A Phase 1, Single-centre, Dose-escalation Study Utilising Both Open-label and Double-blind Placebo-controlled Crossover Design Studies to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Low Doses of Lysergic Acid Diethylamide Ranging From 50 µg to 100 µg in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Tmax (h)
研究概览
简要总结
This study with low-dose LSD comprised 2 substudies in healthy subjects. Subjects who met all inclusion and no exclusion criteria provided written informed consent. Part 1 was an open-label dose-escalation study in hallucinogen non-naïve subjects with significant prior experience with hallucinogens, during which each subject received a single dose of LSD: 50, 75, or 100 µg. Part 2 was a double blind, placebo controlled, randomised, crossover study in hallucinogen naïve subjects with no prior experience with hallucinogens in the last 7 years, during which each subject was assigned to 1 of 8 cohorts and then randomly assigned to receive single doses of LSD 50 µg followed by 75 µg, or placebo followed by 75 µg, with dosing separated by at least 7 days. Subjects were followed up on the day after each dosing, and 1 week and 1 month after the last dose of study treatment. A total of 32 subjects were enrolled.
详细描述
This study with low-dose LSD comprised 2 substudies in different populations of healthy subjects:
Part 1: an open-label dose-escalation study in hallucinogen non-naïve subjects. Part 2: a double blind, placebo controlled, randomised, crossover study in hallucinogen naïve subjects.
Part 1: Open-label, dose escalation study This part was performed in a population of healthy subjects with significant prior experience with hallucinogens. There was a screening period of up to 28 days. Following provision of informed consent and completion of all screening assessments, eligible subjects were assigned to the open-label dose-escalation group.
Following completion of baseline assessments, each subject received a single dose of LSD: 50, 75, or 100 µg. This dose range was selected for assessment based on extensive historical and clinical LSD research. Subjects knew they would receive the experimental drug but were blinded to the dose level received. Subjects were followed up on the day after dosing and at 1 week and 1 month after dosing.
During screening, baseline, treatment, and follow-up, subjects underwent a series of assessments. Included amongst these assessments were cognitive tasks that were administered at baseline before administration of LSD and subsequently during the study. The open-label study subjects also provided samples for PK analysis.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Healthy male or female subject aged 21 to 65 years inclusive.
- •For Part 1, subject has been previously exposed to LSD or any other classic psychedelic drug, including psilocybin, mescaline, and ayahuasca, on more than 3 occasions during their lifetime. For Part 2, Subject has not been previously exposed to LSD or any other classic psychedelic drug, including psilocybin, mescaline, and ayahuasca, during the past 7 years.
- •Subject was able and willing to give written informed consent, adhere to the compliance terms during participation in the study, undergo the examinations and testing set forth in the clinical study protocol, and clearly and reliably communicate their subjective experiences to the investigator.
- •Female participants of childbearing potential and male participants whose partner was of childbearing potential must have been willing to ensure that they or their partner used effective contraception during the study and for 3 months after the final study drug administration.
排除标准
- •A. General Health
- •Subject had a presence or clinically relevant history of any psychiatric, respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as judged by the investigator.
- •Subject had a resting blood pressure exceeding 140 mmHg (systolic) or 90 mmHg (diastolic), averaged across 4 assessments taken at least 1 minute apart on the same day.
- •Subject had a presence or relevant history of organic brain disorders (e.g., intracranial hypertension, aneurisms, impaired consciousness, lethargy, or brain tumour).
- •Subject had a relevant history of atopy, hypersensitivity, skin allergies, or allergic reactions to drugs.
- •Subject had a clinical laboratory test result outside the reference ranges of the testing laboratory and considered clinically significant by the investigator.
- •Subject was positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency (HIV) virus I or II at screening.
- •Subject was a current smoker (i.e., had smoked within 1 month prior to the screening visit).
- •Subject had a medical history that would affect the subject's safety or the study endpoints.
- •Subject had used prescription drugs which might potentially interact with the pharmacokinetics of LSD or therapy within 14 days of first dosing, unless agreed as not clinically relevant by the PI and the Medical Monitor.
