Journal of psychopharmacology (Oxford, England)
August 1, 2021
Rachael L Sumner, Emme Chacko, Rebecca McMillan et al.
68 citations
Ketamine, given at 0.44 mg/kg to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, produced psychedelic experiences that correlated with greater antidepressant response at 24 hours. Specifically, higher scores on spirituality, experience of unity, and insight were linked to larger reductions in depression ratings. Qualitative interviews revealed perceptual changes, loss of control, emotional shifts, a psychedelic afterglow, and lasting changes in perspective on life, people, problems, and depression. The findings suggest the psychedelic experience and afterglow contribute to ketamine's antidepressant effects, and that standard questionnaires may not fully capture these properties.
Translational psychiatry
February 24, 2024
Rachael L Sumner, Rebecca L McMillan, Anna Forsyth et al.
7 citations
Ketamine's antidepressant effects may be driven by acute changes in brain connectivity and GABA receptor dynamics, not primarily by NMDA receptor blockade. In 30 patients with major depressive disorder, resting-state EEG was recorded before and during a 0.44 mg/kg ketamine infusion. Computational modeling revealed a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both changes correlated with antidepressant response. NMDA receptor changes did not survive correction and were not correlated with symptom improvement. The findings suggest that acute fronto-parietal connectivity and GABA-A/AMPA receptor dynamics mediate ketamine's antidepressant properties.
Journal of psychopharmacology (Oxford, England)
April 18, 2025
James D Morse, Soo Hee Jeong, Robin J Murphy et al.
3 citations
After a 10 µg sublingual dose of LSD, the drug's concentration in the blood peaks at about 0.20 µg/L after 1.5 hours and has an elimination half-life of roughly 3 hours. A one-compartment model best describes how the body processes the drug. The small increases in heart rate and perceived drug effect (less than 15% above baseline) limited the ability to model those effects. Two participants who withdrew due to anxiety had intermediate-to-weak CYP2D6 enzyme activity, and several CYP genotypes appeared to influence LSD concentration. No evidence of changes in peripheral BDNF levels was found. The findings provide a pharmacokinetic model and assay useful for future clinical studies, but larger samples are needed to assess CYP genotypes as response biomarkers.
bioRxiv Preprint Server
May 5, 2020
Alexander D Shaw, Suresh D Muthukumaraswamy, Neeraj Saxena et al.
2 citations
preprint
Ketamine alters brain oscillations, increasing high-frequency gamma waves and reducing low-frequency alpha and theta waves. A thalamo-cortical model better explained these changes than a cortex-only model. The model showed that ketamine increases specific synaptic connections: from superficial pyramidal cells to inhibitory interneurons via AMPA and NMDA receptors, and within-layer-5 pyramidal cell gain control via GABA-A and NMDA receptors. Receptor time-constants remained unchanged. These findings support using generative models to understand oscillatory data and provide computational evidence that ketamine alters local neural coupling through multiple neurotransmitter systems.