Neuroscience Letters
July 27, 2006
Mario Beauregard, Vincent Paquette
338 citations
Mystical experiences—specifically a state of union with God—are associated with activation in multiple brain regions. In Carmelite nuns, fMRI revealed significant activity in the right medial orbitofrontal cortex, right middle temporal cortex, right inferior and superior parietal lobules, right caudate, left medial prefrontal cortex, left anterior cingulate cortex, left inferior parietal lobule, left insula, left caudate, left brainstem, and the extra-striate visual cortex. These findings suggest that such experiences are mediated by several brain regions and systems rather than a single area.
Neuroscience Letters
October 28, 2010
Joon Hwan Jang, Wi Hoon Jung, Do‐hyung Kang et al.
267 citations
Long-term meditation practitioners show greater functional connectivity within the default mode network, specifically in the medial prefrontal cortex, compared to non-meditators, even when not actively meditating. This suggests that regular meditation practice may produce lasting changes in brain regions involved in internalized attention and self-referential thought.
Neuroscience Letters
December 10, 2004
Pehr Granqvist, Mats Fredrikson, Patrik Unge et al.
189 citations
A double-blind experiment with 89 participants found no evidence that weak, complex waveform transcranial magnetic stimulation (TMS) fields evoke a sensed presence of a sentient being, mystical experiences, or other somatosensory effects. The magnetic fields tested were about one million times weaker than ordinary TMS fields. Although earlier claims reported such effects in up to 80% of the general population, this replication found no effects in the entire group or in individuals high in suggestibility. Personality characteristics—absorption, signs of abnormal temporal lobe activity, and a new-age lifestyle orientation—significantly predicted outcomes, suggesting that suggestibility, not the magnetic fields, may account for previously reported effects. These results strongly question earlier claims.
Neuroscience Letters
August 15, 2008
Mario Beauregard, Vincent Paquette
105 citations
Mystical experiences—intense feelings of union with God—are common across cultures, but their brain activity had not been measured with EEG. In 14 Carmelite nuns, EEG was recorded during a resting state, a control condition, and a mystical condition. Compared to the control condition, the mystical condition showed increased theta power at frontal, central, and parietal electrodes, and greater gamma1 power at right temporal and parietal sites. Higher ratios of delta/beta, theta/alpha, and theta/beta appeared at several electrodes. Coherence increased in a frontal-parietal theta band and in several alpha-band pairs across both hemispheres. These results indicate that mystical experiences involve measurable changes in brain electrical activity across multiple cortical areas.
Neuroscience Letters
February 13, 2008
Jiřı́ Wackermann, Marc Wittmann, Felix Hasler et al.
95 citations
Psilocybin, a hallucinogenic substance, alters the internal representation of time by increasing the loss rate of the internal duration representation. In two double-blind, placebo-controlled experiments—one with 12 subjects receiving graded doses and another with 9 subjects receiving a very low dose—participants repeatedly reproduced time intervals between 1.5 and 5 seconds. The parameter kappa from the 'dual klepsydra' model was used to assess effects. At 90 minutes after intake, psilocybin significantly increased kappa, indicating a higher loss rate of internal time representation. These findings may relate to qualitative changes in subjective time during altered states of consciousness.
Neuroscience Letters
June 2, 1995
D C Mash, J K Staley, J P Pablo et al.
82 citations
Ibogaine and its metabolite 12-hydroxyibogamine act at the MK-801 binding site within the NMDA-receptor cation channel. Both compounds competitively displaced [3H]MK-801 binding to membranes from human caudate, cerebellum, and frog spinal cord. Ibogaine was 4-6 times more potent than its metabolite, but both were 50-1000 times less potent than MK-801. Ibogaine (100 µM) and 12-hydroxyibogamine (1 mM) blocked NMDA-induced depolarizations in frog motoneurons by 85-90%. The block was use-dependent and resembled that of MK-801. These findings suggest that ibogaine's ability to interrupt drug-seeking behavior may partly result from its action at the MK-801 binding site.
Neuroscience Letters
September 25, 2022
Alaina M Jaster, Jason Younkin, Travis Cuddy et al.
