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.
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.
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.
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.
Pharmacology, biochemistry, and behavior
January 1, 2001
K K Szumlinski, R E Haskew, M Y Balogun et al.
28 citations
Pretreatment with ibogaine or its synthetic derivative 18-methoxycoronaridine reversed the behavioral disinhibition and increased corticosterone levels caused by a low dose of methamphetamine in rats. Methamphetamine alone increased open-arm entries in the elevated plus maze and raised plasma corticosterone, suggesting behavioral disinhibition rather than anxiety reduction. Both iboga compounds blocked these effects without altering general locomotion, indicating a potential mechanism for their anti-addictive properties through modulation of neuroendocrine stress responses.
Psychopharmacology
August 1, 2000
K K Szumlinski, M Y Balogun, I M Maisonneuve et al.
28 citations
Ibogaine and 18-methoxycoronaridine (18-MC), compounds being studied as potential treatments for addiction, increased the behavioral effects of methamphetamine in rats. Rats given methamphetamine daily for seven days and then pretreated with 18-MC showed more movement in response to methamphetamine than those given a placebo. Both ibogaine and 18-MC also intensified repetitive, stereotypic behaviors caused by higher doses of methamphetamine. These results match earlier findings with cocaine, suggesting the iboga agents interact with brain pathways that control hyperactivity from repeated stimulant use. The authors propose this enhancement may partly explain how these agents reduce drug self-administration.
Brain research
August 14, 1992
S D Glick, C A Gallagher, L B Hough et al.
21 citations
Ibogaine pretreatment in rats did not alter brain morphine levels at 30 minutes or 2 hours after injection, but it significantly increased brain amphetamine levels at both time points, with a greater increase at 2 hours. These findings suggest that ibogaine irreversibly inhibits an enzyme that metabolizes amphetamine, indicating that the functional interactions between ibogaine and amphetamine, unlike those with morphine, may stem from a drug-drug interaction in the liver.
European journal of pharmacology
October 8, 1997
I M Maisonneuve, K E Visker, G L Mann et al.
20 citations
Ibogaine and two related compounds (noribogaine and 18-methoxycoronaridine) both inhibit and later enhance cocaine-induced hyperactivity in rats, depending on timing. When given 1 hour before cocaine, all three agents reduced the hyperactivity caused by cocaine. When given 19 hours before cocaine, they instead amplified it. These opposite, time-dependent effects explain conflicting findings in earlier research and were not caused by the drugs' own effects on movement.
European journal of pharmacology
June 16, 2000
K K Szumlinski, I M Maisonneuve, S D Glick
19 citations
Ibogaine, given to rats 19 hours before a cocaine challenge, reversed a key brain change caused by repeated cocaine use: the sensitized dopamine response in the nucleus accumbens. While ibogaine did not alter the dopamine increase from a single cocaine dose, it eliminated the amplified dopamine release that normally occurs in cocaine-sensitized animals. This effect on neuroadaptation may underlie ibogaine's proposed anti-addictive properties.
Neuropharmacology
January 1, 1996
S M Pearl, I M Maisonneuve, S D Glick
16 citations
Prior morphine exposure enhances ibogaine's ability to block morphine-induced dopamine release in the striatum and nucleus accumbens of female rats. Neither morphine pretreatment, ibogaine alone, nor saline altered morphine-induced increases in extracellular dopamine or its metabolites. Only when morphine pretreatment was combined with ibogaine was the morphine-induced elevation of dopamine completely blocked, while metabolites remained unaffected. This suggests that prior drug exposure may influence ibogaine's effectiveness in treating opioid addiction.
Pharmacology, biochemistry, and behavior
July 1, 1999
K K Szumlinski, I M Maisonneuve, S D Glick
14 citations
A single injection of ibogaine, given 19 hours before a cocaine challenge, more strongly amplifies cocaine-induced movement in rats that have a history of chronic cocaine use than in rats without prior cocaine exposure. The effect grows larger after a second ibogaine treatment but disappears within 24 hours when ibogaine is no longer given. Tolerance to cocaine's stimulant effects appeared in rats that received only cocaine without ibogaine. These results show that ibogaine heightens sensitivity to cocaine's psychomotor effects, and the size of this enhancement depends on the animal's past experience with both ibogaine and cocaine.
Psychopharmacology
July 1, 1999
K K Szumlinski, I M Maisonneuve, S D Glick
14 citations
Ibogaine pretreatment amplifies the stimulating effects of cocaine on movement in rats, but the effect depends on the animals' prior cocaine history. In rats previously treated with cocaine for five days and then withdrawn for two weeks, ibogaine increased movement responses to lower cocaine doses (5 and 10 mg/kg) while decreasing the response to a higher dose (40 mg/kg). In rats with no prior cocaine history, ibogaine only enhanced movement responses across all cocaine doses. Chronic cocaine exposure alone also augmented movement responses compared to acute exposure. The findings show a complex interplay between ibogaine, cocaine dose, and prior drug history.
Toxicon : official journal of the International Society on Toxinology
January 1, 2001
K K Szumlinski, I M Maisonneuve, S D Glick
9 citations
No approved therapy exists for stimulant addiction, but ibogaine and its synthetic analog 18-methoxycoronaridine (18-MC) reduce stimulant self-administration in animals. Early findings suggested these agents paradoxically enhance dopamine release and motor behaviors, leading to the hypothesis that they increase sensitivity to stimulant effects. However, recent observations show 18-MC does not affect acute cocaine-induced dopamine, and both ibogaine and 18-MC block sensitized dopamine levels from chronic cocaine. This positive relationship between iboga pretreatment and reversal of dopamine sensitization indicates these agents may attenuate self-administration by reversing neuroadaptations linked to craving and compulsive drug-seeking.