Psilocybin has emerged as a promising therapeutic agent, with clinical benefits attributed to enhanced neuroplasticity rather than acute pharmacological effects. However, the fundamental mechanisms underlying these effects remain poorly understood. Using planarians as a model system, we investigated whether psilocybin enhances associative learning using a conditioned place preference paradigm....
Psilocybin is a serotonergic 5-HT 2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [5-HT]) system. We quantified...
The past two decades have seen a remarkable renaissance in research on psychedelic drugs and ketamine. Following decades of regulatory restriction that severely limited, especially clinical research, a growing body of evidence has shown that psychedelics such as lysergic acid diethylamide and psilocybin can have long-lasting beneficial effects for treatment-resistant depression, drug and...
Psilocybin is found in a family of mushrooms commonly known as Psilocybe. We aimed to study the antinociceptive efficacy of psilocybin using formalin-induced noxious stimuli, a model that comprises both acute and persistent pain in rats. Adult male Sprague–Dawley rats were used. Psilocybin (0.1, 0.3, and 1 mg/kg, IP) or vehicle was administered, and 6 h later, formalin (5%, 50 µL, subcutaneous)...
Pre- and probiotics promote a diverse and functional gut microbiota and have demonstrated both anxiolytic and antidepressant effects; however, how synbiotic diet interacts with antidepressant medications has not been fully investigated. This study sought to evaluate the potential anxiolytic or antidepressant effects of a synbiotic diet in an avian model that presents homologies with...
Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) are synthetic tryptamines with hallucinogenic-like properties that are widely abused worldwide. There, however, has been a paucity of research and a lack of available data on their pharmacological properties. The objective of this study was to investigate the safety...
Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the...
Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis...
Recent evidence suggests that cannabis can impair simple auditory processes, and these alterations might be due to cannabinoid agonism. The effect of cannabinoid agonism on relatively complex processes such as auditory discrimination is unknown. The goal of this study was to examine the impact of WIN 55,212-2, a CB 1 receptor and CB 2 receptor agonism, on auditory discrimination using a...
Despite the efforts of the Drug Enforcement Administration to safeguard the public from hazardous analogs of synthetic hallucinogens, these compounds have increasingly been observed in the illicit drug market. Four novel compounds were found to be similar in structure to the previously described 25X-NBOMe synthetic hallucinogens. These four compounds, 25B-NBOH, 25C-NBOH, 25E-NBOH, and 25I-NBOH...
There has been substantial and growing interest in the therapeutic utility of drugs acting at serotonin 2A subtype (5-HT 2A ) receptors, increasing the need for characterization of potential beneficial and adverse effects of such compounds. Although numerous studies have evaluated the possible rewarding and reinforcing effects of 5-HT 2A receptor agonists, there have been relatively few studies...
Cannabis is a pharmacologically complex plant consisting of hundreds of potentially active compounds. One class of compounds present in cannabis that has received little attention are terpenes. Traditionally thought to impart aroma and flavor to cannabis, it has become increasingly recognized that terpenes might exert therapeutic effects themselves. Several recent reports have also indicated...
Behavioural PharmacologyJune 1, 2023Débora A E Colodete, Nicole R Silva, João Francisco C Pedrazzi et al.
Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two...
2,5-dimethoxy-4-methylamphetamine (DOM) is a kind of hallucinogen of phenylalkylamine. Psychedelic effects mainly include audiovisual synesthesia, complex imagery, disembodiment etc. that can impair control and cognition leading to adverse consequences such as suicide. By now, there are no specific drugs regarding the management of classic hallucinogen use clinically. We evaluated the effects...
Schizophrenia is a serious mental disorder that affects 1% of the world’s population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism...
Supplemental Digital Content is available in the text. The objectives of this study were to determine alcohol consumption after administration of (R)(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) or naltrexone in Long–Evans rats, and to assess the effectiveness of these treatments based on individual differences in alcohol consumption. Adult male Long–Evans rats (N = 16) were given opportunities to...
Recent discoveries from clinical trials with psychedelic-assisted therapy have led to a resurgence of interest in the psychopharmacology of lysergic acid diethylamide (LSD). Preclinical drug discrimination is an invaluable tool to investigate the neurochemical mechanisms underlying subjective drug effects. The current study extends previous drug discrimination research by including both sexes....
Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or ‘Molly’ as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones,...
Recreational abuse of illicit synthetic cathinones is an ongoing public health concern. Recent studies indicate that the methcathinone derivative 4-methylmethcathinone (4-MMC) produces behavioral and neurochemical effects similar to the entactogen 3,4-methylenedioxymethamphetamine (MDMA). Whereas polysubstance abuse is common, most preclinical studies of drug abuse liability only evaluate the...
Ketamine has been shown to induce a rapid antidepressant effect on patients with depression. In many animal models, both rapid and sustained antidepressant activities were also found in response to an antagonist of group II metabotropic glutamate receptors, LY341495, and its mechanism of action seemed to be similar in many ways to the action of ketamine. It has also been found that LY341495...
Most studies on discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) have been conducted using a relatively low dose (1.5 mg/kg), and those studies have invariably implicated serotonergic mechanisms. In contrast, dopaminergic mechanisms mediate the discriminative stimulus effects of amphetamine (AMPH). Some studies have suggested that the discriminative stimulus effects...
Serotonin, one of the first neurotransmitters to be identified, is an evolutionarily old molecule that is highly conserved across the animal kingdom, and widely used throughout the brain. Despite this, ascribing a specific set of functions to brain serotonin and its receptors has been difficult and controversial. The 2A subtype of serotonin receptors (5-HT2A receptor) is the major excitatory...
Cannabis remains the most frequently used illicit drug worldwide. It produces a broad range of acute effects, such as euphoria, increased heart rate and perceptual alterations. Over the last few decades, a substantial number of experiments have been conducted to provide insight into the acute effects of cannabis on cognition. Here, we systematically review studies that investigated the impact...
Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent 'microdosing' (usually one-tenth of a 'full' active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for the efficacy of therapeutic microdosing nor to...
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the...