Neuropharmacology
December 1, 2023
Adam Wojtas, Monika Herian, Marzena Maćkowiak et al.
6 citations
Repeated administration of the hallucinogenic drug 25B-NBOMe (0.3 mg/kg for 7 days) in rats rapidly produced tolerance to its effects on neurotransmitter release and hallucinogenic behavior, as measured by the Wet Dog Shake test. The drug reduced dopamine, serotonin, and glutamate responses in the frontal cortex, striatum, and nucleus accumbens after a challenge dose. Genotoxicity, indicated by DNA damage, was found in the frontal cortex and hippocampus, with increased glial cells in cortical regions but no neuronal loss. Anxiety effects depended on treatment and environmental context, with anxiogenic effects observed after both single and repeated dosing.
Neuropharmacology
July 1, 2023
Joanna Dabrowska
6 citations
Current medications for anxiety disorders and PTSD have limited effectiveness, and no new anxiety drug has been approved since the 1980s. This review discusses promising approaches being revisited or newly developed, including serotonergic psychedelics as low-dose adjuncts to psychotherapy and glucocorticoids given shortly after trauma to interfere with fear memory consolidation. Three key obstacles are identified: too few preclinical studies on fear processing in female animals despite higher anxiety rates in women, poor translation of knowledge about stress effects on fear circuitry across the lifespan into clinical practice, and limited understanding of canonical fear circuitry in adaptive versus maladaptive fear processing. Interoceptive signals linked to emotion regulation may offer new treatment avenues, especially for PTSD with cardiovascular dysregulation.
Neuropharmacology
March 7, 2025
Stefan Modzelewski, Anna Stankiewicz, Napoleon Waszkiewicz et al.
5 citations
A review of psychedelic research finds that studies vary widely in how they report side effects and often follow participants for only a short time. The authors call for future work to describe side effects more clearly and systematically. This limitation makes it difficult to fully understand the risks associated with substances like psilocybin and LSD.
Neuropharmacology
December 1, 1985
G Seeman, G M Brown
5 citations
Indolealkylamine hallucinogens such as 5-methoxy-N,N-dimethyltryptamine (MDMT), bufotenin, and N,N-dimethyltryptamine (DMT) stimulate prolactin secretion when infused directly into the brain's lateral ventricle. MDMT is the most potent, followed by bufotenin, then DMT. Bufotenin, which does not easily cross the blood-brain barrier, produces a prolonged prolactin elevation with a possible biphasic effect at the highest dose (0.02 M). DMT shows a clear dose-response relationship. These findings confirm earlier work and suggest the effect is centrally mediated, not involving peripheral receptors, and that the time course of action differs from peripheral infusion.
Neuropharmacology
December 1, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani et al.
4 citations
Before starting a low-dose LSD regimen, people with major depression held varied expectations shaped largely by media and personal experience. Over half had tried other treatments that failed. Many expected subtle effects or had no specific expectations, while some anticipated changes in consciousness or neural rewiring. Hope served both as a motivator and a buffer against disappointment. The findings underscore how media influences expectations and suggest that current expectancy measures miss important factors specific to psychedelic therapy.
Neuropharmacology
November 15, 2025
A L Zylko, R J Rakoczy, B F Roberts et al.
4 citations
Psilocybin, the psychedelic compound in magic mushrooms, may treat psychiatric disorders, but little is known about how sex and age influence its effects. In a preclinical study on rats, a 1 mg/kg dose of psilocybin did not cause head twitch responses in adolescents but did in adults. Adolescent exposure did not lead to lasting changes in anxiety or behavioral flexibility. Adult females in diestrus had stronger head twitch responses than those in proestrus. The findings indicate age- and sex-dependent differences in psilocybin's effects, with no long-term effects on certain behaviors after adolescent exposure, highlighting the need for inclusive research on age, sex, and hormonal status.
Neuropharmacology
November 5, 2025
Dimitri Daldegan‐bueno, C Donegan, Rachael L. Sumner et al.
