Effect of Medical Marijuana on Neurocognition and Escalation of Use

This trial is a randomized, longitudinal study of medical marijuana (MM) that will: (1)
characterize the impact of MM on indices of addiction, such as CUD, escalation of use,
tolerance, and withdrawal among those who stop using, (2) assess, via dosing diaries, the
effect of MM use patterns on use of other medications, and perception of underlying disease
symptomatology, (3) characterize the impact of MM on neurocognitive performance, including
executive function, memory, attention, and decision-making and (4) examine evidence for
impact of MM on brain structure and function. This study will enroll 200 adults with no prior
history of CUD or heavy marijuana use, who express interest in using MM to treat pain,
insomnia, anxiety, and/or depression. Participants will be randomly assigned to either an
active MM arm (n = 100), or to a waitlist control arm (WLC) (n = 100). Participants will be
assessed at baseline, regularly for 3 months, and at a 6-month and 12-month follow-up for MM
use behaviors, development of CUD, perception of disease symptomatology, and neurocognitive
performance. Urine collected at each visit will be assessed with quantitative assays. MRI
scans will be collected to longitudinally investigate possible brain changes associated with
MM use.

Inclusion Criteria:

1. Men and women aged 18-65 years, inclusive;

2. Competent and willing to provide written informed consent;

3. Desire to use medical marijuana for self-reported pain, sleep, or affective (mood
and/or anxiety including PTSD) symptoms.

4. Not in possession of a medical marijuana card, but expressing intent to get one.

5. Able to communicate in English language.

Exclusion Criteria:

1. Current daily marijuana use (prior to enrollment)

2. Current substance use disorders (e.g. cocaine, opiate, stimulant). Light to moderate
alcohol use is permitted (defined as 16 or less on the AUDIT), and nicotine dependence
is permitted because of the high co-use of nicotine and marijuana. Participants cannot
meet current SCID criteria for a use disorder on any illicit substance other than
nicotine.

3. Pregnant (verified by a urine test).

4. In the opinion of the investigator, not able to safely participate in this study
because of any medical or psychological issues (e.g. psychosis) that might compromise
their safety.