CBD for Opioid Use Disorder

Overseen By Ashanta Carter

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hurd,Yasmin, Ph.D.

Must be taking: Methadone

Disqualifiers: Non-English, Cardiac disease, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

160 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of methadone for at least 14 days before participating.

What data supports the effectiveness of the drug Cannabidiol (CBD) for Opioid Use Disorder?

Preliminary studies suggest that CBD may help reduce cravings and stress-related responses in people with opioid use disorder, potentially supporting its use alongside other treatments. Additionally, CBD has shown promise in reducing cravings for other substances, like cocaine, which may indicate its potential effectiveness for opioid use disorder. ^{1 2 3 4 5}

Is CBD safe for humans?

Research shows that CBD, including its approved form Epidiolex, has a strong safety profile in humans. It does not have abuse potential, does not cause physical dependence, and is generally well-tolerated when used for various conditions. ^{2 3 4 6 7}

How does the drug CBD differ from other treatments for opioid use disorder?

CBD is unique because it is a non-psychoactive component of cannabis that may help reduce the rewarding effects of addictive drugs like opioids, without causing a high or dependence. Unlike traditional treatments, CBD has a low potential for abuse and is being explored for its ability to safely manage substance use disorders. ^{2 3 6 8 9}

Research Team

Yasmin Hurd

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults aged 18-65 with opioid use disorder, currently on methadone maintenance. Participants must have been abstinent from heroin for at least 7 days and cannot be seeking treatment for heroin addiction. They should not have other substance use disorders (except nicotine), be pregnant or breastfeeding, or have certain medical conditions that exclude them from MRI scans.

Inclusion Criteria

Urinary toxicology positive for methadone

I am between 18 and 65 years old.

I have been on methadone treatment of 40mg or more for over 14 days and have take-home doses.

Exclusion Criteria

I am experiencing withdrawal symptoms from opioids.

I am not using any reliable birth control methods.

My kidney function or liver enzymes have never been more than twice the normal limit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive CBD or placebo for 3 daily doses with neuroimaging conducted immediately after the first dose and one week after the last dose

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of adverse events and changes in craving and anxiety

1 week

1 visit (in-person)

Treatment Details

Interventions

• Cannabidiol (CBD)
• Placebo

Trial Overview The study tests the effects of CBD versus a placebo in reducing craving and anxiety in individuals with opioid use disorder on methadone. It involves neuroimaging to observe brain activity after initial and repeated doses of CBD (800mg) over a week.

Participant Groups

Group I: CBD 800mg Experimental Treatment 1 Intervention

Subjects in Arm CBD 800 mg will receive 800mg of Cannabidiol in each of the three test sessions

Group II: Control Placebo Group 1 Intervention

Subjects will receive a harmless, inactive solution to compare and validate the results of the other arms of the study

Cannabidiol (CBD) is already approved in United States, European Union for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Who Is Running the Clinical Trial?

Hurd,Yasmin, Ph.D.

Lead Sponsor

Trials

6

Recruited

320+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

A review of 207 studies identified only 3 randomized clinical trials (RCTs) specifically focused on using cannabidiol (CBD) for cannabis use disorder, highlighting a significant gap in research for CBD's efficacy in treating substance use disorders.

Ongoing trials are enhancing outcome measures by incorporating peripheral biomarkers from the endocannabinoid system, which may help predict how well individuals respond to CBD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. Morel, A., Lebard, P., Dereux, A., et al.[2021]

A study involving healthy volunteers showed that cannabidiol (CBD) can be safely administered alongside high-potency opioids like fentanyl without causing respiratory depression or cardiovascular issues, indicating its potential safety for further research.

The pharmacokinetics of CBD were consistent, with peak plasma concentrations occurring within a few hours after administration, suggesting that CBD does not interfere with the effects of opioids, laying the groundwork for exploring CBD as a treatment for opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Manini, AF., Yiannoulos, G., Bergamaschi, MM., et al.[2018]

Cannabidiol (CBD) has shown promise in preclinical and clinical studies for its ability to inhibit the rewarding effects of addictive substances like cocaine, methamphetamine, and opioids, suggesting its potential as a treatment for substance use disorders.

Despite the encouraging evidence supporting CBD's efficacy in reducing drug addiction behaviors, further research is necessary to fully establish its therapeutic role in addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol and substance use disorder: Dream or reality. Karimi-Haghighi, S., Razavi, Y., Iezzi, D., et al.[2023]

In a trial involving 31 men with crack-cocaine dependence, treatment with 300 mg/day of cannabidiol (CBD) for 10 days did not significantly reduce craving levels compared to a placebo, indicating limited efficacy in managing withdrawal symptoms.

Despite a successful craving induction technique, there were no significant differences in anxiety, depression, or sleep alterations between the CBD and placebo groups, suggesting that CBD may not effectively address these symptoms in crack-cocaine withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of crack-cocaine craving: an exploratory double-blind study. Meneses-Gaya, C., Crippa, JA., Hallak, JE., et al.[2021]

A pilot study involving 10 participants with opioid use disorder (OUD) found that a single dose of 600 mg of cannabidiol (CBD) significantly reduced cue-induced craving and attentional bias towards drug-related cues, suggesting it may help in preventing relapse.

These results indicate that CBD could be a promising adjunctive treatment to medications for OUD, like buprenorphine or methadone, by potentially lowering the brain's response to drug-related triggers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial. Suzuki, J., Prostko, S., Szpak, V., et al.[2023]

Cannabidiol (CBD), specifically in its oral formulation Epidiolex, has been shown to have very low abuse potential and is unlikely to cause physical dependence, as demonstrated by studies in rats and nonhuman primates that showed no significant self-administration or withdrawal signs after chronic treatment.

The pharmacokinetic studies confirmed that the doses used in the experiments resulted in therapeutically relevant plasma levels, supporting the safety and efficacy of CBD for treating seizures in severe forms of epilepsy without the risks associated with addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. Gray, RA., Heal, DJ., Maguire, DR., et al.[2022]

Cannabidiol (CBD) shows promise as a potential treatment for substance use disorders (SUD) due to its ability to regulate the reinforcing and motivational effects of various drugs of abuse, supported by both preclinical and clinical evidence.

CBD has a strong safety profile, lacks reinforcing properties, and is already present in approved medications like Sativex® and Epidiolex®, making it a viable candidate for further research and clinical trials in the management of SUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Cannabidiol in the Therapeutic Intervention for Substance Use Disorders. Navarrete, F., García-Gutiérrez, MS., Gasparyan, A., et al.[2021]

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., et al.[2021]

In a study involving 18 participants, vaporized CBD-dominant cannabis produced the highest blood concentration of CBD (171.1 ng/mL), significantly more than both vaporized CBD (104.6 ng/mL) and oral CBD formulations (13.7 ng/mL).

The study found that CBD alone does not convert to ∆9-THC, as ∆9-THC was only detected in participants using vaporized CBD-dominant cannabis, indicating that CBD-only products are unlikely to result in positive drug tests for THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products. Bergeria, CL., Spindle, TR., Cone, EJ., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Cannabidiol and substance use disorder: Dream or reality. [2023]

4. Brazil pubmed.ncbi.nlm.nih.gov

Cannabidiol for the treatment of crack-cocaine craving: an exploratory double-blind study. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Role of Cannabidiol in the Therapeutic Intervention for Substance Use Disorders. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products. [2023]