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Luke T. J. Williams

10 papers in the library · 1,884 citations · publishing 2014-2022

Papers

Neural correlates of the LSD experience revealed by multimodal neuroimaging.

Proc Natl Acad Sci U S A April 11, 2016 Robin 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.

Neural correlates of the DMT experience assessed with multivariate EEG.

Sci Rep November 19, 2019 Christopher Timmermann, Leor Roseman, Michael Schartner et al. 325 citations

Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity

Biological Psychiatry January 10, 2014 Robin Carhart-Harris, Kevin Murphy, Robert Leech et al. 182 citations

The medial temporal lobes (MTLs) are specifically involved in how MDMA works in the brain, though more research is needed to understand how the drug's characteristic subjective effects emerge from its modulation of spontaneous brain activity.

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial

Psychopharmacology November 26, 2018 Steliana Yanakieva, Naya Polychroni, Neiloufar Family et al. 169 citations

Microdoses of LSD (5, 10, and 20 μg) caused older adults to over-reproduce time intervals of 2000 milliseconds and longer, with the strongest effect at 10 μg. This temporal dilation occurred without noticeable changes in perception, mentation, or concentration, and was independent of any subjective drug effects. The findings suggest that LSD can directly alter interval timing at doses too low to produce conscious psychedelic effects, indicating a dissociation between neurochemical influences on time perception and altered states of consciousness.

LSD modulates music-induced imagery via changes in parahippocampal connectivity.

Eur Neuropsychopharmacol April 12, 2016 Mendel Kaelen, Leor Roseman, Joshua Kahan et al. 143 citations

Psychedelic drugs like LSD are being re-examined for therapeutic use, often combined with music during psychotherapy. In a placebo-controlled fMRI study with 12 healthy volunteers, researchers investigated how LSD and music together affect mental imagery. They found that the combination of LSD and music increased functional connectivity and information flow from the parahippocampal cortex to the visual cortex. This enhanced connectivity correlated with stronger eyes-closed visual imagery, including autobiographical imagery. The findings suggest a neural mechanism by which music and LSD synergistically enhance subjective experiences that may be valuable in therapeutic settings.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

Psychopharmacology December 18, 2019 Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams et al. 142 citations

Repeated low doses of LSD are safe and well tolerated in older adults. In a double-blind, placebo-controlled trial, 48 healthy volunteers aged around 63 received either 5, 10, or 20 micrograms of LSD or a placebo every four days for three weeks. LSD was undetectable in the blood at the 5 microgram dose, while peak levels for higher doses occurred within 30 minutes. Adverse events were no more frequent than with placebo, and tests of cognition, balance, and proprioception showed no impairment. These results support further clinical development of low-dose LSD for treating or preventing Alzheimer's disease.

Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study

Journal of Psychopharmacology March 1, 2022 Neiloufar Family, Peter S. Hendricks, Luke T. J. Williams et al. 23 citations

LSD doses of 50, 75, and 100 micrograms are tolerable and safe in healthy adults when administered in a novel group-based intervention paradigm with one attendant per participant. Thirty-two adults (mean age 28.8 years) received LSD or placebo across open-label and double-blind designs. No serious adverse events occurred; 28% of participants reported at least one mild expected adverse event and one moderate event. Peak blood plasma levels appeared 1.2 to 2 hours after administration, with an apparent half-life of 2.8 to 4.3 hours. LSD produced greater subjective effects than placebo, including mystical-type experiences. Further research is needed in clinical populations.

Perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide in healthy participants within a novel intervention paradigm: Qualitative results from a proof-of-concept study

Journal of Psychopharmacology March 1, 2022 Peter S. Hendricks, Heith Copes, Neiloufar Family et al. 8 citations

In a proof-of-concept study with 31 healthy participants given 50 to 100 µg of LSD, most felt safe throughout the experiment, attributing their comfort to the study structure and support from attendants, which allowed them to let go and immerse themselves. A minority initially worried about having a challenging experience, but those concerns lessened over time. Participants reported transcendent, mystical-type experiences typical of classic psychedelics, with nearly half noting the important role of music during the drug's acute effects. They endorsed the clinical utility of LSD in controlled environments, believing it is safe and could help others. Findings suggest this scalable intervention paradigm is feasible and warrants further research with clinical populations.

Neural correlates of the DMT experience as assessed via multivariate EEG

bioRxiv July 18, 2019 Christopher Timmermann, Leor Roseman, Michael Schartner et al. 4 citations preprint

Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.

Neural correlates of the LSD experience revealed by multimodal neuroimaging

UNC Libraries April 22, 2020 Peter J. Hellyer, Luke T. J. Williams, Ben Sessa et al. 1 citation

Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.