Lysergic acid diethylamide (LSD) is a potent psychedelic with increasing therapeutic interest, yet qualification of target engagement using in vivo neuroimaging has not yet been performed. Using simultaneous positron emission tomography-magnetic resonance imaging technology, we describe multiple brain actions of LSD in seven healthy volunteers blinded to LSD dose received. Here we show that LSD...
Abstract Classic psychedelics, including lysergic acid diethylamide (LSD), are currently under investigation for the treatment of major depressive disorder (MDD). Cognitive dysfunction is common in MDD, but effects of psychedelic treatment on cognitive brain function, measured by magnetic resonance imaging, are sparsely reported. The present study investigated effects of LSD treatment on...
Abstract Background Anxiety disorders are a major health burden and current treatment options yield unsatisfactory results. Psychedelics, such as lysergic acid diethylamide (LSD) that act via agonism on serotonin 2A receptors, have recently been shown to be effective in the treatment of anxiety symptoms. Aims & Objectives Here, we determine the relationship between the acute experience and...
Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin...
For English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-mystical factors (visual experience and...
Objectives: For English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-mystical factors (visual experience...
Mystical dynamics—the notion that mystical oneness may unfold involving ego disintegration, renewal, and luminous light—has been discussed anecdotally by psychedelic researchers and therapists but has not yet been empirically examined in controlled settings. This study investigated the occurrence and dose-dependency of mystical dynamics in healthy participants after administration of...
Classical psychedelics have regained interest for their potential to treat psychiatric and neurological disorders, and explore neural mechanisms supporting perception, cognition, and mood. Acute psychedelic effects have been linked to increases in brain complexity and entropy, but it is unclear if these changes are specific to psychedelics or reflect more general psychoactive effects. Here, we...
Mystical dynamics-the notion that mystical oneness may unfold involving ego disintegration, renewal, and luminous light-has been discussed anecdotally by psychedelic researchers and therapists but has not yet been empirically examined in controlled settings. This study investigated the occurrence and dose-dependency of mystical dynamics in healthy participants after administration of...
Background: Serotonergic psychedelics induce their psychoactive effects by stimulating the brain’s serotonin 2A receptor (5-HT2AR). In humans, a cerebral 5-HT2AR occupancy of ≥60% is required to elicit a profound psychedelic experience with psilocybin [1] and for pigs, a dose corresponding to ∼65% 5-HT2AR occupancy elicits headshakes [2]. We posit that in order to assess biochemical and...
The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the 3D-ASC...
In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD increases global cerebral blood flow and...
Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based...
Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders. Different LSD formulations (base or tartrate, oral or intravenous) are being used. Unclear is whether LSD base and tartrate pharmacokinetics are equivalent. Additionally, LSD's absolute oral bioavailability is unknown. Therefore, we tested the bioequivalence of...
4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is widely used recreationally and has recently gained interest as a treatment for mental health disorders. In this study, a liquid chromatography-tandem mass spectrometry method to quantify 2C-B and its metabolites 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) and 4-bromo-2-hydroxy-5-methoxyphenylacetic acid (B-2-HMPAA) in human plasma was developed...
Psychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have...
Little is known about motives of healthy volunteers to participate in psychedelic trials and how they appraise their study experience retrospectively. This paper explored reasons why healthy people register for psychedelic trials, factors that they considered to contribute to either positive or negative study experiences, and under which circumstances they would seek a psychedelic experience...
Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for...
A 64-year-old male patient who suffered from traumatic life experiences and neuropathic pain after oncological chemotherapy was treated with medium to high doses of lysergic acid diethylamide (LSD) and high doses and microdoses of methylenedioxymethamphetamine (MDMA). At the beginning of treatment, the patient did not experience any acute subjective effects of LSD at a dose of 200 µg. After...
Background: The Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the...
3,4-Methylenedioxymethamphetamine (MDMA, or ecstasy) is a recreational drug being investigated for the treatment of posttraumatic stress disorder. Acute hyponatremia is a potentially serious complication after even a single dose of MDMA. The assumed etiology has been a vasopressin release inducing the syndrome of inappropriate antidiuresis combined with increased thirst, causing polydipsia and...
Background: Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT. Aims: This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients,...
The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human...
Anxiety disorders are a major public health burden with limited treatment options. We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness. This study was an a priori-planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind,...
The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants...