Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CB1 Antagonist ANEB-001 in a THC Challenge Test

A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of CB1 Antagonist ANEB-001 in Healthy Occasional Cannabis Users in a THC Challenge Test.

The aim of this study is to investigate whether ANEB-001 effectively penetrates the brain and inhibits the psychotropic effects of Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. This randomized, placebo-controlled, double-blind study is designed as a proof-of-pharmacology and dose finding study for the antagonistic effect of ANEB-001 during a THC challenge. Results of this study will inform the future potential use of ANEB-001 as an emergency treatment for acute cannabinoid intoxication.

Study Overview

• Status: Completed
• Conditions: Acute Cannabinoid Intoxication
• Intervention / Treatment: Drug: Placebo; Drug: ANEB-001

Detailed Description

This study will evaluate whether ANEB-001 effectively inhibits the psychotropic effects of Δ9-Tetrahydrocannabinol (THC). All cohorts in part A and B of the study will be randomized, double-blind and placebo-controlled. Randomization is deemed appropriate to avoid selection bias for active compound or placebo treatment. A double-blind and placebo-controlled design is deemed appropriate because of the safety, tolerability and pharmacodynamic assessments that will be performed in this study. By double-blinding the study, bias arising from study subject's or investigator's knowledge about treatment assignment is avoided. Part C does not include a placebo group and will therefore not be blinded.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • ZH
    • Leiden, ZH, Netherlands, 2333
      • Centre for Human Drug Research (CHDR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure
• BMI between 18 and 30 kg/m2
• Minimum weight 50 kg
• Occasional cannabis user

Exclusion Criteria:

• Evidence of active or chronic condition that could interfere with, or 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
• Clinically significant abnormalities, as judged by the investigator
• Positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody at screening
• Systolic blood pressure greater than 130 or less than 90 mm Hg and diastolic blood pressure greater than 95 or less than 50 mm Hg at screening Abnormal findings in the resting electrocardiogram
• Use of any medications within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). Exceptions are paracetamol and ibuprofen and topical medications.
• Use of any vitamin, mineral, herbal and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer)
• Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study)
• History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent other than recreative use of THC
• Positive test for drugs of abuse (other than THC) at screening.
• Positive test for drugs of abuse pre-dose
• Clinically significant suicidal ideation in the past 5 years as judged by the investigator or any life-time suicide attempts
• History of cannabis-induced psychosis, schizophrenia or other clinically relevant psychiatric disorders, as judged by the investigator.
• History of a clinically significant mood disorder, including but not limited to major depressive disorder, as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B - Cohort 1 - ANEB-001; Subjects receive 21 mg of THC and 30 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Experimental: Part B - Cohort 2 - ANEB-001; Subjects receive 21 mg of THC and 10 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Experimental: Part A - ANEB-001; Subjects receive THC and varying amounts of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part A - Placebo; Subjects receive THC and placebo	Drug: Placebo; Placebo comparator
Placebo Comparator: Part B - Cohort 1 - Placebo; Subjects receive 21 mg of THC and placebo	Drug: Placebo; Placebo comparator
Placebo Comparator: Part B - Cohort 2 - Placebo; Subjects receive 21 mg of THC and placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 3 - ANEB-001; Subjects receive 21 mg of THC and 1 hour later, 30 mg ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 3 - Placebo; Subjects receive 21 mg THC and 1 hour later, placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 4 - ANEB-001; Subjects receive 40 mg of THC and 1 hour later, 10 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 4 - Placebo; Subjects receive 40 mg of THC and 1 hour later, placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 5 - ANEB-001; Subjects receive 30 mg of THC and 1 hour later, 10 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 5 - Placebo; Subjects receive 30 mg of THC and 1 hour later, 10 mg of ANEB-001	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 6 - ANEB-001; Subjects will consume a high fat meal prior to receiving 30 mg of THC and 1 hour later, 10 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 6 - Placebo; Subjects will consume a high fat meal prior to receiving 30 mg of THC and 1 hour later, placebo	Drug: Placebo; Placebo comparator
Experimental: Part C - Cohort 7 - ANEB-001; Subjects receive a 40 mg dose of THC and a 10 mg dose of ANEB-001	Drug: ANEB-001; Experimental Treatment
Experimental: Part C - Cohort 8 - ANEB-001; Subjects receive a 60 mg dose of THC and a 20 mg dose of ANEB-001	Drug: ANEB-001; Experimental Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Heart Rate in beats/min	Day 1
Subjective Feeling High	Feeling High on a visual analog scale (mm)	Day 1
Postural stability	Body sway (mm);	Day 1
Subjective Alertness	Alertness on a visual analog scale (mm)	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeling of Drug Effect	Feeling of drug effect on a visual analog scale (mm)	Day 1
Subjective Mood	Mood on a visual analog scale (mm)	Day 1
Subjective Calmness	Calmness on a visual analog scale (mm)	Day 1
Symbol Digit Substitution Test (SDST)	Part C Only	Day 1
Visual Verbal Learning Test (VVLT)	Part C Only	Day 1
Timed Up-and-Go test (TUG)	Part C Only	Day 1
Alternate Finger Tapping (AFT)	Part C Only	Day 1
Basic Symptom Inventory (BSI)	Part C Only	Day 1
Brief Psychiatric Rating Scale (BPRS)	Part C Only	Day 1
Clinical Global Impression of Severity (CGIS)	Part C Only	Day 1

Collaborators and Investigators

• Sponsor: Anebulo Pharmaceuticals
• Investigators: Principal Investigator: GJ Groeneveld, MD, PhD, CHDR

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Actual): August 26, 2023
• Study Completion (Actual): August 26, 2023

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: AN01AC11

Drug and device information, study documents

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