Ibogaine Research Database

Identification and quantitation of ibogaine and an o-demethylated metabolite in brain and biological fluids using gas chromatography-mass spectrometry.

This report describes a sensitive method for quantitating ibogaine and a single major metabolite in biological fluids and brain tissue. We identified the metabolite as 12-hydroxy-ibogamine (12-OH-ibogamine or noribogaine) by full-scan, electron-impact gas chromatography-mass spec...

Determination of ibogaine and 12-hydroxy-ibogamine in plasma by gas chromatography-positive ion chemical ionization-mass spectrometry.

Ibogaine, an indolamine derivative, is currently being investigated as a potential agent in the treatment of stimulant and opiate addiction. We developed a rapid, sensitive, and specific method for the analysis of ibogaine and its putative active metabolite, 12-hydroxy-ibogamine ...

Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity.

Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma 2 sites (Ki = 201 nM) and low affinity for sigma 1 sites (Ki = 8554 nM), thus showing 43-fold selectivity for sigma 2 receptors. Tabernanthine (13-methoxyibogamine) and (+/-)-ibogamine had sigma 2 Ki = 194 nM an...

Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin.

Ibogaine is a hallucinogenic indole with putative efficacy for the treatment of cocaine, stimulant and opiate abuse. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part ho...

NMDA antagonist properties of the putative antiaddictive drug, ibogaine.

Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrat...

Ibogaine possesses a selective affinity for sigma 2 receptors.

The alkaloid ibogaine is potentially useful to reduce craving for several drugs of abuse, but its mechanism of action is not known. In the current study, in vitro studies were conducted in order to determine the affinity of ibogaine for sigma receptors. Our results indicate that ...

Effects of ibogaine on responding maintained by food, cocaine and heroin reinforcement in rats.

The effects of ibogaine (40 and 80 mg/kg, i.p.), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, i.p.) given 60 min befor...

Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats.

Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with ...

High affinity ibogaine binding to a mu opioid agonist site.

The naturally occurring indole alkaloid ibogaine is of interest because of its reported ability to block drug seeking behavior for extended periods. The compound also potentiates morphine-induced analgesia in mice and reduces certain naltrexone-precipitated withdrawal signs in mo...

100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug.

Indole alkaloids from Peschiera laeta that enhance vinblastine-mediated cytotoxicity with multidrug-resistant cells.

Coronaridine [1], conoduramine [2], and voacamine [3], three indole alkaloids isolated from Peschiera laeta, have been found to enhance the cytotoxic response mediated by vinblastine [4] with multidrug-resistant KB cells. Inhibition of vinblastine binding with membrane vesicles i...

The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex.

Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (Ki, 1.01 +/- 0.1 microM) of [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptor coupled cation c...

The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine.

Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by bot...

Effect of ibogaine on serotonergic and dopaminergic interactions in striatum from mice and rats.

The effect of ibogaine (Endabuse, NIH 10567) on serotonin uptake and release, and on serotonergic modulation of dopamine release, was measured in striatal tissue from rats and mice. Two hours after treatment in vivo with ibogaine (40 mg/kg i.p.) the uptake of labeled [3H]serotoni...

A preliminary investigation of ibogaine: case reports and recommendations for further study.

A naturally occurring substance, ibogaine, was taken by seven individuals who were addicted to opiates. Ibogaine, an alkaloid with psychotropic effects at doses of 200-300 mg and above, was taken in single doses of 700-1800 mg by the subjects in the study. At the end of the 24-38...

Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum.

We measured the effect of ibogaine on the tritium efflux from isolated mouse striatum preloaded with [3H]dopamine ([3H]DA). Ibogaine increased the basal tritium outflow in a concentration-dependent manner, but it was without effect on electrical stimulation-induced tritium overfl...

Ibogaine reduces preference for cocaine consumption in C57BL/6By mice.

After a period of forced exposure to 300 mg/l cocaine HCl in drinking water for a period of one week, followed by forced exposure to 200 mg/l cocaine for an additional week, male C57BL/6By mice developed a preference for cocaine when given a choice of drinking either water or a s...

Ibogaine modulates cocaine responses which are altered due to environmental habituation: in vivo microvoltammetric and behavioral studies.

Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine ...

Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self-administration in rats. The present study sought to determine if other iboga alkaloids, as we...

Cocaine discrimination is attenuated by isradipine and CGS 10746B.

