Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and...
Psychedelics are mind-altering substances that have shown promising effects in the treatment of neuropsychiatric disorders owing to their antidepressant, anxiolytic and antiaddictive effects. However, data on their developmental toxicity is scarce, which might hinder its therapeutic suitability, and preclinical data on their behavioral effects is mainly restricted to rodents. In this context,...
After years of restrictions due to concerns about their potentially harmful effects, research on psychedelics has entered a new era. Increasing attention has been directed toward their immense therapeutic potential, particularly for psychiatric disorders. Pre-clinical and clinical studies have consistently demonstrated that psychedelic treatments produce therapeutic effects within hours of...
Psilocybin and lisuride are 5-HT2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects....
PAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and...
Accumulating evidence indicates the role of ketamine as a rapid-onset antidepressant, with a rising controversy regarding its cognitive and psychotic effects, especially with long-term use. However, no previous experimental study has directly compared short-term and long-term ketamine effects using a time schedule that simulates infusion protocols in major depressive disorder patients. This...
Noribogaine (Noribo) is the primary metabolite from ibogaine, an atypical psychedelic. The main objective of this study was to evaluate the effect of Noribo on thalamic physiology of calcium channels voltage activation and gene expression and the potential involvement of the 5-HT2A receptor on those effects. Thus, we used male and female, 5-HT2AR knockout (KO) and wild type (WT) mice, injected...
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique neurobiological mechanisms and...
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests...
The mechanism of action of serotonergic psychedelics is increasingly explored worldwide due to their clinical benefits in various psychiatric conditions. Beyond the stimulation of serotonin 2 A (5-HT2A) receptors, psychedelics may desynchronize activity between brain regions, however the involvement of corresponding neurotransmission systems has been largely overlooked. Given that monoaminergic...
Heavy and daily use of cannabis with high contents of Δ9-tetrahydrocannabinol (THC) during adolescence is associated with an increased risk of developing psychotic disorders later in life. Here, we treated mice with THC during adolescence and found that this exposure impaired social interaction and increased vulnerability to develop sensorimotor gating deficiencies comparable to those...
Nasal Esketamine is a rapid-acting intervention for depression, hypothesized to exert its effects through cortical disinhibition. However, the spatio-temporal dynamics of brain network activity and their relationship to the subjective drug experience following Esketamine administration remain elusive. This observational study aims to delineate brain network-level effects of Esketamine by...
Baeocystin is a naturally occurring tryptamine-based compound found in various psychoactive mushrooms, including in several species of Psilocybe genus. Due to its structural similarity to psilocybin, which has shown a therapeutic potential in treatment of psychiatric disorders, there is a growing interest in investigating whether baeocystin exhibits comparable effects. This study investigated...
The development of new drugs is a complex, expensive, and time-consuming process, often fraught with a high likelihood of failure. Amid these obstacles, drug repurposing, which identifies new therapeutic applications for already existing medications, offers a more economical and time-saving approach, particularly in the challenging field of neurological and psychiatric disorders. This narrative...
Treatment-resistant depression (TRD) remains a challenge, with many patients unresponsive to standard antidepressants. NN-dimethyltryptamine (DMT), a fast-acting psychedelic, offers potential benefits due to its rapid onset and short duration. This review, registered with the Open Science Framework (DOI: 10.17605/OSF.IO/6D9WC), summarizes the safety and tolerability of DMT in early-phase...
Novel methods of cannabis use are becoming popular, but the differential impact of these new methods on cognition have not been widely studied. Further, the impact of cannabis on cognition is mediated by delta-9-tetrahydrocannabinol (THC), but few studies have directly compared the pharmacokinetics of different methods. This systematic review (PROSPERO, CRD42023442731) was conducted to...
Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive disorders, substance addiction and anxiety. Pharmacodynamic properties of psilocybin depend on doses used and time after administration. The psilocybin dose range varies depending on whether it is used therapeutically or for recreational purposes in...
Studies of psychedelic use in naturalistic and clinical settings have suggested safety and mental health benefits for adults with histories of childhood maltreatment. Acute psychological mechanisms that predict therapeutic benefits in this population, however, have yet to be determined. Two common group settings of naturalistic psychedelic use - organized ceremonies and raves or other...
Evidence on the neuropsychological consequences of classic psychedelics like psilocybin, LSD, and ayahuasca is conflicting, and little is known about how sporadic use of psychedelics under naturalistic conditions may affect cognitive functioning. Given the growing interest in the therapeutic potential of psychedelics and the rise in non-medical use, further exploration into their...
Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single...
This scoping review addresses the need to comprehensively explore the potential of psychedelic-assisted psychotherapy (PAP) to facilitate recovery from moral injury. Moral injury (MI), characterized by profound psychological distress arising from morally challenging experiences, has garnered increased attention as a complex mental health concern with significant functional sequelae, especially...
The intensity of the psychedelic experience has been hypothesized as the main predictor of response to a psychedelic treatment. This study aimed to investigate factors that may be associated with the intensity of mystical experiences during naturalistic psychedelic use. The data of this comprehensive sample were aggregated from four previous retrospective surveys, where mystical experience...
3,4-Methylenedioxymethamphetamine (MDMA) is a widely recognized entactogen frequently used recreationally. It is known for its interaction with the serotonin and oxytocin systems, which underlie its entactogenic effects in humans. Recently, we demonstrated that the gut-brain axis, mediated by the subdiaphragmatic vagus nerve, contributes to MDMA-induced resilience enhancement in rodents. This...
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration:...
Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of N, N-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of...