Evaluation of the Effects of Cannabidiol (CBD) Compared to Delta-9-Tetrahydrocannabinol (THC) and Alprazolam

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the abuse potential of CBD to determine whether it should remain as a Schedule I drug under the Controlled Substances Act, or be recommended for decontrol.

Detailed Description
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This is a single-dose, randomized, double-blind, placebo- and active-controlled crossover study that evaluates CBD in comparison with THC, alprazolam, and placebo in healthy recreational drug users.

Official Title
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A Human Abuse Potential Study to Evaluate the Subjective and Physiological Effects of Cannabidiol (CBD) Compared to Delta-9-Tetrahydrocannabinol (THC) and Alprazolam in an Inpatient Setting

Conditions
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Cannabis Use Disorder

Intervention / Treatment
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* Drug: THC
* Drug: Alprazolam
* Drug: Placebo oral capsule
* Drug: CBD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures. Male or female subjects 18 to 55 years of age, inclusive. Body mass index (BMI) within the range of 19.0 to 30.0 kg/m2, inclusive, and a minimum weight of at least 50.0 kg. Healthy, as determined by no clinically significant medical history, physical examination, 12-lead ECG, vital signs or laboratory (including hematology, clinical chemistry biochemistry, urinalysis, and serology) findings at Screening, as judged by the investigator. Must be a recreational drug user, defined as meeting all of the following criteria: ≥10 lifetime non-therapeutic experiences (i.e., for psychoactive effects) with CNS depressants (e.g., benzodiazepines, barbiturates, zolpidem, eszopiclone, propofol/fospropofol, gamma-hydroxy-butyrate). ≥10 lifetime non-therapeutic experiences with cannabinoids (e.g., cannabis, hashish, THC, nabilone). At least 3 non-therapeutic uses of a sedative, and at least 3 non-therapeutic uses of a cannabinoid, within the 3 months prior to Screening. Must pass Qualification Phase eligibility criteria. Female subjects of childbearing potential who are not abstinent must be using and willing to continue using medically acceptable contraception throughout the trial and for 30 days after last dose. In the context of this trial, highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include hormonal contraceptives, intrauterine devices/hormone-releasing systems, double-barrier methods, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. Abstinence is only acceptable as true (total) abstinence, when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Non-vasectomized male subjects must agree to a highly effective method of contraception with female partner(s) of childbearing potential and may not donate sperm throughout the trial and for 90 days after the last study drug administration. Able to speak, read, and understand English sufficiently to allow completion of all study assessments. Must be willing and able to abide by all study requirements and restrictions. Exclusion Criteria: contact site directly for more information

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CBD (500 mg)<br>CBD (500 mg) capsule by mouth one time during the 18 day treatment period | Drug: THC<br>* THC capsule<br>Drug: Alprazolam<br>* Alpraxolam capsule<br>* Other names: Xanax;Drug: Placebo oral capsule<br>* Sugar pill capsule<br>* Other names: Placebo;|
| Active Comparator: CBD (1000 mg)<br>CBD (1000 mg) capsule by mouth one time during the 18 day treatment period | Drug: THC<br>* THC capsule<br>Drug: Alprazolam<br>* Alpraxolam capsule<br>* Other names: Xanax;Drug: Placebo oral capsule<br>* Sugar pill capsule<br>* Other names: Placebo;|
| Active Comparator: THC (2.5 mg)<br>THC 2.5 mg capsule by mouth one time during the 18 day treatment period | Drug: Alprazolam<br>* Alpraxolam capsule<br>* Other names: Xanax;Drug: Placebo oral capsule<br>* Sugar pill capsule<br>* Other names: Placebo;Drug: CBD<br>* CBD capsule<br>|
| Active Comparator: THC (30 mg)<br>THC 30 mg capsule by mouth one time during the 18 day treatment period | Drug: Alprazolam<br>* Alpraxolam capsule<br>* Other names: Xanax;Drug: Placebo oral capsule<br>* Sugar pill capsule<br>* Other names: Placebo;Drug: CBD<br>* CBD capsule<br>|
| Active Comparator: Alprazolam<br>Alpraxolam 1.5 mg capsule by mouth one time during the 18 day treatment period | Drug: THC<br>* THC capsule<br>Drug: Placebo oral capsule<br>* Sugar pill capsule<br>* Other names: Placebo;Drug: CBD<br>* CBD capsule<br>|
| Placebo Comparator: Placebo Oral Capsule<br>Placebo capsule by mouth one time during the 18 day treatment period | Drug: THC<br>* THC capsule<br>Drug: Alprazolam<br>* Alpraxolam capsule<br>* Other names: Xanax;Drug: CBD<br>* CBD capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale | Subjects will complete 13 scales. Each Visual Analog Scale is a self-administered assessment evaluating the subjective effects of a study agent. Subjects will be instructed to respond to the questions with regards to how they feel at that moment of the assessment on a 100 mm Likert Scale with 0 being Not at all and 100 being Very or Extremely. All scales are unipolar or bipolar. | 18 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Increased Vital Signs | Number of participants with adverse events as assessed by vital signs | 25 days | 
| Incidence of Increased ECG Reading | Number of participants with adverse events as assessed by ECG | 25 days | 
| Incidence of Clinically Significant Laboratory Values | Number of participants with adverse events as assessed by laboratory changes | 25 days |