Effects of Serotonin Transporter Inhibition on the Subjective Response to LSD in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Visual Analog Scales (VAS) good effect rating
研究概览
简要总结
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. SSRIs like paroxetine are first-line treatments for depression and anxiety disorders. Paroxetine acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to LSD.
详细描述
Participants will be treated with paroxetine (Paroxetine 10 mg daily for 1 week followed by 20 mg daily for 5 weeks) or placebo for 6 weeks. Pretreatment is followed the first study day. A single dose of LSD (0.1 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of LSD and paroxetine, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or paroxetine (cross-over) for another 6 weeks. This is followed by the second study day and administration of LSD (0.1 mg).
Based on a power analysis the sample size is 24 participants (12 female and 12 male).
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)
盲法说明
Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •Participants must be willing to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions.
- •Participants must be willing not to drive a traffic vehicle or to operate machines within 48h after substance administration.
- •Willing to use double-barrier birth control throughout study participation.
- •Body mass index between 18-29 kg/m2.
排除标准
- •Chronic or acute medical condition, including a history of seizures.
- •Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
- •Psychotic 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); QT-time>450 ms (men) or >470 ms (women).
- •Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months.
- •History of acute glaucoma.
- •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 pharmacokinetic or pharmacodynamic interactions with paroxetine).
- •Tobacco smoking (>10 cigarettes/day).
- •Consumption of alcoholic drinks (>20 drinks/week).
研究组 & 干预措施
Pretreatment with paroxetine
Pretreatment with paroxetine (10 mg daily for 1 week followed by 20 mg daily for 5 weeks, per os), followed by administration of LSD (0.1 mg, per os) on the study day
干预措施: Paroxetine (Drug)
Pretreatment with paroxetine
Pretreatment with paroxetine (10 mg daily for 1 week followed by 20 mg daily for 5 weeks, per os), followed by administration of LSD (0.1 mg, per os) on the study day
干预措施: Lysergic Acid Diethylamide (Drug)
Pretreatment with placebo
Pretreatment with placebo for 6 weeks (mannitol, per os), followed by administration of LSD (0.1 mg, per os) on the study day
干预措施: Lysergic Acid Diethylamide (Drug)
Pretreatment with placebo
Pretreatment with placebo for 6 weeks (mannitol, per os), followed by administration of LSD (0.1 mg, per os) on the study day
干预措施: Placebo (Drug)
结局指标
主要结局
Visual Analog Scales (VAS) good effect rating
时间窗: Study sessions per participant will be separated by at least 43 days
VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS items will be used: "any drug effect", "good drug effect", "bad drug effect", "drug high", "anxiety", "nausea", "feeling depressed", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously were inscrutable to me", "talkative", "open", "trust" and "the context of my thought is personal/impersonal". Subjects will mark the scale with vertical lines.
5 dimensions of altered state of consciousness (5D-ASC) total OAV score
时间窗: Study sessions per participant will be separated by at least 43 days
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
- Changes in the electrocardiogram (ECG)(Study sessions per participant will be separated by at least 43 days)
- HTR gene expression(Study sessions per participant will be separated by at least 43 days)
- Adjective mood rating scale (AMRS)(Study sessions per participant will be separated by at least 43 days)
- Psychological Insight Questionnaire (PIQ)(Study sessions per participant will be separated by at least 43 days)
- Body temperature(Study sessions per participant will be separated by at least 43 days)
- States of consciousness questionnaire (SCQ)(Study sessions per participant will be separated by at least 43 days)
- Spiritual Realm Questionnaire (SRQ)(Study sessions per participant will be separated by at least 43 days)
- Blood pressure(Study sessions per participant will be separated by at least 43 days)
- Heart rate(Study sessions per participant will be separated by at least 43 days)
- Plasma concentrations of paroxetine(Study sessions per participant will be separated by at least 43 days)
- Plasma concentrations of LSD(Study sessions per participant will be separated by at least 43 days)