Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcus W. Meinhardt, Ivan Skorodumov, Jérôme Jeanblanc et al.
8 citations
The drug development process in psychiatry faces significant challenges due to low reproducibility rates in animal testing, which often leads to translation failures. To address this issue, we introduce a new approach in psychiatric drug development: a preclinical randomized controlled trial (preRCT). To demonstrate its potential utility, we conducted a multi-center preRCT using the alcohol...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Mina Kheirkhah, Wallace C. Duncan, Qiaoping Yuan et al.
6 citations
Abnormalities during rapid eye movement (REM) sleep contribute to the pathophysiology of major depressive disorder (MDD), but few studies have explored the relationship between REM sleep and treatment-resistant depression (TRD). In MDD, REM sleep abnormalities often manifest as alterations in total night REM Density (RD), RD in the first REM period (RD1), and REM Latency (RL). Among these, RD1...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Francisco Madrid-Gambin, Noemí Haro, Natasha L. Mason et al.
4 citations
Acute intoxication from Δ9-tetrahydrocannabinol (THC, the primary active ingredient of cannabis) can lead to neurocognitive impairment and interference with day-to-day operations, such as driving. Present evaluations of THC-induced impairment in legal settings rely on biological drug tests that solely establish cannabis use, rather than cannabis impairment. The current study evaluated the...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 2025
Janna Cousijn, Yara J Toenders, Anne Marije Kaag et al.
While Cannabis use disorder (CUD) is twice as prevalent in males, females transition more quickly from heavy use to CUD and experience more severe withdrawal. These clinically relevant sex differences contrast the lack of knowledge about the underlying brain mechanisms. This study investigated the relationship between CUD and resting-state functional brain connectivity (RSFC), assessing...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 22, 2025
Briana K Chen, Alicia Whye, Louise C Matthews et al.
2 citations
Serotonin (5-HT) receptors and N-methyl-D-aspartate receptors (NMDARs) have both been implicated in stress-induced psychiatric disorders. However, there is a paucity of studies evaluating the effectiveness of novel combinatorial pharmacological treatments to treat stress-related disorders. Here, we evaluated whether administration of combinatorial (R,S)-ketamine, an NMDAR antagonist and Food...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 19, 2025
Valeria Grasso, Joseph Tennyson, Raag D. Airan et al.
5 citations
Subanesthetic ketamine is currently used as a rapid-acting treatment for varied neuropsychiatric disorders. However, the mechanistic underpinnings of its therapeutic action remain unclear, and emerging clinical and preclinical evidence highlights a potential involvement of the opioid system. We used pharmacological functional ultrasound imaging data acquired during and after ketamine...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 9, 2025
Ellen Bradley, Kimberly Sakai, Gisele Fernandes-Osterhold et al.
23 citations
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2025
Manoela V. Fogaça, Fernanda Daher, Marina R. Picciotto
22 citations
Major depressive disorder (MDD) is associated with disruptions in glutamatergic and GABAergic activity in the medial prefrontal cortex (mPFC), leading to altered synaptic formation and function. Low doses of ketamine rapidly rescue these deficits, inducing fast and sustained antidepressant effects. While it is suggested that ketamine produces a rapid glutamatergic enhancement in the mPFC, the...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2025
Ella Williams, Ursule Taujanskaite, Sunjeev K. Kamboj et al.
There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (N2O)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 1, 2025
Brian D Kangas, Harshawardhan U Deshpande, Sarah L Withey et al.
Although chronic cannabis use during adolescence can alter brain function and impair complex behavioral processes, it is unclear whether such deficits persist into adulthood. Using a coordinated awake neuroimaging and behavioral approach in nonhuman primates, we addressed this issue by examining the impact of chronic adolescent exposure to Δ9-tetrahydrocannabinol (THC) on brain functional...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2024
Isabelle Straumann, Isidora Avedisian, Aaron Klaiber et al.
20 citations
Racemic 3,4-methylenedioxymethamphetamine (MDMA) acutely increases mood, feelings of empathy, trust, and closeness to others and is investigated to assist psychotherapy. Preclinical research indicates that S-MDMA releases monoamines and oxytocin more potently than R-MDMA, whereas R-MDMA more potently stimulates serotonin 5-hydroxytryptamine-2A receptors. S-MDMA may have more stimulant...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2024
Charalampos Brakatselos, Alexia Polissidis, George Ntoulas et al.
10 citations
Repeated administration of ketamine (KET) has been used to model schizophrenia-like symptomatology in rodents, but the psychotomimetic neurobiological and neuroanatomical underpinnings remain elusive. In parallel, the unmet need for a better treatment of schizophrenia requires the development of novel therapeutic strategies. Cannabidiol (CBD), a major non-addictive phytocannabinoid has been...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2024
Ruth H Asch, Chadi G. Abdallah, Richard E Carson et al.
