The Neural Underpinnings of Depression and Cannabis Use in Young People Living With HIV

To elucidate mechanisms of substance use disorders (SUD) and comorbid mental illnesses in people living with HIV (PLWH), the study team seeks to investigate reward and pain circuitry in cannabis use and depression comorbidity, two highly prevalent conditions in PLWH. The study team proposes a tightly integrative study to test the overall hypothesis that cannabis use and depression in young PLWH have an additive effect, inducing both reward deficits and pain hypersensitivity, and that this pattern will predict worse outcomes at 1 year follow-up.


Eligibility Criteria:
Inclusion Criteria:

* HIV seropositivity confirmed with lab report, medical records, or HIV testing.
* Between the ages of 18-39 years
* Fluency in English or Spanish
* Ability to provide informed consent and perform study procedures, including estimated full-scale intelligence quotient (IQ) \>75 to ensure that participants are able to understand the study.
* Cannabis users: To capture a wide range of cannabis use frequency, meeting Diagnostic and Statistical Manual 5 (DSM-5) criteria for Cannabis use Disorder (CUD) will not be required. However, in order to ensure sufficient exposure, cannabis use will be significant (self-reported use on ≥20 of the prior 30 days and positive THC urine toxicology).
* Depressed: In order to capture a wide range of depression illness severity, we will allow participants with subthreshold depression, defined as a raw severity score of ≥12 on the Montgomery Asberg Depression Rating Scale (MADRS).

Exclusion Criteria:

* Perinatally acquired HIV infection, as early neurodevelopmental alterations and HIV legacy effects may exist in this group
* Pregnancy or lactation
* Current Substance Use Disorder other than cannabis or nicotine
* Certified for or self-reported medical cannabis use, or intent to become certified
* Current cocaine use by self-report or urine toxicology
* central nervous system (CNS) disease or injury, or neuro-degenerative disease
* Unique pain syndromes (e.g. multiple sclerosis, rheumatoid arthritis);
* Severe medical illness such as end-stage renal disease, heart failure, cirrhosis, or cancer
* MRI contraindication such as claustrophobia, metallic ink tattoos, or pacemaker.

Depressed cannabis non-users:

* At baseline, all participants will be psychotropic-medication-free for ≥1 month prior to study enrollment (or ≥3 months for medications with longer half-lives). Benzodiazepines and sleeping aids taken on an as-needed basis will be allowed, however we will require a 4-day abstinence period before the scan.
* Exclusionary are participants with a DSM-5 diagnoses of bipolar disorder, psychotic disorders, autism spectrum disorders, and all non-cannabis substance-related disorders will be exclusionary. disorder (PTSD) are not uncommon among depressed individuals and will be
* Anxiety disorders, obsessive-compulsive disorder (OCD), and post-traumatic stress are allowed as long as depressive symptoms are primary.

atypical of depression. • Suicidal ideations (SI) without a specific plan (defined as passive SI) are common in depression and will be allowed. However, if SI constitutes an imminent risk to self or others (defined as active SI), the participant will be withdrawn from the study and emergency procedures will be initiated immediately, including ER admission.

Depressed cannabis users:

• Exclusion criteria will be the same as depressed cannabis non-users except for cannabis use.

Non-depressed cannabis users:

• Will have no major psychiatric conditions other than cannabis use/disorder.

Non-depressed cannabis non-users:

• Exclusion criteria will be the same as for non-depressed cannabis users; in addition participants will not report cannabis use in the prior 90 days and have a urine toxicology test negative for cannabis.