Current neuropharmacology
January 1, 2024
Lisa Burback, Suzette Brémault-phillips, Mirjam J Nijdam et al.
187 citations
Chronic PTSD is a systemic disorder with high allostatic load, shaped by advances in genetics, neurobiology, and brain imaging. Current evidence-based treatments include pharmacological and psychotherapeutic approaches, but outcomes are often suboptimal due to barriers such as comorbidity, emotional dysregulation, suicidality, dissociation, substance use, and trauma-related guilt and shame. These challenges drive emerging novel approaches: early interventions during the Golden Hours, medication augmentation, psychedelics, and brain- and nervous-system-targeted interventions. A phase-oriented treatment framework is recognized to align interventions with the disorder's pathophysiology. Revisions to guidelines and care systems will be needed as innovative treatments gain evidence.
Current neuropharmacology
January 1, 2024
Michel Sabé, Chaomei Chen, Wissam El-Hage et al.
25 citations
A scientometric analysis of 42,170 publications on posttraumatic stress disorder (PTSD) from 1945 to 2022 identified four major research trends: war veterans and refugees, treatment of PTSD/neuroimaging, evidence syntheses, and somatic symptoms of PTSD. The largest cluster focused on evidence synthesis for genetic predisposition and environmental exposures leading to PTSD. War-related trauma research has shifted from battlefield in-person exposure to drone operator trauma and is being outpaced by civilian trauma research, including the COVID-19 pandemic, postpartum, and grief disorder. Recent trends show a burst in PTSD treatment research involving Mhealth, virtual reality, and psychedelic drugs. The USA dominates collaboration networks, with a recent surge of publications from China. Compared to other psychiatric disorders, there is a lack of high-quality randomized controlled trials for pharmacological and nonpharmacological treatments.
Current neuropharmacology
January 1, 2024
Mortimer Mamelak
24 citations
Rodent models of psychological stress mirror many features of major depressive disorder, linking activation of the hypothalamic-pituitary axis to oxidative stress, neuroinflammation, dominance of cholinergic neurotransmission, increased REM sleep pressure, impaired glycolysis and brain glucose utilization, reduced energy production, and decreased glutamate/GABA-glutamine cycling. Rapidly acting antidepressants like scopolamine, ketamine, and ECT raise extracellular glutamate; scopolamine and ketamine increase glutamate/GABA-glutamine cycling in both men and rodents, providing short-term relief. Nightly use of gammahydroxybutyrate (GHB), a GABAB agonist, may achieve more permanent results and possibly prevent depression by inhibiting cholinergic neurotransmission, relieving REM sleep pressure, and generating NADPH and succinate to boost energy and glutamate synthesis.
Current neuropharmacology
January 1, 2025
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati et al.
23 citations
Among patients with treatment-resistant depression who continued esketamine nasal spray for at least six months, 76.2% responded or achieved remission. Of those who had not responded by six months, a subset improved by twelve months. Side effects occurred in 71.8% of patients at six months, decreasing to 42% at twelve months; the most common were sedation and dissociation. Only two patients stopped treatment due to tolerability issues. The findings suggest esketamine is effective and safe for mid- to long-term treatment, with a novel observation of late clinical response in some patients. Results require confirmation in larger samples and longer observation periods.
Current neuropharmacology
March 1, 2011
Z K Binienda, M A Beaudoin, B T Thorn et al.
10 citations
Fast Fourier Transform (FFT) analysis of electrocorticogram (ECoG) recordings in conscious rats reveals that different drugs alter brainwave frequencies in distinct ways. Domoic acid administration links slow-wave delta and theta activity with behavioral seizure type. Ibogaine pretreatment before cocaine increases power in the alpha(1) band, suggesting serotonergic involvement, and lowers the threshold for cocaine-induced electrographic seizures by increasing delta and theta power. Two weeks of daily cocaine reduces slow-wave ECoG activity 24 hours after the last injection, mirroring reduced frontal cortex metabolism in chronic human users. Gamma-hydroxybutyrate (GHB) at 400 and 800 mg/kg increases energy across all except beta(2) bands, producing EEG patterns resembling absence seizures in human petit mal epilepsy.
Current neuropharmacology
January 16, 2025
Sen Wang, Chaoli Huang, Mengyu Wang et al.
4 citations
Depression affects about 300 million people worldwide, and its underlying mechanisms remain unclear. Changes in oligodendrocytes and myelin are implicated in depression pathology. Conventional antidepressants take weeks to work and fail for about one-third of patients. Ketamine provides rapid, sustained antidepressant effects in treatment-resistant patients. Reduced myelination is linked to depression, so repairing myelin damage may be a key mechanism behind ketamine's prolonged effects. This review summarizes the relationship between demyelination and depression and discusses how ketamine might exert antidepressant effects by repairing myelin, offering new insights into the role of myelination in antidepressant mechanisms.
Current neuropharmacology
January 9, 2026
Maria Antonietta De Luca, Cristina Miliano, Amanda Roxburgh et al.
