Psychological Medicine
October 1, 2023
Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi et al.
44 citations
LSD increases the rate at which people learn from both rewards and punishments during a probabilistic reversal learning task, suggesting a state of heightened learning plasticity. Healthy volunteers given intravenous LSD or placebo completed a task where they had to learn which of three stimuli was most often rewarded, with the reward contingencies later reversing. Computational modeling of reinforcement learning showed that LSD primarily enhanced the reward learning rate and also elevated the punishment learning rate, while decreasing stimulus stickiness (a measure of choice repetition), indicating increased exploration. These effects point to a potential mechanism by which LSD could help revise maladaptive associations in clinical treatment.
Comprehensive Psychiatry
July 1, 2025
Luca Pellegrini, Naomi A Fineberg, Sorcha O'Connor et al.
17 citations
A 10 mg dose of psilocybin produced a rapid, moderate-to-large reduction in compulsive symptoms in people with obsessive-compulsive disorder (OCD), lasting up to one week after dosing. In a blinded pharmacological challenge study, 18 adults with at least moderate OCD received a 1 mg and then a 10 mg dose of oral psilocybin, separated by four weeks. One week after the 10 mg dose, scores on the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale showed a significant improvement compared to the 1 mg dose (Cohen's d = 0.74). No effect on depression was detected. The drug was well tolerated with no serious adverse events.
bioRxiv (Cold Spring Harbor Laboratory)
December 9, 2020
Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi et al.
14 citations
preprint
Lysergic acid diethylamide (LSD) increases the speed at which the brain updates the value of actions following feedback, particularly after rewards, and makes behavior more exploratory. In a within-subjects experiment, healthy volunteers received intravenous LSD or placebo and performed a probabilistic reversal learning task where they learned which of three stimuli was most often rewarded, with contingencies later reversing. Computational modeling showed LSD enhanced the reward learning rate and also elevated the punishment learning rate, while reducing stimulus stickiness—a measure of choice repetition regardless of outcomes. Conventional measures of immediate feedback sensitivity were unaffected. These findings suggest LSD induces a state of heightened plasticity that may help revise maladaptive associations in clinical settings.
Cureus
January 29, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
2 citations
The study aims to uncover the neural mechanisms by which psilocybin-assisted therapy affects obsessive-compulsive disorder (OCD) and whether those brain changes align with improvements in cognitive symptoms. A secondary goal is to test whether a low, tolerable dose is both practical and effective as a clinical treatment. The results will provide essential data for designing a future randomized controlled trial.
Cureus
January 1, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
correction
A protocol describes a planned study testing whether a low-moderate dose of psilocybin (10 mg), combined with non-interventional therapy, can improve cognitive flexibility and neuroplasticity in people with obsessive-compulsive disorder (OCD). Twenty blinded participants will receive an active placebo (1 mg psilocybin) in a first session and 10 mg in a second session four weeks later. Cognitive flexibility will be measured with the intradimensional-extradimensional shift task two days after each session, and neuroplasticity will be assessed via electroencephalography immediately after each session. Secondary outcomes include OCD symptom severity and patient-reported measures. The results are expected to clarify neural mechanisms and guide a future randomized controlled trial.
The International Journal of Neuropsychopharmacology
October 31, 2014
Samuel A Barnes, Stephen J Sawiak, Daniele Caprioli et al.
Sub-chronic exposure to the NMDA receptor antagonist phencyclidine (PCP) in rats produced localized reductions in grey matter density in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala, along with reduced cortical thickness in the insular cortex. PCP-treated rats also showed impaired sustained visual attention on a 5-choice serial reaction time task, especially under higher attentional load, but no significant effect on attentional filtering in an acoustic startle paradigm. These findings indicate that NMDA receptor antagonism can cause brain structural abnormalities in regions implicated in schizophrenia and dissociable attentional deficits.