Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects...
Introduction Selective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4–8...
Ketamine, a non-competitive antagonist of the N-methyl-D-aspartate-glutamate receptor (R-NMDA), has a rapid (from 24 h post-dose) and prolonged (up to one week) antidepressant effect in treatment resistant depression and in rodent models of anxiety/depression. Arguments regarding its cellular and molecular mechanisms underlying its antidepressant activity mainly come from animal studies....
This dissertation has taken an interdisciplinary approach to investigate and give insights into psilocybin’s neurobiological underpinnings. Psilocybin is a naturally occurring serotonergic psychedelic and is the main ingredient in hallucinogenic mushrooms. Research has demonstrated that psilocybin profoundly activates the serotonin (5-hydroxytryptamine) 2A (5-HT2A) receptors. Upon activation of...
Recently, a growing number of reports have indicated a positive effect of hallucinogenic-based therapies in different neuropsychiatric disorders. However, hallucinogens belonging to the group of new psychoactive substances (NPS) may produce high toxicity. NPS, due to their multi-receptors affinity, are extremely dangerous for the human body and mental health. An example of hallucinogens that...
Opioid misuse and opioid-involved overdose deaths are a massive public health problem involving the intertwined misuse of prescription opioids for pain management with the emergence of extremely potent fentanyl derivatives, sold as standalone products or adulterants in counterfeit prescription opioids or heroin. The incidence of repeated opioid overdose events indicates a problematic use...
The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in...
Research on classical psychedelics (psilocybin, LSD and DMT) and entactogen, MDMA, has produced a renaissance in the search for more effective drugs to treat psychiatric, neurological and various peripheral disorders. Psychedelics and entactogens act though interaction with 5-HT2A and other serotonergic receptors and/or monoamine reuptake transporters. 5-HT, which serves as a neurotransmitter...
Abstract Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of arousal. Here, we performed chronic electrophysiological recordings from the cortex concomitant with pupillometry in freely moving adult male mice following an injection of a...
Abstract Background and Aims The hallucinogenic drug psilocybin is being widely tested in humans for the treatment of psychiatric disorders. Psilocybin and other psychedelics are proposed to work through serotonin 2a (5-HT2a) receptors, which are tightly linked to immune function. The purpose of the present study was to assess the effects of a single dose of psilocybin on a panel of cytokines,...