BACKGROUND Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity (iFC) as measured by resting-state functional magnetic resonance imaging (rs-fMRI). Specifically, thalamic iFC is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal-limbic cortices (hypoconnectivity). Intriguingly, psychedelics such as lysergic acid diethylamide (LSD) elicit similar thalamocortical-hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical-hypoconnectivity with prefrontal-limbic cortices as current findings are equivocal. Notably, thalamocortical-hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic-induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics. METHODS We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic iFC with two brain networks (auditory-sensorimotor (ASM) and salience (SAL) - corresponding to sensorimotor and prefrontal-limbic cortices, respectively), using a double-blind, placebo-controlled, cross-over design. RESULTS All active substances elicited ASM-thalamic-hyperconnectivity compared to placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with SAL, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns. CONCLUSIONS Psychedelics, empathogens, and psychostimulants evoke thalamocortical-hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics.

<p>Serotonergic psychedelics induce profound changes in consciousness, producing an altered state often referred to as the psychedelic state. The entropic brain hypothesis proposes that this state is marked by increased brain entropy (i.e., greater randomness in neural activity) which is assumed to reflect expanded phenomenal richness, or a broader range of accessible conscious contents. Given the numerous neuroimaging studies reporting heightened entropy under psychedelics, a substantial portion of the field has embraced entropy as a reliable biomarker of the psychedelic state. We argue that this view is inherently oversimplified and offer a more nuanced and comprehensive perspective. We first review evidence supporting the use of entropy metrics and discuss their potential utility. We then identify key empirical, methodological, and conceptual limitations associated with using brain entropy as a psychedelic biomarker, organized into four themes: (1) entropy alterations are not specific to psychedelics; (2) current entropy-based approaches do not accommodate multidimensional operationalizations of conscious states; (3) multiple entropy metrics exist, each with distinct interpretations and varying levels of mutual consistency; and (4) insufficient evidence supports the neurophenomenological equivalence between brain entropy and phenomenal richness. Although substantial questions remain about the validity of entropy-based biomarkers of the psychedelic state, we conclude that the concept warrants further investigation and offer practical suggestions for future research to address these limitations.</p>

Autism Spectrum Disorder (ASD) is a lifelong condition marked by challenges in social communication and repetitive behaviors. Current treatments, primarily behavioral therapies, often fail to address the core symptoms. Recent research has explored the potential of psychedelics, such as LSD, psilocybin, and MDMA, as a new therapeutic approach. While these substances primarily modulate the serotonin 5-HT_2A receptor, their therapeutic effects also involve interactions with other serotonergic, dopaminergic, and glutamatergic pathways, collectively promoting neuroplasticity-the brain's ability to change and adapt. The specific receptors' activation leads to structural and functional changes in the brain that can enhance social behavior and emotional regulation. Studies show that psychedelics may reduce symptoms of conditions like treatment-resistant depression and PTSD, highlighting their therapeutic potential. For ASD specifically, psychedelics may improve psychological flexibility, reduce distress, and enhance social interaction. While promising, the use of these substances requires careful consideration. Psychedelics can induce intense experiences and altered states of consciousness, necessitating strict monitoring and support during therapy. Ethical guidelines, including informed consent, are crucial, especially for vulnerable populations. In conclusion, psychedelics hold significant promise for treating ASD and other psychiatric disorders by promoting neuroplasticity and modulating complex signaling pathways. Continued research and clinical trials, conducted with strong ethical oversight, are essential to realizing their full therapeutic potential.

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various other types of hallucinogens as well, such as thos Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various other types of hallucinogens as…