5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

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Abstract

Functional neurological disorders are frequently encountered in clinical practice. They have a poor prognosis and treatment options are limited. Their etiology is unknown, but leading theories propose a disturbance of somatic self-representation: the mind perceives dysfunction of a body region despite intact motor and sensory pathways. Central to this model is the concept of an abnormal top-down cognitive influence upon sensorimotor function. There is growing interest in the use of 5-HT _2A agonists in the management of neuropsychiatric conditions. Recent studies have shown that these agents induce changes in neural activity that disrupt hierarchical brain dynamics and modulate networks subserving self-related processing. Converging evidence suggests they may hold unique therapeutic potential in functional neurological disorders. This is of importance given the considerable personal and societal burden of this condition and we argue a clinical trial to test this hypothesis is warranted.

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Mechanisms of gamma oscillations.

György Buzsáki, Xiao-Jing Wang (2012)

Gamma rhythms are commonly observed in many brain regions during both waking and sleep states, yet their functions and mechanisms remain a matter of debate. Here we review the cellular and synaptic mechanisms underlying gamma oscillations and outline empirical questions and controversial conceptual issues. Our main points are as follows: First, gamma-band rhythmogenesis is inextricably tied to perisomatic inhibition. Second, gamma oscillations are short-lived and typically emerge from the coordinated interaction of excitation and inhibition, which can be detected as local field potentials. Third, gamma rhythm typically concurs with irregular firing of single neurons, and the network frequency of gamma oscillations varies extensively depending on the underlying mechanism. To document gamma oscillations, efforts should be made to distinguish them from mere increases of gamma-band power and/or increased spiking activity. Fourth, the magnitude of gamma oscillation is modulated by slower rhythms. Such cross-frequency coupling may serve to couple active patches of cortical circuits. Because of their ubiquitous nature and strong correlation with the "operational modes" of local circuits, gamma oscillations continue to provide important clues about neuronal population dynamics in health and disease.

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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Robin L Carhart-Harris, Mark Bolstridge, James Rucker … (2016)

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

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Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.

Matthew W. Johnson, Albert Garcia-Romeu, Mary P Cosimano … (2014)

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Neuropsychopharmacol

Journal ID (iso-abbrev): Int. J. Neuropsychopharmacol

Journal ID (publisher-id): ijnp

Title: International Journal of Neuropsychopharmacology

Publisher: Oxford University Press (US )

ISSN (Print): 1461-1457

ISSN (Electronic): 1469-5111

Publication date Collection: 01 May 2017

Publication date (Electronic): 08 February 2017

Publication date PMC-release: 08 February 2017

Volume: 20

Issue: 5

Pages: 422-427

Affiliations

[1 ]Howard Florey Institute of Neuroscience & Mental Health, University of Melbourne , Australia (Dr Bryson); Department of Neurology, Austin Hospital , Melbourne, Australia (Dr Bryson); Melbourne School of Psychological Sciences, University of Melbourne , Australia (Dr Carter); Department of Psychiatry, Austin Hospital , Melbourne, Australia (Drs Norman and Kanaan); Department of Psychiatry, University of Melbourne , Australia (Drs Norman and Kanaan).

Author notes

Correspondence: Alexander Bryson, MBBS, Melbourne Brain Centre, Kenneth Myer Building 144/30 Royal Parade, Parkville, 3052 Victoria, Australia ( alexandersamuel.bryson@ 123456austin.org.au ).

Article

Publisher ID: pyx011

DOI: 10.1093/ijnp/pyx011

PMC ID: 5417053

PubMed ID: 28177082

SO-VID: 4b0bfb5e-f191-47a5-b0e6-cc9267ff186a

License:

This is an Open Access article distributed under the terms of the Creative Commons Attributioan Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 16 November 2016

Date revision received : 31 January 2017

Date accepted : 06 February 2017

Page count

Pages: 6

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