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

141 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of the study is to better understand the neural mechanisms underlying the rewarding, reinforcing properties of delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, among healthy young adults.

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.

What evidence supports the effectiveness of the drug THC (Tetrahydrocannabinol) for cannabis use?

Research shows that dronabinol, a form of THC, has been used effectively as an add-on treatment for chronic pain, with many patients reporting improvement in their symptoms. Additionally, cannabis-based formulations containing THC have been found to be safe and effective in managing chronic pain, with most patients experiencing symptom relief and only mild side effects. ^{1 2 3 4 5}

Is THC generally safe for human use?

THC, also known as dronabinol, is used in some approved medications and is considered safe when used under medical supervision, but it can have side effects and interact with other drugs. Long-term safety data is still needed, and caution is advised, especially for those using it for medical purposes. ^{5 6 7 8 9}

How is the drug THC unique in treating cannabis use?

THC (Tetrahydrocannabinol) is unique because it is the main psychoactive component of cannabis and acts on the brain's cannabinoid receptors, which may help in managing cannabis use by mimicking the effects of cannabis itself. Unlike other treatments, THC is also used for various conditions like chronic pain and nausea, making it a versatile option. ^{10 11 12 13 14}

Research Team

Natania A Crane, PhD

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

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

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

Treatment Details

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.

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.

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. Switzerland 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. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Dronabinol use in France between 2004 and 2017. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]. [2021]

5. United States 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]

6. England pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids: Pharmacology, Uses, Adverse Drug Events, and Drug Interactions. [2022]

7. United States 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]

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

Safety issues concerning the medical use of cannabis and cannabinoids. [2019]

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

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

10. England 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). [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

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

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

Dark Classics in Chemical Neuroscience: &#916;9-Tetrahydrocannabinol. [2020]

13. Germany pubmed.ncbi.nlm.nih.gov

Simultaneous and sensitive LC-MS/MS determination of tetrahydrocannabinol and metabolites in human plasma. [2019]

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]