Clinical trial NCT04567784: Neuroimaging and CBD for Opiod Use Disorder
Official title: Neuroimaging and CBD for Opiod Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heroin Abuse
Opioid Use Disorder
Substance-Related Disorders
Opioid-Related Disorders
Keywords: Heroin
Opioid
Narcotics
Central Nervous System Depressants
Analgesics
Functional neuroimaging
Magnetic resonance spectroscopy
Lead sponsor: Hurd,Yasmin, Ph.D.
Sponsor class: INDIV
Collaborators: name: Jazz Pharmaceuticals
First posted: 2020-09-29
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized clinical trial in which subjects will receive either placebo or 800mg cannabidiol (CBD).
Primary purpose: TREATMENT

Brief summary: The investigators propose an imaging study to investigate the neurobiological effects of CBD (vs placebo) in participants with opioid use disorder who are maintained on methadone. The purpose of the study is to determine the neural circuits and transmitters associated with the effects of CBD on to reduce craving and anxiety. The neuroimaging will be conducted in participants immediately following their first administration of CBD (800mg or placebo) and one week after the last administration (3 daily doses). This CBD administration protocol was shown in previous studies by the investigators to reduce craving and anxiety in abstinent heroin users.

Detailed description: This study will first use multimodal imaging in individuals with opiod use disorder who are maintained on methadone to determine the neural circuits associated with the effects of CBD on craving and anxiety. Secondly, the investigators will conduct 1H MRS to characterize in-vivo neurochemical levels associated with CBD administration. Altogether, the data obtained will fill critical gaps of knowledge important in the development of a potential non-opioid medication for treating opioid use disorder.

CBD has been shown to be safe in association with opioid use and not to have severe side effects. The oral CBD solution (Epidiolex) to be used in the current study is approved by the FDA for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients 2 years of age and older. Our study will investigate the neurobiological effects of CBD which is critical for its development as a potential treatment for opioid use disorder in the future. Study participation duration will last 2 weeks and will include multimodal imaging techniques to examine neural connectivity, neural activity and glutamate (and other neurometabolites) levels in relation to the impact on cue-induced responses in OUD subjects. The imagining sessions will include CBD/placebo administration; Magnetic Resonance Imaging (MRI) during task and resting-state functional MRI (rs-fMRI) and Magnetic Resonance spectroscopy (MRS); and questionnaires measuring craving, anxiety, depression, elements of cognitive function, and psychiatric history.

Screening: Study candidates will be recruited through flyers, ads and referrals from AIMS clinics. At the initial phone contact candidates will be screened for exclusion criteria and provided study information and, if they remain interested and no exclusion criteria are encountered, invited for in-person screening. Candidates will then undergo the informed consent procedure, be fully screened for eligibility and complete baseline assessments.

Randomization: Participants will be randomly assigned to either CBD or Placebo condition.

Eligibility criteria: Inclusion Criteria:

1. Individuals between 18 and 65 years old.
2. Current methadone maintenance in an opioid treatment program with a dose of =/\>40mg for at least 14 days prior to participation and prescribed take-home methadone medication.
3. Current opioid use disorder (OUD) or OUD in remission while on maintenance therapy with opioid agonist therapy (OAT), as determined by DSM-5 with the M.I.N.I. interview (Mini-International Neuropsychiatric Interview).
4. Urinary toxicology positive for methadone.

Exclusion Criteria:

1. Non-English speaking.
2. Court mandate to treatment.
3. Participation in another pharmacotherapeutic trial in the past 3 months.
4. Poor physical health (as determined by medical screen) that would make study participation unsafe, or would prevent adherence to study procedures, including a history of cardiac disease, arrhythmias, head trauma, and seizures.
5. Psychiatric conditions under DSM-5 (examined with the MINI) that would make study participation unsafe or which would prevent adherence to study procedure; examples include: suicidal or homicidal ideation requiring immediate attention, or inadequately-treated mental health disorder (e.g. active psychosis or uncontrolled bipolar disorder).
6. History of impaired renal function or elevated liver enzymes \>2x the normal at prescreening.
7. QTc Frederica \>500ms.
8. Current pregnancy \[determined by positive urine test\] or breastfeeding.
9. Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm).
10. Medical or psychiatric contraindications for MRI (metal implants, stents, etc).
11. Medical or psychiatric contraindications for CBD administration (e.g., history of hypersensitivity to cannabinoids).
12. Current diagnosis of a moderate or severe substance use disorder (except for opioids and nicotine) in the past 3 months, based on DSM-5.
13. Acute drug intoxication as determined by clinician assessment.
14. Acute opioids withdrawal symptoms (observational and determined by the Clinical Opiate Withdrawal Scale (COWS). A Score of ≥#5 will be considered a positive result for withdrawal symptoms and/or by clinical judgment.
15. Breathalyzer/Alcohol salivary/urine strips positive for alcohol.

Primary outcomes:
measure: CBD effects on in vivo glutamatergic levels within mesocorticolimbic brain regions
timeFrame: 2 MRI Scans (duration 30 mins)
measure: Change in fMRI BOLD signal during cue reactivity
timeFrame: 2 MRI Scans (duration 15 mins)
measure: Change in fMRI BOLD signal acquired during resting-state functional connectivity
timeFrame: 2 MRI Scans (duration 10 mins)
Secondary outcomes:
measure: Change in cue-induced drug craving on the VAS
timeFrame: 1 week post-intervention
measure: Change in cue-induced anxiety on the VAS
timeFrame: 1 week post-intervention
measure: Systolic and diastolic blood pressure (in mmHg)
timeFrame: 2 hours post-dose
measure: Heart rate (in beats/min)
timeFrame: 2 hours post-dose
Other outcomes:
measure: Adverse Events as assessed by the SAFTEE
timeFrame: post-intervention, approximately 1 week
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Yasmin Hurd, PhD
role: PRINCIPAL_INVESTIGATOR
References: