Psychedelics and psychostimulants produce subjective and often positive affective effects in humans. In rats, positive affective states are often associated with frequency-modulated ultrasonic vocalizations (USVs). We examined whether the hallucinogenic 2,5-dimethoxy-4-iodoamphetamine (DOI; 1.25-2.5 mg/kg) and LSD (0.04-0.08 mg/kg), the non-hallucinogenic lisuride (0.03 or 0.3 mg/kg) and the...
Psilocybin, a tryptamine alkaloid found naturally in numerous Psilocybe mushroom species, is currently being investigated for its therapeutic potential in treating several neurobehavioral and psychiatric diseases. Our previous data showed that the 5-HT2B receptor (5-HT2BR) immobility and increases in climbing behavior in the forced swim test (FST), revealing that psilocybin's predictive...
Psychedelic-assisted therapy has emerged as a promising therapeutic approach across several psychiatric disorders, yet the mechanisms linking acute brain-state changes and subjective experience to sustained clinical improvement remain incompletely understood. Here, we extend a previously proposed excitation/inhibition (E/I)-centred dual-phase model of psychedelic action to the therapeutic...
The association between sleep-related phenomena and psychosis has received increasing attention in recent years, as sleep disturbances (e.g., insomnia) have shown robust associations with psychotic symptoms. However, the role of other, more specific sleep processes in psychosis remains unclear, despite their potential importance as symptom-related correlates. Particularly, phenomena such as...
High ventilation breathwork (HVB) is increasingly used in psychotherapeutic and contemplative contexts to induce altered states of consciousness (ASC), yet its neurobiological mechanisms remain poorly understood. Thirty experienced HVB practitioners (mean age 44.97 ± 11.80 years) underwent perfusion and resting-state fMRI to assess acute cerebrovascular and post-acute network changes. Cerebral...
Post-traumatic stress disorder (PTSD) remains difficult to prevent after trauma, highlighting the need for early interventions that reduce the risk of chronic symptom development. This controlled study investigated the preventive potential of 3,4-methylenedioxymethamphetamine (MDMA) in a validated rat model of PTSD induced by predator scent stress (PSS). Adult male Sprague-Dawley rats (N = 175)...
Background: Cannabis use among adolescents with depression is prevalent. Dysfunction of the reward system has been implicated in each condition separately, yet rarely examined together. Here, we investigated resting-state properties of reward networks in an adolescent sample with diverse internalizing psychopathology and cannabis use patterns. Methods: Clinicians interviewed adolescents and...
BackgroundAlcohol use disorder (AUD) remains difficult to treat with lasting success, leading to growing interest in alternative therapeutic approaches. Psychedelic compounds such as Ayahuasca, a traditional brew used in Indigenous Amazonian ceremonies containing N,N-dimethyltryptamine (DMT) along with monoamine oxidase-inhibiting β-carbolines, have shown promise in reducing addictive...
Psychedelics have emerged as a promising novel therapeutic approach for major depressive disorder (MDD). Altered activity and structural atrophy of the prefrontal cortex, hippocampus, and limbic structures are associated with depressive disorders. Psilocybin may reverse the loss of synaptic connections and restore the function of these brain regions. In this study, we investigated the effects...
Despite recent advances in neuropsychiatry, translational development for many targets remains challenging, particularly when receptors exist as families with complex subunit-dependent pharmacology and safety concerns. This is the case for NMDA receptor (NMDAR) antagonists. R,S-ketamine illustrates this issue: although it produces rapid antidepressant effects in the clinic, its use is limited...
Major depressive disorder (MDD) is a leading cause of disability worldwide, and currently available antidepressants remain limited by delayed onset of action, incomplete response, and adverse effects. Ketamine is a rapid-acting antidepressant, whereas xanomeline, an M1/M4 muscarinic receptor agonist, may represent a mechanistically distinct non-monoaminergic strategy. However, the molecular...
Although esketamine shows efficacy for treatment-resistant depression, its potential effectiveness in cancer-related depression (CRD) has not been well-established. We therefore evaluated the real-world effectiveness and safety of esketamine in CRD using a target trial emulation framework based on anonymized electronic health records from the TriNetX network. Adults aged 18-74 years with CRD...
The renewal of psychedelic medicine has garnered significant scientific interest, with large efforts dedicated to the understanding of the complex subjective experiences induced by these substances. The Altered States of Consciousness (ASC) questionnaire represents the most comprehensive instrument for measuring such experiences yet lacks a validated French translation despite its centrality to...
Autism Spectrum Disorder (ASD) is characterized by persistent social-communication deficits, cognitive rigidity, and atypical sensory processing. Current pharmacological treatments, including risperidone and aripiprazole, provide only limited symptomatic relief and do not address the underlying neurobiological mechanisms. Converging evidence implicates dysregulated serotonergic signaling,...
Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) and C3 protein (markers of A1...
Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research regarding its biochemical and clinical properties. This narrative review summarizes the history of ketamine's development, beginning as a general anesthetic, continuing with a discovery of its antidepressant properties, and leading up to its landmark...
Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.
Functional disorders, characterised by symptoms unexplained by organic disease, impose a significant burden on individuals and healthcare systems. Existing treatments are limited in efficacy, with no effective pharmacotherapies. There is growing evidence supporting the treatment potential of psychedelics in neuropsychiatric conditions, including several distinct functional disorders. This...
Ayahuasca is a psychedelic plant brew that has been used in Central and South America for centuries. Recently, there has been an increase in "drug tourism" to places where ayahuasca is legally available as well as increased scientific interest in its potential mental and physical health benefits. Despite a growing body of research over the last decade, no studies to date have systematically...
Major depressive disorder (MDD) is a debilitating neuropsychiatric condition that affects individuals worldwide. While neuronal deficits have long been recognized in depression pathogenesis, astroglia are increasingly gaining attention. Astroglia are essential for maintaining brain homeostasis, and regulate neurotransmission, neuroinflammation, and metabolic processes that are disrupted in MDD....
The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors that may influence the level of altered consciousness during naturalistic psychedelic use, which serves as a proxy for the intensity of the psychedelic experience. A retrospective online survey was conducted on individuals who reported a psychedelic...
BACKGROUND: Recent advancements in psychedelic research have highlighted psilocybin's potential therapeutic benefits for various mental disorders. Understanding its effects on brain function and identifying predictors of individual responses are essential for developing effective treatments. METHODS: This double-blind, randomized, crossover, and placebo-controlled study enrolled 25 healthy...
Recent evidence suggests that psychedelics hold promise in treating a range of neuropsychiatric disorders, highlighting the need to better understand their broader behavioral effects. Many animal-based behavioral assays related to mood, like anxiety and despair-like behavior, highly depend on locomotor activity. However, the influence of psychedelics on movement, especially in emotionally...
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect...