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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how THC, a compound found in cannabis, affects mood, behavior, and brain activity. Researchers seek to understand why individuals may react differently to the same recreational drug. Participants will receive either THC or a placebo during lab visits. Suitable candidates have used cannabis at least 10 times in their life and at least once in the past three months, but not daily. As an Early Phase 1 trial, this research focuses on understanding THC's effects, offering participants a chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that THC is likely to be safe for humans?

Research has shown that THC, the main ingredient in cannabis, is generally safe. Most side effects stem from THC itself. In the short term, it may cause memory problems and coordination difficulties. Long-term use can lead to addiction and changes in brain development. These effects depend on frequency and dosage. For this trial, the dose is 7.5 mg, considered moderate. It's important to remember that each body reacts differently. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using THC for cannabis use disorder because it approaches treatment from a unique angle. Unlike typical treatments that might involve behavioral therapy or medications aimed at reducing withdrawal symptoms, THC itself is the active ingredient being tested. This method explores the idea of using controlled doses of THC to potentially reduce cravings and manage dependence, offering a novel approach compared to the standard options. By targeting the endocannabinoid system directly, researchers hope to provide an innovative solution that may be more effective for some individuals.

What evidence suggests that THC could be an effective treatment for cannabis use?

Research shows that THC, the main active ingredient in cannabis, can influence mood and behavior. Studies have examined THC's impact on cannabis use disorder, but current treatments like motivational enhancement therapy (MET) and cognitive-behavioral therapy (CBT) have only shown modest success. While these therapies help some people reduce cannabis use, they aren't highly effective overall. In this trial, participants will receive either THC or a placebo to understand how THC affects the brain and why reactions vary. Although research continues, THC's role in treating cannabis use disorder remains unclear. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 am in good physical and mental health.

Score of ≥0.25 on the Personality Inventory for DSM-5 (PID-5) Anhedonia subscale

Exclusion Criteria

Unwilling/unable to sign informed consent document

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

Severe mental illness (e.g., psychosis, mania, lifetime moderate-to-severe SUD (including moderate-to-severe CUD))

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11910397/

Effectiveness of cannabis use and cannabis use disorder ... This data synthesis examined the effectiveness of behavioural and pharmacological approaches for cannabis treatment.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S294987592400198X

Cannabis use disorder and substance use treatment ... This study supports conducting an efficacy trial assessing the potential of CHAMPS in improving outcomes for young adults with psychosis using cannabis.

3. jci.org jci.org/articles/view/172887

Cannabis use disorder: from neurobiology to treatment Trials have shown that individually both MET and CBT lead to modest improvements in cannabis-related outcomes (including reduced frequency and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655458/

Cannabis use and cannabis use Disorder - PMC Approximately 17.0% of weekly and 19.0% of daily cannabis smokers met the criteria for cannabis dependence. In addition, in a longitudinal study almost 1 in 19 ...

5. ccorc.mmjoutcomes.org ccorc.mmjoutcomes.org/2025-abstract-gallery/descriptive-outcomes-from-a-survey-investigating-cannabis-use-patterns-among-florida-adults-at-risk-for-alcohol-use-disorder.html

Jennifer Attonito, PhD Florida Atlantic University - CCORC Descriptive Outcomes from a Survey Investigating Cannabis Use Patterns Among Florida Adults at Risk for Alcohol Use Disorder. Jennifer Attonito, PhD

6. samhsa.gov samhsa.gov/substance-use/learn/marijuana/risks

Know the Effects, Risks and Side Effects of Marijuana Research shows that people who use marijuana are more likely to have relationship problems, worse educational outcomes, lower career achievement, and reduced ...

7. cdc.gov cdc.gov/cannabis/health-effects/index.html

Cannabis Health Effects Cannabis use may have a wide range of health effects on the body and brain. · There are several risk factors and negative health outcomes ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4827335/

Adverse Health Effects of Marijuana Use - PubMed Central - NIH Short-term marijuana use can cause impaired memory and motor skills. Long-term use can lead to addiction, altered brain development, and cognitive impairment.

9. mayoclinic.org mayoclinic.org/drugs-supplements-marijuana/art-20364974

Marijuana Medical cannabis, also called weed or marijuana, is generally considered safe. Most of the side effects of cannabis are due to the THC content.

10. canada.ca canada.ca/content/dam/hc-sc/documents/services/campaigns/27-16-1808-Factsheet-Health-Effects-eng-web.pdf

Health effects of cannabis Continued, frequent and heavy cannabis use can cause physical dependency and addiction. Research has shown that THC in cannabis causes an increase in levels of ...