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

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

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.

Study Overview

• Status: Completed
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: THC; Drug: Alprazolam; Drug: Placebo oral capsule; Drug: CBD

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Debra Kelsh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Debra Kelsh, MD, Vince and Associates Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): May 30, 2018

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: January 11, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: NIDA-CBD-Phase1-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No