Brain research bulletin
January 1, 1997
H Sershen, A Hashim, A Lajtha
32 citations
Ibogaine, an indole alkaloid, may help treat drug dependence. Animal studies show it reduces some effects of stimulant drugs, like motor stimulation and self-administration. The mechanism likely involves dopamine, serotonin, NMDA, kappa, and/or sigma receptor sites, based on binding competition studies, though receptor affinity alone does not prove involvement. In vitro perfusion studies help clarify ibogaine's effects on neurotransmitter systems and their functional consequences. This review summarizes evidence for ibogaine's multiple effects, highlighting the potential importance of its action on serotonergic modulation of dopamine release.
Brain research bulletin
April 1, 1999
G B Wells, M C Lopez, J C Tanaka
30 citations
Ibogaine blocks the uptake of dopamine and serotonin in rat brain synaptosomes, with stronger effects on serotonin (IC50 2.6 µM) than dopamine (IC50 20 µM). It inhibits potassium-induced serotonin release but not dopamine release, and triggers a small dopamine release without stimulation. These micromolar-range effects align with ibogaine's low binding affinity for dopamine and serotonin transporters, suggesting that if ibogaine's anti-addictive properties require such concentrations, they likely involve multiple neurotransmitter pathways.
Brain research bulletin
January 1, 1995
H Sershen, A Hashim, A Lajtha
25 citations
Ibogaine, an indole alkaloid, may help interrupt stimulant drug dependency by affecting dopamine release in the brain's striatum. In mouse striatal tissue, the kappa-opioid agonist U 62066 reduced stimulated dopamine release, but ibogaine pretreatment (40 mg/kg IP given 2 hours prior or 2 x 40 mg/kg with animals killed 18 hours later) eliminated this effect. The 5-HT3 agonist phenylbiguanide had a biphasic effect: at 10(-6) M it reduced release, while at 10(-5) M it increased basal outflow. Ibogaine pretreatment did not alter release with 10(-6) M phenylbiguanide but increased stimulated outflow with 10(-5) M. Cocaine (10(-6) M) increased electrically-evoked dopamine release, and ibogaine did not affect this. Ibogaine's modulation of kappa-opioid and 5-HT3 receptors on dopamine terminals may underlie its antiaddictive properties.
Brain research bulletin
January 1, 1996
H Sershen, A Hashim, A Lajtha
19 citations
Ibogaine, an indole alkaloid, inhibits NMDA- and sigma-receptor-mediated dopamine release in mouse striatal tissue. In vitro, ibogaine at 1 µM reduced NMDA-evoked dopamine release by 31% and sigma-receptor-evoked release by 48%. Ibogaine alone at 10 µM increased dopamine efflux, while 1 µM had no effect. The elevated basal dopamine release after evoked release in ibogaine-treated tissue suggests ibogaine may remove tonic inhibition by the kappa-opioid system, which normally reduces dopamine release presynaptically and also inhibits NMDA and sigma receptors.
Brain research bulletin
January 1, 1997
S B Kombian, T M Saleh, N I Fiagbe et al.
14 citations
Ibogaine, a natural alkaloid from Voacanga africana, reduces withdrawal symptoms and craving in drug addiction. Its cellular mechanisms were investigated in parabrachial nucleus neurons using patch-recording techniques. Ibogaine and the plant extract dose-dependently and reversibly suppress excitatory synaptic currents, with ibogaine having an ED50 of 5 microM and the extract 170 micrograms/ml. At higher concentrations, they depolarize neurons, increase firing rate, and raise input resistance. These effects are blocked by the dopamine receptor antagonist haloperidol. The findings indicate ibogaine and the extract alter neuronal excitability and synaptic transmission through dopaminergic and glutamatergic processes, with the extract being about one-hundredth as active as ibogaine.
Brain research bulletin
January 1, 1996
L M Cancela, M Volosin, V A Molina
14 citations
Injecting gangliosides before repeated restraint stress in rats reversed stress-induced reductions in motor activity and body weight, and enhanced certain behavioral responses linked to serotonin receptors. A single stress session or three days of stress alone did not change the response to a serotonin-receptor drug, but combining gangliosides with three days of stress increased forepaw treading and hindlimb abduction. Gangliosides may speed up adaptive changes in serotonin-1 sites and lessen some aftereffects of stress.
Brain research bulletin
October 15, 2023
Saampras Ganesan, Bradford A Moffat, Nicholas T Van Dam et al.
13 citations
Using 7 Tesla functional MRI, a pilot study scanned 10 beginner meditators during focused attention meditation (attending to breathing) and non-focused rest. After adjusting for physiological differences, meditation reduced activity in default-mode network hubs (antero-medial prefrontal and posterior cingulate cortices, precuneus) and visual and thalamic regions compared to rest. These reductions survived stringent corrections for physiological fluctuations. State mindfulness scores rose significantly after the session and remained elevated at a 2-week follow-up. The findings support evidence that focused attention meditation dampens default-mode activity tied to self-referential processing and demonstrate the feasibility of ultra-high field fMRI for meditation research.
Brain research bulletin
November 13, 2025
Xiang Liu, Ziyi Hua, Yongqiang Shu et al.
1 citation
In patients with major depressive disorder, a two-week course of intravenous esketamine combined with sertraline led to improvements in anxiety, depression, suicidal ideation, and cognitive scores. Brain imaging revealed that before treatment, patients had abnormal spontaneous brain activity compared to healthy individuals, with increased regional homogeneity in several brain regions and decreased homogeneity in others. After treatment, the local consistency of the left middle temporal gyrus reversed toward normal levels. Changes in this region correlated with anxiety scale scores, suggesting it may be a key hub linked to depression severity and recovery.
Brain research bulletin
August 1, 2026
Rui Dong, Jiaxin Liu, Yumei Shen et al.
In a mouse model of trigeminal neuralgia (TN) that also shows anxiety-like behavior, esketamine (ES) given for five days dose-dependently reduced pain and anxiety. TN caused damage to neurons in the hippocampus and increased levels of the necroptosis pathway proteins RIPK1, RIPK3, and MLKL. ES treatment reversed these changes, protecting neurons and restoring dendritic spines. Adding a necroptosis activator blocked ES's effects, confirming that ES works by inhibiting the RIPK1/RIPK3/MLKL pathway. The findings highlight necroptosis as a key mechanism linking TN pain to emotional disorders and suggest ES could be repurposed as a treatment for both pain and anxiety in TN.
Brain research bulletin
November 22, 2025
Yinying Sun, Bo Li, Yiting Wang et al.
A low dose of esketamine (2 mg/kg) significantly accelerated awakening from propofol anesthesia in adult C57BL/6J mice. In the prefrontal cortex, esketamine hastened the emergence of γ oscillations and triggered earlier activation of neuronal somata and dendrites in layer V, while delaying activation in layer II/III neurons. It also induced inter-layer phase desynchronization and a premature increase in acetylcholine and 5-hydroxytryptamine levels. The findings suggest that low-dose esketamine facilitates awakening by orchestrating a sequence of neural events in the prefrontal cortex, providing mechanistic insight into paradoxical emergence from anesthesia.