Progress in neuro-psychopharmacology & biological psychiatry
July 13, 2025
Laura Gómez-Acero, Federico Varriano, Nuria Sánchez-Fernández et al.
Adolescent mice treated with THC, the main psychoactive compound in cannabis, later showed impaired social interaction and sensorimotor gating deficits similar to those seen in heavy human cannabis users. The exposure caused long-term disruption of connectivity between the cortex and striatum, which correlated with social problems in adulthood. Molecular changes in the striatum altered the balance among dopamine D2, adenosine A2A, and cannabinoid CB1 receptors, key regulators of the brain's reward system. These results help explain how heavy adolescent cannabis use may increase the risk of psychosis.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
Zhen Xuen Brandon Low, Shin Jie Yong, Hayam A Alrasheed et al.
Long COVID, or post-COVID-19 syndrome (PCS), involves persistent symptoms such as fatigue, sleep problems, olfactory dysfunction, and cognitive issues, with no approved treatments. Recent research links PCS severity to low circulating serotonin levels, suggesting serotonin-modulating therapies may help. This review proposes that serotonergic psychedelics, which act mainly on the 5-HT2A serotonin receptor, could alleviate PCS symptoms through effects on inflammation, neuroplasticity, gastrointestinal function, and endothelial dysfunction. The review also discusses potential benefits for specific symptoms like olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges. Emerging evidence indicates these psychedelics may help, but further high-quality research is needed to confirm their safety and efficacy.
Progress in neuro-psychopharmacology & biological psychiatry
February 8, 2024
Peterson Rech, Rodrigo Miranda Custodio, Maria Laura Rodrigues Uggioni et al.
Nitrous oxide (N2O) shows a rapid therapeutic effect in patients with major depressive disorder and treatment-resistant depression. A systematic review and meta-analysis of randomized clinical trials, including 23 patients with MDD and 86 with TRD, found a large reduction in depression severity (HDRS score) at 24 hours (standardized mean difference -2.36) and a smaller but still significant reduction after one week (SMD -0.60). The evidence suggests N2O may be a fast-acting option for managing decompensated patients, particularly those who do not respond to conventional antidepressants, though more research is needed to determine how long the effect lasts.
Progress in neuro-psychopharmacology & biological psychiatry
December 20, 2022
John Cook, Angelos Halaris
Esketamine, approved by the FDA in early 2019 for treatment resistant depression, works by blocking NMDA receptors and improving symptoms rapidly through glutamatergic activation. Widespread use is limited by concerns about durability of response, especially during maintenance. Since esketamine must be taken with an oral antidepressant, choosing the right combination may improve outcomes. Because many patients with major depressive disorder and treatment resistant depression have dysfunction in dopaminergic pathways, adding a prodopaminergic agent like bupropion could enhance and prolong response. Anecdotal evidence and mechanistic rationale support this approach, and the oral combination of dextromethorphan and bupropion (AXS-05) has shown promise in clinical trials. This paper argues that dopaminergic enhancement may boost esketamine's efficacy and durability, encouraging further research.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2021
Hanna J Szkudlarek, Mar Rodríguez-ruiz, Roger Hudson et al.
In rats, THC infused directly into the medial prefrontal cortex (PFC) caused strong panic-like responses, while CBD did not affect panic but blocked the formation of associative fear memories and impaired latent inhibition and oddity discrimination. CBD counteracted THC-induced panic and prevented THC-driven phosphorylation of ERK1/2. CBD's effects on perception and latent inhibition depended on 5-HT1A receptor transmission and were accompanied by reduced phosphorylation of p70S6K, independently of THC. The findings suggest dissociable molecular mechanisms: THC promotes panic via ERK1/2 phosphorylation, while CBD impairs perceptive functions via 5-HT1A receptors and reduced p70S6K phosphorylation.