The discriminative stimulus properties of cocaine are thought to be mediated by dopaminergic mechanisms that may be modulated by calcium ion influx and/or interact with 5-hydroxytryptamine3 (5-HT3) receptors. To test these possibilities, rats were trained to discriminate between ...

Comparison of the behavioral effects of ibogaine from three sources: mediation of discriminative activity.

Ibogaine is an alkaloid employed for its hallucinatory properties in West Central Africa which has been the subject of alleged efficacy as an aid in the interruption and treatment of chemical dependency. The major sources of the Schedule I agent are: Sigma Chemical Co., the Natio...

Ibogaine induces glial activation in parasagittal zones of the cerebellum.

Ibogaine, an indole alkaloid, has been proposed for treatment of drug addiction, yet its mechanism, site of action, and possible neurotoxicity have not been determined. Since neuronal injury is known to activate neurologlial cells, we investigated potential neurotoxic effects of ...

Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interactions with D-amphetamine.

Systemic administration of ibogaine (40 mg/kg, i.p.) has been reported to induce both acute (1-3 h) and persistent (19-20 h) changes in extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum. In the present study, local administration of ibogai...

Inhibitory effects of ibogaine on cocaine self-administration in rats.

In order to determine the potential anti-addictive properties of ibogaine, we used the cocaine self-administration model in rats. The results indicate that a single injection of ibogaine (40 mg/kg i.p.) produced a significant decrease of cocaine intake, which remained unaltered f...

Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline.

The indole alkaloids ibogaine and harmaline are beta-carboline derivatives that cause both hallucinations and tremor. Reports that ibogaine may have potent anti-addictive properties have led to initiatives that it be tested for the treatment of opiate and cocaine addiction. In th...

Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior.

To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of an ibogaine (40 mg/kg i.p.) pretreatment on in vivo neurochemical and motor effects induced by cocaine (20 mg/kg i.p.) were studied. Ibogaine, administered 19 h earlier, potentiat...

Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats.

Ibogaine, an indolalkylamine, proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic system acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopamine (D...

Interactions of ibogaine and D-amphetamine: in vivo microdialysis and motor behavior in rats.

Ibogaine, an indolalkylamine, has been proposed for use in treating stimulant addiction. In the present study we sought to determine if ibogaine had any effects on the neurochemical and motor changes induced by D-amphetamine that would substantiate the anti-addictive claim. Iboga...

Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice.

In naive mice, ibogaine at a tremorigenic dose (30 mg/kg, ip), did not produce antinociception but did potentiate the antinociceptive potency of morphine in the tail-flick test. In morphine-dependent mice, ibogaine did not eliminate withdrawal symptoms but significantly increased...

Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies.

Assays using radioligands were used to assess the actions of ibogaine and harmaline on various receptor types. Ibogaine congeners showed affinity for opiate receptors whereas harmaline and harmine did not. The Ki for coronaridine was 2.0 microM at mu-opiate receptors. The Kis for...

Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor.

Because of the claim that ibogaine suppresses the symptoms of "narcotic withdrawal" in humans, the effect of ibogaine on naltrexone-precipitated withdrawal signs in morphine-dependent rats was assessed. Morphine was administered subcutaneously through implanted silicone reservoir...

Ibogaine reduces amphetamine-induced locomotor stimulation in C57BL/6By mice, but stimulates locomotor activity in rats.

The effect of ibogaine hydrochloride on locomotor stimulation induced by d-amphetamine sulfate was tested in male C57BL/6By mice and in female Sprague-Dawley rats. In mice, locomotor stimulation induced by d-amphetamine at 1 or 5 mg/kg s.c. was reduced by prior administration of ...

Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD.

The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with ei...

Differential effects of ibogaine pretreatment on brain levels of morphine and (+)-amphetamine.

Previous studies in rats have shown that ibogaine inhibits neurochemical and behavioral effects of morphine yet potentiates similar effects of (+)-amphetamine. To assess whether these different functional interactions have a metabolic basis, brain levels of morphine and (+)-amphe...

Ibogaine antagonizes cocaine-induced locomotor stimulation in mice.

Ibogaine (40 mg/kg i.p.), when given 2 hours before an acute injection of cocaine (25 mg/kg s.c.) to C57BL/6 mice, reduced the cocaine-induced locomotor stimulation. Such stimulation was also reduced in the ibogaine-treated mice when a second injection of cocaine was given 24 hr ...

