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
March 8, 2005
Alexander Freezer, Abdallah Salem, Rodney J. Irvine
34 citations
Co-administration of MDMA with the monoamine oxidase inhibitor moclobemide increases extracellular serotonin in the rat striatum to levels comparable to those produced by PMA, a more toxic recreational drug. MDMA alone raised serotonin by 590%, PMA by 360%. When moclobemide was given before MDMA, serotonin increased by 980%, and serotonin-related behaviors also increased. PMA is also a potent MAO-A inhibitor, which may explain its greater toxicity. These findings suggest that combining MDMA with moclobemide may produce serotonin-related toxicity similar to that of PMA.
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
June 1, 2005
Susan Lautar, Camilo Rojas, Barbara S. Slusher et al.
23 citations
A potent inhibitor of the enzyme dipeptidyl peptidase IV (DPP IV), called AMAC, reduced psychosis-like behaviors in two animal models. In mice given mescaline, AMAC decreased scratching paroxysms by up to 68% depending on dose. In mice given amphetamine, AMAC reduced hyper-locomotion by up to 76%. A similar compound that does not inhibit DPP IV had no effect. AMAC also did not bind to 20 receptors linked to schizophrenia, including dopamine, serotonin, and glutamate receptors. These results suggest that blocking DPP IV may produce antipsychotic effects through a novel mechanism.
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.
Brain Research
December 1, 1971
J. A. Gonzalez-Vegas
15 citations
A compelling finding reveals that excitatory postsynaptic potential increased by 32% in neurons treated with a novel pharmacological agent derived from conducting polymers. In a sample of 150 neurons, this agent enhanced neural signaling while reducing inhibitory postsynaptic potential by 25%. This breakthrough could have significant implications for neuroscience and neuropharmacology, potentially leading to improved treatments for disorders related to neurotransmitter imbalances. The innovative use of microelectrophoresis techniques allows for precise measurement of these effects, advancing our understanding of neural chemistry and biology.
Brain Research
November 21, 1983
P H Hutson, M D Tricklebank, G Curzon
13 citations
Analgesia caused by a brief footshock in rats is reduced by drugs that increase serotonin (5-HT) activity—fenfluramine, which releases serotonin, and 5-MeODMT, a fast-acting serotonin agonist. These reductions are blocked by serotonin antagonists cyproheptadine and methiothepin, but those antagonists alone do not affect the shock-induced pain relief. Thus, the natural analgesia from brief footshock likely does not rely on serotonin mechanisms, though it can be altered by pharmacologically boosting serotonin. 5-MeODMT could also weaken analgesia after it starts, possibly by disrupting memory rather than pain processing directly.
Brain Research
April 1, 1969
M.d. Little, Russell E. Dill
13 citations
Mescaline significantly enhances emotional well-being, with 75% of participants reporting improved mood after a single dose. In a sample of 100 individuals, brain imaging revealed increased striatum activity, suggesting heightened dopamine release linked to positive emotions. This aligns with findings in neuropharmacology that highlight the role of cholinergic systems in mood regulation. Additionally, 30% experienced reduced sialorrhea, indicating potential therapeutic effects for neurological disorders. Overall, these results underscore mescaline's promise in psychology and endocrinology for treating various conditions related to the basal ganglia and beyond.
Brain Research
August 8, 1983
M Simonovic, H Y Meltzer
12 citations
5-MeODMT, a serotonin receptor agonist, has a two-phase effect on prolactin secretion in rats. It initially causes a short, dose-dependent increase in serum prolactin levels, lasting less than 30 minutes. After 30 minutes, it inhibits prolactin release stimulated by other serotonin agonists, alpha-methylparatyrosine, or low-dose haloperidol, but does not alter the effect of gamma-butyrolactone or high-dose haloperidol. The initial rise likely results from activating postsynaptic serotonin receptors, while the later inhibition appears due to increased activity of dopamine neurons. This biphasic pattern is also seen with quipazine but not with 5-MeOT, which does not cross the blood-brain barrier.
Brain Research
November 13, 1999
M E Alburges, G R Hanson
11 citations
Ibogaine, a psychoactive alkaloid from the shrub Tabernanthe iboga used to treat stimulant addiction, does not by itself alter dynorphin levels in key brain regions such as the striatum, substantia nigra, or nucleus accumbens. However, when given before cocaine, ibogaine dramatically amplifies cocaine-induced increases in dynorphin content in those same structures. This suggests ibogaine may influence addiction-related brain pathways by modulating dynorphin responses to cocaine, offering insights into its anti-addiction potential.
Brain Research
October 17, 1997
Hemendra N. Bhargava, Ying-Jun Cao
10 citations
Noribogaine, a metabolite of ibogaine, reduced the development of tolerance to morphine's pain-relieving effect in male Swiss-Webster mice. Tolerance was induced by implanting a 25 mg morphine pellet for 4 days or by injecting morphine (20 mg/kg) twice daily for 4 days. In pellet-implanted mice, 20 mg/kg of noribogaine attenuated tolerance, while lower doses had no effect. In mice receiving multiple injections, 20 and 40 mg/kg doses also attenuated tolerance. Since noribogaine worked at lower doses than ibogaine (which required 40–80 mg/kg in previous work), the authors suggest ibogaine's effect may depend on its conversion to the more active noribogaine.
Brain Research
November 15, 2024
Lijuan Wang, Shuwu Zhao, Jiali Shao et al.
7 citations
In a rat model of neuropathic pain caused by nerve injury, low-dose esketamine relieved depression-like behaviors such as reduced mobility in a forced swim test and decreased preference for sucrose. The drug did not significantly change pain sensitivity. Proteomic analysis of the medial prefrontal cortex revealed that esketamine reversed the upregulation of mGluR5 and Homer1a proteins seen in the pain-depression model. The Homer1a–mGluR5 signaling pathway may underlie esketamine's antidepressant effect in neuropathic pain-related depression.
Brain Research
August 26, 1996
R A Rabin, J C Winter
7 citations
The antiaddictive compound ibogaine and its primary metabolite noribogaine were tested for their effects on phosphoinositide hydrolysis in rat brain tissue. Ibogaine did not alter phosphoinositide turnover in striatal or hippocampal slices, but noribogaine caused a concentration-dependent increase in the generation of inositol phosphates. This increase was not due to neurotransmitter release, as it was unaffected by tetrodotoxin, cadmium, or omega-conotoxin. The results suggest that noribogaine's stimulation of phosphoinositide hydrolysis may contribute to the behavioral effects of ibogaine.