Progress in neuro-psychopharmacology & biological psychiatry
November 3, 2016
Ralf-Peter Behrendt
Hallucinations may not be fundamentally different from normal conscious experiences; both arise from the same neural processes. Conscious experience reflects the formation of event (episodic) memories, linking hallucinations to the hippocampus. Perceptions and misperceptions are manifestations of activity patterns that recurrently emerge in the CA3 network of the hippocampus, which forms allocentric representations of objects in context. The hippocampus integrates sensory information, emotional context, and guides decision-making via the medial prefrontal cortex. Disruptions in relational memory processing in the hippocampus can give rise to hallucinations. Neurobiological and neuroimaging findings in schizophrenia research support this framework.
Progress in neuro-psychopharmacology & biological psychiatry
October 1, 2015
Andrea De Bartolomeis, Francesco Errico, Giuseppe Aceto et al.
Elevated D-aspartate levels in mice altered expression of key postsynaptic density genes involved in glutamate signaling. In mice lacking D-aspartate oxidase (Ddo-/-), which have persistently high brain D-aspartate, Homer1a expression decreased in the prefrontal cortex, Homer1b/c increased in the striatum, and PSD-95 decreased in both striatum and cortex. Acute treatment with phencyclidine (PCP) restored and even potentiated Homer1a expression in the prefrontal cortex of these mutant mice but had limited effects on other genes. These findings suggest that sustained D-aspartate elevation may trigger adaptive changes in Homer1a that could explain protective effects against PCP-induced behavioral alterations.
Progress in neuro-psychopharmacology & biological psychiatry
July 3, 2014
Colm M P O'Tuathaigh, Ilse Gantois, John L. Waddington
Cannabis use increases the risk of developing schizophrenia and related psychotic disorders. Factors such as age at first cannabis use, genetic predisposition, and other environmental risks may influence susceptibility. Genetic studies increasingly implicate genes involved in dopamine signaling in the link between cannabis and psychosis. This review examines human and animal research on the neural basis of these interactions. More studies are needed to understand the long-term and neurodevelopmental effects of cannabis use, which could clarify the cannabis-psychosis relationship.
Progress in neuro-psychopharmacology & biological psychiatry
February 15, 2008
Mikhail Kalinichev, Melanie J Robbins, Elizabeth M Hartfield et al.
In a rat model of acute psychosis induced by phencyclidine (PCP), the drug's effects on movement and gene expression depend on how it is given. Adult male rats received PCP either injected into the abdomen or under the skin. PCP given under the skin produced stronger and longer-lasting hyperactivity, higher drug levels in blood and brain, and greater activation of several immediate early genes in the prefrontal cortex compared to injection into the abdomen. The differences in drug concentration appeared within 30 minutes and lasted up to 4 hours. The subcutaneous route provides a more robust and consistent model for studying acute psychosis.
Progress in neuro-psychopharmacology & biological psychiatry
February 1, 2005
Do-Hoon Kim, Yoo-Sun Moon, Hee-Sung Kim et al.
People who practiced Zen Meditation had higher serum levels of nitric oxide (measured as nitrate+nitrite) and lower levels of malondialdehyde, a marker of oxidative stress, compared with a matched control group that did not practice any stress management technique. The 20 meditators were recruited from a Meditation Center in Seoul, South Korea, and the 20 controls were matched by age and sex. The authors note that a randomized controlled trial is needed to establish a causal relationship between meditation and these biological markers.
Progress in neuro-psychopharmacology & biological psychiatry
January 1, 1990
P Popoli, A Pezzola, A Scotti de Carolis
Clonidine, an alpha-2 adrenergic agonist, caused sedation and synchronized brain electrical activity in rats starting at 0.05 mg/kg. At low and moderate doses of the dissociative anesthetics PCP and ketamine, clonidine fully inhibited their EEG and behavioral effects, but at high doses it potentiated them. Yohimbine reversed both the inhibitory and potentiating effects of clonidine, as well as the sedation and EEG synchronization. Prazosin did not produce these effects, indicating alpha-2 adrenoceptors are involved. The interaction between dissociative anesthetics and central adrenergic receptors appears complex, with possible relevance for improving ketamine anesthesia and treating PCP intoxication.