Cannabis Use and Epigenetic Alterations in Human Male Sperm Cells

Cannabis Use and Epigenetic Alterations in Human Male Sperm Cells: Effects of Exposure and Abstinence (Component 1)

This is a follow-up project to a proof-of-concept study to determine if Cannabis use in male humans is associated with changes in deoxyribonucleic acid (DNA) methylation profile of sperm. This proposal will examine the epigenome of sperm from men actively using Cannabis before and after a period of Cannabis abstinence. The results will be compared to control non-users.

Study Overview

• Status: Completed
• Conditions: Cannabis Use
• Intervention / Treatment: Other: Cannabis use abstinence for 11 weeks

Detailed Description

This project involves recruitment of 72 healthy males between the ages of 18 and 40 years. Forty eight of the participants will be regular cannabis users with a self-reported frequency of at least once weekly over the past 6 months, and a control group of twenty four cannabis non-users. Cannabis users will be asked to quit using cannabis for 11 weeks and will be required to attend 25 visits during the 11 week abstinence/contingency management period. Non-users will be asked to return to the clinic once a week for 11 weeks. Abstinence will be determined by self-report, qualitative urine rapid screening test at the clinic and quantitatively via Enzyme Immunoassay (EIA) analysis of THC (cannabinoids) and, by Liquid Chromatography Tandem Mass Spectrometry (LCMSMS) analysis of 11-nor-9-carboxy-∆ 9-tetrahydrocannabinol (THCCOOH) performed by an analytical lab contracted by the study team. Semen sample for both groups will be collected prior to the start of abstinence and after 11 weeks. Semen analysis and DNA methylation of sperm cells will be compared.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Child and Family Study Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

72 healthy males between the ages of 18 and 40 years. Forty eight - regular Cannabis users with a self-reported frequency of at least once weekly over the past 6 months, Twenty four Cannabis non-users - control group

Description

Inclusion Criteria:

• Male gender
• Between the ages of 18-40 years, inclusive;
• Free from significant medical/psychiatric conditions
• Willingness to provide baseline semen sample and again at the end of study participation
• Willingness to comply
• Ability to communicate verbally and in written form in English.

For the CANNABIS USER group:

• Self-reported Cannabis use of at least once weekly for past 6 months;
• THC level of at least 50 ng/ml (EIA, non-creatinine adjusted value) and THCCOOH level of at least 15ng/ml (LCMSMS, non-creatinine adjusted value);
• Positive result on urine rapid screening test for THC; and
• Willingness to abstain from Cannabis for 11 weeks during the course of the study

For the CANNABIS NON-USER group:

• Self-report of no Cannabis use in the past 6 months; fewer than 10 times lifetime;
• THCCOOH level = 0 ng/ml; (EIA non-creatinine adjusted value) and
• Negative result on urine rapid screening test.

Exclusion Criteria:

• Positive result for any other drugs of abuse on urine rapid screening test (including cocaine, methamphetamine, opiates, benzodiazepines, and barbiturates); or use of nicotine or tobacco products;-Currently prescribed any psychoactive medication;
• Current diagnosis of any significant psychiatric condition, including substance use disorders. For the user group, Cannabis Use Disorder that does not require immediate clinical attention in the opinion of the clinician/investigator will be allowed.
• Score on the Marijuana Screening Inventory-X > 10;
• Score on the Alcohol Use Disorders Identification Test > 8;
• Expired breath CO reading of > 8 ppm at screening and throughout the study.
• Expired Breath Alcohol Level of > 0.000 at screening.
• Urinary cotinine level greater than 2- indicating urinary concentrations of > 30ng/ml cotinine at screening and throughout the study
• Estimated IQ < 80 as assessed by the Kaufman Brief Intelligence Test, Second Edition; and
• Unable to comply with study requirements or otherwise unsuitable for participation in the opinion of the study physician and/or study psychologist.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cannabis User Group; Forty eight participants who are regular Cannabis users with a self-reported frequency of at least once weekly over the past 6 months of screening visit.	Other: Cannabis use abstinence for 11 weeks; Cannabis user group will be asked to abstain from any form of Cannabis use for 11 weeks. During their contingency management phase/abstinence phase, they will be required to come to the clinic for 25 visits over an 11 week period of abstinence.
Non-Cannabis User Group; Twenty four participants who self-report no Cannabis use in the past 6 months of screening visit and fewer than 10 times during their lifetime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group differences in sperm DNA methylation profiles between user and non-user group	We will compare the overall DNA methylation profiles in sperm cells of user and non-user group to replicate findings in the pilot study.	Baseline
Within group change in DNA methylation profiles from baseline to after 11 weeks of Cannabis abstinence	We will compare the overall DNA methylation profiles in sperm cells after an 11 week period of Cannabis abstinence in the user group	Baseline to after 11 weeks of abstinence from Cannabis use.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group differences in the sperm analysis profile between user and non-user group	We will compare the overall sperm analysis profile of user versus non-user group to replicate findings in the pilot study	Baseline
Within group change in sperm analysis profile from baseline to after eleven weeks of Cannabis abstinence	We will compare sperm analysis profile after an eleven week period of Cannabis abstinence in the user group	Baseline to after 11 weeks of abstinence from Cannabis use

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: John Templeton Foundation

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2017
• Primary Completion (Actual): March 16, 2020
• Study Completion (Actual): March 16, 2020

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Cannabis Abstinence Sperm Cells
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse
• Other Study ID Numbers: Pro00086400

Drug and device information, study documents

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