The FASEB Journal
August 26, 2025
Joshua C. Flowers, Paige E. Vetter, McKennon J. Wiles et al.
7 citations
ABSTRACT Chronic stress affects brain functions, leading to the development of mental disorders like anxiety and depression, as well as cognitive decline and social dysfunction. Among many biological changes in chronically stressed brains, disruptions in AMPA Receptor (AMPAR)‐mediated synaptic transmission in the hippocampus are associated with stress responses. We have revealed that low‐dose...
The FASEB Journal
May 1, 2022
Grant C. Glatfelter, David R. Manke, Andrew R. Chadayne et al.
1 citation
4‐phosphorloxy‐ N,N ‐dimethyltryptamine (psilocybin) is a naturally occurring psychedelic compound that is being investigated in clinical studies in conjunction with psychotherapy for treatment of several psychiatric disorders. It is well established that 4‐hydroxy‐ N,N ‐dimethyltryptamine (psilocin) is the bioactive metabolite of psilocybin which mediates its in vivo psychedelic activity in...
The FASEB Journal
May 1, 2022
Deborah Rudin, Dino Luethi, Marius C. Hoener et al.
Objective and hypothesis 4‐Substituted derivatives of 2,5‐dimethoxyamphetamine (referred to as DOX derivatives) exhibit psychedelic and euphoria‐inducing effects, mainly mediated by 5‐HT 2A receptor activation; for this reason, they are used recreationally but also bear therapeutic potential. Studies in humans and animals revealed that 4‐substitution with halogens results in high clinical...
The FASEB Journal
May 1, 2022
Dino Luethi, Deborah Rudin, Marius C. Hoener et al.
Background Various ring‐substituted phenethylamines and amphetamines are used recreationally due to their mind‐altering effects. Furthermore, such psychedelic substances have recently gained increased interest as prospective therapeutics. Here, we studied the pharmacological properties of 4‐alkylated 2,5‐dimethoxyamphetamines in vitro. Specifically, we assessed the effect of the 4‐alkyl chain...
The FASEB Journal
May 1, 2021
Santosh Pothula, Rongjian Liu, Min Wu et al.
A single subanesthetic dose of ketamine exerts rapid antidepressant‐like effects via rapid glutamate efflux, activation of mTORC1 signaling, and enhanced synaptic transmission in the medial prefrontal cortex (mPFC); however, the initial cellular trigger for these synaptic and behavioral actions of ketamine still remains unclear. Here, we used electrophysiology, biochemistry, molecular biology...
The FASEB Journal
May 1, 2021
Chris Bolden, Cameron Tilley, Charles Hay et al.
3,4‐Methylenedioxymethamphetamine (MDMA) is currently one of the most popular club psychostimulant and hallucinogens. MDMA's primary site of action is in the brain where it produces a “euphoric” feeling, this euphoria comes with a multitude of acute toxicities. In the periphery, MDMA acts as an immunosuppressive agent in the periphery decreasing the robust activity of the adaptive and innate...
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...
The FASEB Journal
April 1, 2020
Chris Bolden, C. Tilley, Charles E Hay et al.
3,4‐Methylenedioxymethamphetamine (MDMA) is a popular recreational psychostimulant and hallucinogen typically used in “rave” settings. Despite the “positive” feelings sometimes associated with its use, there are toxicities that accompany its use. In the periphery, MDMA causes immunosuppression that can make users more susceptible to infection. Conversely, in the CNS MDMA initiates a...
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...
The FASEB Journal
April 1, 2019
Madeline M. Pantoni, Stephan G Anagnostaras
±3,4‐methylenedioxymethamphetamine (MDMA) is a recreational drug that is also being pursued as a therapeutic for PTSD and other mood and anxiety disorders. Despite strong evidence of its therapeutic potential, these pursuits are hindered by evidence that MDMA produces robust neurotoxicity and cognitive deficits at high doses. These findings, however, may not generalize to typical recreational...
