Effects of Dimethyltryptamine (DMT) in Healthy Subjects: A Placebo-controlled Cross-over Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Altered states of consciousness profile
研究概览
简要总结
N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings. DMT can be used as a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. DMT is rapidly metabolized by monoamine oxidase (MAO) A. Therefore, it is inactive when administered orally and has a very short duration of action when administered parenterally (<20 min).Therefore, an intravenous administration regime including a bolus and maintenance perfusion has been proposed to induce a stable and prolonged DMT experience allowing to study the psychological and autonomic acute effects of DMT. This administration allows to induce and end an altered state safely and quickly. The goal of the present study is to experimentally test different intravenous DMT administration schedules to investigate the subjective and autonomic effects of DMT in healthy subjects.
详细描述
N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings in the form of Ayahuasca. Similar to lysergic acid diethylamide (LSD) or psilocybin, DMT is considered a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. Pharmacologically, DMT interacts with the serotonin 5-HT2A receptor similar to other classic hallucinogens including LSD and psilocybin. The main difference of DMT in comparison with LSD or psilocybin is inactivity when administered orally without monoamine oxidase (MAO) A inhibition and its short action when administered intravenously or by inhalation. In Ayahuasca, DMT is consumed iin combination with harmala alkaloids that inhibit MAO to increase the oral bioavailability of DMT and to prolong its action after oral use. Alternatively, an intravenous administration regime including a bolus and a one hour maintenance perfusion has been proposed to induce a stable and prolonged DMT experience, allowing to study the psychological and autonomic acute effects of DMT. Also, the maintenance perfusion administration allows to end an altered state of consciousness quickly. In the present study this model will be tested using four modified administration schemes. The goal of this study is to experimentally test different intravenous DMT administration schedules to investigate the subjective and autonomic effects of DMT in healthy subjects. The study is expected to inform researchers on dosing regimes of intravenous DMT as a tool to examine alterations of the mind and is of interest for psychology and psychiatry. This study does not intend to provide any therapeutic benefit for the participants. Currently, no study has validly determined the elimination half-life of DMT and other pharmacokinetic parameters. The key aim is to test the dose-response of DMT as well as the difference between the loading dose bolus and no-bolus perfusion conditions regarding pharmacokinetic, subjective, and autonomic effects including psychological and physical tolerability.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 old
- •Sufficient understanding of the German language
- •Understanding of procedures and risks associated with the study
- •Willing to adhere to the protocol and signing of the consent form
- •Willing to refrain from the consumption of illicit psychoactive substances during the study
- •Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
- •Willing not to operate heavy machinery within 6 h of DMT 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
- •Current or previous major psychiatric disorder
- •Psychotic disorder or bipolar disorder in first-degree relatives
- •Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
- •Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months
- •Pregnancy or current breastfeeding
- •Participation in another clinical trial (currently or within the last 30 days)
- •Use of medication that may interfere with the effects of the study medication
- •Tobacco smoking (>10 cigarettes/day)
- •Consumption of alcoholic beverages (>20 drinks/week)
研究组 & 干预措施
Placebo
Bolus of 0 mg DMT + perfusion of 0 mg/min DMT over 60 min, resulting in a total dose of 0 mg DMT.
干预措施: Saline (Drug)
Low dose
Intravenous bolus of 0 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 54 mg DMT.
干预措施: Dimethyltryptamine (DMT) (Drug)
Low dose
Intravenous bolus of 0 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 54 mg DMT.
干预措施: Saline (Drug)
Low dose with bolus
Intravenous bolus of 15 mg DMT + perfusion of 0.6 mg/min DMT over 90 min, resulting in a total dose of 69 mg DMT.
干预措施: Dimethyltryptamine (DMT) (Drug)
High dose
Intravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg DMT.
干预措施: Dimethyltryptamine (DMT) (Drug)
High dose
Intravenous bolus of 0 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 90 mg DMT.
干预措施: Saline (Drug)
High dose with bolus
Intravenous bolus of 25 mg DMT + perfusion of 1 mg/min DMT over 90 min, resulting in a total dose of 115 mg DMT.
干预措施: Dimethyltryptamine (DMT) (Drug)
结局指标
主要结局
Altered states of consciousness profile
时间窗: 150 minutes
Assessed once on each study day via 5 Dimensions of Altered States of Consciousness (5D-ASC) scale consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects
Subjective effect ratings over time
时间窗: 150 minutes
Assessed 22 times on each study day via Subjective Effect Scale (SES), consisting of 4 questions to be rated on a Likert scale ranging from 1 to 10, with higher ratings indicating stronger effects
次要结局
- Adverse effects(150 minutes)
- Autonomic effects I(150 minutes)
- Plasma levels of blood-derived neurotrophic factor (BDNF)(150 minutes)
- Plasma levels of oxytocin(60 minutes)
- Mystical-type experiences(150 minutes)
- Effect moderation through personality trait V(Baseline)
- Effect moderation through personality trait VII(Baseline)
- Plasma levels of DMT(150 minutes)
- Effect moderation through personality traits III(Baseline)
- Effect moderation through personality trait VI(Baseline)
- Subjective mood ratings(150 minutes)
- Autonomic effects II(150 minutes)
- Renal clearance of DMT(3 hours)
- Effect moderation through personality traits I(Baseline)
- Effect moderation through personality traits II(Baseline)
- Effect moderation through personality trait IV(Baseline)