Cannabis Use and Epigenetic Alterations in Human Male Sperm Cells

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.

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.