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Iboga / Ibogaine

DARK Classics in Chemical Neuroscience: Ibogaine.

October 9, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga’s psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine’s anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the “psychedelic-assisted therapy” approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine (“ecstasy”).
Wasko, M. J., Witt-Enderby, P. A., & Surratt, C. K. (2018). DARK Classics in Chemical Neuroscience: Ibogaine. ACS chemical neuroscience, 9(10), 2475-2483., 10.1021/acschemneuro.8b00294
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Dimensions of consciousness and the psychedelic state

September 19, 2018 / Anthropology & Sociology, Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

It has often been suggested in the popular and academic literature that the psychedelic state qualifies as a higher state of consciousness relative to the state of normal waking awareness. This article subjects this proposal to critical scrutiny, focusing on the question of what it would mean for a state of consciousness to be ‘higher’. We begin by considering the contrast between conscious contents and conscious global states. We then review the changes in conscious global state associated with psychedelic drug use, focusing on the effects of two serotonergic hallucinogens: psilocybin and lysergic acid diethylamide. Limiting our review to findings obtained from lab-based experiments and reported in peer-reviewed journals, we prioritize the more common and reliably induced effects obtained through subjective questionnaires and psychophysical measures. The findings are grouped into three broad categories (sensory perception, cognitive function, and experiences of unity) and demonstrate that although certain aspects of consciousness are improved or enhanced in the psychedelic state, many of the functional capacities that are associated with consciousness are seriously compromised. Psychedelic-induced states of consciousness are indeed remarkable in many ways, but it is inappropriate to regard them as ‘higher’ states of consciousness. The fact that psychedelics affect different aspects of consciousness in fundamentally different ways provides evidence against the unidimensional (or ‘level-based’) view of consciousness, and instead provides strong support for a multidimensional conception of conscious states. The final section of the article considers the implications of this analysis for two prominent theories of consciousness: the Global Workspace Theory and Integrated Information Theory.

Bayne, T., & Carter, O. (2018). Dimensions of consciousness and the psychedelic state. Neuroscience of consciousness, 2018(1), niy008., 10.1093/nc/niy008
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A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification

July 18, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

We examined persisting effects, self-perceived challenges, and potential benefits associated with positive outcomes following ibogaine detoxification using data collected as part of a larger online retrospective study of 73 patients who received treatment for chronic opioid use in Mexico between 2012 and 2015. A mixed-methods design was used comparing treatment responders versus non-responders, as well as content coding of themes from open-ended questions. Most participants reported positive persisting effects of ibogaine detoxification (e.g., enhanced personal sense of gratitude and authenticity, and meaning and appreciation for life). Compared to non-responders, treatment responders endorsed greater persisting changes in their ability to tolerate difficult/painful feelings, capacity for coping with stress, and reduced unhealthy anger. Treatment responders reported greater change in subjective levels of inner peace, joy, feelings of love/openheartedness, and experiences of sacredness in life. Qualitative analyses revealed that treatment responders reported a heightened sense of spiritual awareness and greater connection to their intra-/interpersonal relationships after ibogaine detoxification. Notable challenges of ibogaine detoxification included psychological and health-related difficulties during treatment and challenges with post-treatment integration. Findings highlight the persisting effects associated with positive response to ibogaine detoxification and possible post-treatment needs (i.e., more integration/aftercare resources). Future research using rigorous experimental designs is needed.

Davis, A. K., Renn, E., Windham-Herman, A. M., Polanco, M., & Barsuglia, J. P. (2018). A mixed-method analysis of persisting effects associated with positive outcomes following ibogaine detoxification. Journal of psychoactive drugs, 50(4), 287-297., 10.1080/02791072.2018.1487607.
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Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development.

July 5, 2018 / Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Mental disorders are rising while development of novel psychiatric medications is declining. This stall in innovation has also been linked with intense debates on the current diagnostics and explanations for mental disorders, together constituting a paradigmatic crisis. A radical innovation is psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs. Clinical results so far have shown safety and efficacy, even for “treatment resistant” conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness.

Schenberg, E. E. S. (2018). Psychedelic-assisted psychotherapy: a paradigm shift in psychiatric research and development. Frontiers in pharmacology, 9, 733., 10.3389/fphar.2018.00733
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Cardiac arrest after ibogaine intoxication

June 12, 2018 / Iboga / Ibogaine, Papers, Psychiatry & Medicine, Publications / By / ,

Abstract

Ibogaine is a psychoactive herbal medication with alleged antiaddiction properties. We report a case of ibogaine intoxication mimicking Long-QT syndrome resulting in ventricular flutter and nearby cardiac arrest. A 61-year-old man experienced massive QT prolongation and ventricular flutter at a rate of 270 beats per minute requiring defibrillation after ingestion of a large dose of Ibogaine. The ingested dose of 65-70 mg/kg represents the highest survived ibogaine dose reported to date. As a result of the long plasma half-life of ibogaine, it took 7 days for the patient’s QT interval to normalize.

