Cannabis, HIV and Mental Processing Systems

Study Overview
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Brief Summary
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This study employs novel methods to identify key determinants and consequences of concurrent HIV infection and regular cannabis use. This study will acquire extensive phenotype data from peripheral and brain markers of immune activation, brain structure, and neuropsychological performance (NP) in persons living with HIV (PLWH) receiving combination anti-retroviral therapy (cART) (80 regular cannabis users and 80 non-users) and HIV uninfected (HIV-) controls (80 regular cannabis users and 80 non-users). This study will provide key insights into the effects of regular cannabis and HIV on peripheral and brain markers of immune function and NP in PLWH and HIV- controls. These insights are critical for cure strategies and ongoing HIV treatment initiatives.

Official Title
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Cannabis, HIV and Mental Processing Systems

Conditions
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HIV Infections, Cannabis

Intervention / Treatment
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* Procedure: MRI
* Other: NeuroPsychological Testing
* Procedure: Blood Draw
* Other: Questionnaires
* Procedure: Lumbar Puncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18-70 years old. PLWH must have documented HIV infection for approximately 1 year, be on a cART regimen for approximately ≥3 months, and be virally well-controlled (< 200 copies/mL). HIV- controls must have confirmed HIV- serostatus. Participants must complete at least 9 years of education. Participants must be able to provide informed consent. Female participants must have a negative pregnancy test or written documentation of tubal ligation, hysterectomy, post-menopausal status, etc. and cannot be breastfeeding. Participants should have no contraindications to an MRI scan. Participants should be willing to have cannabis use history confirmed via clinical interview and urine analysis . All inclusion criteria at PI discretion. Exclusion Criteria: History of neurological disorder (e.g., stroke, head injury with loss of consciousness for >5 minutes, developmental learning disability, etc.). Uncontrolled major affective disorder; history of bipolar disorder or schizophrenia. Major depression controlled with no hospitalizations or suicidal ideation in the past year is allowed. Current substance use disorder (SUD) as defined by DSM-5 criteria besides cannabis use disorder (CUD) (though a past SUD > 1 year before the time of study enrolment will be allowed). currently prescribed anti-coagulants (only exclusionary if participant will engage in optional LP). an allergy to lidocaine or similar anesthetic (only exclusionary if participant will engage in optional LP). a history of a bleeding disorder (only exclusionary if participant will engage in optional LP). claustrophobia or a pacemaker that would prevent magnetic resonance imaging (MRI) scanning. all exclusion criteria at PI discretion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV+ Cannabis User<br>Persons diagnosed with HIV who identify as using medical or recreational marijuana | Procedure: MRI<br>* Multimodal neuroimaging on 3T Prisma Fit MRI<br>Other: NeuroPsychological Testing<br>* A series of written, verbal, and motor tasks requiring the participant to follow instructions, remember words and numbers, draw objects, and complete timed actions.<br>Procedure: Blood Draw<br>* Laboratory reports (CMP, CBC, Lipids)<br>Other: Questionnaires<br>* Life history, current behaviors, and substance use surveys<br>Procedure: Lumbar Puncture<br>* Optional procedure which involves obtaining cerebral spinal fluid through a needle in the lower back<br>|
| HIV+ Cannabis Non-User<br>Persons diagnosed with HIV who identify as not using medical or recreational marijuana | Procedure: MRI<br>* Multimodal neuroimaging on 3T Prisma Fit MRI<br>Other: NeuroPsychological Testing<br>* A series of written, verbal, and motor tasks requiring the participant to follow instructions, remember words and numbers, draw objects, and complete timed actions.<br>Procedure: Blood Draw<br>* Laboratory reports (CMP, CBC, Lipids)<br>Other: Questionnaires<br>* Life history, current behaviors, and substance use surveys<br>Procedure: Lumbar Puncture<br>* Optional procedure which involves obtaining cerebral spinal fluid through a needle in the lower back<br>|
| HIV- Cannabis User<br>Persons without HIV who identify as using medical or recreational marijuana | Procedure: MRI<br>* Multimodal neuroimaging on 3T Prisma Fit MRI<br>Other: NeuroPsychological Testing<br>* A series of written, verbal, and motor tasks requiring the participant to follow instructions, remember words and numbers, draw objects, and complete timed actions.<br>Procedure: Blood Draw<br>* Laboratory reports (CMP, CBC, Lipids)<br>Other: Questionnaires<br>* Life history, current behaviors, and substance use surveys<br>Procedure: Lumbar Puncture<br>* Optional procedure which involves obtaining cerebral spinal fluid through a needle in the lower back<br>|
| HIV- Cannabis Non-User<br>Persons without HIV who identify as not using medical or recreational marijuana | Procedure: MRI<br>* Multimodal neuroimaging on 3T Prisma Fit MRI<br>Other: NeuroPsychological Testing<br>* A series of written, verbal, and motor tasks requiring the participant to follow instructions, remember words and numbers, draw objects, and complete timed actions.<br>Procedure: Blood Draw<br>* Laboratory reports (CMP, CBC, Lipids)<br>Other: Questionnaires<br>* Life history, current behaviors, and substance use surveys<br>Procedure: Lumbar Puncture<br>* Optional procedure which involves obtaining cerebral spinal fluid through a needle in the lower back<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of cannabis use on peripheral and brain immune activation and inflammation in virally controlled PLWH on cART. | Validated plasma and cerebrospinal fluid (CSF) markers of immune health and inflammation (e.g., CD14, CD16, Neopterin, etc.), as well as novel neuroimaging methods of neuro-inflammation (e.g., DTI & DBSI, 3T MRI) will be used to evaluate brain inflammation. | Years 1-5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of cannabis use on cognitive performance and brain structure in both PLWH/CB+ and CON/CB+. | Neuropsychological assessment results will be normed and converted into Z scores for comparison with brain volumes calculated from the 3T. | Years 1-5 |