R (−)‐2,5‐Dimethoxy‐4‐iodoamphetamine (DOI) and other compounds with agonist affinity for serotonergic 5‐HT2A receptors are hallucinogenic drugs of abuse, but also have therapeutic potential in numerous neuropsychiatric conditions, including major depressive disorder, post‐traumatic stress disorder, and in the treatment of migraine and cluster headaches. Thus, commonly abused hallucinogens...
The FASEB JournalApril 1, 2017Melodi 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. However, this type of medication takes 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...
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...
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...
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...
Indolethylamine‐N MethylTransferase (INMT) is a small molecule N‐methyltransferase that transfer methyl groups from S‐Adenosyl‐L‐Methionine (SAM) to indoleamines. Methylation of tryptamine produces the hallucinogen, N,N‐dimethyltryptamine (DMT), and methylated serotonin generates bufotenin. In animals, the endogenous production of DMT has been proposed to be a regulator of the Sigma‐1 Receptor...
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...
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....
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...
Recently, there has been an increase in abuse of new synthetic psychostimulant drugs derived from the cathinone structure. These products are typically referred to as “bath salts”, and one of the most common psychoactive constituents of these preparations is 3,4‐methylenedioxypyrovalerone (MDPV). In these studies, we used the conditioned place preference (CPP) paradigm to explore the apparent...
The FASEB JournalApril 1, 2014Lee Berk, Clarice Alphonso, Neha Thakker et al.
Humor associated mirthful laughter (HAML) similar to meditation, both positive brain states, have complex mental processes that can modulate emotions, cognition, memory, sensory perception, consciousness, hormones, immune, and CNS activity. Meditation is used as a non‐pharmacological lifestyle intervention to provide health benefits, from promoting wellness to alleviating symptoms of a variety...
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 JournalApril 1, 2013Kellianne J. Richardson, Keith L Shelton
The abuse‐related CNS effects of nitrous oxide (N 2 O) are poorly understood. In vitro data suggests that N 2 O alters the function of NMDA and GABA A receptors, amongst others. Our goal was to assess the neurotransmitter systems responsible for producing the intoxicating effects of N 2 O using drug discrimination. Twenty‐four mice were trained to discriminate 10 min of exposure to 60% N 2...
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...
Indolealkylamine (IAA) drugs are a major class of serotonin analogs that have high impact as substances of abuse. Among them, 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeO‐DMT) was placed into Schedule I controlled substance status in the United States as of January 19, 2011, which is often co‐abused with harmaline. IAA drugs acts mainly on the serotonin neurotransmission system. Overdose of one...
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...
The interaction of ibogaine and phencyclidine (PCP) with human (h) α3β4 nicotinic acetylcholine receptors (AChRs) in different conformational states was determined using radioligand binding assays, Ca 2+ influx detections, thermodynamic and kinetic measurements. The results show that ibogaine inhibits (±)‐epibatidine‐induced Ca 2+ influx in hα3β4 AChRs with ~9‐fold higher potency than PCP, [ 3...
The drug 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) has been shown to increase feelings of closeness and empathy in humans. Despite evidence of MDMA‐induced neurotoxicity, these unusual pro‐social effects have continued to generate interest in the drug's therapeutic potential. Therefore, determining the mechanisms by which MDMA engenders these effects may allow for the development of...
The FASEB JournalApril 1, 2012Lap Ho, Patricia A. Bloom, Joan Griffiths Vega et al.
Caregiving for a dementia patient is associated with an increased risk for emotional distress, depression, dementia, physical health problems and death. Targeting caregivers as the recipients of interventions may greatly improve patient care. Mindfulness Based Stress Reduction (MBSR) is a clinical intervention based on simple meditation practices which have been shown to reduce stress and...
The FASEB JournalApril 1, 2012Luli R Akinfiresoye, D. M. Lovinger, Y. Tizabi
Studies have shown that therapeutics that act on the glutamatergic system could provide a novel mechanistic approach for the treatment of depression. We previously reported that ketamine, an NMDA antagonist, has a rapid and lasting antidepressant effect both acutely and chronically on depressive‐like behavior in Wistar‐Kyoto (WKY) rats ( Soc Neurosci Abst 2008) . Other studies had suggested...
The neuropharmacology of the sleep and arousal systems involves a complex interplay between multiple neurotransmitter systems. Previous work has downplayed the role of dopamine in sleep and wakefulness, at least in part, because dopamine neurons do not appear to change their firing rates across arousal states. In the present study, we examined the wake promoting effects of amphetamine and...
A recent DEA report and ongoing media accounts show increasing recreational use of 4‐methylmethcathinone (4‐MMC, mephedrone) and 3,4‐methylenedioxypyrovalerone (MDPV). Some severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported. Recent studies showed that 4‐MMC and MDPV enhanced DA neurotransmission, while 4‐MMC also increased 5‐HT neurotransmission, much...
The abuse of MDMA (Ecstasy) peaked in the early 2000s, yet reports of MDMA use from emergency room admission data continue to increase. The potential for cardiovascular effects of MDMA to contribute to its acute toxicity has long been recognized. However, the role of MDMA metabolites in mediating the drug's cardiovascular actions has not been studied. Here we employed radiotelemetry to evaluate...
We here review experimental findings relevant for the pharmacology of conscious experience, an issue largely neglected in pharmacological research. First, we focus on self-awareness, a pivotal component of conscious experience and its integration within the global neuronal network (GNW), a theoretical concept that unifies convergent approaches on the neural bases of conscious processing. We...
Here, we integrated manual observations, computerized event‐based scoring and automated video analysis of zebrafish traces to generate three‐dimensional (3D) swim path reconstruction of general behavioral patterns, thereby improving the characterization and interpretation of complex, anxiety‐related adult zebrafish behavior. Drugs known to evoke a high‐anxiety state (caffeine, repeated morphine...