Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform...
Purpose Current laws prohibiting access to illicit drugs contribute to drug harms as manufacturers and distributors of illicit substances have variable influence over drug supply and quality. Legislation introduced in New Zealand (NZ) in 2021 aimed to address such harm by enabling licenced drug checking providers to directly analyse samples from consumers. This paper aims to detail the use of...
Abstract Psychedelics profoundly alter conscious experience, yet how they reshape the relationship between brain anatomy and function remains unclear. In particular, it is unknown whether psychedelic states reflect a global disruption of structure–function organization or a frequency– and network-specific reconfiguration of neural dynamics relative to the structural connectome. Here we address...
Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.
Background: Depressive disorders affect approximately 280 million globally, with many finding treatments ineffective or limited by side effects. Growing evidence suggests that psychedelic therapies may help alleviate depressive symptoms. Among these, lysergic acid diethylamide (LSD) microdosing shows promise for major depressive disorder (MDD). However, research on LSD microdosing in clinical...
Expectations can impact antidepressant treatment and psychedelic therapy, often enhancing placebo effects and influencing outcomes. However, research in this context is lacking. Our study explored the expectations of participants with major depressive disorder (MDD) before microdosing lysergic acid diethylamide (LSD) in an open-label trial. Twenty-three individuals with MDD completed a...
The analyses described in this SAP will assess the efficacy and safety of LSD (MB-22001) in comparison with active placebo (caffeine). The analysis described cover those for the primary, secondary and safety endpoints described in the Protocol.
Microdosing psychedelics is an increasingly popular phenomenon where small amounts of psychedelic drugs are taken regularly. Qualitative data have been published regarding the experiences of microdosers, but never in the context of a randomised controlled trial. Semi-structured video interviews with 40 healthy males were conducted following a double-blind placebo-controlled trial of 10 µg of...
Major depressive disorder (MDD) affects approximately 5 % of the global population. Classic psychedelics have shown promise in treating various mental health disorders. This study evaluated the feasibility and tolerability of an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label phase 2A trial (LSDDEP1). Nineteen...
Psychedelic-assisted therapy (PAT) has typically been evaluated using conventional randomised controlled trials (RCTs), which assess treatment efficacy under highly controlled conditions. However, PAT constitutes a complex intervention, integrating pharmacological, psychotherapeutic and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional...
Structured Abstract Importance Ketamine has well known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Given prior studies that link specific cortical oscillations with specific therapeutic effects, it is likely that modulating selective aspects...
Abstract Background Depressive disorders affect about 280 million people worldwide, with many struggling to find effective relief. Conventional antidepressants are widely prescribed but often lack efficacy and have side effects, leaving many patients dissatisfied or untreated. Concurrently, psychedelic therapies have gained momentum in both research and ‘in the wild’, with emerging evidence...
Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder characterised by depression, irritability, mood lability, anxiety and physical symptoms that occur exclusively in the last week/s of the menstrual cycle. With a growing global interest in microdosing of psychedelic drugs, an increase in self-medication has occurred, including by those with PMDD. Aim: Qualitative...
Abstract Psilocybin, a naturally occurring psychedelic compound found in certain fungi has long been used by Indigenous cultures within ritual and ceremony for healing and spiritual purposes (Spiers et al., 2024). While emerging evidence points to psychedelic agents being novel avenues for the treatment of substance use disorders, the predominantly Western medical models of psychedelic-assisted...
Microdosing is the practice of taking psychedelic drugs at doses that produce no or minimal perceptible subjective or behavioural effects. This study investigated the pharmacokinetics and pharmacodynamics of microdosed lysergic acid diethylamide (LSD). This was a Phase 1 double-blind placebo-controlled parallel-groups trial with 80 healthy male volunteers (four withdrawals due to anxiety)....
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction...
bioRxivMarch 24, 2025Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.3 citations
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Abstract Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed...
Enhanced creativity is often cited as an effect of microdosing (taking repeated low doses of a psychedelic drug). There have been recent efforts to validate the reported effects of microdosing, however creativity remains a difficult construct to quantify. The current study aimed to assess microdosing's effects on creativity using a multimodal battery of tests as part of a randomised controlled...
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed...
medRxivOctober 21, 2024Pascal Grumbach, Jan Kasper, Joerg F. Hipp et al.1 citation
preprint
Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition (E/I) ratio is discussed as a potential pathomechanism but in-vivo evidence of disturbed neurotransmission underlying these functional alterations remains scarce. We compared rs-fMRI local activity (LCOR) between ASD (N=405, N=395) and...
Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged...
Taking regular low doses of psychedelic drugs (microdosing) is a practice that has drawn recent scientific and media attention for its potential psychotherapeutic effects. Yet, controlled studies evaluating this practice have lagged. Here, we review recent evidence focusing on studies that were conducted with rigorous experimental control. Studies conducted under laboratory settings using...
Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses...
Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms-it is the acute response in the brain that triggers this cascade of events. Computational...
Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to...