Frontiers in pharmacology
January 1, 2023
Kateřina Syrová, Klára Šíchová, Hynek Danda et al.
4 citations
2C-B-Fly-NBOMe, a new psychoactive substance related to the psychedelic entactogen 2C-B, was studied in adult male Wistar rats. After injection, peak drug levels in blood serum occurred at 30 minutes (28 ng/ml) and in brain tissue at 60 minutes (171 ng/g), with the compound still detectable in the brain after 8 hours. The drug dose-dependently reduced locomotor activity and strongly disrupted the acoustic startle response, with a weaker effect on prepulse inhibition. It did not cause significant changes in body temperature. The overall profile resembles that of 2C-B and other NBOMe substances, suggesting slow brain penetration and inhibitory effects on motor performance and sensorimotor gating.
Frontiers in pharmacology
January 1, 2023
Prithvi Hemanth, Pallavi Nistala, Vy T Nguyen et al.
4 citations
For a series of 13 compounds related to the psychedelic agent 2,5-DMA, rat brain 5-HT2 receptor affinities correlate strongly with human 5-HT2A (r = 0.942) and 5-HT2B (r = 0.916) affinities. Human 5-HT2A affinity also correlates with the lipophilicity of the 4-position substituent (r = 0.798). In functional assays, eight of ten compounds acted as agonists at the human 5-HT2B receptor, while two acted as antagonists. Human 5-HT2B affinity, but not agonist action, correlates with substituent lipophilicity (r = 0.750). Rat and human 5-HT2A affinity may approximate human 5-HT2B affinity but cannot predict agonist action. Some 2,5-DMA analogs on the clandestine market may pose cardiac valvulopathy risk with chronic use via h5-HT2B activation.
Frontiers in pharmacology
January 1, 2025
Sarah Delcourte, Amel Bouloufa, Renaud Rovera et al.
3 citations
Bright light stimulation (BLS) alone was ineffective against anxiety- and depressive-like behaviors in a novel mouse model of refractory depression, induced by social isolation and chronic despair during the active dark phase. However, BLS potentiated the effects of antidepressant treatments, including ketamine, through a circuit involving rod retinal photoreceptors, lateral habenula (LHb) astroglia, and serotonin (5-HT). Chemogenetic activation of LHb astroglia or serotonin depletion blocked this potentiating effect. The findings suggest BLS enhances antidepressant efficacy via a previously unknown neural pathway.
Frontiers in pharmacology
January 1, 2024
Carles Colom-Rocha, Cristian Bis-Humbert, M Julia García-Fuster
3 citations
Adolescent exposure to ethanol, alone or combined with cocaine, increases voluntary ethanol consumption in adult male and female rats, but does not cause lasting negative affect. Cocaine alone has no effect on later ethanol intake. In rats exposed to adolescent ethanol, adult treatment with cannabidiol reduces ethanol consumption in both sexes, while ketamine reduces it only in females. These findings identify two potential therapeutic interventions to mitigate the long-term impact of early drug initiation.
Frontiers in pharmacology
January 1, 2015
Eduardo R. Butelman, Mary Jeanne Kreek
3 citations
correction
No Summary
Frontiers in pharmacology
January 1, 2025
Itzchak Angel, Rita Perelroizen, Wendy Deffains et al.
2 citations
Ketamir-2, a new ketamine analog designed for improved oral bioavailability and safety, is a low-affinity NMDA receptor antagonist that selectively binds to the PCP site with an IC50 of about 100 µM. Unlike ketamine, which induces hyperlocomotion in mice—a behavior linked to schizophrenia-like psychomotor agitation—Ketamir-2 does not cause hyperlocomotion. In behavioral tests for anti-depressive and anxiolytic effects (Open Field, Elevated Plus Maze, Forced Swimming Test), Ketamir-2 showed significant effects at variable doses, while ketamine often did not differ from vehicle or showed opposite responses. The findings suggest Ketamir-2 may offer a safer profile without ketamine's dissociative side effects.
Frontiers in pharmacology
January 1, 2025
Denise Elfriede Liesa Lockhofen, Nils Hübner, Ranjan Debnath et al.
2 citations
Ketamine, which blocks the NMDA receptor and temporarily mimics schizophrenia-like symptoms, primarily disrupts how the brain processes distracting stimuli rather than targets or rewards. In a visual attention task with reward-related distractors, healthy volunteers given a subclinical dose of ketamine showed increased gamma band power compared to placebo, especially during salient distractor trials. These effects were linked to the occurrence of negative symptoms. The findings highlight the glutamate system's role in dysfunctional gamma oscillations, early salience processing alterations, and negative symptoms in schizophrenia.
Frontiers in pharmacology
January 1, 2025
Paula Aarseth Tunstad, Tor-Morten Kvam, Malin V Uthaug et al.
2 citations
An anonymous internet survey of Norwegian-speaking adults who had a memorable experience with a classic psychedelic substance found that 85% reported a small to large positive change in subjective wellbeing after the experience. Integration, ego dissolution, and emotional breakthrough had a clear positive predictive effect on self-reported wellbeing. Variables with smaller but significant effects included challenging experiences, nature or ceremony settings, and a therapeutic or seeking intention. The authors view these findings as hypothesis-generating rather than confirmatory due to study limitations.
Frontiers in pharmacology
January 1, 2024
Ying Xiao, Xuefeng Hu, Wei Xing et al.
