Background: 5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of...
PsychopharmacologyApril 9, 2019Vincent T Mensen, Annabel Vreeker, Johan Nordgren et al.
Background: Synthetic cannabinoids (SCs) are a class of new psychoactive substances that have been rapidly evolving around the world throughout recent years. Many different synthetic cannabinoid analogues are on the consumer market and sold under misleading names, like "spice" or "incense." A limited number of studies have reported serious health effects associated with SC use. In this study,...
Rationale Social withdrawal is a core feature of the negative symptoms of schizophrenia. Currently available pharmacotherapies have only limited efficacy towards the negative symptoms, i.e., there is a significant unmet medical need in the treatment of these symptoms. Objective We wanted to confirm whether selective adrenergic α_2C receptor (AR) antagonist therapy could ameliorate acute...
RationaleDepressive syndrome or depression is a debilitating brain disorder affecting numerous people worldwide. Although readily available, current antidepressants have low remission rates and late onset times. Recently, N-methyl-D-aspartate (NMDA) receptor antagonists, like ketamine and methoxetamine (MXE), were found to elicit rapid antidepressant effects. As the search for...
Novel synthetic "bath salt" cathinones continue to appear on the street as abused and addictive drugs. The range of subjective experiences produced by different cathinones suggests that some compounds have primarily dopaminergic activity (possible stimulants) while others have primarily serotonergic activity (possible empathogenics). An understanding of the structure activity relationships...
Over the last decade, many new psychostimulant analogues have appeared on the recreational drug market and most are derivatives of amphetamine or cathinone. Another class of designer drugs is derived from the 2-aminoindan structural template. Several members of this class, including the parent compound 2-aminoindan (2-AI), have been sold as designer drugs. Another aminoindan derivative,...
Rationale The lysergamide lysergic acid diethylamide (LSD) is a prototypical classical hallucinogen with remarkably high potency. LSD remains a popular recreational drug but is also becoming an important research tool for medical and neuroscience studies. Recently, several lysergamides that are close structural analogs of LSD have been sold as recreational drugs, which suggests that further...
Background There is evidence that mGlu2/3 receptors regulate 5-HT_2A signaling, interactions that have been theorized to play a role in the antipsychotic-like effects of mGlu2/3 agonists as well as the hallucinogenic effects of 5-HT_2A agonists. One approach to unraveling this interaction is through the chronic administration of agonists at the two receptors, which should influence the...
RationaleMicrodosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties,...
PsychopharmacologyDecember 2018M Steffens, Claudia Neumann, A-M Kasparbauer et al.
The uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist ketamine has been proposed to model symptoms of psychosis. Inhibitory deficits in the schizophrenia spectrum have been reliably reported using the antisaccade task. Interestingly, although similar antisaccade deficits have been reported following ketamine in non-human primates, ketamine-induced deficits have not been...
RATIONALE: Previous research demonstrating that lysergic acid diethylamide (LSD) produces alterations in time perception has implications for its impact on conscious states and a range of psychological functions that necessitate precise interval timing. However, interpretation of this research is hindered by methodological limitations and an inability to dissociate direct neurochemical effects...
BackgroundResearch suggests that mindfulness-based interventions may improve mindfulness-related capacities (e.g., decentering, non-judging, and non-reacting) and emotion regulation. Previously, our group reported that ayahuasca could be a potential analogue of mindfulness practice. The main aim of the current study was to examine the effects of ayahuasca on emotional regulation and...
Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted. To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance...
Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor agonists. However, the...
PsychopharmacologyNovember 2018Victor A D Holanda, Wilton B Santos, Laila Asth et al.
Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of a Gi protein-coupled receptor named NOP. Both N/OFQ and NOP receptor are widely expressed in brain areas involved in the control of emotional processes. Clinical and preclinical studies support antidepressant effects due to the blockade of NOP receptor signaling. By contrast, NOP receptor activation did not evoke any change in...
(R,S)-ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits rapid and long-lasting antidepressant effects and anti-suicidal ideation in treatment-resistant patients with depression. However, the precise mechanisms underlying the antidepressant actions of (R,S)-ketamine are unknown. Although the previous report demonstrated the deuterium isotope effects in the antidepressant...
3,4-Methylenedioxymethamphetamine (MDMA) preferentially increases synaptic serotonin (5HT). This response was attenuated following repeated exposure but there was recovery as a result of abstinence. Effects of abstinence on self-administration of many drugs have been documented but the impact on MDMA self-administration is unknown. This study compared the effects of abstinence on MDMA and...
While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and...
Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny “ghost-like” hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research has shown that 5-HT2AR activation can induce visual hallucinations,...
Classic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study comparing the neuropsychological effects of multiple doses...
(R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in major depressive disorder. Specifically, its pharmacological efficacy in treatment refractory depression is considered a major breakthrough in the field. However, the mechanism of action of ketamine's rapid effect remains to be determined. In order to identify pathways that are responsible for ketamine's effect, a...
Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation. To compare thermoregulatory and locomotor responses to inhaled ∆9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based...
RATIONALE: Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental...
PsychopharmacologyAugust 1, 2018Masaki Domoto, Hitoki Sasase, Shintaro Wada et al.
5F-AMB is one of the synthetic cannabinoids (SCs) designed to potentiate the ability to activate cannabinoid 1 (CB1) receptors and is abused worldwide. Although inhalation of 5F-AMB elicits serious adverse effects including impaired memory and consciousness, it is not known whether and how 5F-AMB affects the activity of pyramidal neurons in the medial prefrontal cortex (mPFC), a brain region...
Despite ongoing study and research to better understand drug addiction, it continues to be a heavy burden. Only a small percentage of individuals who take drugs of abuse go on to develop addiction. However, there is growing evidence to suggest that a reduction in the serotonin transporter may play an important role for those that transition to compulsive drug taking. Studies have demonstrated...