CNS Spectrums
September 30, 2021
Xénia Gonda, Péter Döme, Joanna C. Neill et al.
77 citations
Major depressive disorder (MDD) and treatment-resistant depression (TRD) remain inadequately addressed by current antidepressants, which have limited efficacy or undesirable side effects linked to their actions on monoamine neurotransmitters (serotonin, norepinephrine, dopamine). New drugs targeting non-monoamine pathways, such as the recently approved intranasal Esketamine (a glutamatergic agent) combined with an oral antidepressant for adult TRD, offer promise. Several glutamatergic and GABAergic drugs are in clinical development, and preliminary positive trial results with psychedelics like psilocybin, Ayahuasca, 5-MeO-DMT, and LSD suggest they may become effective therapies. Expanding beyond monoamine targets appears to yield antidepressants with superior efficacy, safety, and tolerability.
Journal of Psychopharmacology
May 30, 2022
Rebecca Smausz, Joanna C. Neill, John Gigg
60 citations
Psilocybin, a naturally occurring psychedelic compound, alters perception, emotion, and cognition and shows promise for treating brain disorders. This review outlines current understanding of its neurophysiology, focusing on its effects on brain regions within the default-mode network, especially the prefrontal cortex and hippocampus, which likely mediate its consciousness-altering properties. The authors describe specific receptor and cell types involved and note contradictory neuroimaging evidence regarding psilocybin's net effect on activity in these regions.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
Qualitative Health Research
February 17, 2026
Zaynab Khan, Sterre Weaver, Rachael V. Dando et al.
1 citation
Seven women in the United Kingdom with a current or previous cancer diagnosis were interviewed about their attitudes toward using psilocybin for mental health. Four had used psilocybin and three had considered it. Participants viewed psilocybin as a needed alternative to traditional treatments for depression and anxiety linked to their cancer diagnosis, but they felt its illegal status was a major barrier to access. Three themes emerged: somatic healing needs, illegality as both a burden and boundary, and reconnecting self, nature, and mortality. The authors suggest a compassionate access scheme in the UK could transform mental health care for people with cancer.
Psychedelics as Psychiatric Medications
March 1, 2023
Joanna C. Neill, Mohammed Shahid, Rosalind Gittins et al.
Before psychedelic-assisted therapy can be integrated into mainstream medicine, a thorough understanding of its risks and adverse effects is critical. Current clinical trials have left knowledge gaps, and a comprehensive analysis of human receptor pharmacology is needed to guide safe dosing and identify drug-drug interactions with common antidepressants, antipsychotics, and anticonvulsants. Post-approval pharmacovigilance will be essential for patient safety, and future trials must include more ethnically diverse populations. This innovation in psychiatry requires careful, stepwise safety and risk-benefit evaluations to maximize patient benefit.