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...
Background: Psilocybin-assisted therapy (PAT) has emerged as a promising intervention for alcohol use disorder (AUD), yet contemporary clinical evidence has not been systematically synthesized to validate its clinical utility and safety profile. Methods: Contemporary clinical trials of PAT for AUD were identified systematically from PubMed, PsycINFO, and Scopus by two independent reviewers....
Background Classic psychedelics show potential for treating psychiatric disorders, yet the psychological framework of psychedelic-assisted therapy (PAT) remains underspecified. As regulatory approval approaches, defining the contribution of psychological interventions to clinical outcomes is critical for both mechanism inference and implementation. Objectives To systematically review the...
In Basel, only a few hundred meters from where LSD was first synthesized, we tested LSD-assisted therapy for major depression in a randomized trial comparing two high doses with two low doses, each paired with supportive psychotherapy. This Backstory reflects on treating patients, long dosing days, and what remains uncertain.
The research, understanding, and implementation of psychedelic therapies is characterised by a layered complexity that arises from the dynamic interactions between pharmacological and extra-pharmacological factors, and the embeddedness of psychedelics within broader societal, legal, and regulatory systems ill-equipped to accommodate them. This complexity is compounded by an epistemic...
The clinical trial NCT03866252 investigates the antidepressant effects of lysergic acid diethylamide (LSD) in 61 patients with major depressive disorder (MDD) randomized to low-dose LSD (LD-LSD; 2 × 25 μg) or moderate-to-high-dose LSD (HD-LSD; 100 μg followed by 200 μg) 4 weeks apart. Although the trial reports positive clinical outcomes, underlying mechanisms remain unclear. Here, we test...
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...
JAMA Network OpenJanuary 2, 2026Gianluca Andri Florineth, Isabell Klima, Anna Laura Boeker et al.5 citations
Psychedelic-assisted therapy (PAT) is a novel intervention for depressive symptoms, typically delivered with additional psychological therapy sessions. Quantitative evidence on how this concomitant therapy contributes to treatment outcomes is limited, highlighting the need for a systematic synthesis. To evaluate whether the quantity of psychological therapy is associated with symptom reduction...
This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder. This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252). Patients were randomly assigned in a 1:1 ratio to receive supportive psychotherapy and either 100 μg + 200 μg LSD or 25 μg + 25 μg...
Microdosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, LSD's efficacy in reducing ADHD symptoms remains unknown. To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo. This...
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...
• A 60-year-old man with recurrent depression and history of delusions died after psilocybin-assisted therapy. • Psilocybin-triggered delusions and emotional dysregulation may have contributed. • Weak therapeutic alliance hindered assessment of patient's internal state. • Delusional symptoms may contraindicate psychedelic interventions. • This case emphasizes the need for thorough assessment...
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,...
Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD). These...
While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal...
Abstract Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective...
Abstract Lysergic acid diethylamide (LSD) is a potent perception-altering chemical. Since the discovery of its effects almost eighty years ago, LSD has been revered and demonized. Before its ban in the late 1960s, LSD was used to model aspects of psychosis and treat distinct mental disorders such as alcohol addiction and anxiety. The new wave of research on psychedelics as potential treatments...
This study aimed to investigate the efficacy and safety of lysergic acid diethylamide (LSD)-assisted therapy in patients who experienced anxiety with or without association with a life-threatening illness. The study is an investigator-initiated 2-center trial that used a double-blind, placebo-controlled, 2-period, random-order, crossover design with 2 sessions with either oral LSD (200 μg) or...
Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research...
Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.
Abstract Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women,...
Abstract Background LSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is...
Psychiatry has a well-established tradition of comparing drug-induced experiences to psychotic symptoms, based on shared phenomena such as altered perceptions. The present review focuses on experiences induced by classic psychedelics, which are substances capable of eliciting powerful psychoactive effects, characterized by distortions/alterations of several neurocognitive processes (e.g.,...