Targeting Anhedonia in Cocaine Use Disorder

Recent research suggests that anhedonia is a key neurobehavioral dysfunction in Cocaine Use
Disorder (CUD) that contributes to treatment outcomes. Anhedonia, defined here as lack of
interest or pleasure in non-drug rewards, is frequently found in CUD and is related to neural
deficits, such as low striatal dopamine and deficient activation to non-drug rewards in
mesocortical circuits. Interestingly, not all individuals in CUD have these deficits.
Preliminary data suggests that the presence of self-reported anhedonia predicts worse outcome
in contingency management (CM) treatment of CUD. Moreover, low baseline dopamine predicts
failure to attain abstinence in CM while medications that enhance DA increase CM success
rates and responsiveness to rewards.

This study specifically aims to test the contribution of anhedonia to overall CUD severity,
the relationship of anhedonia to outcomes in CM treatment, and the mediating role of
anhedonia in medication enhancement of CM in CUD. To accomplish these aims, individuals with
CUD will be enrolled and will undergo 4 weeks of intensive CM treatment, either with or
without treatment with the dopaminergic drug, d-amphetamine. A medication only group will be
included to solely measure the effects of d-amphetamine. Anhedonia will be assessed using
multi-modal subjective, psychophysiological and behavioral measures of reward functioning at
baseline, and each week of treatment. Functional magnetic resonance imaging (fMRI) measures
of reward functioning will also be taken at baseline and week 4 in a subset of participants
(n = 24)

Inclusion Criteria:

- be between 18 and 60 years of age

- meet Diagnostic and Statistical Manual V (DSM-5) criteria for current cocaine use
disorder of at least moderate severity (≥ 4 symptoms)

- have at least 1 cocaine positive urine sample during the baseline screening period

- be in acceptable health on the basis of interview, medical history and physical exam,
per the judgment of our study physician

- be able to understand the consent form and provide written informed consent

- be able to provide the names of at least 2 persons who can generally locate their
whereabouts.

- if female, agree to use an acceptable method of birth control during study (surgical
sterilization, approved hormonal contraceptives, barrier methods with spermicide, or
intrauterine device).

Exclusion Criteria:

- current DSM-5 diagnosis for substance use disorder of least moderate severity (≥ 4
symptoms), other than cocaine, nicotine, marijuana, or alcohol

- Physical dependence on alcohol requiring medically supervised detoxification, in the
judgment of the study physician

- current amphetamine use (by self-report in past 30 days or positive urine drug
screen), more than 50 lifetime uses of amphetamine, or history of DSM-5 Amphetamine
Use Disorder

- a current DSM-5 axis I psychiatric disorder or neurological disease or disorder
requiring ongoing treatment and/or making study participation unsafe

- significant current suicidal or homicidal ideation

- medical conditions contraindicating d-amphetamine (e.g., significant cardiovascular
disease, liver or kidney disease, seizure disorder, hypotension or hypertension)

- taking medications known to have effects on the central nervous system or that could
cause significant drug interactions with d-amphetamine (e.g., clonidine, prazosin)

- having conditions of probation or parole requiring reports of drug use to officers of
the court

- impending incarceration

- pregnant or nursing for female patients

- inability to read, write, or speak English

Additional Exclusion Criteria for the functional magnetic resonance (fMRI) Sub-Study (in
addition to all listed criteria above for the Main Treatment Study):

- body mass index (BMI) >30, as this may be incompatible with the magnetic resonance
scanner gantry

- any retained metals in the body, including implants and metallic substances (e.g.
aneurysm clips, retained metal particles in metal workers, magnetic dental implants,
ferromagnetic ocular implants, iron-based facial tattoos), as this may cause adverse
effects to participants and interfere with data collection in the MR magnetic field

- inability to tolerate small, enclosed spaces (such as the magnetic resonance scanner
bore)