Pharmacology, biochemistry, and behavior
February 1, 1998
S Helsley, D Fiorella, R A Rabin et al.
35 citations
In rats trained to recognize the hallucinogen ibogaine, two other hallucinogens—LSD and DOM—partially substituted for ibogaine (63% and 66.4% of responses, respectively). This partial substitution was completely blocked by the 5-HT2A antagonist pirenpirone, indicating that LSD and DOM produce ibogaine-like effects through the 5-HT2A receptor. However, pirenpirone did not block ibogaine itself or its effects from harmaline and noribogaine. Ibogaine, noribogaine, and harmaline showed only micromolar affinity for the 5-HT2A receptor (92.5, 34.5, and 42.5 µM). Ibogaine and harmaline, but not noribogaine, protected the receptor from alkylation. The findings suggest that while ibogaine interacts with 5-HT2A receptors, these interactions are not essential for its discriminative stimulus effects.
Brain research
June 13, 1997
S Helsley, C A Dlugos, R J Pentney et al.
19 citations
Repeated administration of ibogaine to male Fischer 344 rats over 60 days did not cause loss of cerebellar Purkinje cells. The ibogaine group had an average of 243,764 Purkinje cells and the control group 230,813, a difference that was not statistically significant. This suggests that chronic ibogaine exposure at a behaviorally active dose does not damage these neurons.
Pharmacology, biochemistry, and behavior
February 1, 1998
S Helsley, R A Filipink, W D Bowen et al.
16 citations
Ibogaine, a hallucinogen with potential for treating addiction, produces its effects through interactions with multiple brain receptors. In rats trained to recognize ibogaine, ligands targeting sigma2 and opiate receptors partially reproduced ibogaine's effects, while sigma1-selective agents did not. Morphine and kappa-selective opioids failed to substitute for ibogaine, but mixed-action opiates like (-)-SKF 10,047 and nalorphine showed intermediate generalization. Naloxone partially blocked ibogaine's effects and fully blocked those of (-)-SKF 10,047 and nalorphine. Neither PCP nor MK-801 substituted for ibogaine, indicating NMDA receptors are not involved. The findings suggest that sigma2 and opiate receptors, but not NMDA receptors, contribute to ibogaine's discriminative stimulus.
Pharmacology, biochemistry, and behavior
July 1, 1999
J C Winter, S Helsley, D Fiorella et al.
14 citations
Pretreatment with the monoamine reuptake inhibitors fluoxetine, fluvoxamine, and venlafaxine increased the discriminative stimulus effects of the hallucinogens LSD, (-)-DOM, and ibogaine in rats trained to recognize these drugs. For 5-MeO-DMT-trained rats, only fluoxetine enhanced drug-appropriate responding. The reuptake inhibitors alone sometimes produced intermediate responding, suggesting partial substitution. Further experiments with (-)-DOM showed that most combinations produced additive rather than truly potentiating effects. The findings extend earlier observations that fluoxetine augments LSD's effects to include other hallucinogens, though the mechanisms and differences between acute and chronic treatment remain unknown.
Life sciences
January 1, 1997
S Helsley, R A Rabin, J C Winter
13 citations
Rats were trained to distinguish the psychoactive drug ibogaine from water. The dose needed to produce the drug effect half the time (ED50) was 4.6 mg/kg. The drug's effect peaked at 60 minutes after injection, with 94% of responses indicating the drug was present, then declined over time; after 8 hours only 6.4% of responses were drug-appropriate. A metabolite of ibogaine, noribogaine, partially substituted for ibogaine (71.6% drug-appropriate responding), while the drug harmaline fully substituted (83.5%), suggesting shared mechanisms.
Progress in neuro-psychopharmacology & biological psychiatry
February 1, 1999
S Helsley, R A Rabin, J C Winter
9 citations
In rats trained to recognize ibogaine's effects, activating 5-HT2C receptors with MK-212 or mCPP produced ibogaine-like responses (79.6% and 76.4% of the time), and this substitution was blocked by the 5-HT2C antagonist metergoline. However, metergoline did not block ibogaine itself, indicating that while ibogaine may activate 5-HT2C receptors, this action is not necessary for its distinctive cue. Neither a 5-HT3 agonist nor antagonist, nor a 5-HT1A agonist or antagonist, substituted for ibogaine, and a 5-HT1A antagonist did not block ibogaine's effects. Thus, 5-HT1A and 5-HT3 receptors appear uninvolved in ibogaine's discriminative stimulus.
Pharmacology, biochemistry, and behavior
September 1, 1997
S Helsley, D Fiorella, R A Rabin et al.
9 citations
Ibogaine, at a potentially neurotoxic dose, did not impair rats' ability to learn or perform a maze task. In a study with 12 rats trained in an 8-arm radial maze, those given ibogaine showed similar learning and accuracy as controls but had lower response rates. When given before maze sessions, ibogaine dose-dependently slowed responding without reducing accuracy. When given after sessions, ibogaine-treated rats made fewer errors than controls. The authors conclude that ibogaine failed to produce any harmful effects on learning or task efficiency.
European journal of pharmacology
March 19, 1998
S Helsley, R A Rabin, J C Winter
6 citations
Rats trained to recognize ibogaine's effects were tested with several beta-carbolines to see which ones produced similar internal sensations. 6-Methoxyharmalan fully mimicked ibogaine in 86.3% of trials, while harmaline had done so in 83.5% in earlier work. Harmine, harmane, harmalol, and tetrahydro-beta-carboline produced partial substitution, but norharmane and DMCM did not. These results suggest that some beta-carbolines share ibogaine-like effects, though whether this extends to anti-addictive properties remains unknown.
The Alkaloids. Chemistry and biology
January 1, 2001
S Helsley, R A Rabin, J C Winter
4 citations
Ibogaine appears to produce its effects through selective interactions with multiple brain receptors, specifically 5-HT2A, 5-HT2C, and sigma 2 receptors, with possible involvement of opiate receptors. Sigma 1, PCP/MK-801, 5-HT3, and 5-HT1A receptors do not play a major role. The hallucinogenic effects may stem from 5-HT2A and 5-HT2C receptor interactions, while antiaddictive properties may result from sigma 2 and opiate receptor interactions. Alternatively, the hallucinogenic properties themselves could underlie the antiaddictive effects, supporting a role for 5-HT2 receptors in therapeutic actions. Many questions remain, and future research combining drug discrimination with other techniques promises to clarify ibogaine's mechanism of action.