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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the body processes and responds to oral forms of THC (Tetrahydrocannabinol) and CBD (Cannabidiol), compounds found in cannabis, to understand potential treatments for substance use disorders. Participants will receive either a placebo or various combinations of THC and CBD to observe their effects on the body and detect any recent cannabis use. Suitable candidates have used cannabis casually (once a week or less) in the past month and are not seeking treatment to stop using it. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that THC, known for alleviating nausea in chemotherapy patients, carries some risks. It can be misused or lead to dependence, causing people to feel the need to take it unnecessarily. THC is already approved for certain medical uses, providing some available safety information.

Research has shown that CBD is generally safe but can cause side effects like drowsiness, tiredness, and an upset stomach. In one study, about 79% of participants reported some side effects, though most were mild.

When used together, THC and CBD appear to have a safety profile similar to when used separately, with no major new risks. However, the combination might help reduce cravings for those trying to quit cannabis.

Overall, despite some side effects, THC and CBD are generally well-tolerated. This trial is in an early phase, focusing primarily on identifying any safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using THC and CBD for treating substance use disorders because these compounds offer a novel approach compared to traditional treatments like behavioral therapies and medications such as methadone or buprenorphine. Unlike standard options, THC and CBD are derived from cannabis and may work by interacting with the body's endocannabinoid system, which plays a role in regulating mood and addiction responses. This trial is particularly intriguing because it explores different combinations: THC alone, CBD alone, and a mixture of both, potentially offering various pathways to reduce cravings and withdrawal symptoms. Additionally, their oral administration is straightforward, which could improve patient compliance and accessibility.

What evidence suggests that this trial's treatments could be effective for substance use disorders?

Research has shown that THC and CBD might help alleviate symptoms related to substance use disorders. In this trial, some participants may receive THC, which could reduce withdrawal symptoms and cravings. Another group will receive CBD, which alone might not effectively treat these disorders but could help with conditions like anxiety. Additionally, some participants will receive a combination of THC and CBD, which has shown positive effects on reducing withdrawal and cravings in people with cannabis use disorder. Although more research is needed, these findings offer hope for their effectiveness in this area. ^{6 7 8 9 10}

Who Is on the Research Team?

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

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Efficacy of cannabidiol alone or in combination with Δ‐9‐ ... Conclusion. Cannabidiol (CBD) monotherapy does not appear to be efficacious for treatment of substance use disorders. CBD primarily exhibits ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306460322001265

Cannabidiol in the context of substance use disorder ... The current systematic review suggests that CBD might offer promising therapeutic potential for the treatment of SUD, based on available animal and human ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7937926/

Clinical Trials of Cannabidiol for Substance Use Disorders There is no published study demonstrating the efficacy of CBD alone to treat any substance use disorder. When choosing stringent inclusion ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772724624000738

Prevalence of cannabidiol use and correlates in U.S. adults CBD appears to be more promising for psychiatric conditions. Meta-analyses found that CBD can ameliorate anxiety, psychosis, substance use disorders, and ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00063/full

Cannabidiol Drugs Clinical Trial Outcomes and Adverse ... The patients in the treatment group reported significant reduction in the number of seizures, with over 90% of patients reporting at least a 25% ...

6. library.samhsa.gov library.samhsa.gov/sites/default/files/pep22-06-04-003.pdf

Cannabidiol (CBD) – Potential Harms, Side Effects, and ... Potential risks and harms associated with CBD use include adverse drug interactions, liver toxicity, and reproductive and developmental effects. ○ Delta-9 THC ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7052834/

Cannabidiol Adverse Effects and Toxicity - PMC Of the 162 patients in the safety and tolerability analysis, 79% reported AEs, 25% somnolence, 11% convulsions, and more than 5% reported somnolence, fatigue, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

EPIDIOLEX (cannabidiol) oral solution - accessdata.fda.gov Risk Summary. There are no adequate data on the developmental risks associated with the use of EPIDIOLEX in pregnant women. Administration of cannabidiol to ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201823003854

Adverse events of epidiolex: A real-world drug safety ... Epidiolex mainly includes drowsiness, reduced appetite, diarrhea, increased transaminases, fatigue, rash, sleep disorders, and infections.

10. epidiolexhcp.com epidiolexhcp.com/resources/frequently-asked-questions

Frequently Asked Questions | EPIDIOLEX® (cannabidiol) Are there long-term safety data for patients using EPIDIOLEX? · 683 patients treated for more than 1 year · 155 patients treated for more than 2 years.