The International Journal of Neuropsychopharmacology
July 9, 2008
Thibault Renoir, Eleni Païzanis, Malika El Yacoubi et al.
58 citations
A single sentence summary is not possible because the abstract contains multiple distinct findings. Four weeks after administering MDMA to mice, the potency of a 5-HT1A receptor agonist to inhibit serotonin neuron firing in the dorsal raphe nucleus doubled, and the hypothermic response to 8-OH-DPAT increased, indicating supersensitivity of 5-HT1A autoreceptors. Brain serotonin levels decreased without changes in citalopram binding. MDMA treatment also reduced hippocampal cell proliferation by 30% and increased immobility in the forced swim test, suggesting depressive-like behavior. These effects were absent in mice lacking the serotonin transporter, indicating the transporter is required for these delayed, antidepressant-opposite effects that may contribute to MDMA-induced mood disorders.
The International Journal of Neuropsychopharmacology
May 10, 2021
Natalie Gukasyan, David B. Yaden, Matthew W. Johnson et al.
56 citations
Psychedelic substances produce unusual changes in conscious experience, leading some to propose they offer unique insights into consciousness. However, psychedelics are unlikely to provide information relevant to the "hard problem of consciousness," which involves explaining how first-person experience emerges. Instead, they bear on multiple "easy problems of consciousness," involving relations between subjectivity, brain function, and behavior. This review discusses common meanings of "consciousness" regarding psychedelics and considers models of their effects on the brain linked to explanatory claims about consciousness. It calls for epistemic humility about psychedelic research's potential to explain the hard problem while noting ways psychedelics may advance study of specific aspects of consciousness.
The International Journal of Neuropsychopharmacology
August 28, 2019
Jiancheng Zhang, Youge Qu, Lijia Chang et al.
56 citations
A single injection of (R)-ketamine (10 mg/kg) rapidly reversed the loss of dendritic spines in the medial prefrontal cortex and hippocampus of mice that had become susceptible after chronic social defeat stress. Spine density was measured three hours after treatment and was significantly increased in the prelimbic area of the medial prefrontal cortex, the Cornu Ammonis3 region, and the dentate gyrus of the hippocampus. The findings suggest that (R)-ketamine's rapid restoration of spine density in these brain regions may underlie its fast-acting antidepressant effects.
The International Journal of Neuropsychopharmacology
December 19, 2014
Mark J. Niciu, David A. Luckenbaugh, Dawn F. Ionescu et al.
55 citations
A single low-dose infusion of the anesthetic ketamine produces rapid antidepressant effects in people with treatment-resistant major depressive disorder. In this trial, depressed individuals with a family history of alcohol use disorder showed a longer-lasting antidepressant response to ketamine compared to those without such a family history. Adding the drug riluzole did not extend or enhance ketamine's antidepressant durability. The findings suggest that family history of alcohol use disorder may predict a more durable ketamine response, which should be accounted for in future ketamine depression studies.
The International Journal of Neuropsychopharmacology
March 25, 2010
Joyce Colussi‐mas, Richard J. Wise, Alex Howard et al.
51 citations
In rats that learned to self-administer MDMA, a later injection of the drug triggered renewed drug-seeking behavior. The strength of this drug seeking was greater in rats that had acquired self-administration more quickly and in those that showed larger MDMA-induced increases in dopamine in the dorsal striatum. Rats that never learned to self-administer MDMA or that received the drug passively did not show this effect. The findings suggest that individual differences in initial sensitivity to MDMA's reinforcing effects and in the drug's ability to elevate striatal dopamine influence the propensity to seek the drug after a period of abstinence.
The International Journal of Neuropsychopharmacology
December 28, 2014
Stephanie M. Gorka, Daniel A. Fitzgerald, Harriet de Wit et al.
43 citations
Δ(9)-Tetrahydrocannabinol (THC) enhances functional connectivity between specific amygdala subregions (basolateral and superficial) and the rostral anterior cingulate/medial prefrontal cortex during social threat processing in healthy adults. This effect may help reduce threat perception or improve socio-emotional regulation, shedding light on the neurocircuitry underlying affective processes. The findings come from a double-blind, placebo-controlled, within-subjects study with 16 participants using functional magnetic resonance imaging.
The International Journal of Neuropsychopharmacology
May 16, 2017
André Schmidt, Felix Müller, Patrick C. Dolder et al.
