Journal of Neurochemistry
September 14, 2021
Urszula Kozłowska, Charles D. Nichols, Kalina Wiatr et al.
78 citations
Abstract The studies of psychedelics, especially psychedelic tryptamines like psilocybin, are rapidly gaining interest in neuroscience research. Much of this interest stems from recent clinical studies demonstrating that they have a unique ability to improve the debilitating symptoms of major depressive disorder (MDD) long‐term after only a single treatment. Indeed, the Food and Drug...
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2021
Aurora Savino, Charles D. Nichols
2 citations
preprint
Abstract Psychedelic drugs are gaining attention from the scientific community as potential new compounds for the treatment of psychiatric diseases such as mood and substance use disorders. The 5-HT 2A receptor has been identified as the main molecular target, and early studies pointed to an effect on the expression of neuroplasticity genes. Analysing RNA-seq data from the prefrontal cortex of...
Research Square
June 15, 2021
Dennis Parker Kelley, Katy Venable, Gerald Billac et al.
1 citation
Abstract Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress and inflammation. N,N-dimethyltryptamine (DMT) is a known neuroprotective, antioxidant, anti-inflammatory, and psychoplastogen with antidepressant effects. Therefore, we tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and “pharmahuasca” (DMT + harmaline) to reduce...
ACS Pharmacology & Translational Science
April 9, 2021
Thomas W. Flanagan, Gerald Billac, Alexus N. Landry et al.
50 citations
Psychedelic drugs can exert potent anti-inflammatory effects. However, anti-inflammatory effects do not appear to correlate with behavioral activity, suggesting different underlying mechanisms. We hypothesized that the distinct structural features of psychedelics underlie functionally selective mechanisms at the target 5-HT2A receptor to elicit maximal anti-inflammatory effects. In order to...
The FASEB Journal
April 1, 2020
Meghan Hibicke, Charles D. Nichols
9 citations
Introduction Psilocybin (PSI) has persistent antidepressant efficacy in human trials. We have shown one dose of PSI to significantly decrease depressive‐like behavior in male Wistar‐Kyoto (WKY) rats for at least five weeks without losing efficacy. However, the outcome assay we used to evaluate depressive‐like behavior, the forced swim test (FST), has been criticized for not providing...
ACS Chemical Neuroscience
March 5, 2020
Meghan Hibicke, Alexus N. Landry, Hannah M. Kramer et al.
211 citations
Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of...
Frontiers in Psychiatry
February 11, 2020
James D. Sexton, Charles D. Nichols, Peter S. Hendricks
45 citations
IntroductionThe majority of contemporary psychedelic research has focused on ayahuasca, lysergic acid diethylamide, and psilocybin, though there are hundreds of novel psychedelic compounds that may have clinical utility. The purpose of the present study was to evaluate the therapeutic potential of classic and novel phenethylamine, tryptamine, and lysergamide psychedelics via a large, nationally...
2020
Charles D. Nichols, P. Hendricks
Abstract Recently, there has been a resurgence of interest in the study of classic serotonergic hallucinogens, now widely referred to as classic psychedelics. These studies include fundamental molecular and cellular neuroscience and pharmacology, neuroimaging, and psychological experiments. In the early days of classic psychedelic research during the 1950s through the 1970s, classic...
Psychopharmacology
December 18, 2019
Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams et al.
142 citations
Abstract Abstract Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT 2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease. Objective This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally...
Journal of Psychopharmacology
July 14, 2019
Livia Ng, Luca Pani, Anaïs Soula et al.
Background: In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is....
The FASEB Journal
April 1, 2019
Meghan Hibicke, Alexus N. Landry, Zoe K. Talman et al.
7 citations
Introduction Psilocybin has recently demonstrated profound efficacy to alleviate depression and anxiety in several clinical trials and has received Breakthrough Status by the FDA. Symptomatic relief after only one or two therapeutic treatments last for at least several months in the vast majority of individuals. It is unclear whether the persistent antidepressant and anxiolytic effects are a...
