Neuropsychopharmacology
September 21, 2026
Balwinder Singh, Hossam M Ali, Alessandro Miola et al.
Disrupted excitation-inhibition (E/I) balance involving GABA and glutamate (Glu) is implicated in the pathophysiology of depression. Ketamine, an NMDA receptor antagonist with rapid antidepressant properties, may modulate this balance, yet proton magnetic resonance spectroscopy (¹H-MRS) studies report inconsistent findings regarding the direction, magnitude, and timing of neurochemical effects....
Neuropsychopharmacology
September 15, 2026
Alexandra Gaillard, Daniel J Fehring, Philip J Sumner et al.
Chronic cannabis use drives neuroadaptations in reward and stress-related circuits that condition the brain to the drug and its associated cues. These changes underlie craving and heighten its sensitivity to cue- and stress-induced triggers, sustaining drug intake and promoting relapse. Task-based functional magnetic resonance imaging of drug cue reactivity paradigms has shown the dorsolateral...
Neuropsychopharmacology
August 29, 2026
Briana K Chen, Brenna L Williams, Anna Darling et al.
Brain-derived neurotrophic factor (BDNF) exon VI promoter is implicated in mediating activity-induced synthesis of hippocampal BDNF. BDNF is implicated in (R,S)-ketamine's antidepressant effects, but its role in (R,S)-ketamine-mediated prophylaxis is unknown. Using BDNF-e6 mice, in which promoter VI-driven BDNF production is disrupted, we tested its necessity for (R,S)-ketamine's prophylactic...
Neuropsychopharmacology
August 22, 2026
Carrie Cuttler, Matteya A Proctor, Nicholas C. Glodosky et al.
People who use cannabis commonly report stress-relieving effects, yet no studies have simultaneously assessed the acute effects of cannabis on multiple stress systems under placebo-controlled conditions. We conducted a randomized, double-blind, placebo-controlled trial in which 120 people (56 men, 52 women, 12 non-binary/transgender) who regularly use cannabis were assigned to vape placebo, a...
Neuropsychopharmacology
July 21, 2026
Alannah Miranda, Breanna M Holloway, Elizabeth Peek et al.
Cannabis use is highly prevalent among people with bipolar disorder, potentially due to a desire to self-medicate against symptoms, such as racing thoughts and poor concentration. Such symptoms are associated with attention and inhibitory control deficits, functions that are regulated in-part by temporal perception. Temporal perception is impaired in BD and is slowed by acute cannabis exposure....
Neuropsychopharmacology
July 20, 2026
Noam Goldway, Itamar Jalon, Yara Agbaria et al.
Abstract Ketamine produces both analgesic and dissociative effects, but whether analgesia depends on dissociation remains debated. This question is part of a broader discussion on whether the subjective experiences elicited by psychoactive drugs are necessary for their therapeutic benefits. Here, we tested whether ketamine-induced analgesia and dissociation show separable behavioral and neural...
Neuropsychopharmacology
July 18, 2026
James J Gattuso, Ahmed Kamal, Jennyfer M. Payet et al.
Abstract Psilocybin is a serotonergic psychedelic drug with emerging therapeutic applications, yet its actions under glutamatergic dysfunction, and relevance to schizophrenia and associated psychiatric disorders, remain unclear. We examined the acute and long-lasting effects of psilocybin (1 mg/kg, intraperitoneal) on behavioral and neural outcomes in the metabotropic glutamate receptor 5...
Neuropsychopharmacology
July 16, 2026
Connor J Haggarty, Christine A Rabinak
Posttraumatic stress disorder (PTSD) is characterized by difficulties in emotion regulation and altered recruitment of prefrontal control systems during cognitive reappraisal. Cannabinoid signaling has been implicated in stress and affect regulation, yet dose-dependent effects of acute delta-9-tetrahydrocannabinol (THC) on the neural mechanisms supporting reappraisal in PTSD remain unclear. In...
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Anhedonia, the blunted responsiveness to previously rewarding stimuli, is a core symptom of several psychiatric disorders. Ketamine and psilocybin have shown promising evidence in ameliorating anhedonic symptoms in clinical trials. The Probabilistic Reward Task (PRT) was developed to objectively quantify reward responsiveness in clinical populations and laboratory animals. Here, the PRT was...
Neuropsychopharmacology
July 7, 2026
Wojciech Pasławski, Daniel Doyon, Carl Johan Ekman et al.
Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.
Neuropsychopharmacology
July 1, 2026
Denis Arikci, Joran Borgulya, Isabelle Straumann et al.
1 citation
Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin...
Neuropsychopharmacology
June 18, 2026
Abigail E. Calder, Vincent J Diehl, Morten P. Lietz et al.
Preclinical studies suggest that lysergic acid diethylamide (LSD) may induce lasting changes in brain function and learning ability, but evidence in humans is uncertain. Motor learning, in particular, has clinical relevance but has not been investigated in human studies of psychedelics. Forty-five healthy subjects (24 women) participated in this randomized crossover trial comparing 100 µg LSD...
Neuropsychopharmacology
June 16, 2026
Nadia S. Hejazi, Mina Kheirkhah, Brady A. Riedner et al.
