Cannabis use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered cannabis use. Cannabis use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this single blind open-label trial is to test the feasibility of administering glutamate modulators in conjunction with motivational enhancement therapy (MET) and mindfulness based relapse prevention (MBRP) for cannabis use disorders.

Individuals diagnosed with cannabis dependence will receive one or two infusions of glutamate modulators during week 2 and week 3 or 4. The participants will also receive 2-week course of MET and 4-week course of MBRP. Participants will meet with staff twice weekly, except for week 2 and potentially week 3 or 4 during which participants will present to the clinic three times. Clinic visits include MET sessions, MBRP sessions, psychiatric monitoring, assessments, and study procedures (e.g., medication administration).

Inclusion Criteria:

• Meets DSM-IV criteria for cannabis dependence, with at least 5 days of use per week over the past 30 days and displaying at least one positive utox during screening
• Physically healthy
• No adverse reactions to study medications
• 21-60 years of age
• Capacity to consent and comply with study procedures
• Seeking treatment

Exclusion Criteria:

• Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance-induced psychosis, and current substance-induced mood disorder.
• Physiological dependence on another substance requiring medical management, such as alcohol, opioids, or benzodiazepines, excluding caffeine, and nicotine.
• Pregnant, interested in becoming pregnant, or lactating
• Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
• Current suicide risk or a history of suicide attempt within the past 2 years
• On psychotropic or other medication whose effect could be disrupted by participation in the study
• Recent history of significant violence (past 2 years).
• Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
• Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), anemia, pulmonary disease, active hepatitis or other liver disease (transaminase levels < 2-3 X the upper limit of normal will be considered acceptable), or untreated diabetes
• Previous history of misuse of study medications
• BMI > 35, or a history of undocumented obstructive sleep apnea
• First degree relative with a psychotic disorder (bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, or psychosis NOS)

Adverse event data were collected throughout the study period (6 weeks)

Open label single-blind trial, with participants given the impression they may get any of several medications.