1 citation
Tablets sold as MDMA frequently contain psychoactive adulterants that vary by region and year, potentially increasing central nervous system harm. A review of studies from 2020 to 2025 covering Continental Europe, the UK, the USA, and Australia found that co-administration of MDMA with common adulterants can exacerbate noxious neurological and psychiatric effects. The composition of tablets differs across these regions, and interactions between MDMA and adulterants may explain some adverse effects seen in users. Expanding drug checking and public health efforts is essential to inform users, first responders, and healthcare professionals about these risks.
Current neuropharmacology
May 15, 2025
Yuanyuan Ding, Shiya Liu, Kaixin Wang et al.
1 citation
General anesthesia induces unconsciousness by disrupting communication between the fronto-parietal networks, which are brain regions critical for attention, executive function, and cognitive control. This review synthesizes findings from functional neuroimaging and neurophysiological studies showing that loss of fronto-parietal connectivity underlies the transition from wakefulness to anesthesia-induced unconsciousness. The authors explain the mechanisms at both neuronal and molecular levels, and discuss how these insights advance understanding of the neural correlates of consciousness and could inform development of anesthetic agents with more targeted effects on conscious states. The review bridges consciousness research and anesthetic pharmacology, offering a framework for future studies on neural mechanisms controlling conscious state transitions.
Current neuropharmacology
April 7, 2025
Marika Alborghetti, Luana Lionetto, Ginevra Lombardozzi et al.
1 citation
In patients with treatment-resistant depression receiving intranasal esketamine (56 mg) alongside another antidepressant, those taking antidepressants that inhibit cytochrome-P450 isoforms (paroxetine, fluoxetine, duloxetine, venlafaxine) had significantly higher serum esketamine levels 20 minutes after dosing and over 72 hours compared to patients on sertraline, citalopram, escitalopram, or vortioxetine. Salivary esketamine levels were several-fold higher than serum levels at all time points and showed high variability. These pharmacokinetic differences did not affect clinical outcomes, but changes in systolic blood pressure positively correlated with serum esketamine levels, suggesting dose reduction may be warranted for patients with cardiovascular comorbidity on those CYP450-inhibiting antidepressants. Small subgroup sizes limit strong conclusions.
Current neuropharmacology
January 1, 2025
Wei Zheng, Limei Gu, Jianqiang Tan et al.
1 citation
Repeated intravenous ketamine infusions rapidly reduce anhedonia in both younger and older adults with major depressive episodes, but older patients show a weaker response. In a study of 135 patients (116 younger, 19 older) receiving six ketamine infusions over 12 days, anhedonia scores dropped significantly in both age groups within 4 hours of the first infusion, with effects maintained throughout treatment. By day 26, younger patients had lower anhedonia scores than older patients. The antianhedonic response rate was 51.7% in younger patients versus 31.6% in older patients, and remission occurred in 24.1% of younger patients but none of the older patients.
Current neuropharmacology
June 30, 2026
Jiaying Wang, Rui Zhang, Yuanyuan Ma et al.
Prenatal exposure to ketamine or its analog 2-fluorodeschloroketamine disrupts mitochondrial energy production in developing brain cells, increasing the risk of neurological damage. Using human cerebral organoids and single-cell RNA sequencing of 83,436 cells, the study found that both substances altered gene networks controlling mitochondrial oxidative phosphorylation in cortical cells. Experiments in fetal mouse neurons confirmed that exposure increased mitochondrial fragmentation and oxidative stress while reducing ATP production capacity. These energy disruptions during rapid brain development can make offspring more vulnerable to neurological issues. The results provide direct evidence of neurodevelopmental toxicity from these substances and identify mitochondrial dysfunction as a probable primary molecular mechanism.
Current neuropharmacology
April 28, 2026
Hongshuang Wang, Xiaobing Li, Feng Yu et al.
Combining psychedelics with music in therapy may improve mental health outcomes by acting on specific brain mechanisms. Psychedelics like psilocybin activate 5-HT2A receptors and BDNF-TrkB signaling, increase neural plasticity, and desynchronize the default mode network, while music guides emotional processing and amplifies psychological insights. This synergy shows promise for treating depression, PTSD, and addiction. The review provides a mechanistic framework for understanding these interactions and identifies neurobiological targets for optimizing future therapeutic protocols.
Current neuropharmacology
April 16, 2026
Xiangying Wei, Shan Xu, Zhaoqiong Zhu
General anesthetics such as ketamine, propofol, isoflurane, and certain opioids show rapid and sustained antidepressant effects in both preclinical and clinical settings, offering a new therapeutic avenue for treatment-resistant depression, which affects about one-third of patients. These effects go beyond traditional monoamine regulation, involving modulation of glutamate and GABA signals and restoration of synaptic plasticity in damaged brain circuits. Despite the promise, balancing benefits against risks and establishing consistent treatment guidelines remain critical for developing new rapid-acting antidepressants for patients who do not respond to standard care.