Steinberg, C., & Deyell, M. W. (2018). Cardiac arrest after ibogaine intoxication. Journal of arrhythmia, 34(4), 455-457.,  10.1002/joa3.12061

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Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

June 5, 2018 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191) of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs) were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid withdrawal during medically supervised detoxification to transition drug dependent individuals to abstinence.
Mash, D. C., Duque, L., Page, B., & Allen-Ferdinand, K. (2018). Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology, 9. 10.3389/fphar.2018.00529
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Ibogaine Acute Administration in Rats Promotes Wakefulness, Long-Lasting REM Sleep Suppression, and a Distinctive Motor Profile

April 27, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Ibogaine is a potent psychedelic alkaloid that has been the focus of intense research because of its intriguing anti-addictive properties. According to anecdotic reports, ibogaine has been originally classified as an oneirogenic psychedelic; i.e., induces a dream-like cognitive activity while awake. However, the effects of ibogaine administration on wakefulness (W) and sleep have not been thoroughly assessed. The main aim of our study was to characterize the acute effects of ibogaine administration on W and sleep. For this purpose, polysomnographic recordings on chronically prepared rats were performed in the light phase during 6 h. Animals were treated with ibogaine (20 and 40 mg/kg) or vehicle, immediately before the beginning of the recordings. Furthermore, in order to evaluate associated motor behaviors during the W period, a different group of animals was tested for 2 h after ibogaine treatment on an open field with video-tracking software. Compared to control, animals treated with ibogaine showed an increase in time spent in W. This effect was accompanied by a decrease in slow wave sleep (SWS) and rapid-eye movements (REM) sleep time. REM sleep latency was significantly increased in animals treated with the higher ibogaine dose. While the effects on W and SWS were observed during the first 2 h of recordings, the decrement in REM sleep time was observed throughout the recording time. Accordingly, ibogaine treatment with the lower dose promoted an increase on locomotion, while tremor and flat body posture were observed only with the higher dose in a time-dependent manner. In contrast, head shake response, a behavior which has been associated in rats with the 5HT2A receptor activation by hallucinogens, was not modified. We conclude that ibogaine promotes a waking state that is accompanied by a robust and long-lasting REM sleep suppression. In addition, it produces a dose-dependent unusual motor profile along with other serotonin-related behaviors. Since ibogaine is metabolized to produce noribogaine, further experiments are needed to elucidate if the metabolite and/or the parent drug produced these effects.
González, J., Prieto, J. P., Rodríguez, P., Cavelli, M., Benedetto, L., Mondino, A., … & Torterolo, P. (2018). Ibogaine Acute Administration in Rats Promotes Wakefulness, Long-Lasting REM Sleep Suppression, and a Distinctive Motor Profile. Frontiers in pharmacology, 9. 10.3389/fphar.2018.00374
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Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

April 2, 2018 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.
Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of psychoactive drugs, 1-10. 10.1080/02791072.2018.1447175
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The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes

February 11, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.
Oreščanin-Dušić, Z., Tatalović, N., Vidonja-Uzelac, T., Nestorov, J., Nikolić-Kokić, A., Mijušković, A., … & Blagojević, D. (2018). The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. Oxidative medicine and cellular longevity, 2018. 10.1155/2018/5969486
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Breaking the cycle of opioid use disorder with Ibogaine

December 7, 2017 / Iboga / Ibogaine, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Ibogaine is an indole alkaloid that comes from the root of the West African shrub Tabernanthe iboga. Ibogaine has been used for centuries in spiritual celebrations, coming of age rituals, and healings among the Babongo and Mitsogo people of West Central Africa. In Africa today, approximately 2–3 million members of the Bwiti religion scattered in groups throughout the countries of the Gabon, Zaire, and the Cameroun take large doses for the “Bwiti initiation ritual”—a powerful “rebirth” ceremony that group members typically undergo before the commencement of their teenage years.
The discovery that ibogaine eliminates the signs and symptoms of opioid withdrawal and diminishes craving for opioids was first made in the 1960s by a group of self-treating individuals with heroin use disorder; a single oral dose administration of ibogaine was associated with a disruption of five addicted individual’s use of opiates for up to 6 months . An underground railroad of individuals in recovery helping others with addictions arose, using ibogaine to help people break their cycle of addiction to heroin, cocaine, and alcohol. Ibogaine is thought to enable individuals with opioid use disorder to transition to abstinence and establish a substance-free recovery through an ibogaine-induced experience that has personal meaning and/or other benefits. Ibogaine’s long-lasting metabolite noribogaine may reset brain circuits to block the intractable cravings and desire to use opioids that set the addiction relapse cycle into motion.
C. Mash, D. (2017). Breaking the cycle of opioid use disorder with Ibogaine. The American Journal of Drug and Alcohol Abuse, 1-3. 10.1080/00952990.2017.1357184
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