4 citations
In an open-label phase 2A trial, 19 participants with major depressive disorder, most of whom were taking antidepressants, took microdoses of LSD twice weekly for eight weeks. No serious adverse events occurred, and one participant withdrew due to anxiety. Depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by 59.5% at the end of the intervention, with improvements sustained for up to six months. Anxiety, rumination, stress, and quality of life also improved. The results provide preliminary evidence that microdosed LSD is safe and feasible for treating moderate depression, but randomized controlled trials are needed.
Neuropharmacology
July 1, 2025
Brennan M Carrithers, Daniel E Roberts, Brandon M Weiss et al.
4 citations
Psychedelic therapy may hold potential for treating personality disorders by promoting adaptive changes in personality, though rigorous research is lacking. This review first examines research on psychedelics in individuals with personality disorders using the DSM-5-TR categorical model, then applies the dimensional DSM-AMPD framework to explore how psychedelics might affect self-functioning, interpersonal functioning, and pathological personality traits. The authors discuss clinical relevance, safety considerations, gaps, and recommendations for treating these complex populations.
Neuropharmacology
May 15, 2025
Mu Xu, Jialiang Wang, Jia Shi et al.
4 citations
Esketamine treatment alleviated sepsis symptoms, cognitive impairment, and decreased mortality in a mouse model of sepsis-associated encephalopathy. It reduced neuroinflammation, oxidative stress, and neuronal loss, and normalized calcium transients while improving dendritic structure and synaptic plasticity in the hippocampal CA1 region. These effects depended on the NF-α1/CREB signaling pathway, as suppressing NF-α1 abolished the protective effects and reversed improvements in calcium transients, dendrites, and post-synaptic plasticity. The findings suggest esketamine protects against hippocampal injury in sepsis through this pathway.
Neuropharmacology
October 17, 2025
Luisa Prochazkova, Josephine Marschall, Dominique P. Lippelt et al.
3 citations
No Summary
Neuropharmacology
November 1, 2024
Thi Mai Loan Nguyen, Jean-Philippe Guilloux, Céline Defaix et al.
3 citations
Ketamine produces rapid and lasting antidepressant effects in depressed patients. A metabolite called (2R,6R)-hydroxynorketamine (HNK) may contribute to these effects. In anxious male mice, blocking the liver enzyme cytochrome P450 with fluconazole before ketamine or HNK altered drug metabolism: it raised ketamine and norketamine levels in blood and brain but sharply reduced HNK levels. Fluconazole also prevented ketamine's sustained antidepressant-like actions in behavioral tests and its enhancement of cortical GABA levels 24 hours after injection. Giving (2R,6R)-HNK alone reversed fluconazole's blockade of ketamine's antidepressant-like activity. The findings suggest that HNK is essential for ketamine's sustained antidepressant effects and that drug interactions with cytochrome P450 inhibitors may affect ketamine treatment in patients.
Neuropharmacology
October 1, 2024
Randall J Olson, Lowell Bartlett, Alex Sonneborn et al.
3 citations
Classic psychedelics like DOI cause lasting changes in experience and show promise for treating depression. In the medial prefrontal cortex of male mice, DOI reduced low-frequency brain waves during rest, preventing the usual synchronization that occurs in less active states. It also increased gamma activity and suppressed fast-spiking neurons both during active and rest periods. These results suggest that DOI induces persistent desynchronization in the medial prefrontal cortex, which may contribute to the longer-lasting effects of psychedelics on brain plasticity and their therapeutic properties.
Neuropharmacology
November 2, 2025
2 citations
No Summary
Neuropharmacology
May 15, 2025
Yazhou Wen, Jin Zhou, Huiling Yu et al.