The FASEB Journal
April 1, 2019
George P Einstein, Michael S Rahman, Carla M Konyk et al.
Evidence in the last few decades have supported claim that meditation can reduce stress and promote health; the effects of which are on physical and mental health, and cognitive performance. There is more evidence about the specific parts of the brain involved in producing these positive influences. The neuronal pathways are not fully understood; the model of chronic pain however may provide...
The FASEB Journal
April 1, 2019
Aboozar Ali, Cynthia Franklin, Yolanda Rangel et al.
Intracerebroventricular (ICV) injection of the kappa opioid agonists produces a marked diuresis in rats via inhibition of vasopressin secretion. Salvinorin A (SalA) is a plant‐derived high affinity agonist for the kappa opioid receptor (KOR). Previous studies have proposed that SalA has similar potency and efficacy as other synthetic kappa agonists in mediating the CNS effects of KOR...
The FASEB Journal
April 1, 2018
Matthias E. Liechti, Dino Luethi
Objective Novel psychoactive substances (NPS) or “bath salts” are increasingly sold over the Internet and used as substitutes for classic recreational substances. Previous studies showed that classic amphetamine‐type stimulants most potently act on the norepinephrine (NE) compared to the dopamine (DA) and serotonin (5‐HT) system and NE activation correlated with the subjective effects across...
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
C. Nichols, Melaine N. Sebastian, Thomas W. Flanagan
We previously discovered that serotonin 5‐HT2A receptor activation with psychedelics has potent anti‐inflammatory activity in both cell culture and whole animals, which indicated potent anti‐inflammatory effects in vascular tissues among others. More recently we found that the psychedelic (R)‐DOI potently prevents the development of allergic asthma in a mouse model. The effects of (R)‐DOI were...
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...
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, 2016
Briana Hempel, Alison Wakeford, Matthew Clasen et al.
Rationale Δ 9 ‐Tetrahydrocannabinol (THC) produces both aversive and rewarding effects in animal models. Given that the balance between a drug's affective properties is thought to underlie its abuse potential, it is important to consider these properties of THC and how they (and their balance) are impacted by various factors. In this context, previous studies have examined the effect of THC...
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, 2015
Émeline L. Maillet, Nicolas Milon, James A. Fishback et al.
1 citation
Noribogaine is the primary metabolite of the anti‐addictive substance ibogaine, which modulates opiate analgesic activity and the components of drug addiction in animal models at brain concentrations of 0.5‐15 µM. In this study, molecular activities of noribogaine at mu (OPRM) and kappa (OPRK) opioid receptors were characterized. Noribogaine was a moderately potent antagonist of the OPRM...
The FASEB Journal
April 1, 2015
Émeline L. Maillet, Qing Chang, Nicolas Milon et al.
Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, is being investigated for treatment of substance abuse‐related disorders. In this study, noribogaine molecular activity at neuronal nicotinic acetylcholine receptors (nAChRs) was characterized. Noribogaine inhibited α3β4, α7 nAChRs, and endogenously...
The FASEB Journal
April 1, 2013
Jonathan M. Slezak, Melanie Mueller, George A. Ricaurte et al.
MDMA (ecstasy), popularized as a “club drug,” is a psychoactive and abused substance. It is often assumed that the behavioral effects of MDMA are due to central actions, though this has not been tested. Using a quaternary analog of MDMA (qMDMA) we tested that assumption by training male Sprague‐Dawley rats (n = 6) to discriminate intraperitoneal (i.p.) injections of 1.7 mg/kg of MDMA HCl from...
The FASEB Journal
April 1, 2012
Evan J. Kyzar, Christopher Collins, Jeremy Green et al.
1 citation
Mescaline, phencyclidine (PCP) and psilocybin are potent hallucinogenic drugs strongly affecting both human and animal behavior. However, these compounds have not been previously investigated in zebrafish (Danio rerio), rapidly gaining popularity as a model in psychopharmacology research. Here, we examine the effects of mescaline, PCP and psilocybin in multiple behavioral paradigms. Mescaline...