Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.
Neuropsychopharmacology
July 7, 2026
Wojciech Pasławski, D Doyon, Carl Johan Ekman et al.
Psilocybin, a rapid-acting antidepressant, reduces levels of the neuropeptide galanin and noradrenaline in cerebrospinal fluid, suggesting that normalization of these co-transmitters is a key pharmacodynamic effect. This finding comes from a secondary analysis of a randomized, placebo-controlled trial with multimodal biomarker measurements. The results indicate a selective effect of psilocybin on these specific neurotransmitters, offering insight into its mechanism of action in major depressive disorder.
Neuropsychopharmacology
June 18, 2026
Abigail E. Calder, Vincent J Diehl, Morten P. Lietz et al.
A single 100 µg dose of lysergic acid diethylamide (LSD) improved offline motor learning the next day and, one week later, reduced perceived stress and increased aspects of cognitive flexibility in 45 healthy adults. Electroencephalography showed that LSD acutely decreased N1 and P2 auditory event-related potential amplitudes, with P2 still modulated after one week. Transcranial magnetic stimulation revealed increased motor-evoked potential amplitude and faster latency under LSD. Brain-derived neurotrophic factor levels were unchanged. The findings suggest lasting effects of LSD on learning and neural signals, while highlighting challenges in measuring long-term potentiation in humans.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
Neuropsychopharmacology
May 13, 2024
Conor H. Murray
MDMA-assisted psychotherapy shows promise for treating psychiatric conditions, with clinical trials over the past decade demonstrating safety and efficacy for posttraumatic stress disorder (PTSD). In 2024, the U.S. Food and Drug Administration granted priority review for a new drug application involving MDMA-assisted psychotherapy for PTSD, following a Breakthrough Therapy designation in 2017. Australia became the first country to authorize MDMA prescriptions for PTSD. Beyond PTSD, evidence from clinical trials indicates that MDMA-assisted psychotherapy is safe, tolerable, and effective for alcohol use disorder, autism, and end-of-life anxiety.
Neuropsychopharmacology
April 16, 2024
Brett D. M. Jones, M. Ishrat Husain
The abstract indicates that the neural effects of psychedelics are primarily characterized by increased complexity in brain activity. This suggests that psychedelics alter brain dynamics by promoting more diverse and flexible patterns of neural connectivity, which may underlie their therapeutic potential and ability to induce altered states of consciousness. The focus is on complexity as a key concept for understanding how these substances affect the brain.
Neuropsychopharmacology
July 20, 2026
Noam Goldway, Itamar Jalon, Yara Agbaria et al.
Ketamine produces both pain relief and dissociation, but it remains unclear whether the two are linked. In a placebo-controlled fMRI study with 37 healthy volunteers, intravenous ketamine reduced pain and induced dissociation, yet the two effects showed distinct brain signatures. Pain was associated with activity in regions like the anterior insula and a pain-predictive brain pattern, while dissociation was linked to reduced connectivity in the default mode network. These neural markers did not correlate with each other, suggesting that ketamine's analgesic and dissociative effects arise through separate mechanisms.
Neuropsychopharmacology
June 1, 2026
correction
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Neuropsychopharmacology
January 1, 2024
Tobias Haeusermann, Winston Chiong
New treatments for mental illness, including psychedelics, ketamine, and neuromodulatory technologies, raise novel ethical questions alongside familiar ones in clinical care and research. This overview examines three key domains of ethical concern: informed consent, the role of expectancy in clinical response, and distributive justice. The authors introduce these issues without presenting empirical findings.
Neuropsychopharmacology
January 1, 2024
Joshua A. Gordon, Nora D. Volkow, George F. Koob
Most treatments for psychiatric and substance use disorders require weeks to become effective, but some, like intravenous ketamine, can relieve symptoms within minutes to hours. Current research aims to discover new rapid-acting psychotherapeutics, including novel drug classes and innovative brain stimulation therapies, which are being studied in clinical and pre-clinical settings. Further investigation into the neurobiological mechanisms, effective therapeutic contexts, and implementation strategies is needed to fully realize the potential of these treatments.
Neuropsychopharmacology
January 1, 2024
Ryan H. Gumpper, Bryan L. Roth
Psychedelics show promise as treatments for neuropsychiatric disorders, though their clinical potential is not fully understood. This review explores current knowledge of their basic biology, pharmacology, and structural biology, highlighting both established facts and unanswered questions as these compounds gain popularity in therapeutic and recreational settings.
Neuropsychopharmacology
May 24, 2013
Efavirenz, an HIV antiretroviral, is misused by crushing and smoking the pills for psychoactive effects. Molecular profiling shows it interacts with multiple targets of abused drugs, including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, its behavioral effects resemble LSD, mediated primarily through the 5-HT(2A) receptor: both reduce ambulation in open-field tests, efavirenz occasions drug-lever responding in rats discriminating LSD, and it induces head-twitch responses in wild-type but not 5-HT(2A)-knockout mice. Despite also having GABAA-potentiating effects and interactions with dopamine and serotonin transporters, efavirenz does not maintain self-administration in rats trained on cocaine or produce conditioned place preference. These findings correlate with subjective experiences in humans who abuse efavirenz and with dose-dependent neuropsychiatric side effects like hallucinations and night terrors in HIV patients.
Neuropsychopharmacology
February 1, 2003
Y. Qu, Lisa Chang, J. Klaff et al.
In unanesthetized adult rats, an injection of the 5-HT2A/2C receptor agonist DOI (2.5 mg/kg intraperitoneally) caused widespread increases of about 60% in the incorporation coefficient of arachidonic acid from blood into brain, particularly in neocortical regions with high densities of 5-HT2A receptors. These increases were entirely blocked by chronic pretreatment with the 5-HT2 receptor antagonist mianserin. The findings suggest that the 5-HT2 syndrome involves widespread activation of phospholipase A2 via 5-HT2A receptors, leading to release of the second messenger arachidonic acid, and that chronic mianserin prevents this activation.