Oral THC and CBD for Substance Use Disorders

(O-TACOFS Trial)

Overseen By Ziva Cooper, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Must not be taking: Illicit drugs, others

Disqualifiers: Substance use disorder, Axis I, others

Compensation: Varies

Number of Visits: 1

Duration: 6 hours

22 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the pharmacokinetics and pharmacodynamics of oral delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and to evaluate detection of recently smoked THC in oral fluid.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that might affect the study outcomes, as current use of such medications is part of the exclusion criteria.

What data supports the effectiveness of the drug for substance use disorders?

Research suggests that cannabidiol (CBD) may help reduce cravings and withdrawal symptoms in substance use disorders, as seen in studies involving crack-cocaine and cannabis use. Additionally, CBD has shown potential in reducing the rewarding effects of addictive drugs like cocaine and methamphetamine, and it has been used successfully in individual cases to reduce illegal drug use and improve mental health symptoms. ^{1 2 3 4 5}

Is oral THC and CBD safe for humans?

CBD is generally considered safe for humans, but it can cause side effects like sleep disturbances, sedation, and anemia, and it may interact with other medications. THC, found in products like Marinol and Syndros, can have psychoactive effects, but specific safety data for THC in substance use disorders is not detailed in the provided research. ^{1 3 6 7 8}

How is the drug CBD unique for treating substance use disorders?

CBD is unique for treating substance use disorders because it lacks the rewarding and addictive properties of other drugs, and it may help reduce withdrawal symptoms and cravings without causing a high. Additionally, CBD has a good safety profile and is being studied for its potential to regulate brain systems involved in addiction, making it a promising option where effective treatments are currently lacking. ^{1 3 5 9 10}

Research Team

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for men and women aged 21-55 who use cannabis weekly or monthly but aren't seeking treatment for it. They must have a BMI of 18.5 - 34kg/m2, be able to do all study tasks, and use contraception. People can't join if they're on meds that affect the study, have significant illnesses, are pregnant or breastfeeding, have respiratory issues, are in another study, don’t use contraception, have severe Cannabis Use Disorder or other substance disorders.

Inclusion Criteria

I have used cannabis once a week or less in the past month.

I can participate in all required study activities.

Have a Body Mass Index from 18.5 - 34kg/m2

Exclusion Criteria

Any other Axis I disorder

I am not taking any medications that could interfere with the study.

I have or had a lung or breathing problem.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral THC and/or CBD or placebo, and undergo pharmacokinetic and pharmacodynamic assessments

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• CBD
• THC

Trial Overview The trial is testing how oral THC (the psychoactive component of cannabis), CBD (a non-psychoactive component), their combination, and a placebo affect individuals. It looks at how these substances move through and act in the body and whether recent smoking can be detected in saliva.

Participant Groups

Group I: 20 mg THC + 20 mg CBD Experimental Treatment 1 Intervention

THC and CBD in sesame and MCT oil

Group II: 20 mg THC Experimental Treatment 1 Intervention

THC suspended in sesame oil

Group III: 20 mg CBD Experimental Treatment 1 Intervention

CBD suspended in MCT oil

Group IV: Placebo Placebo Group 1 Intervention

Oral placebo; sesame and MCT oil

CBD is already approved in United States, European Union, Canada 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

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

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]

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]

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]

A clinical case study of a male patient with schizophrenia and substance use disorders showed that using CBD cigarettes with low THC content (<1%) helped reduce his cravings for high-THC cannabis and led to a cessation of cocaine use.

After 8 years of frequent hospitalizations due to psychotic relapses and substance use, the patient has not been hospitalized since starting the CBD treatment, suggesting that CBD may be a promising adjunctive therapy for cannabis use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder. Meyer, M., Walter, M., Borgwardt, S., et al.[2021]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

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]

High oral doses of cannabidiol (CBD), specifically 300-400 mg per day, have shown efficacy in reducing anxiety and providing anti-addiction effects without increasing adverse effects, based on a review of interventional studies.

Therapeutic benefits of CBD are less clear at lower doses (below 300 mg/day), indicating a need for larger clinical trials to better understand the potential effects of low-dose CBD products, which are widely available as nutraceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. Arnold, JC., McCartney, D., Suraev, A., et al.[2023]

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]

References

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

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

2. Brazil pubmed.ncbi.nlm.nih.gov

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

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Cannabidiol treatment in an adolescent with multiple substance abuse, social anxiety and depression. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

7. 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]

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

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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