A randomized controlled trial to assess the efficacy of extended-release guanfacine to reduce cannabis use frequency in young people with cannabis use disorder following a period of monitored abstinence.

Inclusion Criteria:

1. 12-25 years of age (inclusive) at consent;
2. Seeking treatment for cannabis use;
3. DSM-5 Cannabis Use Disorder, mild, moderate or severe;
4. Self-reported cannabis use on average at least 5 days/week during the 28 days prior to screening with a THC positive urine drug screen on the day of screening; and
5. Able to provide informed consent (both adequate IQ and English fluency; <18-year-olds will provide consent themselves in addition to parent/guardian consent).

Exclusion Criteria:

1. DSM-5 substance use disorder (moderate or severe) except cannabis or nicotine;
2. Any unstable medical, psychiatric or neurological condition or medical contraindicating study participation;
3. Diagnosis of a psychotic or bipolar illness;
4. Acute suicidality as assessed by clinician;
5. Prescribed antipsychotics, benzodiazepines or other sedative medications, or other medications for the treatment of ADHD. If prescribed antidepressants, the participant must have been on a stable dose for more than 2 weeks at screening;
6. A history of heart disease or cardiac risk factors (e.g. arrhythmias);
7. Abnormal liver or thyroid function as indicated by clinically-significant findings on blood tests;
8. Pregnancy, breast feeding or, if sexually active and able to become pregnant, no effective contraception.
9. Intention to enter residential rehabilitation after treatment in the YSAS residential withdrawal facility.