Sex Hormones Impact on Cannabis Response

The Influence of Female Sex Hormones on the Subjective and Cognitive Response to Cannabis

The goal of this study is to systematically determine whether the cannabis response in human females is related to SH fluctuations throughout the menstrual cycle.

Study Overview

• Status: Recruiting
• Conditions: Cannabis
• Intervention / Treatment: Drug: Cannabis; Drug: Knaster Hemp

Detailed Description

Cannabis consumption is increasing globally due to legalization and therapeutic use, prompting concerns about its impact on daily functioning and long-term effects. While research has explored cannabis' risks, the heightened vulnerability of females to its adverse effects has been overlooked. Women experience stronger acute negative reactions and progress to cannabis use disorder faster than men. This gender disparity is likely due to sex hormone (SH) fluctuations related to menstrual cycles, emphasizing the need to study cannabis' differential impact on females to address gender-specific risks and inform treatment approaches. Acute influences of cannabis (300 μg THC/kg bodyweight) on subjective state and cognition will be assessed at three different stages of the menstrual cycle, and compared to a placebo condition in a double-blind, randomized, within-subject study in occasional cannabis using biological females.

Primary Objective: To assess the acute subjective drug effects (good/bad drug effect, drug liking/wanting, anxiety), cognition (attention, working memory, information processing speed, verbal memory, verbal fluency, motor inhibition), and pharmacokinetics of cannabis in females across 3 different phases of the menstrual cycle, compared to a placebo condition.

Secondary Objective(s): to assess the acute effects of cannabis on interoception and pain, in females across 3 different phases of the menstrual cycle, compared to a placebo condition.

Tertiary Objective(s): to assess the acute effects of cannabis on metacognition and expression of inflammatory markers in females across 3 different phases of the menstrual cycle, compared to a placebo condition.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht University
    • Contact: Natasha L Mason, PhD; Phone Number: +31 (0)43 388 1382; Email: natasha.mason@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Biological female
• Used cannabis between 1 time a month and 2 times a week during the previous year
• Age between 18 and 40 years
• Free from psychotropic medication
• Free from hormonal birth control
• A regular menstrual cycle (last 3 cycles a duration between 21 and 35 days).
• Good physical health as determined by medical examination and laboratory analysis
• Absence of any major medical, endocrine and neurological condition as determined by medical examination and laboratory analysis
• Normal weight, body mass index (weight/height2) between 18 and 28 kg/m2
• Written Informed Consent
• Good knowledge and understanding of the English language
• Participants must be willing to refrain from taking illicit psychoactive substances during the study.
• Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drinks after midnight of the evening before the study session, as well as during the study day.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after substance administration.

Exclusion Criteria:

• History of drug addiction (determined by the medical questionnaire, drug questionnaire and medical examination)
• Pregnancy or lactation or pregnancy planned during study participation
• Hypertension (diastolic > 90 mmHg; systolic > 140 mmHg)
• Current or history of psychiatric disorder (determined by the medical questionnaire and medical examination)
• Current presence or history of psychosis in first-degree relatives
• Any chronic or acute medical condition
• History of cardiac dysfunctions (arrhythmia, ischemic heart disease,…)
• Tobacco smoking (>20 per day)
• Excessive drinking (>20 alcoholic consumptions per week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabis; All participants will receive cannabis on 3 separate occasions during different phases of the menstrual cycle.	Drug: Cannabis; Bedrobinol (13.5% THC) resulting in 300 μg/kg bodyweight THC, administered via a Storz and Bickel Mighty Medic vaporiser.; Other Names: Tetrahydrocannabinol
Placebo Comparator: Knaster hemp; All participants will receive knaster hemp on 3 separate occasions during different phases of the menstrual cycle.	Drug: Knaster Hemp; Placebo will consist of knaster hemp, a freely sold aromatic herbal mixture for smoking. Participants will receive a dose of 50 mg of knaster hemp, administered via a Storz and Bickel Mighty Medic vaporiser.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective drug effects	Subjective drug effects will be measured via the drug effect questionnaire	Immediately upon inhalation, up to 3.5 hours post administration
THC concentration in blood	Blood sample will be taken to assess THC concentration in blood.	Baseline (-0.5 hour) and at set time periods up to 3.5 hours post administration
Retrospective rating of drug effects	Retrospective rating of drug effects will be measured via subjective reports on the 5-dimensional altered states of consciousness rating scale	Immediately upon inhalation, up to 3.5 hours post administration
Sensitivity to cannabis reinforcement	Measured via the sensitivity to cannabis reinforcement questionnaire,	Immediately upon inhalation, up to 3.5 hours post administration
Marijuana Craving	Measured via the marijuana craving questionnaire	Immediately upon inhalation, up to 3.5 hours post administration
Anxiety	Measured via the State-Trait anxiety inventory	Immediately upon inhalation, up to 3.5 hours post administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interoception	The Heart rate discrimination task will be used to assess interoception.	+1 hr 15 minutes after administration
Subjective experience of pain	The cold pressor task will be used. Pain is assessed via how many seconds participants can keep their hand in the water.	+2.5 hours after administration
Attention	attention will be assessed via the psychomotor vigilance test	Immediately upon inhalation, up to 3.5 hours post administration
Information processing speed	Will be assessed via the digit symbol substitution test	Immediately upon inhalation, up to 3.5 hours post administration
Verbal Memory	Will be assessed via the Immediate and Delayed Verbal Memory Test	Immediately upon inhalation, up to 3.5 hours post administration
Verbal fluency	Will be assessed via the animal fluency test	Immediately upon inhalation, up to 3.5 hours post administration
Motor Inhibition	Assessed via the stop signal task	Immediately upon inhalation, up to 3.5 hours post administration
Pain threshold	To assess changes in pain threshold, the pressure pain threshold task will be used.	+2.5 hours post administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metacognition	Before and after each task, participants will be shown full text prompts explaining the task, and asking them how well they believe they will do on the task, and upon completion, how well they think they performed.	Immediately upon inhalation, up to 3.5 hours post administration
Inflammatory cytokines	Blood samples will be collected to measure inflammatory cytokine levels	At baseline (-0.5) and 3.5 hours after treatment administration

Collaborators and Investigators

• Sponsor: Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 17, 2025
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cannabis; THC; sex hormones
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol; nabiximols
• Other Study ID Numbers: NL87464.068.24/

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No