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.
Psychological Medicine
December 1, 2023
Paul McCrone, Henry Fisher, Clare Knight et al.
34 citations
Psilocybin-assisted psychotherapy (PAP) may be a cost-effective treatment for severe depression, depending on the price of the drug and the level of therapist support. A decision model compared PAP with conventional medication, cognitive behavioural therapy (CBT), and their combination over six months. PAP produced the highest quality-adjusted life years (0.310) but also the highest expected healthcare cost (£6,132 to £7,652). PAP became cost-effective when therapist support costs were reduced by 50% and the psilocybin price dropped to £400–£800 per person. From a societal perspective, PAP's cost-effectiveness improved further. More long-term outcome data are needed.
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.
Epigenomics
September 1, 2016
Helene A Fachim, Umarat Srisawat, Caroline F Dalton et al.
Rats given phencyclidine (PCP) for 7 days showed increased DNA methylation at one of two specific sites in the parvalbumin gene promoter in both the prefrontal cortex and hippocampus six weeks later, compared to rats given a vehicle. No change was seen in a global measure of DNA methylation. This hypermethylation may contribute to parvalbumin neuron deficits in this animal model of psychosis, which are also observed in schizophrenia.