Effect of Ketanserin, Olanzapine, and Lorazepam After LSD Administration on the Acute Response to LSD in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Duration of subjective response
研究概览
简要总结
The main objective of this study is to determine whether administration of ketanserin (40 mg), olanzapine (10 mg), and lorazepam (2 mg) after administration of LSD (150 µg) attenuates and shortens the subjective LSD response (any drug effect) compared to administration of LSD (150 µg) alone
详细描述
LSD is investigated as treatment for various psychiatric (e.g., depression and anxiety) but also somatic disorders (e.g., cluster headache). In Switzerland, compassionate use of psychedelics including LSD is possible based on single authorizations of the federal office of public health in treatment-resistant patients. Additionally, current social and political changes demonstrate a shift of how psychedelics are seen and how they might be used in therapy in the future.
Despite the good safety profile of LSD, a broader use might increase the number of adverse psychological reactions to LSD. For such occasions, health professionals should have a tool to not only psychologically but also pharmacologically interfere and end states of acute psychedelic-induced distress. In clinical practice, the gamma-butyric acid (GABA) agonistic acting benzodiazepine lorazepam or the atypical neuroleptic olanzapine with affinity to the 5-HT2A, 5-HT2C and dopamine D1-4 receptors are primarily used for the treatment of drug-induced psychotic symptoms. However, the ability of these drugs to block these effects after LSD intake remains to be investigated.
The primary goal of the present study is therefore to investigate whether ketanserin, olanzapine and lorazepam administration after LSD administration might attenuate and shorten the LSD response compared to administration of LSD alone. Additionally, the present study examines changes in quality of the LSD experience after administration of ketanserin, olanzapine or lorazepam and effects on sensorimotor gating and sleep. The study provides insight into the receptor mechanisms involved in alterations of consciousness and specifically the relevance of ongoing 5-HT2A receptor stimulation in the mediation of the psychedelic response to LSD and psychotic symptoms.
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
- •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 and foods from the evenings prior to the study sessions to the end of the study days, limit coffee drinking ≤ 3 cups per day for 7 days prior to 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 contraceptive measures throughout study participation (according to Clinical Trial Facilitation Group (CTFG): Recommendations related to contraception and pregnancy testing in clinical trials)
- •Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session.
- •Body mass index between 18 - 29 kg/m2
排除标准
- •Chronic or acute medical condition
- •Current or previous major psychiatric disorder including psychotic disorder, mania / hypomania, borderline personality disorders.
- •Psychotic disorder or bipolar disorder in first-degree relatives
- •Known hypersensitivity to LSD, ketanserin, olanzapine or lorazepam
- •Hypertension (>140/90 mmHg) or hypotension (SBP < 85 mmHg)
- •Hallucinogenic substance use (not including cannabis) more than 10 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
- •Current substance use disorder (within the last 2 months)
- •Tobacco smoking (>1 cigarette/day)
- •Consumption of alcoholic beverages (>15 drinks/week)
- •Not exhibiting consistent startle responding on the screening day (i.e., over 75% discernible responses to six 108 dB 40 ms startle pulses), as this would preclude the ability to measure fear potentiated startle.
- •Use of strong CYP2D6 inhibitor
- •Use of strong CYP1A2 inhibitor or inducer
研究组 & 干预措施
LSD + ketanserin
干预措施: LSD (150 µg) + ketanserin (40 mg) (Drug)
LSD+ olanzapine
干预措施: LSD (150 µg) + olanzapine (10 mg) (Drug)
LSD+ lorazepam
干预措施: LSD (150 µg) + lorazepam (2 mg) (Drug)
LSD + placebo
干预措施: LSD (150 µg) + placebo (Drug)
Placebo + placebo
干预措施: Placebo + placebo (Drug)
结局指标
主要结局
Duration of subjective response
时间窗: 18 months
Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. VAS will be presented as 100 mm long horizontal lines marked with: "not at all" on the left and any drug effect", "good drug effect", "bad drug effect", "stimulated", "tiredness", "fear", "nausea", "alteration of vision", "alteration of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously mysterious to me", "opposites dissolve", "talkative", "happy", and "trust". Additionally, "my perception is…" from "muted" to "clear", "I feel …" from "relaxed" to "tense", and "I feel my thoughts are …" from "sluggish" to "racing". Subjects will mark the scale with vertical lines.
Extent of subjective response
时间窗: 18 months
Area under the curve (AUEC), Emax, of the VAS-Item "any drug effect"
次要结局
- Alterations of consciousness(18 months)
- Mystical-type effects(18 months)
- Subjective effects I(18 months)
- Subjective effects II(18 months)
- Subjective effects III(24 hours)
- Psychotomimetic effects I(18 months)
- Psychotomimetic effects II(18 months)
- Effects of LSD on mindfulness and decentering I(36 hours)
- Effects of LSD on mindfulness and decentering II(36 hours)
- Challenging experiences(18 months)
- Effects on prepulse inhibition and sensorimotor gating(18 months)
- Blood pressure(18 months)
- Heart rate(18 months)
- Body temperature(18 months)
- Pupil size(18 months)
- LSD concentrations in the blood(18 months)
- Ketanserin concentrations in the blood(18 months)
- Olanzapine concentrations in the blood(18 months)
- Lorazepam concentrations in the blood(18 months)
- Effects of LSD on sleep phases(11 hours)
- Persisting effects(18 months)
- Adverse effects(18 months)
- Emotional effects(18 months)
- Sleepiness(18 months)
- Effect moderation through personality traits I(18 months)
- Effect moderation through personality traits II(18 months)
- Effect moderation through personality traits III(18 months)
- Effect moderation through personality traits IV(18 months)
- Effect moderation through personality traits V(18 months)