THC for Cannabis Use

(RiDE-2 Trial)

Overseen By Natania Crane, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Illinois at Chicago

Must not be taking: THC-interacting drugs

Disqualifiers: Severe mental illness, Heavy nicotine, Pregnancy, others

Compensation: Varies

Number of Visits: 3

Duration: 2 visits

144 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medication that could interact with a single dose of Δ9-THC.

What data supports the effectiveness of the drug THC for cannabis use?

THC, a major component of cannabis, is used in FDA-approved drugs like nabiximols to help with pain and muscle stiffness in multiple sclerosis, and dronabinol for nausea in cancer patients and appetite loss in AIDS patients. This suggests THC can have therapeutic effects, although its use is limited by its mind-altering properties. ^{1 2 3 4 5}

Is THC generally safe for human use?

Cannabis sativa (marijuana), which contains THC, has been frequently reported in safety databases for being associated with adverse events. While not all reports are confirmed adverse events, this suggests there may be safety concerns that require further investigation. ^{6 7 8 9 10}

How is the drug THC unique for treating cannabis use?

THC is unique because it is the main psychoactive component of cannabis and is being studied for its potential to help manage cannabis use itself, which is different from other treatments that might not directly involve cannabinoids. This approach leverages THC's interaction with the body's cannabinoid receptors, which is not a common mechanism in other treatments for cannabis use. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this study is to better understand how people's mood, behavior, and brains respond to different recreational drugs. We are also trying to understand why some people may feel differently or their brain may respond differently than other people after taking the same recreational drug.

Eligibility Criteria

This trial is for healthy individuals interested in how recreational drugs like cannabis affect mood, behavior, and brain response. Participants should not have a history of prescription drug abuse or substance use disorders.

Inclusion Criteria

Body mass index of 18.5-30

I have used cannabis more than 10 times in my life and at least once in the last 3 months, but not every day.

I am in good physical and mental health.

Exclusion Criteria

Unwilling/unable to sign informed consent document

I have tested positive for drugs (except THC) or THC in saliva.

Contraindication for fMRI BOLD study (e.g., metal implants)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive THC or placebo during the first or second laboratory visit, with fMRI scanning to assess mood, behavior, and brain response

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of substance use and CUD/SUD symptoms

2 years

Yearly follow-ups

Treatment Details

Interventions

• THC

Trial Overview The study is testing the effects of THC (the active ingredient in cannabis) compared to a placebo. Participants will receive either THC or an inactive capsule without knowing which one they are taking.

Participant Groups

Group I: THC Experimental Treatment 1 Intervention

Participants will receive THC (7.5 mg) at their first or second laboratory visit.

Group II: Placebo oral capsule Placebo Group 1 Intervention

Participants will receive a placebo at their first or second laboratory visit.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

Cannabinoids from Cannabis sativa, particularly non-psychoactive components like cannabidiol (CBD), have therapeutic potential for various conditions, including pain and spasticity in multiple sclerosis, while minimizing the psychotropic effects of THC.

FDA-approved cannabinoid medications, such as nabiximols, dronabinol, and nabilone, are effective in treating symptoms like chemotherapy-induced nausea and vomiting, and anorexia in AIDS patients, showcasing their clinical relevance across multiple medical fields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids: Therapeutic Use in Clinical Practice. Pagano, C., Navarra, G., Coppola, L., et al.[2022]

Only about 20% of individuals undergoing treatment for cannabis dependence achieve long-term abstinence, highlighting the need for more effective and accessible treatment options.

Psychotherapeutic strategies, especially combination therapies that include motivational interventions and behavioral skills training, have shown larger effect sizes for cannabis dependence compared to other substance use disorders, indicating their potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art treatments for cannabis dependence. Danovitch, I., Gorelick, DA.[2021]

In a 2-year observational study of 585 adult patients using medical cannabis, there was a significant increase in the authorization of THC-dominant and CBD-dominant products, indicating a shift in prescribing patterns.

Patients using CBD-dominant or balanced (THC:CBD) products reported greater improvements in anxiety and well-being compared to those using THC-dominant products, suggesting that the cannabinoid profile can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec. Kalaba, M., MacNair, L., Peters, EN., et al.[2021]

The study analyzed adverse event reports related to herbal supplements from two databases, FAERS and CVAR, revealing that herbal supplements accounted for 2.51% and 6.83% of total reports, respectively, indicating a significant presence of herbal-related safety concerns.

