Evaluation of Cannabidiol on Central Nervous System Function and Cortical Excitability in Healthy Males: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
- Trial ID
- 2023-508311-23-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effects of a single oral dose of 30 mg and 700 mg of **cannabidiol** compared to placebo on central nervous system (CNS) tasks, as measured by the NeuroCart test battery. Additionally, the study aims to assess the impact of these doses on cortical excitability using single and paired pulse transcranial magnetic stimulation-electromyography (TMS-EMG) and TMS-electroencephalography (TMS-EEG). These assessments are clinically relevant as they provide insights into the potential neuromodulatory effects of cannabidiol, which could inform its therapeutic applications in neurological conditions.
Secondary objectives include:
- Assessing the pharmacokinetics (PK) of a single oral dose of 30 mg and 700 mg cannabidiol in healthy subjects within the first 8 hours post-administration.
- Evaluating the safety and tolerability of these doses of cannabidiol.
Participants
The sponsor has not provided information regarding the total number of participants in this clinical trial. The study population consists of **healthy male subjects** aged between 18 and 55 years, with a **body mass index (BMI)** ranging from 18 to 30 kg/m² and a minimum weight of 50 kg. Participants are required to practice effective contraception during the study and for at least 90 days following their last dose of the study treatment. The trial excludes female subjects and does not involve a vulnerable population. Participants must be able to communicate effectively in Dutch and comply with study restrictions. The trial focuses on assessing the effects of cannabidiol on neurological assessments, specifically targeting central nervous system tasks and excitability using TMS-EMG and TMS-EEG methodologies.
Plans and Procedures
The clinical trial is designed as an **explorative, randomized, double-blind, placebo-controlled, 3-way cross-over study**. The primary objective is to assess the effects of a single oral dose of 30 mg and 700 mg of **cannabidiol** compared to placebo on central nervous system (CNS) tasks using the NeuroCart test battery and transcranial magnetic stimulation (TMS). The trial will involve healthy male subjects aged 18 to 55 years, with a body mass index (BMI) between 18 and 30 kg/m². The study is expected to commence on November 20, 2023, and conclude by March 6, 2024, with a maximum treatment period of 12 weeks.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as informed consent and health status. The trial will include multiple dosing visits where subjects will receive either the active treatment or placebo in a cross-over manner. Each dosing visit will be followed by assessments of primary endpoints, including saccadic and smooth pursuit eye movements, adaptive tracking, and working memory load, among others. Secondary endpoints will include pharmacokinetic parameters of cannabidiol, treatment-emergent adverse events, and vital signs monitoring.
The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or adverse events that compromise participant safety. The end-of-study visit will involve final assessments and debriefing. Throughout the study, effective contraception is required, and participants must be willing to comply with study restrictions and communicate effectively in Dutch. The trial is categorized as a Phase 4 therapeutic exploratory study, focusing on neurological assessments.
Treatment
The clinical trial involves the administration of **Clinican CBD 10% oil flavored**, which is an experimental medication containing the active substance **cannabidiol**. This pharmaceutical product is formulated as a **solution in oil** and is intended for **oral use**. The trial protocol specifies two dosage levels: a single oral dose of 30 mg and a higher dose of 700 mg. The maximum daily dose is set at 700 mg, with a total maximum dose of 730 mg over the course of the study. The treatment period is limited to 12 days. The administration of the medication is monitored to ensure participant compliance, and the effects are assessed using the NeuroCart test battery and transcranial magnetic stimulation (TMS) techniques.
In addition to the experimental treatment, a **placebo** is used as a comparator in this randomized, double-blind, placebo-controlled study. The placebo is designed to match the experimental medication in appearance and administration route, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach is critical for maintaining the integrity of the study and for accurately assessing the effects of cannabidiol on central nervous system (CNS) and cortical excitability.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the effects of **cannabidiol** on central nervous system (CNS) tasks and cortical excitability. The primary endpoints include measurements of saccadic and smooth pursuit eye movements, adaptive tracking, N-Back working memory load, and Visual Analog Scales (VAS) such as Bond and Lader and Bowdle. Additionally, the Visual Verbal Learning Test (VVLT) will be used for memory testing. Changes from baseline in motor evoked potential (MEP) and TMS evoked potential (TEP) will be measured using single and paired pulse transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of 2, 15, and 100 milliseconds. Body sway will also be assessed as part of the primary endpoints.
Secondary endpoints will focus on pharmacokinetic (PK) parameters of cannabidiol, analyzed through non-compartmental analysis of plasma concentration-time data. The study will also monitor treatment-emergent serious adverse events (SAEs) and concomitant medication throughout the study at every visit. Vital signs, including pulse rate, systolic blood pressure, and diastolic blood pressure, will be recorded according to the assessment schedule. These efficacy parameters will be collected and analyzed at specified timepoints to determine the impact of cannabidiol compared to placebo in healthy male subjects.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent prior to any study-mandated procedure.
- Healthy male subjects, 18 up and to 55 years of age, inclusive at screening.
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.
- All subjects must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment.
- Has the ability to communicate well with the investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion Criteria
- Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
- Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
- History or presence of conditions which, in the judgment of the investigator, might increase the risk of performing TMS, including but not limited to epilepsy or febrile seizures, intracranial mass lesion, hydrocephalus, clinically significant head injury or trauma, metal objects in the brain or skull, cochlear implant or a deep brain stimulation device.
- Any condition that could interfere with the quality or ability to perform TMS, such as an abnormal sleeping pattern (e.g., working night shifts), dreadlocks or hairpieces that cannot be removed or a rMT of more than 75% of the maximum stimulator output as measured using TMS-EMG during screening.
- Female subjects are excluded because the menstrual cycle can influence TMS-EMG and TMS-EEG measures.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 20 Nov 2023 | — |
| Netherlands | — | — | 24 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Amygdalae Oleum
Raffinatum | Placebo | N/A | — | — | — | N/A |
Clinican CBD 10% oil flavored | Test | SOLUTION IN OIL | ORAL USE | 700 | 12 | PRD10836781 |