Repeated Administration of Cannabis Varying in THC and CBD

The majority of the \>3 million medical cannabis patients in the U.S. use cannabis products to manage pain but many questions remain. This project is designed to answer three questions that will fill important voids in the field's understanding of sustained cannabis use: 1) is abrupt cessation of cannabis associated with increased pain sensitivity; 2) does tolerance develop to the analgesic and abuse-related effects of repeatedly administered cannabis with varying ratios of THC and CBD, and is this tolerance reversible following a period of abstinence; 3) how does repeated cannabis use affect levels of endocannabinoids, and are these changes associated with changes in pain sensitivity and abuse liability? In this study, the investigators will enroll participants (N=100 healthy, cannabis-using men and non-pregnant women, ages 21-65) inpatient for 15 days. They will be randomized to one of four cannabis conditions (n=25/group). Following a day of standardization on which participants will receive their assigned cannabis condition (Day 1), cannabis will be administered repeatedly for 14 days (Day 2-15). The investigators will measure abuse-related effects ("Good Drug Effect"), endocannabinoid levels and two distinct types of experimental pain: The Cold Pressor Test and Quantitative Sensory Testing Thermal Temporal Summation. Given the widespread use of cannabis for pain, understanding the consequences of daily repeated administration of cannabis with THC:CBD ratios that are representative of most medical cannabis products on pain, abuse liability, and endocannabinoids is imperative.

Inclusion Criteria: 1. Males or females, 21-65 years old 2. For females: not pregnant or breast-feeding, and uses an acceptable form of birth control (e.g., condoms, IUD) 3. Uses cannabis on a near-daily basis 4. Not seeking treatment for cannabis use 5. Able to provide informed consent 6. Able to perform study procedures Exclusion Criteria: 1. Meets DSM-V criteria for any Substance Use Disorder other than cannabis, nicotine or caffeine 2. Uses other illicit drugs ≥1 day/week in the prior 4 weeks 3. Medical history, physical, psychiatric examination, or significant illness at the clinical discretion of the study physician; for example, history of heart disease, diabetes, hypertension (BP \> 140/90) or uncontrolled asthma 5\. Use of any prescription or daily use of over-the-counter medications 6. Recurrent, ongoing pain 7. Insensitivity to the thermal stimuli of the Cold Pressor Test or Quantitative Sensory Testing 8. History of physical violence or paranoia during cannabis withdrawal