53 citations
The psychedelic compound DOI triggers more head-twitch behavior—a mouse proxy for human psychedelic effects—in female C57BL/6J mice than in males, a sex difference not seen in 129S6/SvEv mice. The 5-HT2A receptor antagonist volinanserin fully blocked this behavior in both sexes. Despite greater behavioral sensitivity in females, brain and plasma levels of DOI were lower in females 30 and 60 minutes after injection, and no sex difference appeared in frontal-cortex IP1 accumulation. These findings indicate strain-dependent and sex-related differences in the behavioral and pharmacokinetic responses to DOI, underscoring the need to include sex as a biological variable in preclinical psychedelic research.
Neuroscience Letters
January 16, 2013
José L. Moreno, Terrell Holloway, Vinayak Rayannavar et al.
44 citations
Hallucinogenic drugs like LSD, mescaline, and psilocybin all bind strongly to the serotonin 5-HT(2A) receptor. Drugs that affect metabotropic glutamate 2/3 (mGlu2/3) receptors can alter the cellular and behavioral effects of hallucinogens. In mice, chronic treatment (21 days) with the mGlu2/3 receptor antagonist LY341495 (1.5 mg/kg) reduced the hallucinogenic-like effects of LSD (0.24 mg/kg). This treatment decreased binding of a radiolabeled tracer to 5-HT(2A) receptors in the somatosensory cortex of normal mice, but not in mice lacking the mGlu2 receptor. It also reduced head-twitch behavior and the expression of certain genes (c-fos, egr-1, egr-2) that are normally triggered by hallucinogenic drugs. These results suggest that repeatedly blocking mGlu2 receptors dampens the 5-HT(2A) receptor-mediated effects of LSD.
Neuroscience Letters
September 1, 1980
O G Berge, K Hole, H Dahle
34 citations
Injecting 5-methoxy-N,N-dimethyltryptamine into the brain's ventricles altered pain sensitivity in rats, measured by the tail-flick test. Low doses (1.6 to 25 micrograms) reduced tail-flick latencies by 13-24%, indicating hyperalgesia (increased pain sensitivity), likely from decreased activity in descending serotonergic neurons. Moderate doses (50 and 100 micrograms) produced a biphasic response: initial hyperalgesia followed by analgesia. The highest dose (400 micrograms) increased latencies by 28-39%, indicating analgesia, probably by stimulating spinal postsynaptic serotonergic receptors.
Neuroscience Letters
May 19, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
27 citations
Phencyclidine (PCP) causes a head-twitch response in mice and rats that is completely blocked by ritanserin, a serotonin 5-HT2 receptor antagonist, indicating the involvement of 5-HT2 receptors. The same antagonism occurs for head-twitch induced by 5-MeODMT in mice. After ritanserin treatment, PCP and 5-MeODMT still produce head-weaving in mice but not in rats. In rats, 5-MeODMT does not cause head-twitch. These results suggest that PCP-induced head-twitch in rats is mediated by 5-HT2 receptors, making it a useful model for studying those receptors, while 5-MeODMT-induced head-weaving in rats involves 5-HT1 receptors.
Neuroscience Letters
December 23, 1982
T Archer, S O Ogren, S B Ross
24 citations
Drugs that increase serotonin activity—5-MeO-DMT, fenfluramine, and PCA—impair rats' ability to retain fear, as shown by reduced immobility after inescapable shocks. Long-term PCA treatment, which depletes central serotonin neurons, completely blocked the retention impairment caused by acute PCA and fenfluramine, and partially blocked the deficit from 5-MeO-DMT. However, serotonin depletion via PCPA did not block these effects, suggesting different serotonin stores are involved. These findings underscore the role of the ascending serotonin pathway in aversive conditioning in rats.
Neuroscience Letters
April 13, 1992
Y Wada, H Hasegawa, M Nakamura et al.
21 citations
A serotonin receptor agonist, 5-MeODMT, suppresses light-triggered muscle jerks but not abnormal EEG activity in kindled cats. At a dose of 4 mg/kg, the drug reduced photically induced myoclonus for 30 to 60 minutes after injection, accompanied by behavioral signs resembling serotonin syndrome. The findings indicate that serotonin, acting through 5-HT1 receptors, plays a key role in photosensitive epilepsy.
Neuroscience Letters
May 14, 2024
Daniele Cavaleri, Ilaria Riboldi, Cristina Crocamo et al.
