Acute Effects of MDMA Co-administration on the Response to Psilocybin 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
- Acute Subjective effects I
研究概览
简要总结
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with psilocybin in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking, or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which psilocybin is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favorable long-term outcomes in patients experimentally treated with psilocybin or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood, euphoria, comfort, empathy, and feelings of trust. If administered in combination with psilocybin, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with psilocybin and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of psilocybin alone and in combination with MDMA.
详细描述
Psilocybin is a classic serotonergic psychedelic. Clinically, the acute effects of psilocybin last shorter than those of lysergic acid diethylamide (LSD) but are qualitatively very similar. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics including LSD, psilocybin, mescaline, and dimethyltryptamine (DMT). Psilocybin is capable of inducing exceptional subjective effects such as a dream-like alteration of consciousness, affective changes, psychological insight, visual imagery, pseudo-hallucinations and ego-dissolution. The acute subjective effects elicited by psilocybin are mostly positive in humans. However, psychedelic substances like psilocybin may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of psilocybin used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize the effects of psilocybin by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 25 and 65 years.
- •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 drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
- •Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
- •Willing to use effective birth control throughout study participation.
- •Body mass index between 18-29 kg/m2.
排除标准
- •Chronic or acute medical condition
- •Current or previous major psychiatric disorder
- •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)
- •Illicit substance use (not including cannabis) more than 20 times or any time within the previous month
- •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.
- •Tobacco smoking (>10 cigarettes/day).
- •Consumption of alcoholic drinks (>15 drinks/week).
研究组 & 干预措施
20 mg Psilocybin + MDMA placebo
20 mg Psilocybin + MDMA placebo
干预措施: 3,4-Methylenedioxymethamphetamine placebo (Drug)
Psilocybin placebo + MDMA placebo
Psilocybin placebo + MDMA placebo
干预措施: Psilocybin placebo (Drug)
Psilocybin placebo + 100 mg MDMA
Psilocybin placebo + 100 mg MDMA
干预措施: Psilocybin placebo (Drug)
Psilocybin placebo + MDMA placebo
Psilocybin placebo + MDMA placebo
干预措施: 3,4-Methylenedioxymethamphetamine placebo (Drug)
20 mg Psilocybin + 100 mg MDMA
20 mg Psilocybin + 100 mg MDMA
干预措施: Psilocybin (Drug)
20 mg Psilocybin + MDMA placebo
20 mg Psilocybin + MDMA placebo
干预措施: Psilocybin (Drug)
Psilocybin placebo + 100 mg MDMA
Psilocybin placebo + 100 mg MDMA
干预措施: 3,4-Methylenedioxymethamphetamine (Drug)
20 mg Psilocybin + 100 mg MDMA
20 mg Psilocybin + 100 mg MDMA
干预措施: 3,4-Methylenedioxymethamphetamine (Drug)
结局指标
主要结局
Acute Subjective effects I
时间窗: through study completion, an average of 18 months
The Visual Analog Scales (VAS) assesses the intensity and duration of the subjective effect on a scale from 0 - 100 percent with higher scores representing more intense effects. Assessed 12 times on each study day
Acute autonomic effects III (body temperature)
时间窗: through study completion, an average of 18 months
Body temperature will be measured with an ear thermometer.
Acute Subjective effects II
时间窗: through study completion, an average of 18 months
The Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely".
Acute Subjective effects III
时间窗: through study completion, an average of 18 months
5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects.
Acute autonomic effects I (blood pressure)
时间窗: through study completion, an average of 18 months
Blood pressure (systolic and diastolic) will be measured with an automatic oscillometric device.
Acute autonomic effects I (heart rate)
时间窗: through study completion, an average of 18 months
Heart rate will be measured with an automatic oscillometric device.
Acute autonomic effects IV (ECG QT-time)
时间窗: through study completion, an average of 18 months
An ECG will be performed twice: once before and once after substance administration.
次要结局
- Peak plasma concentration (Cmax) of MDMA and metabolites(through study completion, an average of 18 months)
- Time to peak plasma concentration (Tmax) of MDMA and metabolites(through study completion, an average of 18 months)
- Area under the plasma concentration vs. time curve (AUC) of MDMA and metabolites(through study completion, an average of 18 months)
- Elimination half-life values of MDMA and metabolites(through study completion, an average of 18 months)
- Peak plasma concentration (Cmax) of Psilocybin and metabolites(through study completion, an average of 18 months)
- Time to peak plasma concentration (Tmax) of Psilocybin and metabolites(through study completion, an average of 18 months)
- Area under the concentration vs. time curve (AUC) of Psilocybin and metabolites(through study completion, an average of 18 months)
- Elimination half-life values of Psilocybin and metabolites(through study completion, an average of 18 months)
- Plasma concentration of Oxytocin(through study completion, an average of 18 months)
- States of Consciousness Questionnaire(through study completion, an average of 18 months)
- Spiritual Realms Questionnaire(through study completion, an average of 18 months)
- Subacute effects on general and mental well-being I (WEMWBS)(through study completion, an average of 18 months)
- Subacute effects on general and mental well-being II (GHQ-12)(through study completion, an average of 18 months)
- Subacute effects on general and mental well-being III (SPANE)(through study completion, an average of 18 months)
- Subacute effects on general and mental well-being IV (BFW/E)(through study completion, an average of 18 months)
- Subacute effects on general and mental well-being V (GLS)(through study completion, an average of 18 months)
- Adverse effects (acute and subacute)(through study completion, an average of 18 months)
- Effects on Appreciation(through study completion, an average of 18 months)
- Effect moderation by personality traits I (NEO-FFI)(Baseline)
- Effect moderation by personality traits II (FPI-R)(Baseline)
- Effect moderation by personality traits III (SPF)(Baseline)
- Effect moderation by personality traits IV (HEXACO)(Baseline)
- Effect moderation by personality traits V (DSQ-40)(Baseline)