2 citations
Prenatal chronic restraint stress (CRS) in mice induced postpartum depression-like behaviors in mothers and sex-specific behavioral changes in their adolescent offspring: female offspring showed depression-like behaviors, while male offspring exhibited memory deficits. Esketamine, given to mothers on postpartum days 1-5, improved these maternal depression-like behaviors and also corrected the behavioral abnormalities in adolescent offspring. Additionally, prenatal CRS caused heightened secretion of ACTH and CORT in adolescent offspring during acute restraint stress, indicating hyperresponsiveness of the stress hormone system. Esketamine's effects on these hormone levels were not reported.
Neuropharmacology
May 1, 2025
Michael Noback, Johnny A Kenton, Adam K Klein et al.
2 citations
A compound called 2,5-dimethoxy-4-propylamphetamine (DOPR), a psychedelic that activates 5-HT2A receptors, can increase motivation in mice with low baseline motivation without causing hallucinogenic-like effects. In a progressive ratio breakpoint task (PRBT) involving 80 mice, doses as low as 0.0106 mg/kg improved performance only in animals with low initial motivation; high-performing mice were unaffected. The head-twitch response (HTR) assay in 72 mice showed hallucinogenic-like effects only at doses of 0.1 mg/kg or higher. These results suggest that low doses of DOPR might treat amotivated states while avoiding hallucinogenic side effects, warranting further research in rodents with disease-relevant conditions.
Neuropharmacology
July 1, 2026
Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.
1 citation
In helpless mice, the psychedelic compound N,N-dimethyltryptamine (DMT) produced rapid and long-lasting antidepressant effects comparable to the fast-acting antidepressant S-ketamine. DMT at 10 mg/kg reversed escape deficits and reduced immobility in several behavioral tests, with effects lasting up to 8 days, whereas S-ketamine's effects lasted up to 30 hours. DMT also showed anxiolytic-like effects, reversing stress-induced hypolocomotion and increasing open-arm exploration, while S-ketamine did not. Neither drug altered behavior in the novelty-suppressed feeding test. These findings suggest DMT has transdiagnostic therapeutic potential for stress-related disorders.
Neuropharmacology
March 6, 2026
Noah Cavallaro, Priya Rai, David Akins et al.
1 citation
In a first-ever fMRI study of 5-MeO-DMT, a fast-acting psychedelic, brain activity changes were observed that match its quick onset and short peak effects. A previously unknown sex difference in how the brain responds to the drug was also identified. The findings align with the drug's unique pharmacology and clinical reports, offering new insights into its neural effects.
Neuropharmacology
February 1, 2026
Giorgia Corli, Fabrizio De Luca, Sabrine Bilel et al.
1 citation
Repeated exposure to the synthetic cannabinoid AKB48 worsens the visual sensorimotor, sensory gating, and motor reactivity response to the hallucinogens 2C-I and 25I-NBOMe in mice. This effect is more prolonged in males than in females. The underlying mechanism involves neuroplastic changes in the cerebellum and cortex, specifically at serotonin 2A receptors and the serotonin transporter. These changes occur more markedly and rapidly in female mice. The findings highlight a significant interaction between synthetic cannabinoids and psychedelic drugs, which may be relevant to long-term effects and psychiatric consequences of their consumption.
Neuropharmacology
January 21, 2026
Ana Domi, Erika Lucente, Davide Cadeddu et al.
1 citation
Psilocin, the active metabolite of psilocybin, induces a long-lasting decrease in excitatory synaptic strength in the prefrontal cortex of rats, an effect that is independent of sex. This synaptic depression originates presynaptically and is not mediated by 5-HT2A or metabotropic glutamate group 2 receptors, but instead involves enhanced GABAergic inhibition. The effect is partially blocked by a 5-HT1A receptor antagonist and fully blocked by a TrkB receptor antagonist. These sustained changes in synaptic activity may relate to reduced prefrontal connectivity observed in humans and could affect cognitive function.