The FASEB Journal
April 1, 2019
Gerald Billac, Charles D. Nichols
1 citation
Given the recent resurgence of clinical interest in the application of classical serotonergic psychedelics as treatment for various disease states, a comprehensive analysis of the structure‐activity relationship (SAR) is necessary to fully understand the differential expression of behavioral and physiological effects elicited by these compounds. While the field is mostly focused on action...
International Review of Psychiatry
July 4, 2018
Thomas W. Flanagan, Charles D. Nichols
263 citations
Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the...
Trends in Pharmacological Sciences
September 22, 2017
Evan J. Kyzar, Charles D. Nichols, Raul R. Gainetdinov et al.
155 citations
Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials,...
The FASEB Journal
April 1, 2017
Thomas W. Flanagan, Melaine N. Sebastian, Charles D. Nichols
2 citations
Only recently has the full therapeutic value of serotonin [5‐hydroxytryptophan (5‐HT)] receptor activation begun to be explored. Currently there are two 5‐HT 2A receptor agonists in human clinical trials for the treatment of depression and obesity. An exciting new therapeutic avenue in which 5‐HT 2A agonists might be employed is the modulation of inflammation in allergic airways disease. Our...
The FASEB Journal
April 1, 2017
Gerald Billac, Charles D. Nichols
There has been a recent resurgence of clinical interest in the application of psychedelic drugs for the treatment of various disease states. While the field is mostly focused on action within the central nervous system, previously published data from our lab supports the use of these 5‐hydroxytryptamine 2A receptor (5‐HT 2A R) agonists as modulators of the inflammatory pathway in the periphery...
EBioMedicine
September 1, 2016
David Martin, Charles D. Nichols
88 citations
There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT 2A receptors, but the responses of...
The FASEB Journal
April 1, 2016
David Martin, Connie Porretta, Charles D. Nichols
1 citation
Psychedelics, also known as classic serotonin hallucinogens, are currently being investigated by several groups for their potential as therapeutic agents for a variety of psychiatric indications. Although the neural circuitry underlying the effects of psychedelics is being established by others, the role of specific cell types and populations within the brain that respond to these agents remain...
The FASEB Journal
April 1, 2016
Kelly Jean Sherman, Charles D. Nichols
Circadian rhythms modulate biochemical and molecular pathways in living systems. In humans an endogenous clock mechanism is synchronized by a daily light‐dark cycle: sun up and sun down. These external cues from the environment regulate the core‐clock through auto‐regulating circadian genes’ expression levels. These oscillating gene products modulate physiological, biochemical, and molecular...
The FASEB Journal
April 1, 2015
David Martin, Connie Porretta, Charles D. Nichols
1 citation
Serotonin hallucinogens produce a range of cognitive, sensory, and emotional effects in man. Recently, a resurgence of clinical interest in these compounds has developed because they can produce pronounced and long‐lasting psychological changes. While the structural backbones and receptor pharmacology of hallucinogens vary, their primary effects arise from agonism of the 5‐HT 2A receptor....
The FASEB Journal
April 1, 2012
David Martin, David E. Nichols, Charles D. Nichols
The objective of this work is to characterize genetic and proteomic changes in a novel rat model of schizophrenia. Three‐month treatment with low doses of the hallucinogenic drug, LSD, induces a range of abnormal behaviors including social deficits, hyperactivity, and anhedonia. These behavioral changes persist in the absence of drug , and likely result from neuroadaptive changes in the medial...
Cardiovascular Psychiatry and Neurology
October 13, 2009
Charles D. Nichols
43 citations
There are high levels of comorbidity between neuropsychiatric and cardiovascular disorders. A key molecule central to both cognitive and cardiovascular function is the molecule serotonin. In the brain, serotonin modulates neuronal activity and is actively involved in mediating many cognitive functions and behaviors. In the periphery, serotonin is involved in vasoconstriction, inflammation, and...
Journal of Neurochemistry
June 18, 2004
Charles D. Nichols, Elaine Sanders‐bush
62 citations
We recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression...
Molecular Brain Research
March 1, 2003
Charles D. Nichols, Efrain E. Garcia, Elaine Sanders‐bush
1 citation
Lysergic acid diethylamide (LSD) is a psychoactive drug that transiently alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia. Characterizing gene expression profiles after LSD will be important for understanding how it alters behavior, and will lead...