Acute Analgesic Effects of DMT on Experimentally Induced Acute Nociceptive Pain, Hyperalgesia and Allodynia in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Numeric rating scale (NRS) scores (0 - 10)
研究概览
简要总结
N,N-dimethyltryptamine (DMT) is a classical psychedelic with similar effects like LSD or psilocybin. Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. Therefore, the investigators will evaluate the efficacy of DMT on different pain qualities within a model of electrically induced pain in healthy participants. The analgesic effects will be compared to racemic ketamine (active control) and placebo within a cross-over design.
详细描述
Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. For instance, it is unclear whether psychedelics possess acute antinociceptive effects or if they rather modulate secondary pain phenomena such as hyperalgesia, allodynia, and/or functional pain. Here, the investigators will employ a validated electrical stimulation model in healthy volunteers that produces acute nociceptive pain but also features of chronic pain such as hyperalgesia and allodynia. The model is established for the detailed assessment of the analgesic effect of known analgesics or new compounds. Thus, the investigators will evaluate the efficacy of N,N-dimethyltryptamine (DMT), a classical and naturally-occurring psychedelic, on different pain qualities within this model. DMT differs from other classical psychedelics in its very short elimination half-life. Due to its rapid metabolization by monoaminoxidases (MAO), DMT is not orally bioavailable in the absence of MAO-inhibitors and thus has to be administered continuously and intravenously. Recently, the investigators tested several continuous intravenous administration regimes of DMT that lead to the induction of a constant and rapidly adaptable psychedelic state. The regime allows to induce stable DMT effect that can be terminated rapidly. Due to this controllability, a continuous infusion of intravenous DMT is most suitable to assess time and concentration-dependent analgesic effects within the used pain model. The analgesic efficacy of DMT will be compared to ketamine, a known analgesic (positive control), and placebo.
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 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
- •Willing not to operate heavy machinery for 24 hours after the study session.
- •Willing to use effective birth control throughout study participation
- •Body mass index between 18-29 kg/m2 and body weight within 50 - 90kg
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 and/or dissociative substance use (not including cannabis) more than 15 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
Intravenous infusion of DMT
Participants will be administered intravenous DMT.
干预措施: Intravenous infusion of DMT (Drug)
Intravenous infusion of ketamine
Participants will be administered intravenous racemic ketamine.
干预措施: Intravenous infusion of ketamine (Drug)
Intravenous infusion of placebo
Participants will be administered intravenous lacebo (saline infusion).
干预措施: Intravenous infusion of placebo (Drug)
结局指标
主要结局
Numeric rating scale (NRS) scores (0 - 10)
时间窗: During the infusion (55minutes)
Difference of the cumulative NRS scores (area under the effect curves (AUECs)) between the DMT, ketamine (active-control) and placebo condition. NRS 0 represents "no pain at all" whereas 10 represents "the worst pain ever possible".
次要结局
- Area of hyperalgesia and allodynia(During the electrical stimulation (2 hours))
- NRS scores after infusion(After stopping the infusion (65 minutes))
- Association of psychedelic and mystical-type effects with pain scores(During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.)
- Association of the intensity of electrical currents with NRS pain scores(During the electrical stimulation (2 hours))
- Psychometric comparison between DMT, ketamine and placebo(During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.)
- Effect modulation through personality traits(During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.)
- Modulation of personality traits by acute subjective effects(During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.)
- Autonomic effects(During the electrical stimulation (2 hours))
- Association of subjective effect ratings with pain scores(During the electrical stimulation (2 hours))
- Sensory and affective pain scores(Retrospective evaluation after the electrial stimulation at the end of each study session.)
- Plasma levels of DMT and ketamine(During the electrical stimulation (2 hours))