THC for Cannabis Use

Overseen By Shahd Smadi, MA

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Illinois at Chicago

Must not be taking: Antidepressants, Anxiolytics, Stimulants, others

Disqualifiers: Psychosis, Mania, ADHD, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

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, the main mind-altering ingredient in cannabis, affects the brain's reward system in healthy young adults. Participants will receive either a dose of THC or a placebo (inactive capsule) to compare effects. Ideal candidates are healthy young adults who use cannabis occasionally but not daily and are not on medications that affect the brain.

As an Early Phase 1 trial, this research focuses on understanding how THC works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

If you are taking psychoactive medications like antidepressants, anxiolytics, or stimulants, you will need to stop them to participate in this trial. The trial does not specify a washout period, but these medications must not interfere with the study.

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

Research shows that THC, the main active ingredient in cannabis, affects people differently. It has been used for medical purposes, such as pain relief. However, the safety and effects of THC can vary. Some studies have linked THC to issues like impaired driving and other health problems. For instance, THC levels between 2 to 5 nanograms per milliliter in the blood can cause driving difficulties. Despite these concerns, this trial is in the very early stages, meaning there's still limited information about how well people handle THC in this specific setting. Prospective participants should consider these potential risks and discuss them with a healthcare professional. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using THC to address cannabis use disorder because it introduces a unique approach that differs from the typical behavioral therapies or medications like naltrexone and bupropion. Unlike these standard treatments, which often focus on managing cravings or withdrawal symptoms, THC aims to stabilize the endocannabinoid system, potentially reducing dependency by moderating the body's response to cannabis. This novel mechanism could offer a more direct way to help individuals manage their cannabis use more effectively.

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

This trial will compare THC with a placebo to evaluate its effectiveness for cannabis use disorder. Research has shown that THC, the main active ingredient in cannabis, might help with cannabis use disorder by easing withdrawal symptoms. Dronabinol, a synthetic version of THC, helped people adhere to their treatment plans. Studies found that THC can reduce anxiety and other symptoms related to quitting cannabis. However, these findings mostly apply to synthetic THC or combined treatments, not the natural form alone. While these results are promising, more research is needed to fully understand THC's effectiveness for this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Natania A Crane, PhD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for healthy, English-speaking adults with a BMI of 19-26 who've used cannabis over 10 times but not daily. They must have no severe drug use disorders or need for psychoactive meds, and be free from medical conditions that affect MRI results or are worsened by THC.

Inclusion Criteria

Have used cannabis at least 10 times in their life, but report current and past lifetime cannabis use less than 7 days/week (daily)

Must be able to give informed consent

Body mass index of 19-26 (normal/overweight but not obese due to limitations of MRI)

Exclusion Criteria

Current Axis-I Diagnostic Statistical Manual-5 diagnosis (although mild Cannabis Use Disorder (CUD) and mild Alcohol Use Disorder (AUD) are allowed)

Unwilling/unable to sign informed consent document

Currently pregnant confirmed by urine pregnancy test or planning pregnancy or lactating (women)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either THC (7.5 mg) or a placebo during their first or second laboratory visit

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo oral capsule
• THC

Trial Overview

The study examines how THC affects mood and brain responses in non-daily cannabis users compared to a placebo. Participants will undergo fMRI scans to track brain activity changes related to the rewarding effects of THC.

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.

THC is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dronabinol for:

• Appetite loss and weight loss in HIV
• Nausea and vomiting from chemotherapy

Approved in Canada as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Approved in European Union as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

A study of 26 prescribers across France revealed that dronabinol is primarily prescribed for chronic pain related to multiple sclerosis (49.7%) and central neuropathic pain (36.6%), with an average treatment duration of 1 month to 6 years.

About 59% of patients reported a significant reduction in pain (30 to 50%), indicating that dronabinol may be an effective option for managing refractory chronic pain, but further research is needed to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol use in France between 2004 and 2017. Lejczak, S., Rousselot, H., Di Patrizio, P., et al.[2020]

A highly sensitive method was developed to measure THC and its metabolites in plasma, which is crucial for understanding the pharmacological effects of cannabis, especially after administering dronabinol, a THC derivative.

The method demonstrated excellent precision and accuracy, with imprecision below 7% and inaccuracy below 12%, making it reliable for clinical and research applications in monitoring cannabis use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous and sensitive LC-MS/MS determination of tetrahydrocannabinol and metabolites in human plasma. Ferreirós, N., Labocha, S., Walter, C., et al.[2019]

The FDA approved Syndros, an oral solution containing dronabinol (delta-9-THC), on July 1, 2016, indicating its recognized therapeutic use.

