Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness (PDR-Study)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- 5 dimensions of altered state of consciousness (5D-ASC) total OAV score
研究概览
简要总结
Psilocybin (active compound of "magic mushrooms") is a prototypical psychedelic substance that acts via agonism on serotonin (5-HT) 2A receptors. Psilocybin is rapidly metabolized into its active metabolite psilocin. Psilocybin is currently under investigation as potential treatment for various neuropsychiatric disorders. Psilocybin is also widely used for recreational purposes and as research tool in neuroscience. Besides its current clinical development, a clear characterization of the dose-response relationship of psilocybin is lacking. With the present study the investigators aim to close this knowledge gap by administering low (5mg) to high (40mg) single doses of psilocybin to healthy participants. Besides its agonism on 5-HT2A receptors, psilocin also binds to other receptors and inhibits serotonin transporters (SERT). To this data only few studies have investigated these effects and never at a high dose.
详细描述
Psilocybin is widely used for recreational and spiritual purposes. Additionally Psilocybin is currently reused in experimental studies with healthy subjects and in studies investigating its effects on patients suffering from anxiety, depression, addiction personality disorders and other pathological conditions.
The present PDR-study will characterize the subjective effects of different doses of psilocybin using modern psychometric instruments, explore the relationship between the plasma-concentration of psilocybin and its subjective effects, and examine the contribution of the 5-HT2A receptor in the psilocybin-induced alterations of consciousness in a mechanistic study in healthy subjects.
Participants will recieve doses of 5, 10, 20, and 40 mg psilocybin, 40 mg of psilocybin with pretreatment of 40 mg ketanserin, and placebo (control for psilocybin). Placebo pretreatment (control for ketanserin) will be used for all psilocybin administrations without ketanserin. Administrations will be separated by at least 10 days and are in random and counter-balanced order.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 25 and 75 years.
- •Sufficient understanding of the German language.
- •Understanding the procedures and the risks that are associated with the study.
- •Participants must be willing to adhere to the protocol and sign the consent form.
- •Participants must be willing to refrain from taking illicit psychoactive substances during the study (not including cannabis).
- •Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
- •Women of childbearing potential must be willing to use effective birth-control throughout study participation
排除标准
- •Chronic or acute medical condition, including a history of seizures.
- •Body mass index 18-29.9 kg/m2
- •Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
- •Psychotic or bipolar disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g., brain injury, dementia, or lesions of the brain.
- •Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
- •Psychedelic substance use (with the exception of cannabis) more than 20 times or any time within the previous two months
- •Pregnant or nursing women.
- •Participation in another clinical trial (currently or within the last 30 days).
- •Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known to interact with the study substances).
- •Tobacco smoking (>10 cigarettes/day).
- •Consumption of alcoholic drinks (>15 drinks / week).
- •Body weight < 45 kg.
研究组 & 干预措施
40mg Psilocybin plus 40mg Ketanserin
40mg Ketanserin oral followed by 40mg Psilocybin oral one hour later
干预措施: Ketanserin 40mg plus Psilocybin 40mg (Drug)
40mg Psilocybin
40mg Psilocybin oral
干预措施: 40mg Psilocybin (Drug)
20mg Psilocybin
20mg Psilocybin oral
干预措施: 20mg Psilocybin (Drug)
10mg Psilocybin
10mg Psilocybin oral
干预措施: 10mg Psilocybin (Drug)
5mg Psilocybin
5mg Psilocybin oral
干预措施: 5mg Psilocybin (Drug)
Placebo
Placebo followed by Placebo
干预措施: Placebo (Other)
结局指标
主要结局
5 dimensions of altered state of consciousness (5D-ASC) total OAV score
时间窗: 10 hours after substance administration
Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.
次要结局
- Visual Analog Scales (VAS) good effect rating(One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Adjective Mood Rating Scale AMRS(One hour before as well as 3, 6, 10 and 24 hours after substance administration)
- States of consciousness questionnaire (SCQ)(10 hours after substance administration)
- Phenomenological-Autobiographical-Existential Psychedelic Scale extended (PAE-PS-ext)(This questionnaire is administrated once before the first substance day (during screening), and then again 10h after substance administration on everx study visit..)
- Acute autonomic effects I (blood pressure)(One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Acute autonomic effects II (heart rate)(One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Acute autonomic effects III (body temperature)(One hour before, right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Effect moderation by personality traits I (NEO-FFI)(Screening)
- Effect moderation by personality traits II (FPI-R)(Screening)
- Effect moderation by personality traits III (SPF)(Screening)
- Effect moderation by personality traits IV (HEXACO)(Screening)
- Effect moderation by personality traits V (DSQ-40)(Screening)
- Psychological Insight Questionnaire (EBI+)(10 hours after substance administration)
- Changes in the electrocardiogram (ECG)(One hour before and 2 hours after substance administration.)
- Adverse effects (acute and subacute)(One hour before, 10 and 24 hours after substance administration)
- Persisting effects of the psychedelic experiences (PEQ)(End of study (EOS) visit during EOS interview)
- Cognitive Tasks(24 hours after substance administration)
- Peak Plasma concentration of Psilocybin and Metabolites (Cmax)(Right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Elimination half life values (t1/2)(Right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Time to cmax (Tmax)(Right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Area under the concentration-time curve up to 24 h (AUC0-24)(Right after and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10 and 24 hours after substance administration)
- Sleep variables of %REM(14 hours after substance administration until the end of the study day)
- REM Latency(14 hours after substance administration until the end of the study day)
- REM Efficiency(14 hours after substance administration until the end of the study day)