European journal of pharmacology
April 3, 1991
S D Glick, K Rossman, S Steindorf et al.
195 citations
Ibogaine, a naturally occurring alkaloid, reduced intravenous morphine self-administration in rats. The drug caused an acute decrease in morphine intake in the hour after treatment, but this was linked to abnormal motor behavior (whole body tremors). A more notable aftereffect occurred a day later, when ibogaine should have been fully eliminated from the body and no obvious signs of exposure remained. Some rats showed a persistent decrease in morphine intake for days or weeks after a single injection; others required two or three weekly injections before showing such changes, and a few rats were resistant to prolonged aftereffects. The aftereffect was not due to conditioned aversion. Ibogaine also acutely suppressed bar-pressing for water but showed no aftereffect on that behavior, suggesting some specificity for morphine reinforcement.
Brain research
September 19, 1994
S D Glick, M E Kuehne, J Raucci et al.
189 citations
Several iboga alkaloids and the related harmala alkaloid harmaline reduce morphine and cocaine self-administration in rats in a dose-dependent manner (2.5-80 mg/kg) during the hour after treatment. Some alkaloids, including ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine, also decrease intake the following day. In some rats, a single injection or two to three weekly injections produce persistent decreases lasting several days, with R-ibogamine showing the most consistent long-term effects. The study also assessed the tremor-inducing and neurotoxic potential of these compounds and their effects on dopamine levels in brain reward regions.
Brain research
February 7, 1992
D C Deecher, M Teitler, D M Soderlund et al.
143 citations
Ibogaine and related compounds bind to various opioid receptors, with ibogaine showing affinity for kappa-opiate receptors (Ki = 2.08 µM), while harmaline and harmine do not bind to opiate receptors. All tested drugs also affect sodium channels at micromolar concentrations, but neither ibogaine nor harmaline interacts with GABA receptors. The kappa-opioid activity may explain ibogaine's proposed anti-addictive effects, while sodium channel effects could account for the tremor-inducing properties of ibogaine and harmaline.
European journal of pharmacology
June 18, 1991
I M Maisonneuve, R W Keller, S D Glick
127 citations
Ibogaine, a substance claimed to reduce drug craving, alters brain dopamine systems for longer than it remains in the body. In rats, an acute injection of ibogaine decreased dopamine levels in the striatum, increased them in the prefrontal cortex, and had no effect in the nucleus accumbens. Nineteen hours later, dopamine remained lower in the striatum, and metabolite levels were reduced across all three brain regions. When given 19 hours before a low dose of morphine, ibogaine prevented the usual dopamine increase caused by morphine. A high dose of morphine alone did not raise dopamine, making it unclear whether ibogaine blocked or enhanced the low-dose effect. Overall, ibogaine produces lasting changes in brain dopamine systems and alters their response to morphine.
Neuropharmacology
May 1, 1992
S D Glick, K Rossman, N C Rao et al.
121 citations
Ibogaine, a compound reported to suppress narcotic withdrawal in humans, was tested in morphine-dependent rats. Rats received morphine for five days, then ibogaine (20, 40, or 80 mg/kg) or saline 30 minutes before naltrexone-precipitated withdrawal. Doses of 40 and 80 mg/kg significantly reduced four withdrawal signs: wet-dog shakes, grooming, teeth chattering, and diarrhea. Three other signs—weight loss, burying, and flinching—were unaffected. Ibogaine caused head and body tremors lasting 2-3 hours, which might have interfered with withdrawal expression. In a second experiment, ibogaine given 4 hours before naltrexone, when tremors were absent, still significantly reduced the same four withdrawal signs, indicating a genuine anti-withdrawal effect.
Brain research
May 6, 1996
S D Glick, M E Kuehne, I M Maisonneuve et al.
118 citations
A novel synthetic compound, 18-methoxycoronaridine (MC), reduces morphine and cocaine self-administration in rats without the tremors and cerebellar toxicity seen with ibogaine. In acute tests, MC decreased drug intake but did not affect bar-press responding for water. In some rats, a single 40 mg/kg dose of MC produced prolonged decreases in morphine or cocaine intake lasting days or weeks. MC showed no tremorigenic effect, and a high dose of 100 mg/kg caused no cerebellar toxicity. Like ibogaine, MC lowered extracellular dopamine levels in the nucleus accumbens. MC appears to be a safer ibogaine-like agent potentially useful for treating addiction.
