Extended Effects of Cannabis Abstinence on Clinical Symptoms and Cognition in Depression

The prevalence of major depressive disorder (MDD) is \~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. Most studies of cannabis use in MDD are cross-sectional in design, and therefore causal relationships are unclear. This study investigates the effects of cannabis abstinence over a 28-day period in patients with MDD with co-occurring CUD using a randomized controlled design, namely contingent reinforcement.

The prevalence of major depressive disorder (MDD) is \~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. To date, most studies of cannabis use in MDD were cross-sectional in design, and therefore causal relationships are unclear. The investigators previous studies in cannabis dependent patients with schizophrenia suggest that extended cannabis abstinence (up to 28 days) using contingent reinforcement is associated with improvements in specific areas of cognition (e.g. verbal learning and memory) and depressive symptoms. A more recent study using an open-label design demonstrated that 28 days of cannabis abstinence improves depressive symptoms and anhedonia in participants (N=11) with co-occurring MDD and CUD.

The investigators propose a controlled cannabis abstinence paradigm in patients with co-morbid MDD and CUD (N=52) to further investigate these findings. Stabilized MDD patients with moderate to severe CUD will be randomly assigned to one of two groups: 1) A contingent reinforcement (CR) intervention (n=26); 2) a non-contingent reinforcement (NCR) intervention (n=26), which will serve as a time and non-abstinence control. In the CR group, subjects achieving biochemically-verified cannabis abstinence at study endpoint (Day 28) will receive a $300 contingent payment; participants in the NCR group will not receive this contingent payment. The primary outcomes are: 1) cannabis abstinence rates at Day 28 in CR versus NCR groups; 2) changes in mood (depressive), anxiety and sleep symptoms over the 28-day assessment period. Secondary outcomes include cognition.

Eligibility Criteria:
Inclusion Criteria:

* All participants must be between the ages 18-55
* Meet SCID for DSM-5 diagnostic criteria for cannabis use disorder, moderate to severe
* Meet SCID for DSM-5 diagnostic criteria for Major Depressive Disorder
* Be an outpatient receiving a stable dose of antidepressant medication for at least three months (to ensure stability of depressive symptoms
* Have a Hamilton Depression Rating Scale (HDRS-17) at baseline assessment in the range of 12-25..
* Have a Full-Scale IQ ≥ 80 as determined by the WTAR
* Be a non-treatment seeking cannabis user
* Evidence of sufficient motivation and effort as measured by a Test of Memory Malingering (TOMM) score ≥ 45.

Exclusion Criteria:

* Meets criteria for substance use disorder of alcohol or other illicit substances within the past 6 months (with the exception of cannabis, nicotine, or caffeine)
* Positive urine screen for illicit substances other than cannabis, nicotine, or caffeine
* Current suicidal or homicidal ideation
* Psychotic disorder diagnosis (e.g. schizoaffective disorder, major depression with psychotic features) as determined by the SCID
* Treatment seeking for cannabis use
* Meet SCID for DSM-5 diagnostic criteria for Bipolar Disorder
* Head Injury\> 5 minutes LOC
* Exceed upper and lower cut-offs on HSRD-17 (See Inclusion Criteria)