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
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
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.
The International Journal of Neuropsychopharmacology
May 27, 2016
Tomáš Páleníček, Filip Tylš, Michaela Viktorinová et al.
6 citations
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The International Journal of Neuropsychopharmacology
January 30, 2024
Blake A Fordyce, Bryan L Roth
4 citations
Psychedelic compounds from natural sources have been consumed for centuries. Modern scientists now use computational tools, cellular assays, and behavioral metrics to study how these compounds cause changes across molecular, cellular, circuit, and system levels. This paper reviews the history of psychedelics in science, medicine, and culture, outlines current pharmacological research techniques, and identifies gaps in knowledge about the physiological changes induced by psychedelics, the limits of their therapeutic potential, and how to improve treatments becoming accessible worldwide.
The International Journal of Neuropsychopharmacology
March 29, 2025
Michal Lazar, Michal Brownstien, Alexander Botvinnik et al.
3 citations
Mice lacking the SAPAP3 gene (SAPAP3-KO) develop excessive self-grooming at 4–6 months, modeling obsessive-compulsive disorder (OCD). Before that, juvenile (10–13 week) homozygous knockout mice showed anxiety-like behaviors—less time in open field centers and elevated plus maze open arms, fewer marbles buried, and fewer buried Oreos found—compared to wild-type mice. Psilocybin (4.4 mg/kg) did not improve these behaviors. In adult (but not juvenile) male homozygous knockout mice, levels of the synaptic proteins GAP43, synaptophysin, and SV2A increased across multiple brain regions; SV2A also increased in the frontal cortex of adult female homozygotes. These age-dependent protein changes may reflect compensatory plasticity linked to the OCD-like phenotype.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martin Kuchař, Klara Gotwaldova, Jan Borovička et al.
1 citation
Tryptamine concentrations in psychotropic mushrooms vary enormously, which may alter medicinal effects compared to chemically pure psilocybin. Storage conditions strongly affect alkaloid decay: the greatest degradation occurred in fresh mushrooms stored at −80°C, while the least decay was seen in dried biomass kept in the dark at room temperature. The study measured psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin in a large sample set of mushroom genera, using freshly cultivated Psilocybe cubensis fruit bodies for stability monitoring, and analyzed mycelium and individual fruiting body parts with validated UHPLC-MS/MS.
The International Journal of Neuropsychopharmacology
May 27, 2016
Jee-Hyung Suh, Tae Young Lee, Jun Soo Kwon
1 citation
Psilocybin, a hallucinogen that mimics psychotic symptoms, alters brain connectivity in ways similar to psychosis. In a double-blind placebo-controlled trial with 20 healthy subjects, standard coherence analysis showed decreased connectivity in theta, alpha, and beta brainwave bands, particularly in frontotemporal and frontoparietal regions, along with frontal interhemispheric disconnection. Changes in higher frequencies were less significant and often opposite. In contrast, eLORETA connectivity analysis found no changes in lower frequencies but increased connectivity in high gamma (50-100 Hz). These preliminary results suggest psilocybin-induced connectivity changes align with those seen in psychotic patients.
The International Journal of Neuropsychopharmacology
July 6, 2026
Shabah M. Shadli, Neda Nasrollahi, Calvin K. Young et al.
Ketamine at low doses (0.5-1.0 mg/kg I.M.) quickly reduces symptoms in treatment-resistant major depressive disorder (TR-MDD), post-traumatic stress disorder (TR-PTSD), and obsessive-compulsive disorder (TR-OCD), but its neural effects differ by diagnosis. EEG recordings of resting frontal activity before and after ketamine or fentanyl showed that TR-PTSD patients had dose- and band-frequency-dependent power changes (especially alpha at 0.5 mg/kg), while TR-MDD patients showed no such changes. TR-OCD responses differed qualitatively from both. Correlations between EEG power changes and symptom scale improvements varied by band and electrode across different disorder-specific scales. Ketamine's effects and their therapeutic links vary by brain site and frequency band depending on the DSM diagnosis, suggesting disorder-specific systems require a ketamine-sensitive factor to generate the disorder.
The International Journal of Neuropsychopharmacology
May 5, 2026
Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar et al.
