Age: 25 - 60
Healthy Volunteers: Not accepted
Inclusion Criteria:
1. Age 25-60.
2. Regular use (at least 4 times per week) of cannabis concentrates for the last year.
3. Not currently seeking to cut down or stop cannabis use.
4. At least one episode of 3 consecutive days of cannabis abstinence with no experience of severe withdrawal symptoms (i.e., >=4 DSM-5 Cannabis Withdrawal symptoms rated as "severe"), in the last 90 days.
5. At least two symptoms of a DSM-5 cannabis use disorder.
Exclusion Criteria:
1. Use of any illicit substance besides alcohol, nicotine, or cannabis (e.g., cocaine, opiates, methamphetamine, MDMA, benzodiazepines, or barbiturates) in the past 60 days, as indicated by self-report and urine toxicology screening at the beginning of each study visit.
2. Use of CBD-containing products other than cannabis concentrates in the past 90 days.
3. Alcohol use on 3 or more days per week, and/or > 3 drinks per drinking day in the past 60 days. Participants must also have a breath alcohol level of 0 at the beginning of each study visit.
4. Daily nicotine use.
5. Meets DSM-5 diagnostic criteria for a psychotic disorder (e.g., schizophrenia, schizophreniform disorder, schizoaffective disorder), bipolar disorder, or major depression with suicidal ideation, or has a history of treatment for these disorders.
6. Current cardiovascular or respiratory disease (e.g., coronary artery disease, severe asthma, chronic obstructive pulmonary disease, etc.)
7. Current use of any psychotropic (e.g., antidepressants, anxiogenics) or hepatotoxic medications.
8. Currently use of anti-epileptic medications (e.g., clobazam, sodium valproate) or medications known to have major interactions with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, and/or teriflunomide) or a history of seizures.
9. Current use of strong or moderate CYP3A4 inhibitors or inducers (commonly used examples not captured by other exclusion criteria include protease inhibitors, macrolide antibiotics \[e.g., erythromycin\], azole antifungals \[e.g., ketoconazole\], verapamil, and grapefruit juice).
10. Current use of strong or moderate CYP2C19 inhibitors or inducers (commonly used examples not captured by other exclusion criteria include proton pump inhibitors, prednisone, and norethisterone).
11. Current or past hepatocellular disease, as indicated by medical history or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of the normal range at screening.
12. For female participants, pregnancy or trying to become pregnant. A positive pregnancy test at the beginning of any study visit will result in exclusion from ongoing study participation.
13. For female participants, currently lactating.
14. For female patients of childbearing potential, not willing to use at least an approved method of birth control while taking the study medication, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal (one year).
15. Current suicidality risk as indicated during the conduct of the C-SSRS with concurrence after a study physician's or PI evaluation if the response to C-SSRS questions 1 or 2 is "yes".