41 citations
Methylphenidate and modafinil, but not MDMA (ecstasy), improved the ability to stop a motor response in healthy adults. Using brain imaging, methylphenidate broadly activated frontal, temporal, and parietal regions, including the anterior cingulate cortex and presupplementary motor area, more than modafinil did. Modafinil increased activation in the right middle frontal gyrus and parietal lobule, while MDMA activated the right middle/inferior frontal gyrus and superior parietal lobule without improving performance. The findings suggest that methylphenidate may be superior to modafinil and MDMA for enhancing cognitive performance related to response inhibition in healthy people.
The International Journal of Neuropsychopharmacology
July 23, 2020
Danilo de Gregorio, Joshua Dean Conway, Martha-Lopez Canul et al.
39 citations
Chronic exposure to a low dose of THC (1 mg/kg) during adolescence in rats leads to depressive-like behaviors (increased immobility in the forced swim test and anhedonia in the sucrose preference test) and anxiety-like behavior (fewer open-arm entries in the elevated plus maze). Adult exposure also produces anxiety but not depressive-like behaviors. Both adolescent and adult THC exposure reduce the activity of serotonin neurons in the dorsal raphe, while noradrenergic neurons in the locus coeruleus remain unaffected. These findings suggest that the serotonin system is vulnerable to chronic low-dose THC, and that adolescents are particularly susceptible to THC-induced depressive effects.
The International Journal of Neuropsychopharmacology
October 14, 2010
María Juliana Orejarena, Laurence Lanfumey, Rafaël Maldonado et al.
38 citations
The serotonin 5-HT2A receptor plays a crucial role in the reinforcing and addictive properties of MDMA. In experiments with mice, those lacking the 5-HT2A receptor showed reduced self-administration of MDMA at both 0.125 and 0.25 mg/kg per infusion compared to normal mice. MDMA increased horizontal locomotion more in the knockout mice than in normal mice. Dopamine release in the nucleus accumbens was lower in knockout mice both at baseline and after MDMA challenge. Cue-induced reinstatement of MDMA-seeking behavior was blocked by a selective 5-HT2A receptor antagonist at 0.5 mg/kg. These findings suggest that 5-HT2A receptors are essential for MDMA's reinforcing effects and for relapse triggered by drug-associated cues, likely through modulation of dopamine activity in the brain's reward pathway.
The International Journal of Neuropsychopharmacology
February 12, 2016
Marta Valle, Montserrat Puntes, Jimena Coimbra et al.
31 citations
Salvinorin-A, a terpene from the plant Salvia divinorum, induces an intense but short-lasting altered state of awareness similar to classical psychedelics, but it acts on kappa-opioid receptors rather than serotonin-2A receptors. In a double-blind, placebo-controlled study with 24 healthy volunteers experienced with psychedelics, inhalation of 1 mg of vaporized salvinorin-A severely reduced external sensory perception, caused intense visual and auditory modifications, and increased systolic blood pressure, cortisol, and prolactin. These effects were effectively blocked by the opioid antagonist naltrexone (50 mg orally) but not by the serotonin-2A antagonist ketanserin (40 mg orally), confirming that salvinorin-A's mechanism involves kappa-opioid receptor agonism and not serotonin-2A agonism.
The International Journal of Neuropsychopharmacology
April 24, 2014
Hong‐yi Chiu, Ming‐huan Chan, Mei-Yi Lee et al.
31 citations
A single-day 'binge' dosing regimen of methamphetamine in male mice impaired recognition memory, reduced social behaviors, and increased sensitivity to a hallucinogenic drug that activates serotonin 5-HT2A receptors. The heightened behavioral, molecular, and electrophysiological responses to the hallucinogen were linked to an up-regulation of 5-HT2A receptors in the medial prefrontal cortex, while 5-HT2C and 5-HT1A receptors remained unchanged. These findings suggest that methamphetamine-induced changes in 5-HT2A receptor expression may contribute to psychosis-like behaviors and could inform therapies for methamphetamine-related psychiatric disorders.
The International Journal of Neuropsychopharmacology
June 10, 2013
José L. Moreno, Javier González‐maeso
30 citations
Psychedelic drugs like LSD and dissociative drugs like PCP produce psychotic and cognitive symptoms in healthy people that resemble aspects of schizophrenia. Serotonin 5-HT2A and metabotropic glutamate 2 receptors are involved in how these drugs work. This review examines recent studies using LSD-like and PCP-like drugs in rodents that link these receptors to the biology of schizophrenia and its treatment.
