THC for Cannabis Effects

(THC-Gender Trial)

Overseen By Leigh Taylor Flynn, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Estrogen, Oral contraceptives

Disqualifiers: Cannabis naive, Major stressors

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

Compensation: Varies

Number of Visits: 11

Duration: 1 day

100 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but women cannot participate if they are taking estrogen supplements or birth control pills.

What data supports the effectiveness of the drug THC for its intended effects?

Research shows that THC, a component of cannabis, has been used effectively to manage chronic pain and other conditions like nausea from chemotherapy and appetite loss in AIDS patients. Studies indicate that cannabis-based treatments, including those with THC, can improve symptoms like pain and anxiety, although the effectiveness can vary depending on the specific formulation used. ^{1 2 3 4 5}

Is THC generally safe for human use?

THC, also known as dronabinol, is used in some FDA-approved medications like Syndros and Marinol, but it is classified as a Schedule II controlled substance, indicating it has a potential for abuse and dependence. Safety concerns exist, especially regarding adverse effects and drug interactions, and long-term safety data is still needed. Caution is advised when using THC, particularly for those with other medical conditions or who are taking other medications. ^{6 7 8 9 10}

How is the drug THC unique compared to other treatments?

THC is unique because it acts as a partial agonist at cannabinoid type 1 (CB1) receptors in the brain, which is different from many other pain or nausea treatments. It is also known for its psychoactive effects, which can be both a therapeutic benefit and a side effect, unlike non-psychoactive treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of the study is to characterize the acute effects of cannabinoids in women relative to men and to begin probing the mechanisms that may underlie gender differences.

Eligibility Criteria

This trial is for people who have tried cannabis at least once and are in good physical and mental health. Women can't join if they're taking estrogen supplements or birth control pills, and it's not for anyone who has never used cannabis or those dealing with major stress recently.

Inclusion Criteria

I am in good physical and mental health.

At least one lifetime exposure to cannabis

Exclusion Criteria

Major current or recent stressors

I am currently taking estrogen supplements or oral contraceptive pills.

Cannabis naive individuals

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either active THC or placebo intravenously over 10 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 day

Monitoring at +10, +80, and +200 minutes after infusion

Treatment Details

Interventions

• Placebo
• THC

Trial Overview The study is looking into how THC (the active component of cannabis) affects men and women differently when taken acutely. Participants will receive either THC or a placebo to compare the immediate effects between genders.

Participant Groups

Group I: THC Active Control 1 Intervention

Active THC (0.015mg/kg) administered intravenously over 10 minutes.

Group II: Placebo Placebo Group 1 Intervention

Control: small amount of alcohol intravenously (quarter teaspoon), with no THC over 10 minutes.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

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 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 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]

A meta-analysis of 72 controlled clinical trials indicates that cannabinoids have significant therapeutic potential for various conditions, including as antiemetics, appetite stimulants, and analgesics.

Cannabinoids may be beneficial in treating debilitating diseases such as cancer and AIDS, as well as neurological disorders like multiple sclerosis and epilepsy, highlighting their diverse applications in medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. Ben Amar, M.[2022]

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 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]

A total of 183 cases in the FDA Adverse Event Reporting System identified delta-8 tetrahydrocannabinol (D8-THC) as a suspect drug, with the most common adverse effects being respiratory issues like dyspnea and seizures.

The reporting odds ratios for adverse effects associated with D8-THC showed a significant increase, more than doubling from 2019 to 2021, suggesting a potential safety concern regarding its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta-8, a Cannabis-Derived Tetrahydrocannabinol Isomer: Evaluating Case Report Data in the Food and Drug Administration Adverse Event Reporting System (FAERS) Database. Simon, TA., Simon, JH., Heaning, EG., et al.[2023]

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]

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 single oral dose of 10 mg of THC was well tolerated in cancer pain patients and showed potential for mild pain relief, suggesting it may be a viable option for managing pain.

In contrast, a higher dose of 20 mg resulted in significant side effects such as somnolence, dizziness, and blurred vision, which could limit its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Noyes, R., Brunk, SF., Avery, DA., et al.[2021]

Delta9-tetrahydrocannabinol (delta9-THC) does not achieve the maximum activation of cannabinoid receptors compared to stronger agonists like CP55940, and at high concentrations, it can act as an antagonist.

Cannabinol is identified as a weak agonist of cannabinoid receptors, while cannabidiol functions as an antagonist at micromolar concentrations, indicating diverse roles of these cannabinoids in receptor activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Petitet, F., Jeantaud, B., Reibaud, M., et al.[2019]

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: Δ9-Tetrahydrocannabinol. Banister, SD., Arnold, JC., Connor, M., et al.[2020]

Cannabis sativa, commonly known as marijuana, has a long history of use for therapeutic, intoxicating, and spiritual purposes, and its legal status is evolving, which may enhance understanding of its effects and challenges, particularly with potent extracts.

The active compounds Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been identified, with Δ9-THC being responsible for psychoactive effects and CBD being non-intoxicating, making it a focus for potential clinical applications without the risk of abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin. Canseco-Alba, A., Rodríguez-Manzo, G.[2023]

References

1. 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]

2. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabinoids: Therapeutic Use in Clinical Practice. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. [2022]

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

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]

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

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Delta-8, a Cannabis-Derived Tetrahydrocannabinol Isomer: Evaluating Case Report Data in the Food and Drug Administration Adverse Event Reporting System (FAERS) Database. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

10. 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]

11. 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]

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

The analgesic properties of delta-9-tetrahydrocannabinol and codeine. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. [2019]

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

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol. [2020]

15. Mexico pubmed.ncbi.nlm.nih.gov

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin. [2023]