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.

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.

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)

Random allocation of participants to the treatment order will be done using Sealed Envelope software, by one experimenter who does not come in direct contact with the participants. The study will be double blind to the subject and the testing experimenter. One experimenter will be respond for preparing the drug treatment. If a subject is withdrawn from the study, the replacement subject will be allocated to the same treatment sequence as the subject they are replacing. Following completion of all data collection the study will be fully unblinded.