Abstract Background Recent clinical trials show that serotonergic psychedelics, including the prototypical hallucinogen lysergic acid diethylamide (LSD), present a great promise for treating affective disorders. While the hallucinogenic activities of LSD are commonly attributed to stimulation of 5-HT2A receptors, their role in LSD’s antidepressant response is still in debate. Interestingly, LSD...
Ayahuasca is a traditional Amazonian brew composed primarily of Banisteriopsis caapi and Psychotria viridis, drawing increasing interest for its psychedelic effects and potential therapeutic applications. Its pharmacological action is based on the synergistic combination of β-carbolines (harmine, tetrahydroharmine, and harmaline), which act as reversible inhibitors of monoamine oxidase A...
Abstract Background Among the innovative treatments investigated for depression, psilocybin appears to play an extremely promising role, with several studies showing remission rates up to 70% in patients with treatment-resistant depression (TRD) treated with protocols involving a single or double dose administration [1,2]. Psilocybin is a psychedelic compound belonging to the tryptamine class,...
Abstract Background Psychedelics hold potential as therapeutics in psychological disorders. Even if they primarily act on 5-HT2A receptors, their mechanisms and effects on the brain are not well understood. Simply activating 5-HT2A receptors does not induce psychedelic effects. For example, psilocybin and lisuride both bind to 5-HT2A receptors, but only psilocybin induces hallucinogenic...
Overdose fatalities involving cocaine continue to rise with over 5.3 million cocaine users reported in the United States in 2022. The abuse liability of cocaine is reliant upon inhibition of dopamine (DA) reuptake and consequent increase in DA efflux in meso-corticolimbic circuitry that controls reward and motivation. Cocaine also increases serotonin (5-HT) efflux which is integral in cocaine...
Psychedelic drugs that activate 5-HT2A receptors have been long used for cultural, medicinal and recreational purposes. Interest in psychedelics for treating psychiatric disorders has resurged recently and is well documented; less well recognised are their anti-inflammatory properties. Growing evidence now demonstrates that psychedelics modulate immune responses, including inhibiting...
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an...
By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes. A PubMed literature search covering the past 30 years was conducted using keywords such as "5-HT2A...
bioRxiv Preprint ServerJuly 23, 2025Tomas Del Olmo, Mathilde Decourcelle, Martial Séveno et al.
preprint
The serotonin (5-HT)2A receptor is the primary target of numerous psychoactive drugs including serotonergic psychedelics, and mediates psychedelics-induced neuroplasticity, but the signaling mechanisms involved remain poorly characterized. Using quantitative phosphoproteomics, we show that the administration of the hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) to...
Recent clinical trials show that serotonergic psychedelics, including the prototypical hallucinogen lysergic acid diethylamide (LSD), possess a great promise for treating affective disorders. Interestingly, LSD displays strong functional activity on 5-HT2B receptors and a modulatory role of the latter receptors in anxious and depressive-like behaviors has been reported. Using behavioral and in...
Alzheimer's disease (AD) is the leading cause of dementia. There are limited approved medications that delay cognitive decline or lessen neuropsychiatric symptoms. Numerous clinical trials for AD using a single drug administration have failed to meet therapeutic endpoints, which is most likely due to the complexity of AD. A multimodal therapeutic intervention is more likely to improve symptoms...
The mechanism of action of serotonergic psychedelics is increasingly explored worldwide due to their clinical benefits in various psychiatric conditions. Beyond the stimulation of serotonin 2 A (5-HT2A) receptors, psychedelics may desynchronize activity between brain regions, however the involvement of corresponding neurotransmission systems has been largely overlooked. Given that monoaminergic...
Background: Classic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and reduction. Methods: A systematic...
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or H2 histamine receptors. However, whether psilocybin or psilocin acts at...
Visual perception appears largely stable in time. However, psychophysical studies have revealed that theta waves (4-8 Hz) can modulate perception and have been linked to various cognitive states and functions. Neither the contribution of theta waves to cortical activity nor their impact during aberrant brain states have been resolved at high spatiotemporal scales. Here, using cortex-wide...
This work presents a comprehensive theory of consciousness grounded in mathematical formalism and supported by clinical data analysis. The framework developed herein demonstrates that consciousness exists as a continuous, non-monotonic function across a high-dimensional neurochemical space, with dopamine serving as the primary intensity regulator and serotonin (5-HT2A) as the complexity...
Serotonergic psychedelics exert their effects via their high affinity for serotonin (5-HT) receptors, particularly through activating 5-HT2A receptors (5-HT2AR), employing the frontal cortex-dependent head-twitch response (HTR). Although universally believed to be so, studies have not yet fully ascertained whether 5-HT2AR activation is the sole initiator of these psychedelic effects. This is...
CureusJuly 1, 2025Akshita Suleria, Sakshi Verma, Khanij Arya et al.
Lysergic acid diethylamide (LSD) is an ergot-derived psychedelic agent that produces perceptual and psychic effects of heightened sensations by acting on the dopaminergic, adrenergic, and serotonergic pathways in the brain and periphery, with 5-hydroxytryptamine 2A (5-HT2A) as the primary target molecule. Its action on these receptors in the central nervous system is comparatively well studied...
Research on psychedelic drugs, such as psilocybin, LSD or DMT, is a burgeoning field, with an increasing number of studies showing their promise in treatment of mental disorders as well as examining their mechanism of action. Determining their effect on the brain is crucial from clinical standpoint, but also offers highly promising avenues of advancement in basic neuroscience—functional...
Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy...