Brain Research Bulletin
April 30, 2016
Theresa M. Carbonaro, Michael B. Gatch
258 citations
N,N-dimethyltryptamine (DMT) is an indole alkaloid found in plants and animals, known for producing brief, intense psychedelic effects. Evidence suggests endogenous DMT may act as a neurotransmitter in the periphery and central nervous system. This review covers recreational use, potential endogenous roles, pharmacokinetics, mechanisms of action, clinical uses, and adverse effects. DMT appears to have limited neurotoxicity and few adverse effects, except for intense cardiovascular effects when given intravenously in large doses. It may be a useful experimental tool for exploring brain function and a clinical tool for treating anxiety and psychosis.
Brain Research Bulletin
March 11, 2016
Elisabet Domínguez‐clavé, Joaquim Soler, Matilde Elices et al.
220 citations
Ayahuasca, a tea made from the vine Banisteriopsis caapi and often combined with Psychotria viridis leaves, induces a transient altered state of consciousness marked by introspection, visions, enhanced emotions, and personal memory recall. Its psychoactive effects come from N,N-dimethyltryptamine (DMT), a 5-HT2A receptor agonist, and β-carboline alkaloids that inhibit monoamine oxidase. A growing body of evidence suggests ayahuasca may help treat substance use disorders, anxiety, and depression. The review discusses how ayahuasca intake increases mindfulness facets related to acceptance and detached observation of thoughts and emotions. The authors conclude ayahuasca shows promise for enhancing self-acceptance and enabling safe exposure to emotional events, potentially useful for impulse-related, personality, and substance use disorders and trauma, though more research is needed.
Brain Research Bulletin
May 4, 2016
Rachel R. Horsley, Eva Lhotková, Kateřina Hájková et al.
38 citations
Methoxetamine (MXE), a novel psychoactive compound used as a substitute for ketamine, was tested in Wistar rats across a series of behavioral tasks. At lower doses (5 and 10 mg/kg), MXE stimulated locomotion, increased thigmotaxis, and decreased time spent in the center of an open field, indicating anxiogenic effects. At a higher dose (40 mg/kg), it reduced locomotion and increased time in the center, suggesting sedation or anesthesia. MXE disrupted prepulse inhibition (PPI) and reduced habituation. The drug accumulated in the brain, with brain-to-serum ratios between 2.06 and 2.93, and its effects lasted at least 60–90 minutes.
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
May 1, 1977
David E. Nichols, William Pfister, G.k.w. Yim et al.
10 citations
The S-(-) enantiomer of 2-amino-1,2,3,4-tetrahydronaphthalene (2-AT) produces selective central effects in mice and rabbits that resemble those of hallucinogens such as mescaline. A stereochemical analysis of these findings suggests that the structural relationship between mescaline and other phenethylamine-type hallucinogens may involve a correspondence between the aromatic ring of the phenethylamines and the pyrrole portion of the indole nucleus in LSD.
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.
Brain Research Bulletin
October 27, 2025
Shu Wang, Wei Song, Yuanyuan Gao et al.
A single dose of esketamine rapidly improved depressive-like behavior in a mouse model of Parkinson disease. The drug increased expression of GPR109A in the medial prefrontal cortex and reduced levels of pro-inflammatory markers TNF-α, IL-1β, and IL-6. Blocking GPR109A with mepenzolate bromide eliminated these benefits, indicating that GPR109A signaling is necessary for esketamine's antidepressant and anti-inflammatory effects. The findings suggest that esketamine alleviates Parkinson-related depression by suppressing microglial inflammation via GPR109A.
Brain Research Bulletin
September 1, 2026
Qiang Chen, Yating Zhang, Chenrui Liu et al.
Trait mindfulness and hypnosis susceptibility share neural mechanisms involving the prefrontal cortex, anterior cingulate cortex, enhanced theta and alpha EEG rhythms, and dynamic interactions between the salience and central executive networks, suggesting a role in attentional regulation. An integrative framework based on predictive coding for interoception proposes that trait mindfulness enhances perceptual inference and metacognitive awareness, whereas hypnosis susceptibility facilitates acceptance of high-precision prior cues (suggestions) and promotes active inference. This unified perspective may guide future research and clinical translation, such as anxiety interventions.
Brain Research Bulletin
May 1, 2026
Ladina Philomena Gubser, Anna Stefania Trippel, Niklaus Zoelch et al.
A single intravenous dose of R,S-ketamine (0.71 mg/kg bodyweight) administered over 40 minutes to 10 healthy volunteers did not significantly increase glutamate levels in the nucleus accumbens (NAc) when measured by proton magnetic resonance spectroscopy. However, individual changes in glutamate were positively associated with anxious ego dissolution and reductions in vigilance, suggesting that ketamine-induced glutamate alterations in the NAc may underlie specific alterations in perception and consciousness.
Brain Research Bulletin
February 1, 2022
Yan Wei, Tong Wang, Lei Liao et al.
The spleen filters blood and supports the immune system. New evidence shows it also influences brain function in health and disease through immune modulation. In mice, systemic inflammation or chronic social defeat stress causes spleen enlargement (splenomegaly). The antidepressant arketamine can reverse both splenomegaly and depression-like behaviors in stressed mice. A direct brain-to-spleen pathway exists: neurons in the paraventricular nucleus and central amygdala regulate humoral immune defense. Vagal nerve signaling also contributes to brain-spleen communication. This review summarizes recent findings on the brain-spleen axis.
