Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)
研究概览
简要总结
The purpose of the present trial is to test the efficacy of Ayahuasca in treatment-resistant depression. Ayahuasca is a decoction of two plants, long used by Amazonian Amerindians. Traditionally, it is prepared by decoction of a bush (Psychotria viridis) with a liana (Banisteriopsis caapi). P. viridis is a rich source of N,N-dimethyltryptamine (DMT), a serotonergic agonist, and B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A), such as harmine, harmaline. The study is designed as a randomized placebo controlled trial with two parallel arms, and it will also evaluate changes of different biomarkers of depression including anatomical and functional Magnetic Resonance Imaging (MRI), serum levels of BDNF, TNF-a, cortisol, IL-6, and IL-10, polysomnography, neuropsychological, psychiatric scales and questionnaires.
详细描述
- Background
The therapeutic effectiveness of currently available antidepressant is low. Less than 50% of the patients achieve remission after single treatment, and about 30% after four different treatments. Besides low response rates, pharmacological treatment are associated with several side effects and response onset is usually long (~2-3 weeks). Thus, great effort has been made to the development of alternative antidepressants. For instance, ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and potent antidepressant effects in treatment of major depressive and bipolar disorders.
This proposal aims at testing the antidepressant effects of Ayahuasca, traditionally prepared by decoction of two plants: Psychotria viridis and Banisteriopsis caapi, long used by Amazonian Amerindians. P. viridis is a rich source of the serotonergic agonist N,N-dimethyltryptamine (DMT), whereas B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A) such as harmine, harmaline, and tetrahydroharmine, a serotonin reuptake inhibitor.
Common effects of Ayahuasca include sedation, gastrointestinal distress, changes of spatiotemporal scaling, dissociation, sense of well-being, insights, feelings of apprehension, increased interoceptive attention and sensory pseudo-hallucinations. Effects begin at 30-40 min after oral intake, and last up to 4 hours. Previous studies suggest the absence of psychological, neuropsychological or psychiatric harm caused by prolonged Ayahuasca consumption, and it is not addictive, on the contrary, it also shows promise in treating addiction.
Recently, two preliminary open label studies have tested tolerability, safety and the antidepressant effect of Ayahuasca in treatment-resistant depression. In the first study, six patients were recruited, in the second, 17 patients. The results show significant decrease in depression severity (HAM-D & MADRS scales) already at 2 hours after intake, which lasted for 21 days. Although the results are promising, they must be considered with caution, specially due to the lack of control of the placebo effect, which is generally high in clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 18-60 years old;
- •Diagnostic of major depressive disorder (DSM-IV);
- •At least two previous unsuccessful antidepressant medications;
- •Current depressive episode (HAM-D >= 17).
排除标准
- •History of psychosis;
- •Present or past history of bipolar disorder or schizophrenia;
- •Diagnosis of current clinical disease, based on history, physical examination and routine hematologic and biochemical tests;
- •Serious and imminent suicidal risk;
- •Pregnancy, current drug or alcohol dependence;
- •Previous experience with ayahuasca.
研究组 & 干预措施
placebo
patients receiving a passive placebo
干预措施: placebo (Drug)
Ayahuasca
patients receiving Ayahuasca
干预措施: Ayahuasca (Drug)
结局指标
主要结局
Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)
时间窗: seven days after dosing
changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing. Minimum and maximum scores are 0 and 50, respectively. Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2. Lower HAM-D score indicates less severe depression (better outcome). Usual cutoff points are a total score ranging from: 0 to 7 indicates that the patient is in the normal range (no depression); 8 to 16 indicates "mild depression"; 17 to 23 indicates "moderate depression"; a score of 24 and greater indicates "severe depression".
次要结局
- Number of Participants With a Score Lower Then or Equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at D7(seven days after dosing)
- Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7(one, two and seven days after dosing)
- Number of Participants With Reduction of 50% or More in Hamilton Depression Rating Scale(HAM-D) Scores at D7(seven days after dosing)
- Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7(one, two, and seven days after dosing)
- Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7(one, two and seven days after dosing)
研究者
Draulio Barros de Araujo
Professor
Universidade Federal do Rio Grande do Norte