Annals of the New York Academy of Sciences
September 1, 2000
S D Glick, I M Maisonneuve, K K Szumlinski
89 citations
18-Methoxycoronaridine (18-MC), a safer iboga alkaloid, reduces self-administration of morphine, cocaine, ethanol, and nicotine in rats without affecting nondrug reward, unlike ibogaine. Both compounds block opioid withdrawal and dopamine release in the nucleus accumbens, but only ibogaine raises serotonin levels and enhances cocaine-induced dopamine. Ibogaine causes tremors and cerebellar damage at high doses; 18-MC does not. 18-MC has lower affinity for NMDA, sigma-2, sodium channels, and serotonin transporter than ibogaine. The findings suggest 18-MC has a narrower action profile and a substantially better therapeutic index than ibogaine.
Brain research
March 13, 1992
I M Maisonneuve, K L Rossman, R W Keller et al.
86 citations
Ibogaine, a compound proposed for treating addiction to opiates and stimulants, produces both immediate and lasting changes in brain dopamine levels. One hour after a single injection, dopamine decreased by 50% while its metabolite HVA increased by 37–100% in the striatum, nucleus accumbens, and prefrontal cortex. Nineteen hours later, another metabolite, DOPAC, was reduced in the nucleus accumbens and striatum, and striatal DOPAC remained low after a week. No significant neurochemical changes were present after one month. Ibogaine pretreatment also reduced the stimulatory effect of morphine on movement when morphine was given 19 hours or a week later, but not after a month. These findings suggest ibogaine's effects on dopamine systems coincide with a sustained dampening of morphine-induced motor activity.
Pharmacology, biochemistry, and behavior
October 1, 1997
A H Rezvani, D H Overstreet, Y Yang et al.
78 citations
A single injection of 18-methoxycoronaridine (18-MC), a nontoxic ibogaine analogue, dose dependently reduced alcohol consumption and preference in alcohol-preferring rats, while water intake increased correspondingly. Only the highest dose (40 mg/kg) also decreased food intake. The mechanism by which 18-MC suppresses alcohol intake is not yet fully understood but may involve modulation of neurotransmitters that regulate alcohol consumption.
Brain research
March 27, 1995
S M Pearl, K Herrick-Davis, M Teitler et al.
78 citations
Noribogaine, a suspected metabolite of ibogaine, binds more strongly than ibogaine to all three types of opioid receptors. Ibogaine had highest affinity for kappa receptors, less for mu, and no measurable affinity for delta receptors. Noribogaine showed higher affinity for kappa, mu, and delta receptors, suggesting it is active in the body and may contribute to ibogaine's effects.
Life sciences
January 1, 1996
L B Hough, S M Pearl, S D Glick
72 citations
Ibogaine, a substance being studied for anti-addictive properties, was measured in rats' plasma, brain, kidney, liver, and fat after injection into the abdomen or under the skin. One hour after a 40 mg/kg dose into the abdomen, drug levels ranged from 106 ng/ml in plasma to 11,308 ng/g in fat, with higher levels after injection under the skin. Levels dropped 10-20 fold after 12 hours. The results indicate that ibogaine undergoes a substantial first-pass effect when given into the abdomen, accumulates heavily in fat due to its lipophilic nature, and its persistence in fat may contribute to a long duration of action.
Annals of the New York Academy of Sciences
January 1, 2000
S D Glick, I M Maisonneuve
64 citations
Ibogaine, an alkaloid from the African shrub Tabernanthe iboga, shows promise for treating drug abuse but has problematic side effects. A safer derivative, 18-methoxycoronaridine (18-MC), appears equally effective in rats: both ibogaine and 18-MC (40 mg/kg) reduce self-administration of morphine, cocaine, ethanol, and nicotine, but only 18-MC leaves non-drug reward (water) unaffected. Both compounds lower dopamine in the nucleus accumbens and block morphine- and nicotine-induced dopamine release, but ibogaine uniquely raises serotonin and enhances cocaine-induced dopamine. Ibogaine causes whole body tremors and, at high doses (≥100 mg/kg), cerebellar damage and bradycardia; 18-MC does not. The data indicate 18-MC should be safer and at least as efficacious as an anti-addictive medication.
