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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how THC, the main active compound in cannabis, affects men and women differently. Researchers seek to understand the acute (short-term) effects of cannabinoids and uncover any gender-based differences. Participants will receive either a small dose of THC or a placebo (a control substance with no THC). The study seeks individuals who have used cannabis at least once and are in good physical and mental health.

As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking insights into THC's effects.

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.

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

Research has shown that THC, the main ingredient in cannabis, has been studied in forms like dronabinol. The FDA has approved dronabinol for other uses, providing insight into THC's safety. Common side effects of dronabinol include dizziness and fatigue. More serious, but less common, effects can include dehydration and changes in the body's mineral balance.

In studies, some individuals have felt very happy or suspicious after taking THC. Others have experienced nausea, stomach pain, or significant drowsiness. These reactions are usually not severe but can be uncomfortable.

The study's focus on THC in a specific setting highlights the importance of being aware of these possible effects. While THC is generally well-tolerated, considering these side effects is crucial for those thinking about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cannabis-related effects focus on behavioral therapy or medications that indirectly address symptoms. But THC, the study drug, works differently by directly targeting the cannabinoid receptors in the brain responsible for the psychoactive effects of cannabis. Unlike other therapies, which might take longer to show results, THC is administered intravenously, allowing for rapid onset and precise dosing. Researchers are excited about this treatment because it offers a more direct and immediate approach to understanding and potentially managing the effects of cannabis.

What evidence suggests that THC might be an effective treatment for cannabis effects?

Research has shown that THC, a component of cannabis, has promising effects on various medical conditions. In this trial, participants will receive either THC or a placebo. Studies have found that THC and similar compounds can be more effective than a placebo in reducing nausea and vomiting. Specifically, 70% to 90% of patients using cannabis for cancer symptoms reported improvement. THC has also been linked to easing symptoms of anxiety, Tourette syndrome, and anorexia nervosa. Additionally, these compounds have been found to aid in pain relief, with more patients experiencing significant pain reduction compared to those taking a placebo. Overall, THC offers potential benefits for treating several symptoms and conditions. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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

At least one lifetime exposure to cannabis

I am in good physical and mental health.

Exclusion Criteria

Major current or recent stressors

I am currently taking estrogen supplements or oral contraceptive pills.

Cannabis naive individuals

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK425767/

Therapeutic Effects of Cannabis and Cannabinoids - NCBI - NIH In their review the investigators state that cannabinoids were highly effective, being more efficacious than the placebo and similar to conventional antiemetics ...

2. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1490621/full

Meta-analysis of medical cannabis outcomes and ... Patient-reported outcome measures indicate that 70%–90% of patients who used cannabis to directly treat cancer symptoms reported improvements, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0272735825000479

The differential effects of medicinal cannabis on mental ... A narrative review reported that THC and CBD were associated with reduced symptoms of anxiety, TS, anorexia nervosa, cannabis use disorder, and opioid use ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2338251

Cannabinoids for Medical Use: A Systematic Review and ... The average number of patients who reported a reduction in pain of at least 30% was greater with cannabinoids than with placebo (OR, 1.41 [95% CI, 0.99-2.00]; 8 ...

5. bmj.com bmj.com/content/382/bmj-2022-072348

Balancing risks and benefits of cannabis use: umbrella ... Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf

MARINOL (dronabinol) capsules, for oral use In some cases, these adverse reactions were severe (e.g., dehydration, electrolyte abnormalities) and required dose reduction or drug ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/dronabinol-oral-route/description/drg-20063560

Dronabinol (oral route) - Side effects & dosage However, children are more sensitive to the mental and nerve effects of this medicine. Safety and efficacy have not been established.

8. webmd.com webmd.com/drugs/2/drug-8774-1840/dronabinol-oral/dronabinol-solution-oral/details

Dronabinol (Marinol, Syndros) - Uses, Side Effects, and More Common side effects with dronabinol include dizziness and tiredness. Dronabinol is a controlled substance because it can be misused or lead to ...

9. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/20218-dronabinol-capsules

Dronabinol (Marinol): Uses & Side Effects You are at increased risk of serious heart and/or nervous system side effects if these substances are used together.

10. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557531/

Dronabinol - StatPearls - NCBI Bookshelf - NIH Other Adverse Effects: The most common adverse reactions (≥3%) include abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, abnormal ...