The International Journal of Neuropsychopharmacology
August 1, 2025
Nicolo Fabila, Nimshitha Pavathuparambil Abdul Manaph, V Rudkowsky et al.
Psilocybin, at a dose of 2 mg/kg, did not reduce compulsive eating in a rat model of binge eating disorder. Female rats given intermittent access to a high-fat/high-sugar diet for 10 weeks showed no change in how quickly they started eating or how much they ate after psilocybin treatment, compared to saline. The compound may have affected freezing behavior, suggesting possible modulation of fear-related learning and memory circuits, though analysis is ongoing. Binge eating disorder is the most common eating disorder and current treatments are limited. Psilocybin is known to promote neuroplasticity, but at this dose it did not alter compulsive-like eating behavior in the conditioned suppression test.
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
February 1, 2025
Rebecca Harding, Natalie Ertl, Rayyan Zafar
Both escitalopram and psilocybin therapy reduced impulsivity and anhedonia in people with major depressive disorder, but they altered brain connectivity in different ways. Psilocybin increased connectivity between the amygdala and the left anterior insula and putamen, and between the limbic striatal network and the bilateral insula, paracingulate, and temporoparietal junction. Escitalopram decreased connectivity between the amygdala and the right cerebellum and occipital cortex, and between the limbic striatum and the insula. The escitalopram-induced reduction in limbic striatal–insula connectivity correlated with reduced anhedonia. These results suggest the two treatments affect reward-related brain circuitry through distinct mechanisms.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martha Lopez Canul, Vivienne Nguyen, Antonio Inserra et al.
Acute administration of psilocybin reduced mechanical allodynia in a rat model of neuropathic pain but had no effect on acute thermal pain in mice. In the neuropathic pain model, psilocybin at 3 mg/kg and 10 mg/kg significantly increased mechanical withdrawal thresholds at 0.5, 1, and 2 hours after administration compared to vehicle, with no difference between the two doses. In the hot plate test, psilocybin did not raise the thermal withdrawal threshold. These preliminary findings suggest psilocybin's pain-reducing action may specifically target neuropathic pain rather than generalized acute nociception, indicating potential for treating neuropathic pain.
The International Journal of Neuropsychopharmacology
February 1, 2025
Sofia Nasini, Sara Tidei, Benedetta Barzon et al.
Repeated low-dose psilocybin (0.05 mg/kg) given to adult male mice for 30 days was safe and well tolerated, with no effect on body weight. The treatment produced anxiolytic-like effects: mice spent more time in the light compartment of the light/dark box, showed shorter latency to choose the first arm in the T-maze, and reduced grooming in the open field. No changes were seen in the elevated plus maze, forced swim test, or sociability test. In the cued Morris water maze, psilocybin-treated mice reached the submerged platform faster across all three days and made more successful trials on days 1 and 2, suggesting possible enhancement of spatial memory and learning that requires further study.
The International Journal of Neuropsychopharmacology
February 1, 2025
Leonard Lerer, Kathleen Spear, Jeet Varia et al.
In a zebrafish model of depression, both synthetic psilocybin and an extract from psychedelic mushrooms reversed stress-induced behavioral changes, making the fish behave similarly to non-stressed controls. The mushroom extract produced more neurotransmitter precursors in the brain than synthetic psilocybin, though no significant behavioral differences between the two treatments were observed. Whole-brain metabolomics revealed increases in GABA, vitamin B6, glutamine, and NADH, along with a decrease in xanthosine, suggesting possible neuroplastic effects. This work demonstrates the potential of zebrafish models for studying psychedelic compounds.
The International Journal of Neuropsychopharmacology
February 1, 2025
Hui-Ju Wu, *Mu-Hong Chen, Wei-Chen Lin
People with treatment-resistant depression have higher blood levels of neurofilament light chain (NFL), a marker of nerve cell damage, than healthy individuals. Among 71 patients with treatment-resistant depression randomly assigned to receive a single low-dose infusion of ketamine (0.5 mg/kg, 0.2 mg/kg) or placebo, higher baseline NFL concentrations were linked to worse depressive symptoms afterward, as measured by the Hamilton Depression Rating Scale. This suggests that NFL levels might help predict how well someone will respond to low-dose ketamine treatment for depression.
The International Journal of Neuropsychopharmacology
February 1, 2025
Zitong Wang, Yanbo Zhang, Xin‐min Li
Psilocybin at 1.0 mg/kg reduced depressive-like behavior and cognitive impairment in stressed Wistar rats but not in treatment-resistant Wistar-Kyoto rats. It downregulated ACTH and corticosterone in Wistar rats, upregulated TSH and melatonin in both strains, and increased BDNF levels in blood and brain regions including the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Psilocybin also upregulated CB1R and TrkB, activated Akt, ERK, and mTOR pathways, and increased 2-AG levels across brain regions. The findings suggest psilocybin mitigates stress-induced HPA axis dysregulation by modulating BDNF signaling mediated by the endocannabinoid system, offering insights into antidepressant mechanisms.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martine Skumlien, Tom P. Freeman, Daniel L. Hall et al.
In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and cannabidiol (CBD) does not moderate this effect. The adolescent reward circuitry is not differentially sensitive to the acute effects of cannabis on reward anticipation. This double-blind, placebo-controlled, crossover study with 23 adults (26-29 years) and 24 adolescents (16-17 years) used functional magnetic resonance imaging (fMRI) to measure brain activity during a monetary reward anticipation task after inhaling cannabis with tetrahydrocannabinol (THC), THC plus CBD, or placebo. THC acutely reduced reward anticipation activity in the ventral striatum and right insula compared with placebo. THC plus CBD also reduced activity in these regions. The effects were the same in adolescents and adults.
The International Journal of Neuropsychopharmacology
May 24, 2018
Dino Luethi, Matthias E Liechti
Rapidly measuring the in vitro pharmacological activity of new psychoactive substances can help predict their psychoactive doses and effects in humans, aiding in the appropriate legal scheduling of these substances.
The International Journal of Neuropsychopharmacology
May 27, 2016
Xiangyang Zhang, Dachun Chen, Raymond J. Cho et al.
Psilocybin, a hallucinogen that models acute psychosis, alters brain connectivity in ways similar to psychotic disorders. In a double-blind placebo-controlled trial with 20 healthy subjects, standard coherence analysis showed decreased connectivity in theta, alpha, and beta bands, especially in frontotemporal and frontoparietal regions and between frontal hemispheres. Higher frequencies showed less significant changes, often in the opposite direction. Lagged coherence analysis revealed increased connectivity in high gamma (50-100 Hz) but no changes in lower frequencies. These preliminary findings suggest psilocybin induces brain connectivity changes characteristic of psychosis, supporting its use as a model for studying psychotic symptoms.