13 citations
Ketamine and esketamine are known to relieve depression, but how they work at the molecular level remains unclear. This mini-review summarizes studies using metabolomics to examine metabolic changes after low-dose ketamine or esketamine in animals and humans. Both types of studies show alterations in pathways related to energy production (tricarboxylic acid cycle, glycolysis, pentose phosphate pathway), lipid and amino acid metabolism, the kynurenine pathway, and the urea cycle. These findings suggest the drugs influence mitochondrial function, energy metabolism, membrane maintenance, and cell signaling. Metabolomics may help uncover markers of treatment response and guide personalized depression care, though more research is needed to distinguish effects of the racemic drug from its enantiomers.
Neuroscience Letters
August 14, 1989
B A Heidenreich, G V Rebec
13 citations
In rats pretreated with a high dose of D-amphetamine for six days, serotonergic neurons in the dorsal raphe nucleus showed a trend toward increased spontaneous firing rate and reduced responsiveness to the autoreceptor agonist 5-MeODMT compared to controls. The most notable effect was a strong correlation between spontaneous activity and drug response: faster-firing cells required higher doses of 5-MeODMT to be inhibited. No such correlation appeared in control animals. These results suggest that repeated amphetamine administration alters serotonergic autoreceptor sensitivity in the dorsal raphe.
Neuroscience Letters
July 19, 1988
P K Eide, K Hole
11 citations
Injecting substance P into the spinal cord of mice temporarily caused a behavioral syndrome but no lasting toxic effects or changes in pain sensitivity measured by tail-flick response to heat. However, when given 30 minutes later, the pain-suppressing effect of the serotonin receptor agonist 5-MeODMT was markedly reduced. Skin temperatures were nearly identical between substance P and control groups, ruling out temperature changes as a confound. These results indicate a functional interaction between substance P and serotonin in spinal pain processing, suggesting that intrathecal substance P modulates serotonin receptor function.
Neuroscience Letters
January 1, 1980
Naotoshi Murakami, Yoshihiro Sakai, Shigeki Ooki
9 citations
In rats trained to press a bar to escape radiant heat, intraperitoneal injections of LSD (8-16 micrograms) dose-dependently increased bar-pressing rates. During this increase, rectal temperature rose while tail-skin and selected ambient temperature decreased. The findings suggest LSD-induced hyperthermia results from action on effector pathways rather than an upward resetting of the thermostat.
Neuroscience Letters
June 21, 2024
Carlos M Contreras, Ana G Gutiérrez-García
4 citations
Ketamine, a dissociative anesthetic proposed for treatment-resistant depression, produces beneficial clinical effects only after its psychotropic actions fade, suggesting dose-independent mechanisms. This study compared an anesthetic dose of ketamine with a high dose of fluoxetine in Wistar rats 24 hours after administration. Fluoxetine reduced immobility in the forced swim test without affecting locomotor activity, while ketamine strongly decreased locomotor activity and did not change immobility. In separate rats, lateral septal nucleus (LSN) stimulation produced a long-lasting inhibitory afterdischarge in prelimbic and infralimbic cortices. Both ketamine and fluoxetine accentuated this inhibition, indicating that despite different neurotransmission actions, antidepressants may share a common final pathway involving forebrain structures linked to emotional regulation.
Neuroscience Letters
December 13, 1982
A A Larson
4 citations
Injecting 100 micrograms of 5-MeODMT into the spinal subarachnoid space of conscious rats reduced nociceptive reflex reaction times, indicating a hyperalgesic effect. Administration into the thoracic region decreased the average percent of control reaction time by 14%, while injection into the lumbosacral region produced a 25% decrease. This facilitatory effect on pain perception mimics tryptamine rather than serotonin, suggesting 5-MeODMT interacts with tryptaminergic receptors in the spinal cord.
Neuroscience Letters
August 10, 2024
Isis M. Ornelas, Beatriz de S. Carrilho, Matheus Antonio V. de C. Ventura et al.
3 citations
Lysergic acid diethylamide (LSD), a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders, is absorbed by the nematode Caenorhabditis elegans and acutely reduces its speed, an effect similar to that of endogenous serotonin. This response is partially mediated by the serotonergic receptors SER-1 and SER-4. The findings highlight the potential of C. elegans as a new experimental model for psychedelic research.