Syndros is classified as a Schedule II controlled substance by the DEA, highlighting its potential for abuse but also its medical value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans- tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule. [2018]

Δ9-THC, the main psychoactive component of cannabis, is an approved treatment for various medical conditions such as chronic pain and chemotherapy-induced nausea, highlighting its therapeutic efficacy.

Despite its medical uses, Δ9-THC raises concerns regarding potential risks, including psychosis, cognitive impairment, and addiction, which contribute to ongoing debates about its safety and societal impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dark Classics in Chemical Neuroscience: &#916;9-Tetrahydrocannabinol. Banister, SD., Arnold, JC., Connor, M., et al.[2020]

Natural cannabinoids are increasingly used in medical settings and consumer health products, but they carry risks of adverse drug events and interactions due to their complex pharmacology.

Synthetic cannabinoids are more potent than natural ones and can lead to severe reactions, highlighting the need for caution, especially in vulnerable populations at risk for drug-drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids: Pharmacology, Uses, Adverse Drug Events, and Drug Interactions. Brown, JD., Rivera Rivera, KJ., Hernandez, LYC., et al.[2022]

The FDA approved Syndros, an oral solution containing dronabinol (delta-9-THC), on July 1, 2016, indicating its recognized therapeutic potential.

Following FDA approval, the DEA classified Syndros as a Schedule II controlled substance, reflecting its potential for abuse but also its accepted medical use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments. [2017]

The study found that the EMIT II Plus® Cannabinoid immunoassay can detect 11-nor-9-carboxy-Δ8-tetrahydrocannabinol (Δ8-THC-COOH) at concentrations of 30 ng/mL or higher, indicating that current testing methods may not adequately differentiate between Δ8-THC and Δ9-THC metabolites.

Gas chromatography-mass spectrometry (GC-MS) methods can effectively separate Δ8-THC-COOH from Δ9-THC-COOH, allowing for independent identification of these compounds, which is crucial for accurate drug testing and legal implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Delta-9-Tetrahydrocannabinol Carboxylic Acid (Δ9-THC-COOH) Immunoassay and a Gas Chromatography-Mass Spectrometry (GC-MS) Method for the Detection of Delta-8-Tetrahydrocannabinol Carboxylic Acid (Δ8-THC-COOH). Baird, SN., Frazee, CC., Garg, U.[2023]

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]

The safety of cannabis and cannabinoid medications is a significant concern, and while some safety information can be drawn from recreational use studies, medical and recreational users may experience different effects.

There is a pressing need for long-term safety monitoring of cannabinoid use in patients, as clinical experience is still developing, which will help inform both therapeutic decisions and public policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. Ware, MA., Tawfik, VL.[2019]

In a study of 1,145 patients with refractory chronic pain, adding Δ9-tetrahydrocannabinol (dronabinol) to their treatment significantly reduced average pain intensity from 46.3 to 26.8 mm on a visual analog scale over 12 weeks.

Dronabinol was well tolerated, with 46.8% of patients reporting mild drug-related adverse events, and many patients were able to reduce or stop other pain medications during the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. Ueberall, MA., Horlemann, J., Schuermann, N., et al.[2022]

Cannabinoids, including THC and other receptor agonists, show potential efficacy in treating serious medical conditions, particularly in inflammation and pain management, but they also pose challenges such as undesirable central nervous system side effects and difficulties in dose optimization.

The development of cannabinoid-based therapies faces hurdles related to quality control and dosage standardization, especially for botanically derived products, but recent guidance suggests that these challenges can be addressed, highlighting the need for further research into their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview. McCarberg, BH., Barkin, RL.[2013]

In a study of 2,112 adult patients with chronic pain, 92.5% reported improvement in their primary symptoms after using cannabis-based oral formulations, indicating high efficacy as an adjuvant treatment.

The majority of patients experienced minimal side effects, with 71.7% reporting none, and the most common mild side effects, such as somnolence and dizziness, tended to decrease over time, suggesting that these formulations are safe for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. Moreno-Sanz, G., Madiedo, A., Hernandez, P., et al.[2022]

In a survey of 10,010 patients in Germany, dronabinol was the most commonly prescribed cannabis-based medicine (65%), primarily for treating pain (73%), with side effects like tiredness and dizziness being consistent with known profiles of cannabis products.

Patients using cannabis flowers were generally younger and more likely to be male, with different treatment patterns and diagnoses compared to those using other cannabis medicines, indicating a need for careful monitoring and reporting in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]. Schmidt-Wolf, G., Cremer-Schaeffer, P.[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]

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