Brain research
March 25, 1996
S D Glick, S M Pearl, J Cai et al.
63 citations
Ibogaine, a natural alkaloid, is claimed to reduce opioid and stimulant addiction for six months after a single dose, though it is eliminated from the body within hours. A metabolite, noribogaine, may explain this prolonged effect. In rats, a 40 mg/kg dose of noribogaine decreased morphine and cocaine self-administration, reduced morphine-induced locomotor stimulation, and lowered dopamine levels in the nucleus accumbens and striatum—effects similar to those of ibogaine at the same dose, but without ibogaine-like tremors. These findings suggest noribogaine mediates ibogaine's anti-addictive properties.
Brain research
October 21, 1996
H H Molinari, I M Maisonneuve, S D Glick
61 citations
High doses of ibogaine (100 mg/kg or repeated doses) cause degeneration of cerebellar Purkinje cells in rats, particularly in lobules 5 and 6, which may lead to motor deficits in the head and upper extremities. In contrast, a lower dose (40 mg/kg) that is effective in reducing morphine and cocaine self-administration produces no more degeneration than saline. The findings suggest that ibogaine's degenerative effects and its anti-addictive properties stem from different mechanisms of action.
European journal of pharmacology
March 3, 1992
I M Maisonneuve, S D Glick
59 citations
A single injection of ibogaine (40 mg/kg) given to rats 19 hours before cocaine (20 mg/kg) made cocaine's effects stronger: it increased the rise in dopamine levels in the striatum and nucleus accumbens and boosted cocaine-stimulated motor activity. The authors note that while high cocaine doses can cause aversion through anxiety, it remains unknown whether this ibogaine-induced potentiation would also produce aversion and reduce cocaine addiction.
Pharmacology, biochemistry, and behavior
August 1, 1997
S M Pearl, L B Hough, D L Boyd et al.
58 citations
Ibogaine, a substance studied for antiaddictive properties, produces stronger behavioral effects in female rats than in males, correlating with higher ibogaine levels in their brains and plasma. Five hours after a 40 mg/kg dose, ibogaine antagonized morphine-induced locomotor activity only in females. At 19 hours after 10-60 mg/kg ibogaine or one hour after 5-40 mg/kg noribogaine (a metabolite), antagonism was greater in females. Brain and plasma levels of ibogaine and noribogaine were higher in females given the same dose. Levels were much lower at 19 hours than earlier, unlike a prior human study. Subcutaneous injection produced greater antagonism than intraperitoneal, consistent with higher brain levels. Sex differences likely stem from lower ibogaine bioavailability in males.
Brain research
May 1, 1992
I M Maisonneuve, R W Keller, S D Glick
53 citations
Ibogaine, a substance proposed for treating stimulant addiction, was tested in rats. When given 19 hours before D-amphetamine, ibogaine increased the rise in extracellular dopamine in the striatum and nucleus accumbens and enhanced the motor-stimulating effects of D-amphetamine across several doses. These results suggest ibogaine might increase the reinforcing efficacy of D-amphetamine, but because high doses of D-amphetamine can be aversive, the potentiation could also reduce reinforcing efficacy.
Brain research
August 3, 1998
D Wei, I M Maisonneuve, M E Kuehne et al.
48 citations
Ibogaine, its metabolite noribogaine, and the related compound 18-methoxycoronaridine (18-MC) have been claimed to reduce addiction in animal models, but their mechanisms are unclear. In awake female rats, ibogaine caused large increases in extracellular serotonin in the nucleus accumbens (up to 25-fold) and striatum (up to 10-fold), noribogaine produced moderate increases (up to 8-fold and 5-fold), and 18-MC had no effect. These results suggest that the serotonin system may not be essential for anti-addictive effects; ibogaine may both release and block reuptake of serotonin; its hallucinogenic effect may involve serotonin stimulation; and 18-MC likely lacks serotonin transporter affinity and is unlikely to be a hallucinogen.
Psychopharmacology
October 1, 1998
S D Glick, I M Maisonneuve, K E Visker et al.
45 citations
Two animal experiments tested whether ibogaine and its synthetic version 18-methoxycoronaridine (18-MC) can block nicotine's effects in rats. Pretreatment with 18-MC significantly reduced nicotine-induced dopamine release in the brain's reward center, the nucleus accumbens. In a self-administration test, both compounds decreased rats' preference for nicotine for at least 24 hours. While ibogaine initially suppressed both nicotine and water intake, 18-MC selectively reduced nicotine consumption without affecting water intake. The results suggest 18-MC could be a prototype for a new smoking cessation treatment.
