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.
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.
European journal of pharmacology
June 6, 1995
W D Bowen, B J Vilner, W Williams et al.
95 citations
Ibogaine binds moderately to sigma-2 receptors (Ki = 201 nM) and weakly to sigma-1 receptors (Ki = 8554 nM), showing 43-fold selectivity for sigma-2. Related compounds tabernanthine and ibogamine also bind sigma-2 with similar affinity but have higher sigma-1 affinity, resulting in about 14-fold selectivity. A potential ibogaine metabolite, O-des-methyl-ibogaine, has much weaker sigma-2 affinity (Ki = 5226 nM) and no significant sigma-1 affinity. Coronaridine and harmaline lack significant affinity for either sigma subtype. These findings suggest sigma-2 receptors may contribute to ibogaine's effects.
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
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.
European journal of pharmacology
August 8, 1996
R T Layer, P Skolnick, C M Bertha et al.
48 citations
Ibogaine, a psychoactive alkaloid, is more potent than its analogs at blocking NMDA receptors, a brain target linked to addiction. In lab tests, ibogaine inhibited [3H]MK-801 binding to NMDA receptors most strongly (Ki ≈ 1.2 µM), while similar compounds like O-desmethylibogaine were less potent (Ki ≈ 5.5 µM) and O-t-butyl-O-desmethylibogaine much weaker (Ki ≈ 179 µM). In morphine-dependent mice, only ibogaine reduced withdrawal jumping triggered by naloxone, suggesting its anti-addictive effects stem from NMDA receptor antagonism.
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.
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.