The FASEB JournalAugust 26, 2025Joshua 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...
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...
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...
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...
A record ~100,000 fatalities due to drug overdoses was reported in the U.S. for the twelve months preceding April 2021. Opioids account for most deaths, and recurrent opioid use may lead to the development of opioid use disorder (OUD), a debilitating chronic disorder. Current medication‐assisted OUD treatment (e.g., buprenorphine) mitigates withdrawal, reduces mortality, and reduces intake of...
The FASEB JournalMay 1, 2022Thomas Basala, Brigitte Morin, John Durocher
According to the CDC, most children and about 1 in 3 adults in the United States fail to reach their age group recommended quantity of sleep. Recently, non‐pharmacological sleep aids, such as meditation, have gained popularity. However, to our knowledge there is no research data that compares sleep metrics or psychological well‐being between those that meditate in the morning vs. in the...
The use of 3,4‐methylenedioxymethamphetamine (MDMA) has recently gained interest as a potential therapeutic tool for the treatment of post‐traumatic stress disorder (PTSD). However, the mechanism of action of this drug has not yet been fully elucidated. Here we demonstrate that MDMA acts by targeting the trace amine associated receptor 1 (TAAR1), an intracellular G‐protein coupled receptor...
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...
Previous preclinical studies have demonstrated that 3,4‐methylenedioxymethamphetamine (MDMA) dose‐dependently increases pro‐social behavior and affiliative vocalizations in male nonhuman primates. As diagnostic criteria for several psychiatric diseases includes deficits in social functioning, examining the conditions under which MDMA selectively increases pro‐social behavior may provide...
The FASEB JournalMay 1, 2021Chris Bolden, Cameron Tilley, Charles E 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...
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 JournalApril 1, 2020Chris Bolden, Cameron 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...
We have recently described the biochemical cascade through which the psychostimulant amphetamine leads to internalization of the dopamine and norepinephrine transporters, (DAT and NET). Amphetamine is a relatively high affinity substrate for DAT and NET and they both serve as efficient conduits for amphetamine entry into the cell. Once inside the cell, amphetamine activates the trace amine...
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...
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...
±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 JournalApril 1, 2019Aboozar 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 JournalApril 1, 2019George 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 JournalApril 1, 2019Melodi Ann Bowman, Melissa Vitela, W. Anthony Owens et al.
Twenty percent of adults are diagnosed with major depressive disorder, which is typically treated with selective serotonin reuptake inhibitors (SSRIs). However, SSRIs take approximately six weeks to produce therapeutic effects. Recently, low doses of ketamine, a noncompetitive N‐methyl‐ D‐aspartate (NMDA) receptor antagonist, have been shown to produce rapid and long‐lasting antidepressant...
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...
Background Racemic (R,S)‐ ketamine produces a rapid and long‐lasting antidepressant response in treatment resistant patients with major depressive disorder (MDD). However, the production of psychotomimetic effects and a propensity for abuse have limited its therapeutic use. The individual isomers of ketamine are being investigated for treatment of MDD with proponents stating each isomer has an...
The FASEB JournalApril 1, 2018John Durocher, Hannah Marti, Brigitte Morin et al.
Mindfulness meditation has been shown to have numerous health benefits when used over the course of days or weeks, but the effect of a single session on aortic pulsatility and anxiety is unclear. Therefore we sought to determine if a single session of mindfulness meditation could effectively reduce aortic pulsatile load and anxiety. Fourteen adults (24±8 years) with mild to moderate anxiety (≥8...
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...
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...
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...