The International Journal of Neuropsychopharmacology
July 5, 2021
Sven Melker Hagsäter, Robert Pettersson, Christopher Pettersson et al.
29 citations
Activating the 5-HT2A serotonin receptor with drugs such as psilocybin reduces conditioned fear in male rats, an effect blocked by a 5-HT2A inverse agonist. Inverse agonists alone did not change fear behavior, but they unmasked a fear-reducing effect of the SSRI escitalopram, which by itself had no effect. These results suggest that 5-HT2A receptor activation is not required for normal conditioned freezing but can dampen fear when over-activated. In the presence of an SSRI, the 5-HT2A receptor appears to oppose the anti-freezing effect of increased serotonin levels.
The International Journal of Neuropsychopharmacology
December 2, 2008
Sami Ben Hamida, A. Tracqui, Anne Pereira de Vasconcelos et al.
27 citations
Taking the club drug ecstasy (MDMA) together with alcohol (ethanol) increases the drug's levels in the blood and brain, which may explain why alcohol amplifies MDMA's stimulant effects. In rats, alcohol raised MDMA concentrations in the blood, hippocampus, frontal cortex, and striatum within 15 to 60 minutes after injection, without changing the proportion converted to its active metabolite MDA. MDMA and MDA accumulated more in the striatum and cortex than in the hippocampus. These higher brain and blood levels suggest that combining alcohol with MDMA could increase the risk of neurotoxicity and potential for abuse.
The International Journal of Neuropsychopharmacology
August 1, 2005
Eszter Kirilly, Anita Benkő, Linda Ferrington et al.
26 citations
A single dose of MDMA (15 mg/kg) in male Dark Agouti rats caused lasting damage to the serotonin system, shown by 30–60% reductions in paroxetine binding in the forebrain and decreased brain glucose metabolism in aggression-related areas. Despite this neurotoxicity, aggressive behaviors (biting, boxing, wrestling) were not significantly different from controls three weeks later, and the acute anti-aggressive effects of MDMA and two 5-HT1B receptor agonists remained intact. The findings suggest that aggressive behavior and the acute anti-aggressive action of MDMA are preserved even with substantial serotonergic damage, at least under the social isolation conditions of the resident-intruder test.
The International Journal of Neuropsychopharmacology
November 22, 2017
André Schmidt, Felix Müller, Patrick C. Dolder et al.
25 citations
Modafinil, but not methylphenidate or MDMA, increased brain activity in a limbic-cortical-striatal-pallidal-thalamic circuit and the amygdala when healthy subjects viewed fearful faces. Activation in frontal brain regions correlated with increased feelings of fearfulness and depressiveness after modafinil. Despite modafinil's cognitive enhancement effects, potential adverse effects on emotion processing should be considered.
The International Journal of Neuropsychopharmacology
January 11, 2013
Tori L. Schaefer, Curtis E. Grace, A Braun et al.
24 citations
In rats, treatment with the recreational drug MDMA during a developmental period equivalent to the human third trimester causes long-term spatial and egocentric learning and memory deficits, along with serotonin reductions. Pretreatment with the antidepressant citalopram, a selective serotonin reuptake inhibitor, did not prevent these cognitive deficits. Unexpectedly, citalopram alone produced learning deficits as severe as those caused by MDMA. These are the first findings showing cognitive impairments from developmental exposure to a selective serotonin reuptake inhibitor, suggesting the need for further research on the long-term safety of antidepressants during pregnancy.
The International Journal of Neuropsychopharmacology
August 10, 2022
Anne Weigand, Matti Gärtner, Milan Scheidegger et al.
22 citations
Activity in the pregenual anterior cingulate cortex (pgACC) during emotional stimulation can predict how well a single intravenous infusion of ketamine will relieve depression symptoms in people with major depressive disorder. In 24 patients, pgACC activity was linked to an increase in glutamate in the same brain region 24 hours after the infusion, and this glutamate increase was associated with greater symptom improvement. The findings suggest pgACC activity may serve as a neuroimaging biomarker for early treatment response to ketamine.
The International Journal of Neuropsychopharmacology
February 8, 2017
Alexander Bryson, Olivia Carter, Trevor R. Norman et al.
19 citations
Functional neurological disorders are common, have poor outcomes, and few treatments exist. Their cause is unknown, but leading theories suggest a disturbance in how the mind represents the body, with abnormal top-down cognitive influences on sensorimotor function despite intact neural pathways. Recent studies indicate that 5-HT2A agonists, such as psychedelics, alter brain activity in ways that disrupt hierarchical dynamics and modulate networks involved in self-processing. Converging evidence suggests these agents may hold unique therapeutic potential for these disorders. Given the personal and societal burden, the authors argue a clinical trial to test this hypothesis is warranted.
