Phase 1 Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Safety of Physiological indices
研究概览
简要总结
The goal of this phase 1 study is to investigate the safety and efficacy of dimethyltryptamine (DMT) in individuals with depression and healthy controls. We hypothesize that administration of DMT will result in decreases in depression, associated symptoms, and neuroplastic changes in depressed subjects. We expect that DMT will induce changes in neuroplasticity as indexed using electroencephalographic (EEG) measures and tasks in both depressed individuals and healthy volunteers, though to different degrees. These neuronal changes may in parallel cause changes in mood measured both in healthy and depressed subjects, which will be captured using appropriate psychometric measures of mood.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Some Common Inclusion Criteria:
- •Males and females
- •Age 21 to 65 years
- •Body mass index between 18-35 kg/m2
- •Willing to refrain from taking any medications not approved by the study physician
- •Willing to refrain from using street drugs and alcohol
- •Negative urine drug screen
- •Willing and able to abstain from smoking throughout each test session
- •Women who are of child-bearing potential (WOCBP) and sexually active must be willing to practice an effective means of birth control
- •Willing not to drive to and from the testing session
- •Some Inclusion Criteria for Subjects with MDD:
- •Diagnosed with Major Depressive Disorder (MDD)
- •Unsatisfactory response to antidepressants
- •Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study
- •Not engaged in treatment
- •Consent to allow the research team to communicate with mental health provider.
- •Only subjects who get support for participation in the trial from their mental health clinician will be eligible to be enrolled in the study
- •Some Common
排除标准
- •Medications that might significantly interfere with the effects of the study medications
- •Cognitive dysfunction that could interfere with study participation
- •Alcohol or substance use disorder
- •Any lifetime history of hallucinogen use disorder
- •Regular use or misuse of hallucinogens
- •History of intolerance to perceptual altering drugs
- •Significant blood pressure problems
- •Pregnancy or currently breast feeding (lactation)
- •Any unstable medical conditions
- •Significant cardiovascular disease
- •Significantly abnormal laboratory test results
- •History of serotonin syndrome
- •Some Exclusion criteria for MDD subjects:
- •Current primary psychiatric disorder other than MDD
- •Medically significant condition rendering unsuitability for the study
- •Some Exclusion criteria for healthy controls:
- •No current DSM-V psychiatric disorder, excluding nicotine and caffeine use disorder
- •No family history of serious mental illness (e.g., schizophrenia, bipolar disorder)
- •Some Inclusion criteria for healthy controls:
- •No current DSM-5 psychiatric disorder, excluding nicotine and caffeine use disorder
- •No lifetime use of psychiatric medication >3 months (proxy for psychiatric disorders)
研究组 & 干预措施
0.5 mg over 5 minutes and then 2 mg over and 55 minutes
THC-Medium Dose
干预措施: THC-Medium Dose (Drug)
Placebo
干预措施: DMT-Medium Dose (Drug)
Placebo
干预措施: THC-Medium Dose (Drug)
Placebo
干预措施: DMT-Low Dose (Drug)
Placebo
干预措施: THC-Low Dose (Drug)
0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes
Low Dose THC
干预措施: THC-Low Dose (Drug)
14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.
Medium Dose DMT
干预措施: DMT-Medium Dose (Drug)
10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes
Low dose DMT
干预措施: DMT-Low Dose (Drug)
结局指标
主要结局
Safety of Physiological indices
时间窗: Time Frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration]blood pressure and heart rate will be measured before, during, and after the dosing on each test day.
Pulse oximetry will be measured continuously.
Psychedelic Effects
时间窗: From start Test Day Time points (Minutes): -60, +30, +120.
The 30-item revised Mystical Experience Questionnaire (MEQ30) will be used to measure mystical/psychedelic experiences associated with drugs like psilocybin
Psychotomimetic Effects
时间窗: Test Day Time points (Minutes): -60, +30, +120
To capture the effects of DMT/THC/placebo on perception, thought, and sensory processing, participants will be measured using the Psychotomimetic States Inventory
Anxiety
时间窗: Test Day Time points (Minutes): -60, +30, +120
Will be assessed using a visual analog scale that subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture anxiety.
Depression
时间窗: From start of test day (-60), +30, and +120.
subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the depression.
Intensity of the Experience
时间窗: Test Day Time points (Minutes): +150 - +180
The Challenging Experience Questionnaire (CEQ) a 26 item likert-scale style survey will be used to provide a phenomenological profile specifically of challenging aspects of experiences with psilocybin
Drug Reinforcing Effects
时间窗: Test Day Time points (Minutes): +120
Will be assessed with questions such as: * How likely are you to use this drug recreationally? 0 (not at all) ------------------------100 (most of all) * How much are you willing to pay for the acute effects that you experienced during the dosing session? $0-------------------$100 Shortly after resolution of effects, participants will be instructed to retroactively rate the highest effects experienced since the last time they were prompted to provide a rating.
Tolerability of Overt Adverse Effects
时间窗: Test Day Time points (Minutes): -60, +30, +120, 180 (end of test day)
Tolerability defined by the US FDA as "the degree to which overt adverse effects can be tolerated" by a subject was assessed \[60\]. At the end of the test day, after all drug effects have worn off, participants will be asked to score 1) the overall experience on a visual analog scale \[VAS\] (0 = intolerable to 100 = well-tolerated).
Electrophysiological
时间窗: Resting State EEG: Will be collected the day after each dosing session. [Time Frame: -60 minutes before DMT administration until +180 minutes after DMT administration].
次要结局
- Expectancy Effects(Subjects will be tested for expectancy effects at screening, and before each dosing session.)
- Adequacy of blinding(Time Frame: 0; immediately after DMT administration, and +180 minutes at the end of the study)
- Blood(Blood sample measurements will be repeated approximately 0, 20, 30, and 60 minutes after drug administration)
- Changes in personality domains (NEO personality inventory)([Time Frame: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration])
- Psychological Flexibility(Time Frame: +180 minutes after DMT administration)
研究者
Deepak C. D'Souza
Deepak Cyril D'Souza, MD
Yale University