Vaped Marijuana to Attenuate Naloxone-Precipitated Withdrawal

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05114460
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 6
• Anticipated Duration (Months): 25.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The goal of the proposed, proof-of-concept study is to test the combined effects of vaporized marijuana [Delta-9-tetrahydracannabinol (THC)] with NLX as a proof of concept towards the possible development of a combined overdose reversal agent with improved tolerability.

Condition or Disease	Intervention/Treatment	Phase
Opioid Overdose	Drug: Naloxone; Drug: Marijuana	Phase 2

Detailed Description

The goal of the proposed, proof-of-concept study is to test the combined effects of vaporized marijuana [Delta-9-tetrahydracannabinol (THC)] with NLX as a proof of concept towards the possible development of a combined overdose reversal agent with improved tolerability. Marijuana plant material will be obtained from the National Institutes on Drug Abuse (NIDA). In clinical studies, oral synthetic THC reduced the severity of opioid withdrawal during opioid detoxification. Clinically, cannabinoid drugs like Marinol® (oral synthetic THC), Sativex ® (nabixomols), and Cesamet® (nabilone) are used to treat nausea and vomiting, common symptoms of opioid withdrawal. This study will investigate the ability of vaporized marijuana (V-MJ) (0.00, 12.5, and 25 mg: concentration= 11.7% THC + 0.04% CBD) to reduce the severity of opioid withdrawal precipitated by intranasal (IN) NLX (0.0 and 4.0 mg). This trial will recruit healthy participants with opioid use disorder (N=16, completers). Testing will begin following stabilization on oral morphine (120 mg/day), which will continue throughout the trial. During each testing session, a single V-MJ + naloxone dose combination will be assessed (in randomized order), with 48 hours between testing sessions. Laboratory testing sessions will consist of a modified naloxone challenge procedure, which quantifies the severity of naloxone-precipitated opioid withdrawal.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Ability of Vaped Marijuana to Reduce the Severity of Naloxone-Precipitated Withdrawal
• Actual Study Start Date: Nov 1, 2021
• Anticipated Primary Completion Date: Sep 30, 2023
• Anticipated Study Completion Date: Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Naloxone 0 mg + MJ 0.0 mg Intranasal naloxone in combination with vaped marijuana	Drug: Naloxone; Intranasal Naloxone; Drug: Marijuana; Vaped Marijuana
Active Comparator: Naloxone 0 mg + MJ 12.5 mg Intranasal naloxone in combination with vaped marijuana	Drug: Marijuana; Vaped Marijuana
Active Comparator: Naloxone 0 mg + MJ 25 mg Intranasal naloxone in combination with vaped marijuana (MJ)	Drug: Marijuana; Vaped Marijuana
Active Comparator: Naloxone 4 mg + MJ 0.0 mg Intranasal naloxone in combination with vaped marijuana (MJ)	Drug: Naloxone; Intranasal Naloxone
Experimental: Naloxone 4 mg + MJ 12.5 mg Intranasal naloxone in combination with vaped marijuana (MJ)	Drug: Naloxone; Intranasal Naloxone; Drug: Marijuana; Vaped Marijuana
Experimental: Naloxone 4 mg + MJ 25 mg Intranasal naloxone in combination with vaped marijuana (MJ)	Drug: Naloxone; Intranasal Naloxone; Drug: Marijuana; Vaped Marijuana

Outcome Measures

Primary Outcome Measures

1. Clinical Opiate Withdrawal Scale (COWS) [4-weeks trial]

   Clinical Opiate Withdrawal Scale is an 11-item, clinician-administered measure designed to quantify the severity of opioid withdrawal. The COWS evaluates the severity of the following symptoms on a scale of 0-4 or 5: resting pulse rate, sweating, restlessness, pupil size, bone or joint aches, runny nose or tearing, gastrointestinal upset, tremor, yawning, anxiety, or irritability, and gooseflesh. The score on the COWS ranges from 0 to 48 points with withdrawal ratings between 5-12 considered mild, 13-24 as moderate, 25-36 as moderately severe, and >36 considered severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18-55 years of age.

2. Diagnostic criteria for Opioid Use Disorder (OUD) moderate-severe (304.00) as per DSM-V, including physiological dependence and not currently seeking treatment for OUD.

3. Self-reported opioid use for nontherapeutic purposes; and positive urine drug screen for opioids.

4. Physically healthy.

5. Normal body weight/Within 20% of body weight (for appropriate frame) according to 1983 Metropolitan Weight tables.

6. Able to perform study procedures.

7. Females must be either:

8. Post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile -or

9. Women of childbearing potential must agree to use an acceptable double-barrier method of contraception during screening and study participation.

10. Must smoke < three cannabis cigarettes three times a week (or the vaping equivalent) for the four weeks before screening.

Exclusion Criteria:

1. Seeking treatment for Opioid Use Disorder.

2. Current or history of a psychiatric condition that would affect participants' ability to provide informed consent (e.g., mood disorder with functional impairment or schizophrenia) or make participant hazardous for the participant (e.g., recent suicidal ideation) or staff (e.g., significant history of violence).

3. Current DSM-V diagnosis of substance use disorders requiring medically managed detoxification, other than OUD (e.g., alcohol or benzodiazepine dependence).

4. Medical condition resulting in chronic pain (>3 months).

5. Clinically significant abnormality on physical examination, vital signs, screening laboratory tests, or 12- lead ECG.

6. Significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, or neurologic disorder.

7. Any surgical, or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study drugs.

8. Baseline hypotension, orthostatic hypotension or syncope, hypertension (blood pressure

140/90), pulmonary hypertension or heart disease.

1. Any of the following values for laboratory tests:

2. positive pregnancy test,

3. hemoglobin < 12 g/dL in males and < 11 g/dL in females,

4. neutrophil count < 1.0 × 109/L,

5. platelet count < 75 × 109/L,

6. creatinine clearance < 50 ml/min per modified Cockcroft-Gault equation,

7. aspartate aminotransferase or alanine aminotransferase > 3.0 × upper limit of normal.

8. Hypersensitivity to opioids, history of significant adverse reactions to cannabinoids, and allergy or contraindication to any other drugs administered as a part of this investigation.

9. Use of an investigational agent within 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Jermaine Jones, PhD, New York State Psychiatric Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jermaine Jones, Principal Investigator, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT05114460
• Other Study ID Numbers: 8061
• First Posted: Nov 10, 2021
• Last Update Posted: Dec 2, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Opiate Overdose; Naloxone

Study Results

No Results Posted as of Dec 2, 2021