD) in rats and in a binge model of alcohol drinking in mice...

The iboga alkaloids scaffold shows great potential as a pharmacophore in drug candidates for the treatment of neuropsychiatric disorders. Thus, the study of the reactivity of this type of motif is particularly useful for the generation of new analogs suitable for medicinal chemistry goals. In this article, we analyzed the oxidation pattern of ibogaine and voacangine using dioxygen, peroxo compounds, and iodine as oxidizing agents. Special focus was placed on the study of the regio- and stereochemistry of the oxidation processes according to the oxidative agent and starting material...

The opioid epidemic and limited access to treatment for opioid withdrawal (OW) and opioid use disorder (OUD) has led individuals to seek alternative treatments. This narrative review aims to educate clinicians on the mechanisms of action, toxicity, and applications of psychoactive plant-based substances patients may be using to self-treat OUD and OW. We specifically discuss ayahuasca, ibogaine, and kratom as they have the most evidence for applications in OUD and OW from the last decade (2012-2022). Evidence suggests these substances may have efficacy in treating OW and OUD through several therapeutic mechanisms including their unique pharmacodynamic effects, rituals performed around ingestion, and increased neuroplasticity...

The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects, and stabilizes the inward-open conformation. Unfortunately, ibogaine's promiscuity and cardiotoxicity limit the understanding of inward-open state ligands. We docked over 200 million small molecules against the inward-open state of the SERT...

Serotonin transporter (SERT) plays a fundamental role in taking the synaptic cleft serotonin back to the presynaptic neuron. The discovery of allosteric SERT modulators represents the next-generation medication for psychiatric disorders such as depression. Here, based on the cryo-EM structures of ibogaine in complex with SERT in distinct conformations, the multiple functional structures of the transporter bound to serotonin, including outward-open (OOholo ), outward-occluded (OCholo ), and inward-open (IOholo and IOholo '), were carefully characterized by induced-fit docking Gaussian-accelerated molecular dynamics (IFD-GaMD) simulation and the free-energy landscape analysis...

In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects...

[This corrects the article DOI: 10.3389/fphar.2022.927984.].

Ibogaine is a psychoactive alkaloid derived from the west-African shrub Tabernanthe iboga. Western cultures are increasing the interest for the substance due to its claimed anti addictive properties, although the evidence supporting this effect is still preliminary. The use of ibogaine often occurs with no medical supervision in uncontrolled settings, and its use has been associated with several reports of severe adverse events. This review aims to evaluate the clinical studies of ibogaine, with a focus on administration settings, to elucidate specific criteria that may promote safer contexts for ibogaine use...

Renewed interest in psychedelic substances in the 21st century has seen the exploration of psychedelic treatments for various psychiatric disorders including substance use disorder (SUD). This review aimed to assess the effectiveness of psychedelic treatments for people with SUD and those falling below diagnostic thresholds (i.e. substance misuse). We systematically searched 11 databases, trial registries, and psychedelic organization websites for empirical studies examining adults undergoing psychedelic treatment for SUD or substance misuse, published in the English language, between 2000 and 2021...

Ibogaine is a powerful psychoactive substance that not only alters perception, mood and affect, but also stops addictive behaviors. Ibogaine has a very long history of ethnobotanical use in low doses to combat fatigue, hunger and thirst and, in high doses as a sacrament in African ritual contexts. In the 1960's, American and European self-help groups provided public testimonials that a single dose of ibogaine alleviated drug craving, opioid withdrawal symptoms, and prevented relapse for weeks, months and sometimes years...

The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive...

The serotonin transporter (SERT/SLC6A4) is arguably the most extensively studied solute carrier (SLC). During its eponymous action - that is, the retrieval of serotonin from the extracellular space - SERT undergoes a conformational cycle. Typical inhibitors (antidepressant drugs and cocaine), partial and full substrates (amphetamines and their derivatives), and atypical inhibitors (ibogaine analogues) bind preferentially to different states in this cycle. This results in competitive or non-competitive transport inhibition...

BACKGROUND: Past research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers...

IMPORTANCE: Psychedelic drugs are becoming accessible in the US through a patchwork of state legislative reforms. This shift necessitates consensus on treatment models, education and guidance for health care professionals, and planning for implementation and regulation. OBJECTIVE: To assess trends in psychedelics legislative reform and legalization in the US to provide guidance to health care professionals, policy makers, and the public. EVIDENCE REVIEW: Data were compiled from legislative databases (BillTrack50, LexisNexis, and Ballotpedia) from January 1, 2019, to September 28, 2022...

INTRODUCTION: Ibogaine is one of the alkaloids naturally found in plants such as Tabernanthe iboga, which has been traditionally used by members of the Bwiti culture. Since the discovery of its anti-addictive properties by Howard S. Lotsof in 1962, ibogaine has been used experimentally to treat substance use disorders (SUD), especially those involving opioids. We aim to provide a detailed understanding of the underlying psychological aspects of underground ibogaine use for the treatment of SUD...