- •Subject had used over the counter (OTC) medication or therapy, including megadose vitamin therapy (but excluding routine vitamins) within 7 days of first dosing, unless agreed as not clinically relevant by the PI and the Medical Monitor.
- •Subject had donated or received any blood or blood products within the previous 3 months prior to first dosing.
- •Subject could not use a computer to complete simple tasks such as responding to an email.
- •Subject had used any investigational drug or participated in any clinical trial within 3 months of their first dosing.
- •Subject had a current sleep disorder.
- •Subject had a history of cataracts, active glaucoma or any other ophthalmic condition that could interfere with the eye blink assessment.
- •Subject had veins unsuitable for venepuncture and/or cannulation.
- •Subject had a corrected QT interval using Fridericia's correction >450 milliseconds.
- •Subject was unlikely to cooperate with the requirements of the study, in the opinion of the PI or designee.
- •Subject was pregnant or lactating
- •Exclusion Part 2 only: Subject had a history of drug abuse or dependence in the last 12 months, had current drug abuse or dependence or had a positive result for drugs of abuse and alcohol tests at screening or admission.
- •B. Psychiatric Health
- •Subject had a current or past history of meeting Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria for schizophrenia or other psychotic disorders (unless substance induced or due to a medical condition), bipolar I or II disorder, a major depressive episode, a manic or hypomanic episode, alcohol dependence or abuse (in the past 5 years), substance dependence and abuse (in the past 5 years), current panic disorder, obsessive compulsive disorder, social anxiety disorder, generalised anxiety disorder, anorexia, bulimia or post-traumatic stress disorder
- •Subject had a first- or second-degree relative with schizophrenia, other psychotic disorders (unless substance-induced or due to a medical condition), or bipolar I or II disorder.
- •Subject was receiving chronic administration of tricyclic antidepressants or lithium or acute administration of serotonin reuptake inhibitors, haloperidol, serotonin reuptake inhibitors or monoamine oxidase inhibitors.
- •Subject was taking OTC doses of 5-hydroxytryptophan or St John's Wort or ayahuasca (which contains monoamine oxidase inhibitors in addition to dimethyltryptamine).
研究组 & 干预措施
Group 1 N=3
Single dose, follow-up visits at one day, one week, and one month after dose.
干预措施: Lysergic Acid Diethylamide (LSD) 50µg (Drug)
Group 2 N=7
Single dose, follow-up visits at one day, one week, and one month after dose.
干预措施: Lysergic Acid Diethylamide (LSD) 75µg (Drug)
Group 3 N=3
Single dose, follow-up visits at one day, one week, and one month after dose.
干预措施: Lysergic Acid Diethylamide (LSD) 100µg (Drug)
Group 4 N=10
Randomized treatment with placebo followed by single dose, separated by 7 days. Follow-up visits at one day, one week, and one month after last dose.
干预措施: Placebo/Lysergic Acid Diethylamide (LSD) 75µg (Drug)
Group 5 N=9
Randomized treatment with single dose followed by second dose, separated by 7 days. Follow-up visits at one day, one week, and one month after last dose.
干预措施: Lysergic Acid Diethylamide (LSD) 50µg/75µg (Drug)
结局指标
主要结局
Tmax (h)
时间窗: 24 hours
Tmax (h): time to reach maximum plasma concentration, T1/2 (h): time to reach half of maximum drug plasma concentration
AUC 0-24h ( pg/mL*h) over time
时间窗: 24 hours
AUC 0-24h ( pg/mL\*h): area under the plasma concentration-time curve profiles from time zero to the 24 hour sample determined using the linear trapezoidal rule
Assessment of Adverse Events by % frequency
时间窗: 1 year
Assessment of Adverse Events by % frequency to assess the safety and tolerability of LSD
Cmax (pg/mL)drug
时间窗: 24 hours
Cmax (pg/mL): maximum drug plasma concentration
次要结局
- Assess ego dissolution by the EDI(12 hours)
- Assess subjective drug effects using a VAS.(12 hours)
- Assess the characteristics of altered states of consciousness assessed by the MEQ(12 hours)
- Assess subjective drug effects on the 5D-ASC(12 hours)