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.
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.
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.
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.
Brain research
January 1, 2025
Leonor Miranda
59 citations
Activating 5HT2A receptors in the anterior cingulate cortex (ACC) with psychedelic drugs reduces anxious preoccupation, obsessional thoughts, and anhedonia while promoting cognitive flexibility and long-lasting mood improvements. This occurs through enhanced AMPA receptor signaling that alters the AMPA-to-NMDA activity ratio, dismantling established neuronal connections and aiding new ones, which benefits fear extinction and reversal learning. Psychedelics also strengthen connectivity from the dorsal ACC and Salience Network to the Default Mode Network and Central Executive Network, improving attentional shifting and anti-anhedonic effects, while reducing the Default Mode Network's inhibitory influence over the Central Executive Network to decrease overevaluation of internal states. Downstream effects include reduced amygdala reactivity to threats and enhanced mesolimbic dopamine, improving anxiety and natural reward experience.
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.
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.
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.
Brain research
June 13, 1994
P M Lalley
37 citations
5-MeO-DMT, a compound that activates serotonin receptors, had two distinct effects on brainstem respiratory neurons in cats. Larger doses (43 ± 8.9 μg/kg) silenced these neurons by hyperpolarizing them, an effect reduced by a serotonin receptor blocker given intravenously but not locally. Smaller doses (27 ± 2.78 μg/kg) increased the firing rate of both inspiratory and expiratory neurons, making inspiratory bursts shorter and expiratory bursts start earlier relative to breathing rhythm. The larger-dose depression appears to involve both presynaptic network effects and postsynaptic activation of 5HT-1A receptors, while the smaller-dose excitation likely results from binding to 5HT-1A receptors on early inspiratory neurons.
Brain research
April 29, 1985
T Archer, B G Minor, C Post
37 citations
Depleting noradrenaline in rats reversed the pain-relieving effect of the 5-HT agonist 5-MeO-DMT, turning it into pain hypersensitivity in a shock-titration test and completely blocking its antinociceptive effects in hot-plate and tail-flick tests. Depleting serotonin stores did not alter the analgesia caused by 5-MeO-DMT. The results provide strong evidence that central noradrenaline depletion affects the analgesic action of the 5-HT agonist, suggesting an important tonic influence of the noradrenaline system on the descending spinal 5-HT pathway.
Brain research
January 5, 2012
Andrew A Fingelkurts, Alexander A Fingelkurts, Carlos F H Neves
35 citations
The hierarchical operational architectonics (OA) framework offers an alternative to common machine consciousness methods by proposing a theory-driven approach based on the brain's functional architecture. It describes the neurophysiological basis of phenomenal consciousness as a hierarchy of brain operations captured in the electromagnetic field. The authors argue that engineering machine consciousness requires duplicating this hierarchy and its rules. They hope the framework will inspire mathematicians and computer scientists to formalize these principles, which are the building blocks of consciousness and thought.
Brain research
October 21, 1996
S F Ali, G D Newport, W Slikker et al.
29 citations
A single injection of ibogaine (IBO) rapidly increases the hormones prolactin and corticosterone in adult male rats, with prolactin returning to normal within 60 minutes and corticosterone within 24 hours. IBO also reduces dopamine in the striatum and frontal cortex for up to two hours while raising dopamine metabolites, indicating altered dopamine processing. Some dopamine metabolite levels remain below normal 24 hours later. Serotonin and its metabolite decrease only in the striatum at 60 minutes. These effects may relate to ibogaine's reported ability to help reduce drug craving, but further research is needed.
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.
Brain research
June 22, 1998
S J Mah, Y Tang, P E Liauw et al.
