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Lysergic acid diethylamide (LSD) in palliative care: a randomised, double-blind, active-placebo controlled phase II study

Research Project | 3 Project Members

Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic psychedelics, including lysergic acid diethylamide (LSD) and psilocybin, produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic psychedelics may produce antinociceptive effects.

Safety and efficacy of LSD as treatment for cluster headache: a randomized, double-blind, placebo-controlled phase II study

Research Project | 1 Project Members

Cluster headache (CH) is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD (pulse regimen) for patients with CH.

Psychological, physiological, endocrine, and pharmacokinetic effects of LSD in a controlled study

Research Project | 2 Project Members

Background: Lysergic acid diethylamide (LSD) is the prototype hallucinogen used recreationally worldwide. In the 50-70s, LSD was also used to study psychotic-like states in normals ("model psychosis") and in "psycholytic psychotherapy". Clinical research using LSD has been prohibited in most countries over the last 30 years and there is now a renewed interest in the pharmacology of this substance. Potential research and therapeutic uses of LSD are now re-recognized and may include its use in brain research, treatment of cluster headache, and aid in psychotherapy and in terminally ill patients. Recently, a first placebo-controlled study in patients suffering from anxiety associated with advanced-stage life threatening diseases has been completed in Switzerland. However, most initial studies conducted with LSD do not meet todays' research standards and many effects of the substance including those on the endocrine system and the pharmacokinetic-pharmacodynamic relationship are unknown. Study aim: To characterize the acute psychological, physiological, endocrine, and pharmacokinetic, as well as long-term psychological effects of LSD in humans (psychotherapists). Methods: Placebo-controlled, double-blind, randomized two-phase cross-over study to test the effects of LSD (200 mg) or placebo in 16 well-educated middle aged healthy human subjects. Outcome measures of acute effects will include: validated psychometric tests, physiological effects, neuroendocrine measures, plasma concentration-time profiles of LSD, and adverse effects. Additionally, long-term psychological effects of LSD will be assessed 1 and 12 months after the experience. Significance. LSD is the most famous psychedelic substance. LSD is continued to be used recreationally. There is also a professional need for more clinical data on its role in experimental research and possible therapeutic applications (headache, psychotherapy, palliative medicine). This would be the first placebo-controlled and methodologically sound evaluation of the pharmacological and long-term psychological effects of LSD in humans. In addition, the endocrine effects of LSD are unknown. A better and contemporary understanding of the pharmacology of LSD is important in the light of its widespread recreational and potential scientific uses. The study will provide a first and solid account of the clinical pharmacological characteristics of the drug that are very likely to form a basis for further studies. Such ensuing experimental work in the near future may include the use of LSD in a psychotherapeutic setting in professional therapists as participants and a functional magnetic resonance imaging study to define the neuronal correlates of the effects of LSD.

Pharmacology and Toxicology of Amphetamine-type Substances

Research Project | 4 Project Members

Use of amphetamine-type substances including MDMA (ecstasy), methylphenidate (Ritalin), and novel cathinone designer drugs is prevalent in our society. In particular, the pharmacology and toxicology of the cathinones is poorly known and will be characterized in this project. In addition, we investigate the pharmacological effects of MDMA and Ritalin with regard to effects on emotion recognition, empathy, and social behavior in humans. Social cognition (emotion recognition and empathy) is critical for human social interactions. MDMA produces subjective feelings of openness and closeness to others and is said to have "empathogenic" effect. However, it is unknown whether MDMA indeed improves affective perception and enhances emotional or cognitive empathy. Such effects are relevant with regart to the recreational use of MDMA but also to its potential therapeutic use in psychotherapy. Methylphenidate is widely used in the treatment of attention deficit hyperactivity disorder (ADHD). In addition, methylphenidate is also abused as a party drug and its use for cognitive enhancement as so-called 'smart drug' has become a focus of concern. Whether methylphenidate use affects social cognition is not known. However, it is possible that part of the therapeutic benefits of this amphetamine derives from enhanced face emotion recognition which has been shown to be impaired in children with ADHD. Our clinical studies will also produce important data on the pharmacological mechanism of action of amphetamines that will inform emergency physicians on how to treat intoxications with these drugs.

Effect of ketanserin, olanzapine, and lorazepam after LSD administration on the acute response to LSD in healthy subjects (LBL-Study)

Research Project | 3 Project Members

Acute LSD administration may induce schizophrenia-like symptoms, including pseudohallucinations, visionary restructuralization, and ego-dissolution, but also prepulse inhibition disruption, which seems primarily associated with the activity at the 5-HT_2Areceptor. However, the exact mechanisms underlying psychosis-like symptoms of LSD remain to be investigated. The primary goal of the study is to investigate whether ketanserin, olanzapine, and lorazepam administration after LSD administration might attenuate and shorten the LSD response compared to the administration of LSD alone. Additionally, the present study examines changes in the quality of the LSD experience after administration of ketanserin, olanzapine, or lorazepam and its effects on sensorimotor gating and sleep. The study provides insight into the receptor mechanisms involved in alterations of consciousness and, specifically, the relevance of ongoing 5-HT_2A receptor stimulation in the mediation of the psychedelic response to LSD and psychotic symptoms.