1 citation
A novel formulation combining deuterated dextromethorphan (SAL0114) with bupropion showed twice the metabolic stability of standard dextromethorphan in both laboratory and mouse tests, and bupropion further increased its exposure by 2.4 times. The combination demonstrated superior antidepressant and synergistic effects in mouse and rat models compared with the non-deuterated dextromethorphan-bupropion combination, while maintaining the same in vitro activity. Deuteration did not alter the compound's activity but improved its stability, potentially reducing neurologic side effects from metabolites and allowing lower bupropion doses. Clinical studies are needed to confirm these preclinical findings.
Frontiers in pharmacology
January 1, 2023
Nataliya Vorobyeva, Alena A Kozlova
1 citation
correction
No Summary
Frontiers in pharmacology
January 1, 2026
Michael B Gatch, Shuping Jia, Ritu A Shetty et al.
Two synthetic cathinones found on the street, N-cyclohexyl butylone and N-cyclohexyl methylone, were tested for their psychostimulant effects in mice and rats. Both compounds stimulated locomotor activity in mice, but were less potent and less effective than methamphetamine. In rats trained to discriminate methamphetamine or cocaine from saline, N-cyclohexyl butylone fully substituted for those drugs, suggesting it could produce similar psychoactive effects and motivate illicit use. N-cyclohexyl methylone failed to fully substitute for methamphetamine or cocaine and caused convulsions at higher doses, indicating greater danger but possibly lower abuse liability. Neither compound substituted for MDMA. The large N-cyclohexyl chemical group likely reduced the drugs' effectiveness, but a longer side chain in N-cyclohexyl butylone may have counteracted this.
Frontiers in pharmacology
January 1, 2026
Yang Qu, Shujin Li, Li Tian et al.
A meta-analysis of nine randomized controlled trials involving 1,449 patients found that esketamine improves symptoms in treatment-resistant depression but significantly increases dose-dependent adverse events. Compared with controls, esketamine raised the risk of nine adverse events including nausea, dissociation, dizziness, vertigo, elevated blood pressure, and somnolence. Risks were strongly dose-dependent: the high-dose group (≥56 mg or 0.40 mg/kg) had a greater risk than the low-dose group (≤28 mg or 0.20 mg/kg), with relative risk for nausea of 3.72 versus 1.69 and for dissociation of 10.65 versus 3.27. Although esketamine improved clinical response rate (relative risk = 1.94), it increased treatment discontinuation due to adverse events by 2.22-fold. Clinical use should adopt personalized dosing strategies balancing efficacy and tolerability.
Frontiers in pharmacology
January 1, 2026
Joseph Geraci, Erik Viirre, Bessi Qorri et al.
Classic psychedelics like LSD, psilocybin, and DMT affect perception and brain plasticity mainly by activating the 5-HT2A receptor and triggering calcium-dependent signaling. A speculative but testable hypothesis suggests these biochemical cascades might connect with quantum processes in the brain, specifically through nuclear spin dynamics in phosphate-based 'Posner molecules' (Ca9(PO4)6). Intense 5-HT2A-driven neural activity and calcium flux during psychedelic use could allow phosphorus nuclear spins in these molecules to become entangled and shielded from decoherence, later influencing neuronal signaling when the clusters release calcium. This framework, building on Fisher's quantum cognition model, proposes testable predictions and outlines short-, medium-, and long-term experiments to confirm or refute quantum involvement, which could transform understanding of mind-brain relationships and psychiatric treatment.
Frontiers in pharmacology
January 1, 2026
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal et al.
MDMA (Ecstasy) suppressed helping behavior in adult male rats at doses of 5 mg/kg and 10 mg/kg, fully eliminating the behavior, while lower doses (1 mg/kg and 0.5 mg/kg) caused partial inhibition only after the rats switched roles. The lowest dose (0.25 mg/kg) had no effect. Electrophysiological recordings showed that MDMA reinforced long-term depression in the nucleus accumbens core and increased long-term potentiation in the anterior cingulate cortex, with the latter depending on serotonin and oxytocin. These neuroplastic effects align with mechanisms thought to promote prosocial behavior, yet the drug disrupted helping behavior, suggesting MDMA may impair neural processes essential for executing helping actions without reducing the willingness to help.
Frontiers in pharmacology
January 1, 2026
Michaela Krivosova, Matteo Marcatili, Gessica Guerrera et al.
In a real-world group of 32 patients with treatment-resistant depression receiving intranasal esketamine over two months, no single demographic, clinical, or genetic variable—including BDNF (rs6265), OPRM1 (rs1799971) polymorphisms, or CYP2B6, CYP2C9, and CYP3A4 metabolizer status—reliably predicted treatment response. Adjunctive psychotherapy was the only factor significantly associated with remission. Most patients received the standard 84 mg dose, so nominal dosing explained little of the outcome variability. Exploratory analyses suggested that metabolic phenotype and concomitant pharmacotherapy may contribute to inter-individual differences. The findings support a multidimensional, clinically oriented approach to optimizing esketamine treatment rather than relying on a single predictor. The small sample size may have limited the ability to detect modest associations, so results are exploratory.
Frontiers in pharmacology
January 1, 2024
Luan Oliveira Ferreira, Esther Padilha da Silveira, Clarissa A Paz et al.
Ketamine, increasingly used illicitly alongside alcohol, alters brain activity in ways that depend on dose. In late-adolescent male rats, ketamine alone increased delta, theta, beta, and gamma brainwaves, most strongly at 30 mg/kg, while reducing alpha waves. Alcohol alone reduced all brainwaves. Combined, ketamine enhanced alcohol's depressant effect on alpha waves at all doses. A low ketamine dose (10 mg/kg) boosted alcohol's reduction of theta and beta waves, whereas a high dose (30 mg/kg) produced neuronal hyperexcitability, increasing delta, theta, beta, and gamma bandpower. The intermediate dose (20 mg/kg) reversed alcohol-induced reductions in theta and gamma waves.