The International Journal of Neuropsychopharmacology
February 14, 2014
Vibe G. Frøkjær, David Erritzøe, Klaus K. Holst et al.
19 citations
Prefrontal serotonin transporter binding is positively associated with the cortisol awakening response, a measure of hypothalamic-pituitary-adrenal-axis output, in both MDMA users and non-users. MDMA users showed a significantly higher cortisol awakening response than non-users. The findings suggest that the inhibitory control on HPA-axis output is less efficient after recent MDMA use, likely through mechanisms beyond those compensated by reduced serotonin transporter levels.
The International Journal of Neuropsychopharmacology
November 29, 2024
Helen M Collins
18 citations
Psychedelics are being investigated as treatments for several mental health conditions, including obsessive–compulsive disorder (OCD). Since the 1960s, case studies have reported improvements in obsessive and compulsive behaviors after recreational psychedelic use. A small 2006 open-label trial found that psilocybin significantly reduced OCD symptoms, and rodent models show reduced compulsive behaviors after psilocybin. However, the mechanisms remain unclear, with hypotheses involving acute pharmacological effects, neuroplasticity changes, and altered resting state neural networks. This review evaluates evidence for psychedelics in OCD treatment, discusses mechanisms, and notes ongoing trials addressing current knowledge gaps.
The International Journal of Neuropsychopharmacology
March 1, 2003
Tarek Zghoul, Pierre Blier
13 citations
LSD enhances the inhibitory effect of serotonin on neurons in the orbitofrontal cortex, a brain region linked to obsessive-compulsive disorder (OCD), while reducing serotonin's inhibitory effect in the hippocampus, a region linked to depression. In rats under anesthesia, LSD applied directly to neurons decreased their firing rate and boosted serotonin's inhibitory action in the orbitofrontal cortex, but weakened it in the hippocampus. After four daily injections of LSD, the same pattern persisted 24 hours after the last dose, suggesting a lasting change in serotonin responsiveness. This enhancement in the orbitofrontal cortex may explain why some hallucinogens have anti-OCD effects that outlast their psychotomimetic action.
The International Journal of Neuropsychopharmacology
December 3, 2021
Benjamin Hackl, Hannes Todt, Helmut Kubista et al.
11 citations
Psilocybin, the hallucinogen in magic mushrooms, is being studied for psychiatric disorders, but safety concerns arose after reports of cardiac events and QT interval prolongation linked to its metabolite psilocin. Clinical concentrations of psilocin do not significantly inhibit the hERG potassium channel, a key risk factor for adverse cardiac effects. Therefore, hERG channel blockage by psilocin is not responsible for psilocybin-associated cardiotoxicity.
The International Journal of Neuropsychopharmacology
May 27, 2016
Filip Tylš, Michaela Viktorinová, Dominika Prokopcova et al.
10 citations
Among first-episode, drug-naive Han Chinese patients with schizophrenia, 24.5% had impaired glucose tolerance, compared to none of the healthy controls. Patients also had higher fasting and two-hour glucose levels, greater insulin resistance, and higher waist circumference, BMI, and triglycerides. Those with impaired glucose tolerance were older, had later schizophrenia onset, and scored higher on total and negative symptom scales, but showed no greater cognitive impairment except on an emotional intelligence measure. Abnormal glucose metabolism may be linked to clinical symptoms but not cognitive impairment in early schizophrenia.
The International Journal of Neuropsychopharmacology
May 25, 2025
Ines Erkizia-Santamaría, Nerea Martínez-Álvarez, Leyre Salinas-Novoa et al.
7 citations
The intensity of acute psychedelic effects from psilocybin is inversely related to cortical serotonin levels. In mice, the head-twitch response—a behavioral measure of psychedelic-like effects—was lower in animals lacking the serotonin 2A receptor and was dose-dependently reduced by the antidepressant citalopram, which increases synaptic serotonin. Conversely, depleting serotonin with p-chlorophenylalanine potentiated the response. A serotonin 1A receptor agonist also decreased the response, indicating functional interaction between receptor types. These findings suggest that prior antidepressant treatment may influence individual variability in acute responses to psilocybin, with implications for optimizing psychedelic-based therapies.