Psychedelics as Psychiatric Medications
March 1, 2023
David Castle, Nicole Ledwos, David Nutt
The renewed scientific interest in psychedelics and related drugs is promising for treating mental health disorders and addictions, but many questions remain unanswered. Key uncertainties include how these drugs work in the brain, how their biological effects interact with psychological support to produce therapeutic change, the duration of benefits, and long-term safety. The necessity of the psychedelic experience for therapeutic benefit, safe delivery of psychological support, integration into mainstream healthcare, funding, therapist training, and gold-standard trial designs addressing blinding, placebo response, and expectancy bias are all outstanding issues that need resolution as research expands across more disorders.
May 10, 2022
Robin Carhart-Harris, Richard E. Daws, David Nutt
preprint
The authors respond to a critique of their earlier work that questioned whether psilocybin truly opens depressed minds. They address the skeptic's arguments, defending their original evidence and conclusions about psilocybin's effects on depression. The response clarifies methodological points and reaffirms the potential of psilocybin as a treatment for depression, while acknowledging the need for further research to address lingering doubts.
Journal of Psychopharmacology
July 14, 2019
Livia Ng, Luca Pani, Anaïs Soula et al.
Claims about the positive effects of microdosing psychedelics on mood and cognition have entered public discussion, but scientific studies are scarce and no consensus on what microdosing means exists. This critique identifies questions future research must answer and offers guidelines, focusing on psilocybin due to its potential clinical approval and short-lasting effects. While anecdotal reports emphasize benefits, the paper concludes that future studies should also investigate potential risks of repeated low-dose administrations. Preclinical and clinical research examining biological measures like heart rate and receptor turnover, as well as cognitive parameters such as memory and attention, is needed to uncover possible negative consequences.
May 23, 2018
David Nutt
Recent findings on the neurobiology of serotonin receptors and the mechanisms by which psychedelics have therapeutic potential in psychiatry are summarized. The text describes these topics but does not present specific results, data, or conclusions.
ChemRxiv
Vito Federico Palmisano, Claudio Agnorelli, Andrea Fagiolini et al.
The ability of classic psychedelics to permeate neuronal membranes and reach intracellular 5-HT2A receptors is critical for their therapeutic effects. Using molecular dynamics simulations, this computational study examined how structural modifications to tryptamines affect membrane permeability. Dimethylation of the primary amine group and adding a methoxy group at position 5 increased permeability. In contrast, substitutions at other positions on the indole ring and protonation of the molecules raised the energy barrier at the bilayer center, making the compounds highly impermeable. These findings can guide future drug design to develop psychedelics with enhanced activity.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
March 21, 2026
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
A single intravenous dose of ketamine (1 mg/kg) in eleven healthy men altered brain chemistry and connectivity days later. Glutamate levels rose in the anterior cingulate cortex (ACC). Functional coupling between the ACC and the dorsolateral prefrontal cortex decreased, while coupling between the ACC and the amygdala increased. Participants whose PET scans indicated increased synaptic plasticity showed reduced intrinsic activity in default mode network (DMN) regions. The findings suggest the DMN is a central hub where ketamine may reshape brain hierarchies, offering clues to its therapeutic mechanisms.
arXiv Preprint Archive
November 29, 2024
Claudio Agnorelli, Meg J. Spriggs, Kate Godfrey et al.
Psychedelics like LSD and psilocybin can rewire brain connections after just one dose, unlike traditional psychiatric medications. These compounds boost the brain's natural plasticity, helping neurons form new pathways and adapt to change. Studies show they create a window of enhanced learning and adaptation, leading to lasting improvements in mood and behavior.
arXiv Preprint Archive
May 26, 2014
Enzo Tagliazucchi, Robin Carhart-Harris, Robert Leech et al.
Psilocybin, the active compound in magic mushrooms, dramatically expands the brain's repertoire of connectivity states, revealing how consciousness can be altered. Using advanced brain imaging, researchers tracked neural activity before and after psilocybin administration. Results showed increased signal variability in memory and emotion-processing regions, while higher brain networks displayed enhanced flexibility in their communication patterns.