Brain Research Bulletin
December 22, 2020
D. D. Vecchia, L. Kanazawa, E. Wendler et al.
Ketamine reversed depressive-like behaviors and short-term memory impairment in rats with Parkinson's disease-like brain lesions. Male rats received a toxin injection into the substantia nigra pars compacta, which caused short-term social memory loss, reduced sucrose preference (anhedonia), and increased immobility in a forced swim test. Ketamine at 5, 10, and 15 mg/kg once weekly reversed all these effects, with the anti-immobility effect linked to increased swimming, suggesting a serotonergic mechanism. Imipramine also reduced immobility. Neither ketamine nor imipramine restored the dopamine-producing cells lost to the toxin. The results suggest ketamine may help treat depression and memory problems in Parkinson's disease.
Brain Research Bulletin
March 1, 2018
The-Vinh Tran, Se Jin Park, Eun-Joo Shin et al.
Repeated treatment of mice with phencyclidine (PCP), a drug that induces schizophrenia-like symptoms, increased expression of the platelet-activating factor receptor (PAF-R) in the prefrontal cortex and hippocampus, with a greater increase in the prefrontal cortex. This was accompanied by increased activity of the proinflammatory molecule nuclear factor kappa B (NF-κB). Blocking PAF-R with the antagonist ginkgolide B, using PAF-R knockout mice, or inhibiting NF-κB with pyrrolidine dithiocarbamate each reduced PCP-induced abnormal behaviors including reduced sociability, depression, cognitive impairment, and behavioral sensitization. The findings suggest PAF-R drives PCP-induced neuropsychotoxicity through an NF-κB-dependent mechanism and may be linked to schizophrenia-like behavior.
Brain Research Bulletin
September 1, 2017
Kevin Kai-Ting Po, Joseph Wai-Hin Leung, Jackie Ngai-Man Chan et al.
Dextromethorphan (DXM), a common ingredient in cough medicine, is abused by adolescents and can cause euphoria, dissociation, hallucinations, and depressive symptoms with chronic use. Lycium barbarum (wolfberry), a traditional Chinese medicine for neurodegenerative diseases, may reduce depression-like behavior. In a rat study, DXM-treated animals showed increased depression-like and social anxiety-like behaviors after two weeks. Co-treatment with Lycium barbarum polysaccharide (LBP) reduced these adverse effects. Histological analysis revealed that LBP did not promote hippocampal neurogenesis alone but lessened the suppression of neurogenesis caused by DXM. These findings suggest wolfberry could be an adjunct treatment for mood disturbances during cough syrup abuse rehabilitation.
Brain Research Bulletin
April 29, 2010
Antonietta Manna, Antonino Raffone, Mauro Gianni Perrucci et al.
Meditation can be divided into focused attention (FA) and open monitoring (OM) styles, which involve different attentional and awareness processes. In a functional magnetic resonance imaging study, Theravada Buddhist monks expert in both FA and OM meditation, along with novices with 10 days of practice, were scanned. Expert meditators showed massive self-regulation of fronto-parietal and insular areas in the left hemisphere, depending on the meditation state. Anterior cingulate and dorsolateral prefrontal cortices played opposing roles in executive control of attention. The findings resolve a controversy about whether meditation involves hypo- or hyperfrontality, and suggest that mental practice reorganizes brain activity patterns, especially in prefrontal cortex and insula.
Brain Research Bulletin
January 15, 2010
Michela Mazzetti, Claudia Bellucci, Katia Mattarozzi et al.
People with narcolepsy-cataplexy (NC) produce longer and more complex dream reports after the first REM period of the night than healthy controls, suggesting their dream-generation cognitive processes reach optimal functioning earlier. In a study of 14 NC patients and matched controls, dream recall rates were similar (about 90%), but NC patients' spontaneous reports after the first REM awakening were longer and more structurally complex, and half also provided prompted reports of additional dream content. After the third REM awakening, both groups gave prompted reports at similar rates. The findings indicate that in NC the brain mechanisms for constructing dream narratives become fully active earlier in the night, and raise the question of whether prompted and spontaneous reports describe the same or different dreams.
Brain Research Bulletin
October 22, 2008
Carlo Cipolli, Claudia Bellucci, Katia Mattarozzi et al.
People with narcolepsy with cataplexy (NC) experience longer and more complex dream stories during the first REM sleep period of the night compared to healthy individuals. Dream recall rates were similar between groups, at about 85%. The findings suggest that the cognitive processes that generate dreams reach their optimal functioning earlier in the night in NC patients than in normal subjects.
Brain Research Bulletin
March 15, 2005
Róbert Bódizs, Melinda Sverteczki, Alpár Sándor Lázár et al.
During the wake-sleep transition, a REM-like 1.5-3.0 Hz rhythmic activity in the parahippocampal cortex increases, peaking after about 30 seconds of sleep onset and reaching 82% of the level seen during REM sleep. This activity follows the dropout of alpha waves but is not linked to short-term changes in alpha or sleep spindles. Non-REM slow activity below 1.25 Hz steadily increases in both scalp and parahippocampal recordings. The findings suggest that this REM-like parahippocampal slow activity results from the switching off of hypothalamic wake-promoting centers at sleep onset, which inhibits hippocampal function and may contribute to hypnagogic hallucinations.