Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine, on drug-induced locomotor behavior depends on the previous drug history of the animal. To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically with either saline or cocaine. Rats were chronically...
Two studies were conducted to assess, in vivo, potential anti-nicotinic effects of the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine (18-MC). As previously demonstrated for ibogaine, using microdialysis, pretreatment (19h beforehand) with 18-MC (40 mg/kg, i.p.) significantly attenuated nicotine-induced dopamine release in the nucleus accumbens of awake and freely...
The iboga alkaloid, ibogaine, its metabolite, noribogaine, and the congener, 18-methoxycoronaridine (18-MC) have all been claimed to have anti-addictive properties in animal models, but the mechanisms underlying these effects are unclear. Ibogaine and noribogaine were shown to have affinity for the serotonin transporter, and inhibition of serotonin reuptake has been proposed to be involved in...
Ibogaine, an alkaloid found in the root bark of the African shrub Tabernanthe iboga, has been claimed to interrupt opioid dependence in humans; in animals, it has been shown to inhibit morphine self-administration and to attenuate signs of morphine withdrawal. However, ibogaine has some neurotoxicity, and because of this, efficacious and safer congeners of ibogaine have been sought,...
Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine's interactions with drugs of abuse, and to investigate the mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can...
The purpose of this study was to clarify the effects of iboga agents on cocaine-induced hyperactivity. Both inhibition and enhancement of cocaine-induced activity by ibogaine have been reported. In the present study, rats were treated with either ibogaine (40 mg/kg, i.p.), noribogaine (40 mg/kg, i.p.), 18-methoxycoronaridine (40 mg/kg, i.p.), or saline, 1 or 19 h prior to the administration of...
We previously reported that single administration of ibogaine, an indol alkaloid with antiaddictive properties, dose dependently reduced alcohol intake in three strains of alcohol-preferring rats. The present study examined the effect of different doses of a newly developed nontoxic ibogaine analogue, 18-methoxycoronaridine (18-MC), on alcohol intake. Selectively bred alcohol-preferring rats...
The present study demonstrates that the putative antiaddictive agent ibogaine produces more robust behavioral effects in female than in male rats and that these behavioral differences correlate with higher levels of ibogaine in the brain and plasma of female rats. There were no differences in basal locomotor activity between the sexes, and the response of rats to ibogaine differed between the...
Ibogaine, a putatively anti-addictive alkaloid, binds to kappa-opioid and NMDA receptors. In the present study we investigated the roles of kappa-opioid and NMDA actions in mediating ibogaine's (40 mg/kg, i.p.) behavioral and neurochemical effects in rats. A combination of a kappa-opioid antagonist (norbinaltorphimine, 10 mg/kg, s.c.) and a NMDA agonist (NMDA, 20 mg/kg, i.p.) partially...
There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of this study was to examine the dopamine response to repeated i.v. infusions of nicotine. Using in vivo microdialysis in awake and freely moving male Sprague-Dawley rats, we demonstrated that i.v. nicotine infusions (0.16 mg/kg or 0.32 mg/kg per infusion)...
The potential modulation of morphine antinociception by the putative anti-addictive agent ibogaine and its active metabolite (noribogaine) was investigated in rats with the radiant heat tail-flick test. Ibogaine pretreatment (40 mg/kg, i.p., 19 h) significantly decreased morphine (4 mg/kg, s.c.) antinociception, with no effects in the absence of morphine. However, co-administration of ibogaine...
Ibogaine is claimed to be an effective treatment for opiate and stimulant addiction. O'Hearn and Molliver, however, showed that ibogaine causes degeneration of cerebellar Purkinje cells in rats. The present study re-examined cerebellar responses to the high doses of ibogaine used by O'Hearn and Molliver (100 mg/kg or 3 x 100 mg/kg) and sought to determine whether a lower dose (40 mg/kg), one...
Ibogaine, a naturally occurring iboga alkaloid, has been claimed to be effective in treating addiction to opioids and stimulants, and has been reported to inhibit morphine and cocaine self-administration in rats. However, ibogaine also has acute nonspecific side effects (e.g. tremors, decreased motivated behavior in general) as well as neurotoxic effects (Purkinje cell loss) manifested in the...
Ibogaine is a naturally occurring alkaloid that has been claimed to be effective in treating addiction to opioids and stimulants; a single dose is claimed to be effective for 6 months. Analogously, studies in rats have demonstrated prolonged (one or more days) effects of ibogaine on morphine and cocaine self-administration even though ibogaine is mostly eliminated from the body in several...
The distribution of the putative anti-addictive substance ibogaine was measured in plasma, brain, kidney, liver and fat after ip and sc administration in rats. One hr after ip dosing (40 mg/kg), drug levels ranged from 106 ng/ml (plasma) to 11,308 ng/g (fat), with significantly higher values after sc administration of the same dose. Drug levels were 10-20 fold lower 12 hr after the same dose....
The present study examines the effect of prior morphine exposure on ibogaine antagonism of morphine-induced dopamine release. Female Sprague-Dawley rats were pretreated once a day for 2 days with morphine (20 mg/kg, i.p.) or saline and given a low dose of ibogaine (10 mg/kg, i.p.) or saline 5 hr after the last morphine or saline injection. Nineteen hours later, rats (awake and freely moving)...
Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1-4 days with morphine (5, 10, 20 or 30 mg/kg, i.p.) or saline and then received...
Radioligand-binding studies were performed to ascertain the actions of noribogaine, a suspected metabolite of ibogaine, on opioid receptors. Consistent with previous results, ibogaine showed highest affinity for kappa opioid receptors (Ki = 3.77 +/- 0.81 microM), less affinity for mu receptors (Ki = 11.04 +/- 0.66 microM) and no affinity for delta receptors (Ki > 100 microM). Noribogaine showed...
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 well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self-administration of...
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 ibogaine to the striatum and nucleus accumbens produced effects that mimicked both the acute and persistent effects of...
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 (+)-amphetamine were measured by gas chromatography-mass spectrometry after ibogaine pretreatment (19 h before injection of...
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 reservoirs for 5 days. Ibogaine (20, 40 or 80 mg/kg, i.p.) or saline was administered 30 min prior to challenge with...
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. Ibogaine (40 mg/kg, i.p.) injected 19 h prior to a D-amphetamine challenge (1.25 mg/kg, i.p.) potentiated the expected...
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 (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at...
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, potentiated the increase in extracellular dopamine levels in striatum and nucleus accumbens as well as the stimulated motor...