Brain research
February 28, 1997
S D Glick, I M Maisonneuve, S M Pearl
38 citations
Ibogaine, a substance with potential anti-addictive properties, works through two brain receptor systems: kappa-opioid and NMDA. In rats, blocking kappa-opioid receptors and activating NMDA receptors together partially prevented ibogaine's ability to reduce morphine self-administration and to counteract morphine-induced hyperactivity. Either treatment alone, or in combination, also blocked ibogaine's effects on dopamine release and metabolism in the striatum. These results suggest that ibogaine's anti-addictive effects rely on both its kappa-opioid agonist and NMDA antagonist actions.
Psychopharmacology
February 1, 1997
I M Maisonneuve, G L Mann, C R Deibel et al.
38 citations
Intravenous nicotine infusions in rats increase extracellular dopamine in a dose- and order-dependent manner, with acute tolerance appearing when infusions are spaced one hour apart but not when spaced three hours apart. Pretreatment with ibogaine 19 hours before nicotine attenuates this dopamine increase, suggesting ibogaine may reduce nicotine's rewarding effect.
Brain research
November 19, 1993
S D Glick, K Rossman, S Wang et al.
38 citations
Ibogaine, given systemically, alters dopamine and its metabolites in brain reward regions. When applied directly to the striatum and nucleus accumbens, high concentrations (200-400 µM) mimicked the acute effects of systemic ibogaine, lowering dopamine and raising metabolite levels, while a low concentration (10 µM) reproduced the persistent effect of lowering DOPAC. This suggests ibogaine acts directly on dopaminergic nerve terminals and that long-lasting effects may stem from persisting low ibogaine levels. Locally applied ibogaine also enhanced amphetamine's effect on dopamine, and systemic ibogaine pretreatment enhanced locally applied amphetamine's effect, indicating a pharmacodynamic mechanism contributes to their interaction. The relevance to ibogaine's anti-addictive claims remains unclear.
Neuroreport
May 11, 1998
B Rho, S D Glick
35 citations
Ibogaine, a natural alkaloid from the African shrub Tabernanthe iboga, can interrupt opioid dependence in humans and reduce morphine self-administration and withdrawal signs in animals, but it has neurotoxicity. A safer synthetic congener, 18-Methoxycoronaridine (18-MC), mimics ibogaine's effects on morphine self-administration in animals without neurotoxicity. In this study, 18-MC attenuated five of seven signs of morphine withdrawal in rats. The data suggest that 18-MC will ameliorate symptoms of opioid dependence in humans.
Biochemical pharmacology
January 6, 1995
C A Gallagher, L B Hough, S M Keefner et al.
32 citations
A new chemical method to measure the alkaloid ibogaine in biological samples uses extraction, derivatization, and gas chromatography-mass spectrometry, with a deuterated internal standard. Standard curves for ibogaine (50-400 ng) were linear. The detection limit is about 20 ng/mL of tissue extract (180 ng/g tissue), with a coefficient of variation of 8 to 12.5%. Aqueous ibogaine solutions (1-10 mg/mL) stored at 10°C for up to 7 months showed no more than 10% loss. Measuring brain ibogaine in rats 1 and 19 hours after a 40 mg/kg dose suggests rapid drug disappearance. The method will help reveal ibogaine's pharmacokinetic properties.
Psychopharmacology
October 1, 1995
S M Pearl, D W Johnson, S D Glick
31 citations
Prior morphine exposure enhances ibogaine's ability to reduce morphine-induced locomotor stimulation in female rats. Rats pretreated with morphine (10, 20, or 30 mg/kg) before receiving ibogaine (40 mg/kg) showed significantly less locomotor activity when later given morphine (5 mg/kg), compared to rats pretreated with saline. This effect occurred across a range of ibogaine (5–60 mg/kg) and morphine test (2.5–5 mg/kg) doses. Even low ibogaine doses (5 and 10 mg/kg) that alone had no effect became effective after morphine pretreatment. The findings suggest that an individual's history of opioid exposure may influence ibogaine's efficacy against opioid addiction.