Effects and aftereffects of ibogaine on morphine self-administration in rats.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in ra...

Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study.

Ibogaine, an indolalkylamine, has been claimed to be effective in abolishing drug craving in heroin and cocaine addicts. The present study used in vivo microdialysis to determine the effects of ibogaine on extracellular levels of dopamine (DA) and its metabolites and the effects ...

Ibogaine fails to reduce naloxone-precipitated withdrawal in the morphine dependent rat.

Ibogaine fails to reduce naloxone-precipitated withdrawal in the morphine-dependent rat.

Because of anecdotal reports in which ibogaine eliminates opioid withdrawal symptoms in humans, we studied this phenomenon in the rat model. Ibogaine (5, 10, 20 and 40 mg kg-1, s.c.) was administered 15 min before naloxone (0.5 mg kg-1, s.c.) in morphine dependent rats (3 days af...

Non-amphetaminic central stimulation by alkaloids from the ibogane an vobasine series.

Heyneanine hydroxyindolenine, a new indole alkaloid from Ervatamia coronaria var. plena.

The whole plant of Ervatamia coronaria var. plena obtained from Thailand has afforded a new indole alkaloid 19S-heyneanine hydroxyindolenine whose structure was deduced through interpretation of spectral data. Nine known alkaloids, coronaridine, coronaridine hydroxyindolenine, vo...

Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats.

Ibogaine, an indole alkaloid, administered intracerebroventricularly 4-16 micrograms, attenuated a naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats. It appears that ibogaine has a more consistent effect on certain selective withdrawal signs related to ...

Neocortical rhythmic slow activity during wakefulness and paradoxical sleep in rats.

In the present study, we investigated the different types of neocortical rhythmic slow activity (RSA) during wakefulness and paradoxical sleep as well as their pharmacological modification. During wakefulness, the high-frequency (7-9 Hz) RSA1 type, which is atropine-resistant, is...

Benzodiazepine receptors are involved in tabernanthine-induced tremor: in vitro and in vivo evidence.

Tabernanthine, an indol alkaloid, is structurally related to carbolines (harmane, harmaline) which, in vitro, displace specific flunitrazepam binding to brain benzodiazepine receptors. In vivo, both tabernanthine and carbolines cause a fine general tremor, suggesting that a possi...

Cytostatic, cytotoxic and mutagenic effects of voacristine, an indole alkaloid in wild-type and repair-deficient yeasts.

Voacristine, an indole alkaloid isolated from the leaves of Ervatamia coronaria (Stapf.) (Apocynaceae) has dose-dependent cytostatic and cytotoxic effects on cultures of Saccharomyces cerevisiae. These inhibitory effects take place only in growing cells. Among the different repai...

Peripheral cardiovascular effects of tabernanthine tartrate in anaesthetized rats.

The peripheral cardiovascular effects of tabernanthine tartrate have been studied in anaesthetized rats. Our results confirm that the bradycardic effect of tabernanthine is not inhibited by vagotomy, atropine or propranolol. On the contrary, bivagotomy, atropine treatment, as wel...

Effects of tabernanthine on calcium and catecholamine stimulated contractions of isolated vascular and cardiac muscle.

The Iboga alkaloid tabernanthine (80 microM) non-competitively antagonized contractions in both the rat aorta and mesenteric artery induced by cumulative additions of noradrenaline and calcium. Tabernanthine (8, 40 and 80 microM) antagonized the K+ depolarization-induced contract...

Phytochemical investigation of Tabernaemontana crassa.

From the stembark of Tabernaemontana crassa the alkaloid ibogaine was isolated as the major component. Ibogaine showed activity against the gram-positive Bacillus subtilis. Conopharyngine was identified as one of the minor compounds....

Evidence for an antagonistic action of tabernanthine on hypoxia-induced changes in brain serotonin levels.

The effects of tabernanthine on serotonin (5-HT) levels were determined in several brain areas of rats exposed to various simulated altitudes (1800, 5200, 7000 m). The 5-HT synthesis inhibitor, para-chlorophenylalanine (PCPA), was used to dissociate the effects occurring at synth...

Evidence for an activating effect of tabernanthine on rat brain catecholamine synthesis and elimination.

Tabernanthine increased the synthesis and elimination of catecholamines (CA) in the striatum and the rest of the brain, but not in the hypothalamus. These data provide evidence that tabernanthine may activate CA turnover of some brain structures by acting at 2 steps of the metabo...