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
November 25, 1996
A A Bagal, L B Hough, J W Nalwalk et al.
23 citations
Ibogaine, a putative anti-addictive agent, and its active metabolite noribogaine modulate morphine's pain-killing (antinociceptive) effects in rats, depending on timing and dose. When given 19 hours before morphine, ibogaine significantly reduced morphine's antinociception, but had no effect alone. In contrast, co-administration of ibogaine (1-40 mg/kg) with morphine increased antinociception in a dose-dependent manner. Co-administration of noribogaine (40 mg/kg) with morphine also enhanced antinociception, while noribogaine pretreatment (19 hours) had no effect. The findings indicate that ibogaine acutely potentiates morphine antinociception, likely through noribogaine, but the delayed inhibitory effect after 19 hours is not explained by noribogaine.
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.
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.
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.
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.
Methods and findings in experimental and clinical pharmacology
March 1, 2000
L B Hough, A A Bagal, S D Glick
7 citations
After a 20 mg/kg intravenous infusion in rats, ibogaine levels in plasma declined rapidly in a two-phase pattern, with an initial half-life of 7.3 minutes and a terminal half-life of 3.3 hours. Drug clearance was 5.9 L/h. Three hours after infusion, ibogaine concentrations in brain, liver, and kidney were 143–170 ng/g, but in adipose tissue the concentration was much higher at 3,328 ng/g. This sequestration in fat likely causes the drug to persist in the body longer than the terminal half-life suggests. The initial rapid disappearance from plasma may result from metabolic demethylation and redistribution to tissues.
British journal of pharmacology
April 1, 2000
M K Mundey, N A Blaylock, R Mason et al.
6 citations
Ibogaine and 18-methoxycoronaridine, alkaloids with reported anti-addictive properties, modulated electrically-evoked contractions in smooth muscle preparations but did not selectively interact with mu-opioid receptors. In guinea-pig ileum, both drugs concentration-dependently inhibited cholinergic contractions (ibogaine pIC50 5.28, 18-methoxycoronaridine pIC50 5.05), an effect not blocked by naloxone. In rat vas deferens, they enhanced purinergic contractions and caused a 3- to 5-fold rightward shift of DAMGO-induced inhibition. In guinea-pig bladder, both drugs doubled the purinergic component of neurogenic contractions without affecting cholinergic contractions. Ibogaine, but not 18-methoxycoronaridine, enhanced spontaneous contractions of rat portal vein. The pronounced enhancement of purinergic contractions is a novel finding warranting further investigation.