Inhaled THC for Cannabis Response Differences by Gender

(THC-Gender-II Trial)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Yale University

Disqualifiers: Cannabis naive, major stressors

Trial Summary

What is the purpose of this trial?

This trial examines how inhaling THC affects women compared to men and explores why these differences might exist.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Inhaled THC for cannabis response differences by gender?

Research indicates that cannabis, including THC, can have different effects based on gender, with women often experiencing higher peak blood concentrations and subjective effects. This suggests that gender may influence the effectiveness and experience of inhaled THC, highlighting the importance of considering sex differences in treatment responses. ^{1 2 3 4 5}

Is inhaled THC generally safe for humans?

Research shows that inhaled THC can cause increased heart rate and feelings of anxiety, especially in women. Women may also experience more adverse effects at higher doses compared to men. It's important to start with lower doses and be aware of potential anxious reactions. ^{1 2 3 4 6}

How does inhaled THC differ from other cannabis treatments?

Inhaled THC is unique because it is administered through inhalation, which allows for rapid absorption and onset of effects compared to oral cannabis products. This method may also highlight sex differences in response to THC, as studies suggest that males and females may experience different effects and side effects from cannabis. ^{2 4 5 6 7}

Research Team

Eligibility Criteria

This trial is for healthy men and women who have tried cannabis at least once. It's not suitable for those who've never used cannabis or are currently dealing with major stress.

Inclusion Criteria

I am in good physical and mental health.

You have used cannabis at least once in your life.

Exclusion Criteria

You are experiencing a lot of stress right now or have recently experienced a major life event.

People who have never used cannabis before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either 4 mg vaporized THC or inhaled placebo to assess acute effects

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Inhaled THC (Cannabinoid)
• Placebo (Other)

Trial Overview The study is looking into how inhaled THC (the active ingredient in cannabis) affects men and women differently by comparing it to a placebo, which has no active ingredients.

Participant Groups

Group I: Delta-9-Tetrahydrocannabinol (THC) Active Control 1 Intervention

4 mg vaporized THC will be administered.

Group II: Placebo Placebo Group 1 Intervention

Inhaled placebo (no active cannabinoids)

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

Findings from Research

Research indicates that there are significant sex differences in how individuals respond to cannabinoid compounds, particularly when exposure occurs during adolescence.

The differences may be linked to variations in the endocannabinoid system and the metabolism of delta9-tetrahydrocannabinol, highlighting the importance of including female subjects in both basic and epidemiological studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-dependent vulnerability to cannabis abuse in adolescence. Rubino, T., Parolaro, D.[2022]

The review highlights that while men traditionally have higher rates of cannabis use and Cannabis Use Disorder, the gap is narrowing as more women are using cannabis for medical purposes, raising important questions about sex-dependent effects.

It emphasizes the need to understand the hormonal and pharmacological mechanisms behind these sex differences, particularly regarding the therapeutic potential and abuse liability of cannabis and cannabinoids, which are crucial for public health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective. Cooper, ZD., Craft, RM.[2023]

In a study of 1249 chronic pain patients using a metered-dose inhaler for medical cannabis, no significant sex differences were found in the effectiveness or safety of treatment over 240 days, indicating that both men and women respond similarly to cannabis for pain relief and sleep improvement.

The overall rate of adverse events was low and equal between sexes at 10%, and pharmacokinetic analyses showed no significant differences in how Δ9-THC was processed in the body, suggesting that medical cannabis can be safely administered to both men and women without concern for differing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Sex Differences in Efficacy, Safety and Pharmacokinetics in Patients Treated with Cannabis by a Metered-Dose Inhaler. Aviram, J., Glezerman, M., Hayam, E., et al.[2023]

In a study involving 50 participants (27 males and 23 females) who infrequently used cannabis, females showed higher peak blood levels of the active metabolite 11-OH-THC and reported stronger subjective effects from cannabis compared to males, even after adjusting for body weight.

The findings suggest that females may experience greater anxiety-related effects from cannabis, indicating a need for public health recommendations to consider lower starting doses for females and warnings about potential acute anxiety reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in the acute effects of oral and vaporized cannabis among healthy adults. Sholler, DJ., Strickland, JC., Spindle, TR., et al.[2022]

In a study involving 40 participants (21 males and 19 females), vaporized cannabis with 13.75 mg of THC showed significant effects on various measures, but only minor sex differences were observed after accounting for body mass index (BMI) and plasma THC levels.

Males performed better on a divided attention task and had higher peak plasma levels of a THC metabolite compared to females, but no significant differences were found in subjective drug effects or cardiovascular responses, suggesting that acute cannabis effects may not differ greatly between sexes at this moderate dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials. Arkell, TR., Kevin, RC., Vinckenbosch, F., et al.[2022]

In a study involving 84 healthy adults (38 males and 46 females) taking varying doses of THC over 7 days, females reported significantly more adverse events (AEs) than males at high doses, indicating a potential increased sensitivity to THC's effects in women.

While females experienced greater feelings of relaxation at high doses, males reported higher enjoyment of the effects from placebo, suggesting that sex differences in subjective experiences may vary based on THC dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex Differences in the Safety and Subjective Effects of Two Oral Δ9-Tetrahydrocannabinol-Containing Cannabis Products over Multiple Doses Among Healthy Adults. MacNair, L., Eglit, GML., Mosesova, I., et al.[2023]

Women are more susceptible to cannabinoid abuse and dependence compared to men, experiencing more severe withdrawal symptoms and a higher likelihood of relapse, as indicated by various studies on human and rodent subjects.

Sex differences in cannabinoid response are influenced by gonadal hormones, particularly estradiol, suggesting that understanding these mechanisms could lead to sex-specific treatments for marijuana dependence and therapeutic use of cannabinoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in cannabinoid pharmacology: a reflection of differences in the endocannabinoid system? Craft, RM., Marusich, JA., Wiley, JL.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Sex-dependent vulnerability to cannabis abuse in adolescence. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective. [2023]

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

Evaluating Sex Differences in Efficacy, Safety and Pharmacokinetics in Patients Treated with Cannabis by a Metered-Dose Inhaler. [2023]

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

Sex differences in the acute effects of oral and vaporized cannabis among healthy adults. [2022]

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

Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials. [2022]

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

Sex Differences in the Safety and Subjective Effects of Two Oral Δ9-Tetrahydrocannabinol-Containing Cannabis Products over Multiple Doses Among Healthy Adults. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Sex differences in cannabinoid pharmacology: a reflection of differences in the endocannabinoid system? [2022]