Between 2013 and 2026, neuropsychopharmacology advanced from stagnation to momentum, producing several first-in-class treatments: rapid-acting drugs for treatment-resistant depression (intranasal esketamine), psychedelic-assisted therapy for PTSD and depression, neuroactive steroid GABA-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression, non-dopaminergic muscarinic agonists (xanomeline-trospium) for schizophrenia, orexin receptor antagonists for insomnia, and anti-amyloid monoclonal antibodies (lecanemab, donanemab) for early Alzheimer's disease.
The International Journal of Neuropsychopharmacology
August 1, 2025
Guy M. Goodwin
A single 25-mg dose of synthetic psilocybin (COMP360) produced larger and more durable reductions in depression severity than a 1-mg control in adults with treatment-resistant depression. Dose-dependent improvements on the Montgomery-Asberg Depression Rating Scale were evident from day 2, remained statistically significant through week 6, and were numerically still present at week 12. The intensity of the psychedelic experience, particularly feelings of boundlessness, was linked to better clinical outcomes. Over 90% of adverse events were mild or moderate. The findings suggest COMP360 may become a useful treatment for treatment-resistant depression, though suicidality remains a concern.
The International Journal of Neuropsychopharmacology
August 1, 2025
Thibault Renoir, J. Gattuso, Bilgenur Bezcioglu et al.
Acute psilocybin reduced compulsive grooming in male mice for up to one week and in both sexes shortly after dosing, but chronic psilocybin did not improve anxiety-like, depressive-like, or compulsive-like behaviors or social deficits. The findings suggest acute psilocybin may help reduce compulsive behaviors, while repeated low-dose use offers limited benefits. The study used SAPAP3 knockout mice, a model of obsessive-compulsive disorder, and found differences in serotonin receptor signaling between genotypes. Results highlight the need for caution as psychedelic-assisted therapy gains approval, especially regarding microdosing.
The International Journal of Neuropsychopharmacology
August 1, 2025
B. D. Richardson, Marco Pileggi, Thomas Prudhomme et al.
Psilocybin and lisuride both bind to 5-HT2A receptors, but only psilocybin produces hallucinogenic effects. In adult male mice, both drugs inhibited serotonin neuron activity in the dorsal raphe nucleus and dopamine neuron firing in the substantia nigra. A 5-HT2A antagonist blocked psilocybin's serotonin inhibition but not lisuride's, suggesting different mechanisms. Only lisuride showed an antidepressant-like effect at the highest doses. Psilocybin, but not lisuride, elicited head-twitch responses, and lisuride blocked those induced by psilocybin. Both drugs reduced locomotion. The findings indicate lisuride has antidepressant and sedative effects without hallucinogenic action, likely due to its distinct effects on serotonin and dopamine neurons.
The International Journal of Neuropsychopharmacology
August 1, 2025
Valeria Bruno, Bruce Richardson, Martha López-canul et al.
In adult male rats, a high dose of psilocybin (10 mg/kg) did not produce rewarding effects in the conditioned place preference (CPP) paradigm, as there was no significant difference in time spent in the drug-paired compartment versus the vehicle-paired compartment. Psilocybin increased head-twitching, dog-shaking, and defecation while decreasing grooming, body licking, and rearing during conditioning sessions. These behavioral differences disappeared 48 hours after the last injection, indicating no long-term changes. The findings suggest psilocybin lacks rewarding properties and does not cause physical dependence, supporting its safety profile and therapeutic potential.
The International Journal of Neuropsychopharmacology
August 1, 2025
Yana Babii, C. Barbara, Dorota Bederska‐łojewska et al.
Hallucinogens from different classes, such as scopolamine and psilocybin, show rapid antidepressant effects that are enhanced by blocking group II metabotropic glutamate (mGlu2/3) receptors. In mice, scopolamine reversed depressive-like behaviors induced by chronic mild stress, and a selective M1 muscarinic antagonist produced dose-dependent antidepressant effects potentiated by an mGlu2 receptor negative allosteric modulator. Scopolamine increased extracellular dopamine, serotonin, and glutamate in the frontal cortex, while the mGlu2 modulator had opposite effects on glutamate. A low dose of the mGlu2/3 antagonist LY341495 boosted the antidepressant effect of low-dose psilocybin in the tail suspension test, with rapid onset and long duration, while also reducing hallucinogenic-like head twitch responses. Combined targeting of these systems may allow lower doses and fewer side effects while maintaining antidepressant efficacy.
