Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
Proc Natl Acad Sci U S A
January 28, 2019
Katrin H. Preller, Adeel Razi, Peter Zeidman et al.
303 citations
LSD alters communication within brain pathways that filter sensory information, according to a brain imaging study. Using a double-blind, placebo-controlled design with 25 healthy participants, researchers found that LSD increased signaling from the thalamus to the posterior cingulate cortex—an effect dependent on serotonin 2A receptor activation—and decreased signaling from the ventral striatum to the thalamus independently of those receptors. These changes in directed connectivity within cortico-striato-thalamo-cortical loops support the thalamic filter model of psychedelic action, which proposes that psychedelics disrupt the gating of sensory information to the cortex. The findings advance understanding of how psychedelics alter consciousness and may inform development of new therapeutics.
Proc Natl Acad Sci U S A
February 1, 2022
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
148 citations
During conscious states, the cortex operates near a mathematically specific critical point called the edge-of-chaos, the boundary between stability and chaos. Applying a modified 0-1 chaos test to ECoG and MEG recordings from humans and macaques, evidence suggests that unconscious states—such as generalized seizure and anesthesia—involve a shift of low-frequency cortical oscillations away from this critical point, disrupting information processing. Psychedelic states tune these oscillations closer to the critical point, potentially increasing information richness. Analysis of clinical EEG from patients with disorders of consciousness indicates that measuring proximity to this critical point may serve as a clinical index of consciousness.
Proc Natl Acad Sci U S A
May 1, 1968
S H Snyder, E Richelson
51 citations
The article examines how the three-dimensional shapes of psychedelic molecules—their steric factors—influence their ability to produce psychotropic effects. By analyzing molecular structures, the authors identify specific spatial arrangements that correlate with psychoactive potency. The findings suggest that steric hindrance and molecular geometry play crucial roles in determining whether a compound will induce altered states of consciousness. This structural understanding may guide the design of new psychedelic compounds with predictable effects.
Proc Natl Acad Sci U S A
September 15, 2025
Peter Whitridge
The abstract questions whether the combination of vilca and tobacco snuff used at the ancient Peruvian site of Chavín was intended to produce an effect similar to ayahuasca. It suggests that the specific mixture may have been chosen for its psychoactive properties, possibly to induce altered states of consciousness in ritual contexts. The text does not provide a definitive answer but raises the hypothesis that the blend was designed to mimic or parallel the visionary experiences associated with ayahuasca.
Proc Natl Acad Sci U S A
January 3, 2024
Carolyn Beans
Gut microbiota may play a role in social anxiety disorder (SAD), a disabling condition marked by intense fear and avoidance of social situations. In mice, altering the gut microbiome affected social anxiety-like behaviors, suggesting that the microbiota-gut-brain axis could be a target for developing new treatments. The findings indicate that biological mechanisms involving gut bacteria contribute to SAD, offering a potential avenue for novel therapeutic strategies beyond current approaches.