20 citations
Ibogaine, at low concentrations below 10 microM, selectively inhibits catecholamine release triggered by nicotinic acetylcholine receptor activation in cultured bovine chromaffin cells, while not affecting release caused by membrane depolarization or sodium channel activation. This inhibition is not reversed by kappa opioid receptor antagonists, indicating the effect is not mediated through kappa opioid receptors. The inhibition by low-dose ibogaine is rapidly reversible, whereas higher doses produce inhibition lasting at least 19 hours after removal. These findings suggest ibogaine acts at the nicotinic acetylcholine receptor, relevant to its potential anti-addictive effects and development of treatments for nicotine addiction.
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.
Brain research
March 28, 1997
H N Bhargava, Y J Cao, G M Zhao
19 citations
Ibogaine, a compound from the African shrub Tabernanthe iboga, did not alter pain relief (antinociception) produced by morphine, U-50,488H, or DPDPE in male Swiss-Webster mice when given 10 minutes before these opioids. Ibogaine alone had no effect on pain sensitivity. However, its metabolite noribogaine enhanced morphine's pain-relieving effect at doses of 40 and 80 mg/kg, particularly with a lower morphine dose (5 mg/kg). Noribogaine did not affect pain relief from U-50,488H or DPDPE. The authors conclude that ibogaine's reported ability to reduce drug self-administration likely does not involve direct interaction with multiple opioid receptors, but its metabolite noribogaine may interact with mu-opioid receptors to enhance morphine's effects.
Brain research
February 6, 1999
M E Alburges, G R Hanson
18 citations
Ibogaine, a psychoactive compound from the West African shrub Tabernanthe iboga, increases neurotensin-like immunoreactivity (NTLI) in the striatum, nucleus accumbens, and substantia nigra of rats 12 hours after administration, but not in the frontal cortex. These increases are blocked by a D1 dopamine receptor antagonist in all three regions and by a D2 antagonist only in the substantia nigra. Ibogaine pretreatment also blocks cocaine-induced NTLI increases in the striatum and substantia nigra. The findings suggest neurotensin may mediate ibogaine's interactions with the dopamine system and contribute to its pharmacological effects against stimulant addiction.
Brain research
March 28, 1997
Y J Cao, H N Bhargava
18 citations
Ibogaine, a compound from the African shrub Tabernanthe iboga, selectively blocks the development of tolerance to morphine's pain-relieving effect in male Swiss-Webster mice. Mice given morphine, U-50,488H, or DPDPE (agonists for mu-, kappa-, and delta-opioid receptors, respectively) twice daily for four days became tolerant to these drugs' antinociceptive effects. Ibogaine at 40 or 80 mg/kg, given before each morphine injection, prevented tolerance to morphine, but 20 mg/kg did not. Ibogaine did not affect tolerance to kappa- or delta-receptor agonists at any dose. The results suggest ibogaine specifically inhibits tolerance to mu-opioid receptor agonists.
Brain research
April 2, 2004
Beth Levant, Thomas L Pazdernik
17 citations
Ibogaine, a hallucinogenic alkaloid proposed for treating opioid addiction, alters brain energy use differently in drug-naive versus morphine-dependent rats. In drug-naive rats, ibogaine increased glucose utilization in the parietal, cingulate, and occipital cortices and cerebellum, consistent with its hallucinogenic and tremor-inducing effects. In morphine-dependent rats, ibogaine caused a global decrease in brain glucose utilization, most notably in regions including the preoptic areas, nucleus accumbens shell, locus coeruleus, and flocculus. These distinct patterns suggest that ibogaine's hallucinogenic and anti-addictive effects may involve different brain mechanisms.
Brain research
March 27, 1999
X Yu, S Z Imam, G D Newport et al.
17 citations
In female C57BL/6N mice, methamphetamine caused a rise in body temperature and increased levels of a stress protein (HSP-72) in the caudate nucleus. Ibogaine alone lowered body temperature. When ibogaine was given before methamphetamine, it completely prevented the hyperthermia and reduced HSP-72 expression. These results suggest ibogaine can block methamphetamine-induced brain stress and temperature changes.