Neuroscience Letters
June 21, 2024
Barbara G Ferri, Cintia O De Novais, Viviana C T Rojas et al.
3 citations
In a rat model of sepsis-associated encephalopathy, the psychedelic phenethylamine 25H-NBOMe reduced depressive-like behaviors and signs of neuroinflammation. Rats that underwent cecal ligation and puncture surgery to induce sepsis showed decreased immobility and increased swimming times in the forced swim test after treatment, indicating fewer depressive symptoms. The compound also increased head-twitch responses, confirming its psychoactive effects, and lowered GFAP expression in the prefrontal cortex, suggesting reduced astrogliosis. The findings indicate that 25H-NBOMe can alleviate post-sepsis depression and neuroinflammation, but its psychedelic properties warrant investigation of similar compounds with fewer psychoactive effects.
Neuroscience Letters
June 21, 2024
Yingbing Tu, Bin Xu
3 citations
Esketamine improved spatial learning and memory in triple transgenic Alzheimer's disease (3xTg-AD) mice. The drug increased expression of TRIM24, which activated the PI3K/AKT pathway in the hippocampus. Depleting TRIM24 reversed these cognitive benefits and blocked PI3K/AKT signaling. Esketamine also reduced neuroinflammation—lowering pro-inflammatory molecules, GFAP, and p-Tau—but this effect was lost when TRIM24 was knocked down. Blocking the PI3K/AKT pathway worsened cognitive deficits and inflammation. Thus, esketamine may counteract Alzheimer's-related cognitive decline by suppressing neuroinflammation through the TRIM24/PI3K/AKT axis.
Neuroscience Letters
November 20, 2024
Angeliki Metaxia Styla, Nikolaos Pitsikas
2 citations
A combination of low, individually inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) given after training prevented impairments in both non-spatial and spatial recognition memory in rats. The findings, though preliminary, suggest that pairing these two drugs might offer a new approach for treating memory problems common in Alzheimer's disease.
Neuroscience Letters
January 18, 2024
Hector Vargas-Perez, Fernando Minauro-Sanmiguel, Ryan Ting-A-Kee et al.
2 citations
A classic theory of addiction, opponent-process theory, holds that a drug's immediate rewarding effects are followed by an aversive aftereffect that drives continued use. This study tested whether a 5-HT2A agonist (4-AcO-DMT, a psychedelic) follows that pattern in male rats. In a standard place-preference test 24 hours after dosing—when the drug had cleared—the rats showed no preference for the drug-paired location, suggesting no rewarding aftereffect. However, when the test was modified to capture only the acute drug effect, the rats did show a place preference, indicating the drug itself was rewarding. In a separate test measuring only the 24-hour aftereffect, that aftereffect also produced a strong place preference.
Neuroscience Letters
May 23, 2025
Diane Joss, Gunes Sevinc, John W. Denninger et al.
1 citation
Among 94 chronically stressed but otherwise healthy adults randomized to eight weeks of meditation, yoga, or stress education, only the meditation group showed a significant reduction in resting-state functional connectivity between the posterior cingulate cortex and the left hippocampus. Changes in this brain connectivity were correlated with improvements in perceived stress, allostatic load, and anti-inflammatory gene expression, suggesting that meditation's neural effects are closely linked to physical wellness biomarkers. No such changes occurred in the yoga or stress education groups, indicating this neurobiological mechanism may be unique to meditation training.
Neuroscience Letters
July 1, 2026
Sara Salgues, Geoffrey Duran, Arnaud Fournel et al.
Experiences like sensing a presence or feeling insects crawling under the skin occur in psychiatric, neurological, and toxicological contexts but also frequently in the general population. This exploratory study examined whether resting-state electrocortical oscillatory activity is associated with proneness to such experiences. Participants completed the Complex Bodily Hallucinatory Experiences Scale (CBHES) and underwent eyes-closed resting-state EEG. Significant correlations between CBHES scores and oscillatory activity were found only in three left-lateralized clusters in the delta frequency range: the middle insula, superior anterior temporal lobe, and orbitofrontal cortex. These findings suggest that complex bodily hallucinations involve multiple cognitive mechanisms and that intrinsic resting-state EEG activity is a candidate neurophysiological correlate of proneness to such experiences.