11 citations
The development of novel radiotracers for Positron Emission Tomography (PET) imaging agents targeting the synaptic vesicle glycoprotein 2 A (SV2A), an integral glycoprotein present in the membrane of all synaptic vesicles throughout the central nervous system, provides a method for the in vivo quantification of synaptic density. This is of particular interest in neuropsychiatric disorders given...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2024
Ji-Woon Kim, Benjamin Kleinfelter, Ege T Kavalali et al.
3 citations
Prevailing hypotheses on the mechanisms of antidepressant action posit that antidepressants directly counteract deficiencies in major neurotransmitter signaling systems that underlie depression. The rapidly acting antidepressant ketamine has been postulated to correct excess glutamatergic signaling via glutamatergic antagonism leading to the rescue of neuronal structural deficits and reversal...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2024
Michelle K Piazza, Ege T Kavalali, Lisa M Monteggia
21 citations
Synaptic plasticity occurs via multiple mechanisms to regulate synaptic efficacy. Homeostatic and Hebbian plasticity are two such mechanisms by which neuronal synapses can be altered. Although these two processes are mechanistically distinct, they converge on downstream regulation of AMPA receptor activity to modify glutamatergic neurotransmission. However, much remains to be explored regarding...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2024
Reinoud Kaldewaij, Paula C Salamone, Adam Enmalm et al.
19 citations
A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences and has therefore been used to model an altered state of self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms for ketamine's effects on the bodily sense of self in the...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2024
Conor H. Murray, Joel Frohlich, Connor J Haggarty et al.
30 citations
Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2024
Lora Khatib, Jon G Dean, Valeria Oliva et al.
9 citations
Chronic low back pain (cLBP) is the most prevalent chronic pain condition. There are no treatments that haven been found to directly assuage evoked cLBP. To this extent, mindfulness-meditation is a promising pain therapy. Yet, it is unclear if meditation can be utilized to directly attenuate evoked chronic pain through endogenous opioids. A double-blind, randomized, and placebo-controlled...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 1, 2024
Hanna Molla, Royce Lee, Ilaria Tare et al.
37 citations
Recent studies and anecdotal reports suggest that psychedelics can improve mood states, even at low doses. However, few placebo-controlled studies have examined the acute effects of low doses of LSD in individuals with psychiatric symptoms. In the current study, we examined the acute and sub-acute effect of a low dose of LSD (26 µg) on subjective effects and mood in volunteers with mild...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 1, 2024
Thomas J. Kelly, Emma M. Bonniwell, Lianwei Mu et al.
26 citations
Psychedelics such as psilocybin show great promise for the treatment of depression and PTSD, but their long duration of action poses practical limitations for patient access. 4-OH-DiPT is a fast-acting and shorter-lasting derivative of psilocybin. Here we characterized the pharmacological profile of 4-OH-DiPT and examined its impact on fear extinction learning as well as a potential mechanism...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2024
Mehdi Sekssaoui, Joël Bockaert, Philippe Marin et al.
76 citations
Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Increasing clinical evidence indicates that the...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2024
Jihye Kim, Michelle J He, Alina K Widmann et al.
47 citations
Neurotrophic factors are a family of growth factors that modulate cellular growth, survival, and differentiation. For many decades, it has been generally believed that a lack of neurotrophic support led to the decreased neuronal synaptic plasticity, death, and loss of non-neuronal supportive cells seen in neuropsychiatric disorders. Traditional psychiatric medications that lead to immediate...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2024
Maurizio Fava
22 citations
The emergence of new molecular targets, together with the development of new approaches to neuropsychiatric diseases, involving psychedelics as well as gene and cell therapies, are creating the need to improve the efficiency of mechanistic and/or efficacy clinical trials. This review article will discuss a number of issues that have hampered our ability to detect therapeutic signals, from...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2024
Zack Blumenfeld, Kallol Bera, Eero Castrén et al.
10 citations
We begin by summarizing several examples of antidepressants whose therapeutic actions begin when they encounter their targets in the cytoplasm or in the lumen of an organelle. These actions contrast with the prevailing view that most neuropharmacological actions begin when drugs engage their therapeutic targets at extracellular binding sites of plasma membrane targets-ion channels, receptors,...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2024
Melissa A Simon
6 citations
Psychedelics are a promising approach to caring for persons living with severe mental illness. However, as with all clinical treatments and research in the US, health equity concerns must be considered and addressed. Ensuring health equity and health justice in psychedelic care delivery and research will require strategies to not only reduce disparities and preempt future disparities among...