Slow-wave activity (SWA), a key indicator of sleep homeostasis, is often diminished in individuals with treatment-resistant depression (TRD). Ketamine, a rapid-acting antidepressant, increases SWA during the first period of non-rapid eye movement (NREM1) sleep. However, research into how ketamine affects sleep and its connection to treatment outcomes in TRD has been limited by small sample...
Neuropsychopharmacology
June 2, 2026
Sarah A Thomas, Meghan A Gonsalves, Gillian LeBlanc et al.
Approximately 10-20% of U.S. adolescents report past-year cannabis use (CU). Although regular CU beginning in adolescence is expected to blunt dopamine-related neurophysiology, this hypothesis has not been tested in adolescents due to methodological limitations. However, neurophysiology contributing to dopamine can be noninvasively indexed via subcortical tissue iron measured with magnetic...
Neuropsychopharmacology
June 1, 2026
Ted Obi, Kerry J. Ressler
Post-traumatic stress disorder (PTSD) remains one of psychiatry's most challenging disorders, common, disabling, and biologically complex. Despite decades of research, only sertraline and paroxetine are FDA-approved, both with modest efficacy. Even first-line trauma-focused psychotherapies leave up to half of patients with persistent symptoms. However, advances in neurobiology are reframing...
Neuropsychopharmacology
June 1, 2026
Trevonn M Gyles, Eric M Parise, Molly S Estill et al.
Treatment-resistant depression (TRD), defined by unsuccessful response to multiple antidepressants, affects approximately one-third of individuals with major depressive disorder, yet its underlying molecular mechanisms remain poorly understood. Here, we developed a preclinical model of TRD in which mice exposed to chronic social defeat stress were sequentially treated with fluoxetine (FLX) and...
Neuropsychopharmacology
June 1, 2026
Philip D. Harvey, Charles B. Nemeroff
correction
“Adapted from Mian et al. (2025), with permission.” needs to be added to Fig. 1 caption. Thus, the correct Fig. 1 caption reads: Fig. 1 Thereapeutic Intent, legality and structure. Adapted from Mian et al. (2025), with permission. For instance, a medication that is approved by the FDA for prescription by physicians for a specific condition, manufactured under supervision, and dispensed by a...
Neuropsychopharmacology
May 25, 2026
Sheida Shadani, Kaspar McCoy, Lina Ong et al.
With the resurgence of psychedelic research and growing evidence of their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological variable on the prosocial effects of...
Neuropsychopharmacology
May 9, 2026
Ana Maria Raymundi, Nathalie Carla Cardoso, Gabriel Costa Lourenço et al.
In PTSD, microglia are more engaged in fear-related circuits, where they participate in fear memory processing responses. The reconsolidation-impairing effect of Δ⁹-tetrahydrocannabinol (THC), the primary psychoactive constituent of Cannabis, is typically linked to cannabinoid type-1 receptor (CB1) signaling. THC also engages peroxisome proliferator-activated receptor gamma (PPARγ), and both...
Neuropsychopharmacology
May 9, 2026
Claudia Poluga, S. S. Dheda, Nadia Boachie et al.
Cannabis withdrawal in cannabis use disorder (CUD) increase the risk of relapse and lacks effective treatments. The endocannabinoid enzyme fatty acid amide hydrolase (FAAH) may influence cannabis use and withdrawal, but the relationship between FAAH levels and withdrawal symptoms remains unclear. This study aims to investigate changes in FAAH levels during short-term abstinence from cannabis...
Neuropsychopharmacology
March 27, 2026
Kade L Huckstep, Billi Newton, Grace Bailey et al.
Comorbidity between post-traumatic stress disorder (PTSD) and alcohol use is common and mutually-reinforcing, yet there are no pharmacological strategies that specifically target trauma-linked escalation of alcohol intake. We evaluated whether 3,4-methylenedioxymethamphetamine (MDMA), given in a therapy-adjunctive fashion (30 min before fear extinction), could facilitate extinction of...
Neuropsychopharmacology
February 18, 2026
Itishree Sahoo, Sairam Masadi, Ashwath Maheswari et al.
3 citations
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We hypothesized psilocybin given during adolescence, a time of heightened neuroplasticity, particularly in the forebrain, would affect emotional behavior and the associated underlying neuroanatomy, neurocircuitry, and epigenetics. Female and male mice...
Neuropsychopharmacology
February 13, 2026
Fabrizio Ascone, Valeria Buzzelli, Francesca Mottarlini et al.
2 citations
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal development and circuit remodeling,...
Neuropsychopharmacology
February 2, 2026
Maya C Gaines-Smith, Justin M Silverman, Michael Fiorillo et al.
3 citations
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potential psychotherapeutic adjunct for treatment-resistant psychiatric disorders, yet its neurobiological mechanisms - particularly those related to its stereoisomers and sex-specific effects - remain poorly understood. Here, we report stereoselective and...
Neuropsychopharmacology
February 1, 2026
Dongsun Park, Gwangho Lee, Bokyum Kim et al.
1 citation
Ketamine has emerged as a rapid-acting antidepressant that challenges classical monoaminergic frameworks and highlights the importance of synaptic and circuit-level plasticity in mood regulation. This review examines the hippocampus as a key site through which ketamine exerts both rapid and sustained antidepressant effects. We synthesize evidence showing that ketamine enhances hippocampal...