bioRxiv
May 29, 2026
LSD induces gene expression patterns that oppose the transcriptional signatures of brain aging and dementia. By comparing chronic LSD treatment in rodents with age- and dementia-related gene expression changes in the human prefrontal cortex, the authors show that LSD's effects are strongly anti-correlated with these disease programs, a reversal specific compared to other pharmacological perturbations and reproducible across datasets and species. LSD also counteracts amyloid-β-induced structural and molecular alterations in primary cortical neurons, linking transcriptomic opposition to functional rescue under neurodegenerative stress. These findings suggest LSD modulates molecular and cellular pathways associated with brain aging and neurodegeneration.
Brain stimulation
May 21, 2026
Lucas L Dwiel, Mackenzi L Prina, Elise M Bragg et al.
Pretreating rats with LSD before electrically stimulating the infralimbic cortex produces larger and longer-lasting changes in brain activity than stimulation alone. The combination activates the mTOR signaling pathway and alters perineuronal net integrity, suggesting a mechanism for enhanced neuroplasticity. Brain activity during stimulation did not predict the persistent changes seen minutes or days later. These findings support developing psychedelic-assisted brain stimulation approaches to improve durability of stimulation effects, potentially reducing relapse rates in clinical treatments.
UNC Libraries
May 21, 2026
Gavin Schmitz
Psychedelics are being investigated as therapeutic tools, but their brain-region-specific effects and signaling mechanisms are not fully understood. A comprehensive study of about 40 diverse psychedelic substances from the tryptamine, phenethylamine, and lysergamide classes found that all tested compounds activate the 5-HT2A serotonin receptor, while also showing serotonergic, dopaminergic, and adrenergic activity. The 5-HT2A receptor is enriched in layer V pyramidal neurons in rodent and human cortices. Electrophysiological studies identified a population of 5-HT2A receptor neurons in the prelimbic and anterior cingulate regions of the prefrontal cortex. Psilocin and a 5-HT2A-preferring compound increased firing in these neurons via a 5-HT2A- and Gαq-dependent mechanism, whereas the non-hallucinogenic LSD analog 2-bromo-LSD reduced firing in both 5-HT2A and non-5-HT2A neurons through a different mechanism.
bioRxiv : the preprint server for biology
May 11, 2026
Jared Plotkin, Elaine Zhu, Mélanie Druart et al.
A single dose of LSD in rats persistently reduces the emotional, or affective, component of pain, without altering basic sensation. This effect is produced by LSD acting directly in the anterior cingulate cortex (ACC), a brain region that assigns negative value to painful stimuli. Recordings of neural activity showed that LSD suppresses the ACC's responses to painful input, reducing how the brain encodes the unpleasantness of pain. Although LSD increased the intrinsic excitability of ACC neurons in isolated tissue, it paradoxically reduced their maximum firing in response to painful stimuli in living animals. These results suggest that psychedelics can disrupt the brain's transformation of a painful signal into an aversive experience.
Cell Reports Medicine
May 7, 2026
Mihai Avram, Aurore Menegaux, Felix Müller et al.
1 citation
Lysergic acid diethylamide (LSD) may alleviate depression by altering white matter microstructure in the brain, potentially reflecting enhanced neuroplasticity. In a clinical trial of 61 patients with major depressive disorder, those receiving moderate-to-high doses (100 μg then 200 μg) showed increased fractional anisotropy in several white matter tracts, including the internal and external capsule, sagittal stratum, and fornix/stria terminalis. These microstructural changes correlated with improvements in depressive symptoms measured at 2, 6, and 12 weeks. The findings suggest that LSD-induced white matter changes are linked to antidepressant effects.
SLEEP
May 1, 2026
Denise Vidot, Bria-Necole Diggs, Amrit Baral et al.
Among daily cannabis consumers aged 18–35, about 56% reported lifetime psychedelic use, with psilocybin most common (50%), followed by LSD (29%) and DMT (3.5%). Overall, 33% had subthreshold insomnia, 3.2% moderate-severity clinical insomnia, and 1.6% severe clinical insomnia. LSD and DMT were associated with moderate-to-severe clinical insomnia: 17.7% of LSD users vs. 0.0% of non-users, and 50.0% of DMT users vs. 3.6% of non-users. Psilocybin showed no significant association. LSD users also reported more frequent sleep-related interference with daily functioning. No differences were found in cannabis use for sleep or demographics by psychedelic use.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Brian O'Mahony, Colm Harrington, Andrew Harkin et al.
Psychedelic drugs are being studied as treatments for mental health conditions and used recreationally, but they can cause intense psychological distress known as a "bad trip," which may lead to emergency care or psychiatric hospitalization. Managing these episodes should prioritize non-pharmacological strategies, but when those are insufficient, medications that can safely end the psychedelic state are needed. This review systematically evaluates candidate abortive agents, including serotonin antagonists, antipsychotics, and certain anxiety and depression drugs, considering their mechanisms, safety, and suitability for acute care. The authors propose a provisional framework for pharmacological management and identify priorities for future research.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Sunjuri Sun, Laura W Wesseldijk et al.
In a large twin study using the Swedish Twin Registry, people who reported using psychedelics had lower odds of having a history of migraine. Among identical twins, the twin who used psychedelics was less likely to have migraine than their co-twin who did not. The association was significant in males but not in females. These results suggest a possible link between psychedelic use and reduced migraine likelihood, with sex differences that need further study.