Common herbs associated with adverse events included Avena sativa (oats), Cannabis sativa (marijuana), and Hypericum perforatum (St John's Wort), highlighting the need for further investigation into the safety profiles of these supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying Herbal Adverse Events From Spontaneous Reporting Systems Using Taxonomic Name Resolution Approach. Sharma, V., Gelin, LFF., Sarkar, IN.[2020]

The study presents a curated and standardized version of the FDA Adverse Event Reporting System (FAERS) data, which enhances the quality and usability of drug safety surveillance by removing duplicates and standardizing drug and outcome vocabularies.

This new resource will facilitate faster and more reliable drug safety research by providing pre-computed statistics and reducing the time needed for data management, ultimately improving the identification of adverse drug reactions (ADRs) post-marketing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A curated and standardized adverse drug event resource to accelerate drug safety research. Banda, JM., Evans, L., Vanguri, RS., et al.[2020]

The proposed three-part framework for analyzing adverse events includes phases for documenting incidents, conducting in-depth reviews, and assessing the association between exposure and adverse events, which can enhance product safety.

By standardizing the evaluation of adverse events through this framework, companies can better manage risks and improve consumer products based on reliable data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-market surveillance of consumer products: Framework for adverse event management. Kingston, R., Sioris, K., Gualtieri, J., et al.[2022]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

This study provides the first plasma pharmacokinetic data on free THC concentrations after repeated high-dose oral administration, showing that THC levels remained above 1 microgram/L for at least 24 hours after dosing.

The research indicates that while free THC levels did not increase during oral dosing, metabolites like 11-OH-THC and THCCOOH steadily rose, suggesting that the body processes THC differently over time, which is important for understanding its effects and duration in the system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Schwilke, EW., Schwope, DM., Karschner, EL., et al.[2021]

In a phase 2 trial involving 65 patients with chronic abdominal pain, THC tablets did not show a significant difference in pain relief compared to placebo, with both groups experiencing similar reductions in pain scores over 50-52 days.

THC was found to be safe and well-tolerated, although more patients in the THC group discontinued due to mild or moderate adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. de Vries, M., van Rijckevorsel, DCM., Vissers, KCP., et al.[2018]

A review of 11 studies involving 266 subjects showed that intravenous THC has a relatively low risk of serious adverse events, with only one serious event reported and 70 minor events occurring in 9.7% of subjects.

Most participants (94%) reported no increase in their desire to use cannabis after the study, indicating that intravenous THC may not lead to increased cannabis use, especially with careful subject selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of studies with intravenous Δ⁹-tetrahydrocannabinol in humans, with case histories. Carbuto, M., Sewell, RA., Williams, A., et al.[2021]

References

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

Cannabinoids: Therapeutic Use in Clinical Practice. [2022]

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

Recommendations for Reducing the Risk of Cannabis Use-Related Adverse Psychosis Outcomes: A Public Mental Health-Oriented Evidence Review. [2023]

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

Exclusive Therapeutic Use of Cannabis in a Large Sample of Daily Cannabis Users in France: A Cross-Sectional Survey. [2023]

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

State of the art treatments for cannabis dependence. [2021]

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

Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec. [2021]

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

Identifying Herbal Adverse Events From Spontaneous Reporting Systems Using Taxonomic Name Resolution Approach. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A curated and standardized adverse drug event resource to accelerate drug safety research. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Post-market surveillance of consumer products: Framework for adverse event management. [2022]

9. Australia pubmed.ncbi.nlm.nih.gov

Detection of serious adverse drug reactions using diagnostic codes in the International Statistical Classification of Diseases and Related Health Problems. [2021]

10. England pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. [2021]

11. Norway pubmed.ncbi.nlm.nih.gov

[Cannabis and cannabinoids as drugs]. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Delta9-tetrahydrocannabinol content of commercially available hemp products. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. [2021]

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

Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. [2018]

15. Germany pubmed.ncbi.nlm.nih.gov

The safety of studies with intravenous Δ⁹-tetrahydrocannabinol in humans, with case histories. [2021]