The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has well documented prosocial effects and is currently under clinical investigation as a treatment for patients with PTSD, autism, and other conditions. Early clinical trials have found that MDMA-assisted therapy may have robust long-lasting therapeutic effects, yet the mechanism by which acute treatments produce these long-term...
In recent years, rigid analogs of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid compounds such as DOB-DFLY reportedly have higher potency than their non-rigid...
&NA; Methoxetamine (MXE) is a novel psychoactive substance that can induce several short‐term effects on emotional states and behavior. However, little is known about the persistent emotional and behavioral effects of MXE. Moreover, neurotoxic effects of MXE have been hypothesized, but never demonstrated in vivo. To clarify these issues, rats received repeated treatment with MXE every other day...
NeuropharmacologyJanuary 2019Rocio Saravia, Marc Ten-Blanco, Marina Julià-Hernández et al.
Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the...
We have previously demonstrated that an acute dose of Δ9-tetrahydrocanninbinol (THC), administered prior to extinction learning, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). It remains unknown whether THC-induced changes in fear-extinction neural...
Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may...
RationaleWe reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology - the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances - particularly in non-clinical settings.MethodsWe...
Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were...
2,5-Dimethoxyphenethylamines (2C compounds) are 5-HT2A/2C receptor agonists that induce hallucinogenic effects. N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT2A receptors, and two such analogs, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) and 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe),...
5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT1A/5-HT2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals...
Substantial effort has been devoted toward understanding the psychopharmacological effects of tryptamine hallucinogens, which are thought to be mediated by activation of 5-HT2A and 5-HT1A receptors. Recently, several psychoactive tryptamines based on the N,N-diallyltryptamine (DALT) scaffold have been encountered as recreational drugs. Despite the apparent widespread use of DALT derivatives in...
NeuropharmacologyNovember 2018I Ivan Ezquerra-Romano, W Lawn, E Krupitsky et al.
Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into...
Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a...
In recent years, there is renewed interest in the study of various hallucinogens for their potential therapeutic effects. In the United States of America (USA), the abuse potential assessment of a drug is carried out as part of the general safety and efficacy evaluation of a drug. Additionally, the abuse potential assessment is taken under consideration in determining if a drug needs to be...
The development of 5-HT2A receptor agonists has been considerably marginalized since the demonstration that the tryptaminergic drugs, LSD and psilocybin, or the phenylakylamine drugs, mescaline and DOI, exert their hallucinogenic properties via the stimulation of 5-HT2A receptors. Nonetheless, the ability of drugs to stimulate 5-HT2A receptors is not necessarily associated with psychedelic...
The entropic brain hypothesis proposes that within upper and lower limits, after which consciousness may be lost, the entropy of spontaneous brain activity indexes the informational richness of conscious states. Here the hypothesis is revisited four years on from its original publication. It is shown that the principle that the entropy of brain activity is elevated in the psychedelic state is...
Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA...
Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g., MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e., no approved medical use. For...
Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the...
NeuropharmacologySeptember 1, 2018Dylan Chou, Hsien-Yu Peng, Tzer-Bin Lin et al.
It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and...
Sub-anesthetic doses of the non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonist ketamine evoke transient psychotomimetic effects, followed by persistent antidepressant effects in treatment-resistant depressed patients and rodents through still poorly understood mechanisms. Since phencyclidine (PCP) disinhibits thalamo-cortical networks by blocking NMDA-Rs on GABAergic neurons of...
NeuropharmacologyJuly 15, 2018Ashley M Fortress, Ian M Smith, Kevin C H Pang
Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of...
Edible cannabis-infused products are an increasingly popular method of using cannabis in the United States. Yet, preclinical research to determine mechanisms underlying abuse of Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, has focused primarily on the effects of parenteral administration. The purpose of this study was to examine the rewarding and aversive...
(±)-cis-4,4′-Dimethylaminorex (4,4′-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effects of 4,4′-DMAR on human high-affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin...
This review assesses the abuse potential of medically-administered psilocybin, following the structure of the 8 factors of the US Controlled Substances Act (CSA). Research suggests the potential safety and efficacy of psilocybin in treating cancer-related psychiatric distress and substance use disorders, setting the occasion for this review. A more extensive assessment of abuse potential...