Sex Hormones Impact on Cannabis Response

Official title

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

Overview

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.

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.

Interventions

• Drug Cannabis
  Bedrobinol (13.5% THC) resulting in 300 μg/kg bodyweight THC, administered via a Storz and Bickel Mighty Medic vaporiser.
• 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.

Primary outcome measures

• Subjective drug effects [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• THC concentration in blood [Time frame: Baseline (-0.5 hour) and at set time periods up to 3.5 hours post administration]
• Retrospective rating of drug effects [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Sensitivity to cannabis reinforcement [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Marijuana Craving [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Anxiety [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]

Secondary outcome measures (8)

• Interoception [Time frame: +1 hr 15 minutes after administration]
• Subjective experience of pain [Time frame: +2.5 hours after administration]
• Attention [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Information processing speed [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Verbal Memory [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Verbal fluency [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Motor Inhibition [Time frame: Immediately upon inhalation, up to 3.5 hours post administration]
• Pain threshold [Time frame: +2.5 hours post administration]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

Netherlands · 1 center

• Maastricht University — Maastricht

Identifiers

NCT: NCT07417059 · NL87464.068.24/

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