Psychedelic research is progressing at breakneck speed and is creating new challenges for drug developers, regulatory authorities, and legislators. Most “classic” psychedelics undergoing clinical investigation are C-I controlled drugs with perceived high potential for abuse and no medical use. These and next-generation psychedelic drug-candidates require sci...
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remissi...
Many neuropsychiatric conditions, including depression, involve synaptic loss and atrophy of the prefrontal cortex. The rapid regrowth of cortical neurons has been hypothesized to explain the rapid and enduring therapeutic effects of psychedelics and the dissociative anesthetic ketamine. However, safety concerns related to hallucinogenic/dissociative propert...
Repeated self-administration of small doses of psychedelics, known as microdosing, has been associated with perceived improvements in psychological functioning. However, few studies have examined effects at the daily level. Drawing on data from a naturalistic, prospective, international survey of adults who microdose (N = 1435), we assessed self-reported wit...
A meta-analysis comprising 17 randomized trials has found that rates of control group improvement in depression studies were lower in psilocybin trials than in studies of esketamine or a selective serotonin reuptake inhibitor (SSRI). The results suggest that psilocybin's overall efficacy in the treatment of depression might be overestimated.
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-li...
Since the earliest LSD research, psychedelics have been claimed to enhance autobiographical memory. Revisiting and processing autobiographical memories has further been suggested to be a major component of the therapeutic action of psychedelics. However, modern psychedelic research has largely neglected autobiographical elements of psychedelic experiences, a...
Introduction: Treatment-Resistant Depression (TRD) affects approximately 30-50% of patients with Major Depressive Disorder (MDD) who fail to respond to at least two adequate antidepressant trials. This condition presents substantial clinical and functional challenges, and no universally accepted treatment algorithm currently exists. Emerging therapeutic stra...
BACKGROUND: In recent years, there has been a resurgence of scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related effects of psilocybin and its impact on behavior remain underexplored. AIMS: We aimed to evaluate the potential rewarding effects of high doses of psiloc...
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propag...
Background: Depressive disorders are a major global health challenge, with many individuals unresponsive to existing treatments. Novel psychedelic therapies show promise but require further research. Objectives: This study aimed to evaluate the feasibility, safety and effectiveness of psilocybin with psychotherapeutic support for treatment-resistant depressi...
Background: Post-traumatic stress disorder (PTSD) is a debilitating condition for which there are few efficacious treatments. Psilocybin is being studied for use in treatment-resistant depression but has not yet been investigated in PTSD. Aims: The trial’s primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participant...
BACKGROUND AND AIMS: Drug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A rece...
Background: Current trauma treatment options often fail to meet patients' needs. Despite the availability of established interventions, many trauma treatments fail to adequately meet patients' needs. In parallel, there has been renewed scientific and public interest in the therapeutic potential of psychedelics and related compounds, accompanied by increasing...
Objective: Hallucinogen-persisting Perception Disorder (HPPD) is a rare condition characterized by the re-experiencing of one or more perceptual symptoms that an individual experienced while intoxicated with a hallucinogenic substance when the individual is sober. While there are several case reports of HPPD in adult patients, there is a scarcity of document...
RATIONALE: Anecdotal evidence suggests that psychedelic researchers often have personal experiences with psychedelic substances. While such experiences may benefit research, concerns have been raised about potential biases and "excessive enthusiasm." However, the prevalence of personal experiences, their perceived relevance, and their association with opinio...
Use of selective serotonin reuptake inhibitor (SSRI) antidepressants has been associated with reduced intensity of emotional experience. Conversely, some research has shown that use of psilocybin in patients with depression leads to an increase in responsiveness to emotional face stimuli, suggesting that the psychedelic generates a transient elevation in moo...