Opioid Overdose
Conditions
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.
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.
Interventions
DRUGNaloxone
Intranasal Naloxone
DRUGMarijuana
Vaped Marijuana
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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: 1. Post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile -or 2. Women of childbearing potential must agree to use an acceptable double-barrier method of contraception during screening and study participation. 8. 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. 9. Any of the following values for laboratory tests: 1. positive pregnancy test, 2. hemoglobin \< 12 g/dL in males and \< 11 g/dL in females, 3. neutrophil count \< 1.0 × 109/L, 4. platelet count \< 75 × 109/L, 5. creatinine clearance \< 50 ml/min per modified Cockcroft-Gault equation, 6. aspartate aminotransferase or alanine aminotransferase \> 3.0 × upper limit of normal. 10. 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. 11. Use of an investigational agent within 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Opiate Withdrawal Scale (COWS) | 4-week trial: Peak COWS score throughout the testing session for each dose combination. | 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. |
Countries
United States
Participant flow
Recruitment details
2 participants were enrolled however, 1 participant withdrew from the study prior to completing any of the testing sessions (i.e., periods).
Pre-assignment details
After enrollment/admission and prior to testing participants were transition from illicit opioids onto a stable daily dose of a prescription opioid.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Two participants were enrolled in the within-subjects trial. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 39 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Clinical Opiate Withdrawal Scale (COWS)
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.
Time frame: 4-week trial: Peak COWS score throughout the testing session for each dose combination.
Population: Data are only available from 1 participant and the other participant enrolled did not complete any testing sessions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naloxone 0 mg + MJ 0.0 mg | Clinical Opiate Withdrawal Scale (COWS) | 2 units on a scale |
| Naloxone 0 mg + MJ 12.5 mg | Clinical Opiate Withdrawal Scale (COWS) | 2 units on a scale |
| Naloxone 0 mg + MJ 25 mg | Clinical Opiate Withdrawal Scale (COWS) | 4 units on a scale |
| Naloxone 4 mg + MJ 0.0 mg | Clinical Opiate Withdrawal Scale (COWS) | 27 units on a scale |
| Naloxone 4 mg + MJ 12.5 mg | Clinical Opiate Withdrawal Scale (COWS) | 21 units on a scale |
| Naloxone 4 mg + MJ 25 mg | Clinical Opiate Withdrawal Scale (COWS) | 20 units on a scale |