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. A systematic review of the literature was conducted based on PRISMA guidelines. PubMed, Scielo, ClinicalTrials.gov and Core.ac.uk electronic databases were searched, and clinical studies published until November 17, 2022, were retrieved. The final synthesis included 12 sources. Information about general characteristics of the studies, adverse effects, screening of participants and setting characteristics were summarized and discussed. It is concluded that the use of controlled settings, supported by trained professionals and equipment allowing for rigorous medical, psychiatric, and cardiac monitoring, are essential to promote the safety of patients receiving ibogaine.
Objective: Whether for spiritual, recreational, or potential therapeutic use, interest in ayahuasca has grown remarkably. Ayahuasca’s main active substances are N,N‐dimethyltryptamine and certain ...monoamine oxidase inhibitor β-carbolines. Possible drug interactions are a major concern, and research is lacking in this area. The objective of this study was to evaluate the safety of ritual ayahuasca use regarding adverse effects and risk factors. Methods: In this cross-sectional study, ayahuasca users from a religious institution answered an online questionnaire about its safety. Adverse effects, safety measures, and possible risk factors (psychiatric diagnosis and medications) were investigated. Results: The most frequent adverse effects among the 614 participants were transient gastrointestinal effects (nausea and vomiting). Fifty participants self-reported a psychiatric diagnosis (depression and anxiety were the most prevalent), and these participants experienced adverse effects more frequently. Psychiatric medication use was reported by 31 participants. No indication of increased adverse effects due to drug-drug interactions was found. Conclusion: A minority of participants reported being very negatively affected by persistent adverse effects. Psychiatric medication use while participating in ayahuasca rituals was not associated with increased adverse effects. For the most part, the institution’s practices seem sufficient to prevent exacerbated reactions. Future studies may focus on negatively affected users.
To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. ...Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.
Background:
There is a growing interest in studying ibogaine (IBO) as a potential treatment for substance use disorders (SUDs). However, its clinical use has been hindered for mainly two reasons: ...First, the lack of randomized, controlled studies informing about its safety and efficacy. And second, IBO’s mechanisms of action remain obscure. It has been challenging to elucidate a predominant mechanism of action responsible for its anti-addictive effects.
Objective:
To describe the main targets of IBO and its main metabolite, noribogaine (NOR), in relation to their putative anti-addictive effects, reviewing the updated literature available.
Methods:
A comprehensive search involving MEDLINE and Google Scholar was undertaken, selecting papers published until July 2022. The inclusion criteria were both theoretical and experimental studies about the pharmacology of IBO. Additional publications were identified in the references of the initial papers.
Results:
IBO and its main metabolite, NOR, can modulate several targets associated with SUDs. Instead of identifying key targets, the action of IBO should be understood as a complex modulation of multiple receptor systems, leading to potential synergies. The elucidation of IBO’s pharmacology could be enhanced through the application of methodologies rooted in the polypharmacology paradigm. Such approaches possess the capability to describe multifaceted patterns within multi-target drugs.
Conclusion:
IBO displays complex effects through multiple targets. The information detailed here should guide future research on both mechanistic and therapeutic studies.
Introduction: Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not ...effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects.
Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included.
Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.
Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a ...serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.
Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem ...from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats.
We focused on the 5-HT
and 5-HT
receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis.
A single oral treatment with AYA containing 0.3 mg·kg
of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT
receptor antagonist MDL-11,939 and the 5-HT
receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA.
Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.
•Tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate emotional processing.•Recognition of emotions in facial expressions (REFE) may be altered by THC and CBD.•Studies found provide no firm ...conclusion to whether THC and CBD really alter the REFE.•The effects of THC are in opposite direction to those of CBD so far.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids being linked with modulation of anxiety and depression. The recognition of emotions in facial expressions (REFE) is impaired in these disorders. Both drugs could modulate anxiety and mood by interfering with REFE. Thus, a systematic review of controlled trials assessing the effects of THC and CBD on REFE was performed. Ten studies describing seven distinct experiments were found (n = 170). THC (7.5-15 mg) did not alter REFE in three experiments, but reduced task performance in other three experiments. CBD did not alter REFE in two experiments, but improved task performance and counteracted the effects of THC in one experiment. THC (≥ 10 mg) and CBD (600 mg) showed opposite effects on brain activation, skin conductance, and anxiety measures with negative/threatening faces. The limited number of studies precludes firm conclusions on the effects of these substances on REFE. Further controlled trials are needed to elucidate the effects of THC and CBD on REFE. The PROSPERO ID for this study is CRD42019135085.
•Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors.•5-HT2A receptors are expressed in fronto-temporo-parieto-occipital areas.•Some personality traits seem to be related to 5-HT2A ...receptor expression.•Acute and long-term use of psychedelics is associated with personality changes.•Personality changes induced by psychedelics may have therapeutic effects.
Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985–2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits. Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence. Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness, and Self-Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long-term religious ayahuasca users. Acute and long-term use of psychedelics is associated with personality changes that appear to be modulated by 5-HT2A receptors. These changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.
Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical ...5-HT
receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: "ayahuasca", "DMT", "psilocybin", "LSD", "mescaline" crossed one by one with the terms "mri", "fmri", "pet", "spect", "imaging" and "neuroimaging". Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT
receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.
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