Neuropharmacology
October 15, 2025
Marion Hendrickx, Antoine Dampierre, Emmanuel Drouin
1 citation
Mescaline, a psychedelic compound, has shown promise in enhancing therapeutic outcomes for individuals undergoing intervention counseling. In a sample of 150 participants, 75% reported significant improvements in psychological well-being post-treatment. This aligns with historical psychiatry practices that explore the intersection of psychoanalysis and psychedelics. The study highlights the ambivalence surrounding these substances, emphasizing their potential relevance in modern medicine. By foregrounding these findings within the context of epistemology and historical scientific studies, new perspectives on mental health treatment emerge, advocating for a reevaluation of traditional approaches.
Neuropharmacology
September 15, 2026
Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wrobel et al.
Ketamine rapidly reorganizes fast brain rhythms differently across cortical networks. In freely moving rats, neocortical gamma power increased broadly, while the olfactory bulb showed suppressed gamma alongside robust high-frequency oscillations (HFO; 130-180 Hz). Local blockade of non-NMDA glutamate receptors in the olfactory bulb suppressed ketamine-enhanced HFO in the bulb, ventral striatum, and prefrontal cortex without affecting neocortical gamma, indicating separate circuit mechanisms. Within the bulb, a kainate receptor antagonist markedly reduced HFO, while AMPA receptor blockade had minimal effect. Blocking GABA-A receptors reduced HFO power while increasing gamma power, showing that fast inhibition is necessary for HFO expression. The findings suggest that tonic kainate-dependent depolarization recruits interneurons to generate an inhibitory network rhythm that drives HFO propagation through olfactory-limbic circuits.
Neuropharmacology
June 6, 2026
In male and female Long Evans rats, distinct subtypes of medium spiny neurons in the nucleus accumbens play different roles in reinstatement of ketamine-seeking behavior. The findings suggest that specific neuronal populations contribute to relapse triggered by drug-associated cues, with potential differences between sexes.
Neuropharmacology
June 1, 2026
In rats, a single low dose of ketamine more effectively than repeated low doses counteracts cognitive impairment and depressive-like behavior caused by the chemotherapy drug doxorubicin. The single dose better reduced brain inflammation and normalized levels of glutamate transporter GLT-1, serotonin transporter SERT, dopamine transporter DAT, and brain-derived neurotrophic factor (BDNF)/TrkB signaling. Repeated dosing showed weaker or no benefits on these molecular markers.
Neuropharmacology
May 1, 2026
Jairo S Acosta-Vargas, Natalia De Las Heras-Martínez, Alberto Marcos et al.
Adolescent rats exposed to vaporized THC, alone or with CBD, showed no significant changes in behavioral traits or alcohol self-administration compared to controls. However, females exhibited a more vulnerable pattern of alcohol consumption and seeking. In THC-exposed males, a negative correlation appeared between sucrose preference and compulsive alcohol seeking; in females, THC disrupted the link between novelty preference and alcohol intake and was associated with a negative correlation between goal-tracking and compulsive seeking. Naltrexone reduced alcohol intake most effectively in THC-exposed rats versus those given a high-CBD/low-THC mixture. Adolescent cannabinoid exposure has limited effects on overall alcohol risk but may alter psychological underpinnings of alcohol-related behaviors and increase naltrexone potency, with sex differences highlighting the need for personalized interventions.
Neuropharmacology
February 9, 2026
Mikael Palner, Elisabeth Kolesnik, Christina Baun et al.
The study tested whether the psychedelic compound N,N-dimethyltryptamine (DMT) exists naturally in the mammalian brain and acts as a co-transmitter with serotonin. In rats, blocking monoamine oxidase with pargyline did not allow detection of endogenous DMT, while blocking acidic metabolite transport with probenecid slightly elevated the DMT metabolite 3-indoleacetic acid, likely from tryptamine. Exogenous DMT was rapidly taken up and cleared from the brain, with peak concentrations at 45 minutes and near-complete washout by 210 minutes. Blocking serotonin reuptake or vesicular monoamine transporters did not alter DMT levels. The results do not support the hypothesis that DMT is an endogenous co-transmitter with serotonin.