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...
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...
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...
Psychedelics have shown promising antidepressant effects in recent phase 2 randomized controlled trials, with phase 3 studies underway. While therapeutic outcomes are encouraging, the underlying mechanisms—from receptor-level pharmacology to subjective experience and context—remain only partially understood. We highlight clinical and mechanistic advances and outline priorities for future...
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...
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...
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...
Klassische Psychedelika wie Psilocybin, Lysergsäurediethylamid (LSD), Ayahuasca oder 5-Methoxy-Dimethyltryptamin (5-MeO-DMT) stehen wieder vermehrt im Fokus des psychiatrisch-psychotherapeutischen und neurowissenschaftlichen Interesses. Dies ist vor allem auf aktuelle klinische Studien zurückzuführen, die einen möglichen therapeutischen Nutzen von Psychedelika in der Behandlung verschiedener...
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...
Evidence for case–control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of...
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...
Zusammenfassung In den letzten Jahren erlebte die klinische Forschung zur therapeutischen Wirksamkeit von Psychedelika eine Art Renaissance. Der aktuelle Stand wissenschaftlicher Erkenntnisse zur Wirksamkeit bei verschiedenen psychiatrischen Indikationen, wie auch die bereits unter bestimmten Voraussetzungen genehmigungsfähige Anwendung einiger psychedelischer Substanzen in der klinischen...
Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.
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.,...
Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We...
Abstract It has been reported that serotonergic hallucinogens like lysergic acid diethylamide (LSD) induce decreases in functional connectivity within various resting-state networks. These alterations were seen as reflecting specific neuronal effects of hallucinogens and it was speculated that these shifts in connectivity underlie the characteristic subjective drug effects. In this study, we...
A 39-year-old female patient suffering from severe, treatment-resistant depression and other symptoms associated with a complex personality disorder was admitted to our open psychiatric ward for an experimental treatment with lysergic acid diethylamide (LSD). The substance was administered in repeated weekly and ascending doses. Curiously, there were no substantial acute subjective effects of...
Abstract Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25...
Abstract Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and d -amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and d -amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three...
Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as...
Aims The aim of the present study was to characterize the pharmacokinetics and exposure–subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients. Method LSD (100 μg) was administered in 27 healthy subjects using a placebo‐controlled, double‐blind, cross‐over design. Plasma levels of LSD, nor‐LSD,...
In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and Web of Science were searched for studies published from inception to August 24, 2018, without any language restriction. Sixteen independent studies comprising 356 MDMA users and 311 controls were included. Of these, five studies...
LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current...