Inhaled THC for Cannabis Response Differences by Gender

(THC-Gender-II Trial)

Overseen By Carly Hewes, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Disqualifiers: Cannabis naive, major stressors

Compensation: Varies

Number of Visits: 1

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how inhaled THC affects men and women differently. Researchers aim to understand the reasons behind these differences. Participants will receive either a low dose of THC or a placebo, which contains no active ingredients. The trial suits individuals who have used cannabis at least once and are in good physical and mental health. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that inhaled THC is generally safe for users. Previous studies have found no major safety issues for both men and women using THC. For instance, one study found no significant safety differences between males and females using THC, suggesting that both handle it similarly in terms of safety.

Although limited data exists specifically on vaporized THC in humans, THC has been approved for other uses, indicating a certain level of safety. However, since this trial is in the early stages, it primarily focuses on understanding the treatment's safety. Early-stage trials aim to ensure the treatment does not cause harm, making safety a top priority.

Overall, inhaled THC appears safe, but this trial will help confirm that by examining any possible gender differences in reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about inhaled THC for cannabis response differences by gender because it provides a unique opportunity to explore how different genders might react to cannabis. Unlike typical oral or topical cannabis treatments, this trial uses vaporized THC, allowing for faster onset of effects. This method could lead to a better understanding of personalized cannabis therapies, potentially enhancing effectiveness and reducing side effects based on gender-specific responses.

What evidence suggests that inhaled THC could be effective for cannabis response differences by gender?

This trial will compare the effects of inhaled THC with a placebo to study cannabis response differences by gender. Research has shown that inhaled THC, the main active ingredient in cannabis, can affect men and women differently. One study with mice indicated that males experienced more pain relief from THC, but this difference diminished with age. Another study found no major differences between men and women in how the body processes THC or in its safety. However, women might experience different effects, such as an increase in sexual desire, compared to men. Overall, THC has various effects, and researchers continue to study how these differ between men and women. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled THC
• Placebo

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10471687/

Sex differences in acute delta-9-tetrahydrocannabinol (Δ9 ... Male B6 mice were more sensitive to the acute antinociceptive effects of Δ 9 -THC than female littermates, an effect which dissipated with age.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04704271?term=tetrahydrocannabinol&aggFilters=status:rec%20enr%20act&viewType=Table&rank=8

Gender Related Differences in the Acute Effects of Delta-9- ... Study Plan ; Active Comparator : Delta-9- Tetrahydrocannabinol (THC). 4 mg vaporized THC will be administered. · Drug : Inhaled THC ; Placebo Comparator : Placebo.

3. withpower.com withpower.com/trial/phase-1-marijuana-abuse-9-2019-34363

Inhaled THC for Cannabis Response Differences by Gender 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 ...

4. mdpi.com mdpi.com/1424-8247/16/10/1426

Evaluating Sex Differences in Efficacy, Safety and ... Results: Following the first two weeks, no significant sex differences were found in the effectiveness or safety of MC treatment (p > 0.05).

5. sciencedirect.com sciencedirect.com/science/article/pii/S0361923025003429

Review Sex-specific responses to cannabis exposure Additionally, women are more likely to report an increase in sexual desire following cannabis consumption, while men experience a large range of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04704271

Gender Related Differences in the Acute Effects of Delta-9- ... To characterize the acute effects of vaporized THC in women relative to men and to begin probing the mechanisms that may underlie gender differences. Official ...

7. journals.sagepub.com journals.sagepub.com/doi/full/10.1089/can.2022.0340

Sex Differences in the Safety and Subjective Effects of Two ... There is a paucity of data on sex differences in safety and subjective effects after repeated use of varying oral doses of Δ9-tetrahydrocannabinol (THC; the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10979821/

Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female ... We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37895897/

Evaluating Sex Differences in Efficacy, Safety and ... Results: Following the first two weeks, no significant sex differences were found in the effectiveness or safety of MC treatment (p > 0.05).