Harman Brar
Virtual reality is used as a therapeutic tool for anxiety, PTSD, and depression through exposure therapy and simulated environments, but its potential to mimic psychedelic experiences has not been examined. Research suggests individuals in VR simulated psychedelic experiences undergo effects similar to those from psychedelic drugs, though the physiological impact on the brain and mind is largely unexplored. To determine whether VR can mimic psychedelics, targeting 5-HT receptor activity in the frontal lobe is proposed as a hypothesis. This paper examines drug mechanisms of psychedelics, the theoretical application of VR-based psychedelic therapy, and postulates a method to measure the effectiveness of psychedelic simulations for psychopathology.
Cristina Delgado-Sallent, Pau Nebot, Thomas Gener et al.
preprint
Psychosis induced by the NMDAR antagonist phencyclidine in mice causes hypersynchronization and disrupted communication between the prefrontal cortex and hippocampus, including increased oscillatory power at delta, high gamma, and high frequencies, aberrant cross-frequency coupling, enhanced cross-regional coupling and phase coherence, and a reversal of the direction of theta-frequency information flow from hippocampus-to-prefrontal-cortex to delta rhythms traveling in the opposite direction. Three antipsychotic drugs—haloperidol, clozapine, and risperidone—rescued most of these changes, suggesting common cellular mechanisms. Selective serotonin receptor agents rescued power, coupling, and phase coherence but not the directionality, indicating additional targets are needed.
Khush Jain, Fariah Rizwani, Nisarg Sawant et al.
In a mouse model of depression induced by chronic unpredictable mild stress, harmaline, a monoamine oxidase inhibitor from Peganum harmala, reversed depression-like behaviors. Mice given daily oral doses of harmaline (15 mg/kg) for 21 days showed improved performance in behavioral tests and, compared to stressed controls, had lower serum corticosterone and higher brain levels of serotonin, norepinephrine, and dopamine. Harmaline also reduced oxidative stress markers and pro-inflammatory cytokines. These effects were comparable to those of the standard antidepressant imipramine (30 mg/kg). The findings suggest harmaline may mitigate stress-induced depressive disorders by modulating monoamines, oxidative stress, and neuroinflammation.
Alex Jinich-Diamant
preprint
Mystical states induced by psychedelics, meditation, or fasting all converge on the same brain state: a transient near-critical regime. Serotonergic psychedelics relax top-down priors by sensitizing layer 5 pyramidal neurons; open-monitoring meditation elevates cortical entropy through altered thalamocortical connectivity; caloric restriction destabilizes the default mode network by attenuating metabolic support for high-level attractors. The depth of the mystical state, not the method of induction, predicts lasting therapeutic benefit, suggesting conscious experience itself is the mechanistic agent of change. This framework proposes that near-critical dynamics may allow field-theoretic and quantum-coherent contributions to consciousness to become detectable.
Preprints.org
Enzo Tagliazucchi
2 citations
preprint
Serotonergic psychedelics alter conscious awareness, perception, mood, emotion, and cognition, but their effects resist simple classification like stimulant or sedative. Their defining feature is temporarily inducing an altered state of consciousness. Because only humans can explicitly report conscious experiences, studying these compounds requires non-invasive neuroimaging techniques in healthy subjects. This review examines how neuroimaging has been applied to investigate the neural correlates of altered consciousness caused by serotonergic psychedelics.
Preprints.org
Kainat Riaz, Sejal Suneel, Mohammad Hamza Bin Abdul Malik et al.
1 citation
preprint
Half of patients with post-traumatic stress disorder (PTSD) do not respond to standard pharmacotherapy or psychotherapy. A review of six phase II randomized controlled trials indicates that MDMA-assisted psychotherapy can reduce PTSD symptoms, even in treatment-resistant cases, by increasing neurohormones such as dopamine, serotonin, norepinephrine, and oxytocin and by modulating brain regions involved in fear and anxiety. The FDA has granted MDMA-assisted psychotherapy a "Breakthrough Therapy" designation. Further research is needed to determine whether the benefits outweigh the risks and whether this approach can be integrated into existing treatment options.
Research Square
Ulrich Gergs, Hannes Jacob, Pauline Braekow et al.
1 citation
LSD increases the force and rate of heart muscle contraction by activating H2-histamine receptors in humans, and also acts as a partial agonist at 5-HT4 serotonin receptors in mice. In human atrial tissue from heart surgery patients, LSD's contractile effects were blocked by cimetidine, an H2-receptor antagonist. These findings clarify the cardiac effects of LSD, which is being studied again for psychiatric uses.
Research Square
Taqwa B. Thanoon, Zeina A. Althanoon
Depression during pregnancy can harm offspring brain development and behavior. Common antidepressants like SSRIs carry risks because they cross the placenta. Ketamine is being explored as an alternative. This study in mice examined the effects of ketamine on offspring of mothers that experienced stress. Female mice were divided into groups: control, maternal stress, stress plus fluoxetine, and stress plus ketamine. Behavioral tests measured anxiety, anhedonia, and despair in the offspring. Maternal stress increased anxiety-like behaviors, and both ketamine and fluoxetine reversed some effects. However, fluoxetine was more effective at reducing despair. Ketamine moderately reduced anhedonia compared to controls. More research on dose and timing is needed to optimize ketamine treatment.
Tony Montgomery
A simple endogenous tryptamine can profoundly alter perception and self-modeling. The Birth Echo Hypothesis proposes that during a narrow perinatal window around delivery, a convergence of stress, sensory novelty, and neuromodulators biases encoding of high-salience sensorimotor templates. In adulthood, exogenous DMT may reconfigure brain dynamics via 5-HT2A and sigma-1 receptors, making these preverbal templates accessible as archetypal, emotionally intense, synesthetic content. DMT is framed as a co-modulator within an evolved perinatal regulatory ensemble. Testable predictions include adult DMT phenomenology showing perinatal-consistent motifs, neonatal EEG/fMRI state-space similarity to adult DMT states, and peri-parturient biospecimens revealing DMT-pathway marker co-variation. The hypothesis reframes psychedelic phenomenology as structural re-expression of early sensorimotor templates.
Burton J. Tabaac, Kenneth Shinozuka, Anne Weisman et al.
preprint
5-MeO-DMT, a psychedelic found in toad venom and some plants, shows rapid antidepressant effects in early clinical trials. A Phase 2b trial reported that 57.5% of participants with treatment-resistant depression achieved remission within eight days. Other Phase 2a and 2b trials suggest it may reduce depressive symptoms more effectively than existing treatments like SSRIs. The substance appears low-risk in controlled settings, though most studies are small and only two double-blind randomized controlled trials have been conducted in clinical populations. Long-term effects need further study, and its possible link to near-death experiences remains debated.