The International Journal of Neuropsychopharmacology
August 1, 2025
Andrew S. Gibbons, Paul Liknaitzky, Suresh Sundram
Generalised Anxiety Disorder (GAD) is often treated with psilocybin-assisted therapy (PAT), but only about 44% of participants respond. This multi-omic study compared blood samples from 11 responders and 13 non-responders after a 6-week PAT regime. Five genes were differentially expressed between groups, including CTXN2-AS1 and HLA-V. A panel of four genes (CTXN2-AS1, DUT-AS1, HLA-V, and PARP16) could distinguish 45% of responders from all other participants. These findings suggest potential blood biomarkers for predicting PAT response in GAD, though validation in larger cohorts is needed.
The International Journal of Neuropsychopharmacology
August 1, 2025
Cassandra J. Hatzipantelis, David E. Olson, Danielle S. Stolzenberg
In a mouse model of peripartum mood disorder, a single dose of psilocybin did not improve impaired caregiving, maternal withdrawal, or anxiety-like behaviors; treated dams were more anxious and had increased risk of overall behavioral impairments two weeks after injection. In contrast, virgin female mice given the same dose showed reduced anxiety and lower risk of behavioral impairments. Additionally, a single postnatal exposure to psilocybin through breastmilk increased the risk of behavioral phenotypes related to mood and sociability disorders in both male and female offspring when they reached adulthood. These findings suggest psilocybin may pose risks during the postpartum period for mothers and their offspring.
The International Journal of Neuropsychopharmacology
August 1, 2025
N Acevdo, David Castle, Susan L. Rossell
Obsessive compulsive disorder, body dysmorphic disorder, and anorexia nervosa share overlapping cognitive-behavioral and neurobiological features, yet conventional treatments often yield suboptimal outcomes. Psilocybin-assisted psychotherapy shows transdiagnostic potential by improving insight, emotional regulation, and well-being. This paper presents a protocol for an open-label basket trial testing psilocybin-assisted psychotherapy across these three conditions. The protocol was developed from scoping reviews, an international Delphi study on best practices, and qualitative interviews with patients. It uses a transdiagnostic, non-directive approach, includes a psychoeducation booklet and video, a treatment manual for clinicians, clinician- and patient-reported outcomes, opt-in additional support, and long-term follow-up.
The International Journal of Neuropsychopharmacology
August 1, 2025
Giovanni Martinotti, Clara Cavallotto, G D’andrea et al.
Psilocybin, a psychedelic compound that acts on serotonin receptors, shows promise for treatment-resistant depression, with remission rates up to 70% in some studies. The antidepressant and psychedelic effects may be separable, with the latter linked to 5-HT2A receptors. By co-administering the 5-HT2A antagonist ketanserin, psilocybin's hallucinogenic effects can be minimized, reducing bias from the mystical experience and improving clinical feasibility. A proposed study will randomly assign 68 treatment-resistant depression patients to receive either non-psychedelic psilocybin (two 25 mg doses, preceded by ketanserin) or accelerated repetitive transcranial magnetic stimulation (arTMS). Outcomes will be compared at day 60 using psychometric tests, EEG, and fMRI.
The International Journal of Neuropsychopharmacology
August 1, 2025
Yuko Ohtani, Hiroe Tani, Shiori Honda et al.
A higher baseline ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex predicted greater improvement in depressive symptoms after ketamine treatment in adults with treatment-resistant depression. In the ketamine group, a reduction in this Glx/GABA ratio correlated with symptom improvement, but no such association appeared in the placebo group. The findings suggest that the balance between excitatory and inhibitory neurotransmission in this brain region may serve as a biomarker for predicting antidepressant response to ketamine.
The International Journal of Neuropsychopharmacology
August 1, 2025
Bernard Lerer, Michal Brownstien, Mitchell A. Lazar et al.
Psilocybin and a psychedelic mushroom extract reduced compulsive marble burying and excessive self-grooming in mouse models of obsessive-compulsive disorder (OCD). A single dose of psilocybin remained effective for more than 21 days in SAPAP3-knockout mice, which model OCD and Tourette's syndrome. The mushroom extract showed slightly greater efficacy than psilocybin alone. Two novel compounds, one hallucinogenic and one non-hallucinogenic, were also effective in both mouse models. The non-hallucinogenic compound HBL20017 may offer therapeutic benefit for OCD without inducing psychedelic effects.