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Cannabis Use, Cognition, and the Endocannabinoid System in HIV

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ClinicalTrials.gov Identifier: NCT04883255
Recruitment Status : Not yet recruiting
First Posted : May 12, 2021
Last Update Posted : May 19, 2022
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Arpi Minassian, University of California, San Diego

Brief Summary:
Understanding how co-morbidities in persons with HIV (PWH) such as substance use affect risk-taking, decision-making, and other cognitive behaviors is important given implications for everyday functioning and transmission risk. The high prevalence of cannabis use in PWH, medicinally and recreationally, may indicate disease severity, impart therapeutic benefits, or adverse consequences. In fact, cannabis is recommended to those with HIV to alleviate nausea, improve appetite, relieve pain, and lift mood. To-date, the consequences of cannabis use in PWH remain unclear as do potential interactions with HIV treatments. In healthy participants, heavy cannabis use is associated with cognitive deficits e.g., risky decision-making, response disinhibition and inattention, but pro-cognitive effects in PWH may exist at mild use levels due to its anti-inflammatory and anti-excitotoxic properties. Furthermore, little has been done to determine the effects of cannabis use on the endocannabinoid (EC) system in general or in PWH. This study will determine the effects of the two primary cannabis constituents (Δ9-tetrahydrocannabinol [THC], cannabidiol [CBD]) vs. placebo on risky decision-making, response inhibition, reward learning, temporal perception, and motivation, plus EC and homovanillic acid (HVA; a surrogate for dopamine activity) levels in HIV+ and HIV- subjects. Participants with infrequent cannabis use will undergo baseline cognitive testing and biomarker assays with antiretrovirals (ART) use quantified. They will be randomized to a 5-day course of either THC, CBD, or placebo and return for follow-up testing and re-assaying of ECs and HVA levels.

Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: 10 mg Δ9-tetrahydrocannabinol (THC) Drug: 600 mg cannabidiol (CBD) Drug: Placebo Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Cannabis Use, Cognition, and the Endocannabinoid System in HIV
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : January 31, 2026
Estimated Study Completion Date : January 31, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Marijuana

Arm Intervention/treatment
Experimental: HIV-positive subjects
Adult human subjects seropositive for HIV-1
Drug: 10 mg Δ9-tetrahydrocannabinol (THC)
5-day course of orally-administered THC (dronabinol), 10 mg

Drug: 600 mg cannabidiol (CBD)
5-day course of orally-administered CBD, 600 mg

Drug: Placebo
5-day course of orally-administered placebo

Active Comparator: Healthy Comparison Volunteers
Adult human subjects without HIV
Drug: 10 mg Δ9-tetrahydrocannabinol (THC)
5-day course of orally-administered THC (dronabinol), 10 mg

Drug: 600 mg cannabidiol (CBD)
5-day course of orally-administered CBD, 600 mg

Drug: Placebo
5-day course of orally-administered placebo




Primary Outcome Measures :
  1. change in Iowa Gambling Task score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower scores reflect increased risk-taking

  2. change in Human Temporal Bisection Task score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Scores reflect fast or slow perception of timing.

  3. change in Probabilistic Learning Task score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower scores reflect poorer learning.

  4. change in Progressive Ratio Task score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower scores reflect lower motivation or willingness to work for a reward.

  5. change in Continuous Performance Task score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower scores reflect worse attention.

  6. change in human Behavioral Pattern Monitor activity and exploration score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Higher scores reflect motor hyperactivity and increased exploration.

  7. change in prepulse inhibition percentage score from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower scores reflect worse sensorimotor gating.

  8. change in cerebrospinal fluid (CSF) anandamide (AEA) quantity from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower AEA signifies less amounts of this endocannabinoid in the central nervous system.

  9. change in cerebrospinal fluid (CSF) 2-Arachidonoylglycerol (2-AG) quantity from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower 2-AG signifies less amounts of this endocannabinoid in the central nervous system.

  10. change in cerebrospinal fluid (CSF) homovanillic acid (HVA) quantity from baseline to post-intervention [ Time Frame: baseline and 5 days after drug initiation ]
    This is an experimental measure and not a scale with specific anchor points. Lower HVA signifies less amounts of this dopamine metabolite in the central nervous system.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Aged 18 and older
  • Possess the capacity to provide informed consent to a set of neurobehavioral, neuromedical and cognitive assessment procedures. Individuals unable to provide such consent will not be enrolled into the study.
  • HIV Status: HIV status will be determined using the MedMira Rapid Test (Halifax, Nova Scotia, Canada). If the result differs from the participant's self-report a confirmatory Western Blot will be performed.
  • Infrequent use of cannabis, defined as 1-4 times per month. Must have used cannabis at least five times in the past two years without an adverse reaction.
  • Willing to abstain from cannabis for at least 2 days prior the baseline visit. Although there is no definitive method for determining abstinence over this period, abstinence will be confirmed as best as possible by using an oral fluid testing device (Draeger 5000) employed by law enforcement officers to detect recent cannabis use. An oral fluid value of > 5ng suggests recent use, although in some cases it has been reported that individuals may show > 5ng up to 20 hours after use. Thus, should the oral fluid sample indicate > 5ng THC, the assessment may be canceled and rescheduled.

Exclusion Criteria

  • Inability to provide informed consent
  • Significant chronic renal disease (unrelated to HIV), significant chronic pulmonary disease (unrelated to HIV), or Hepatitis C Virus infection
  • Head injury with loss of consciousness for greater than 30 minutes or resulting in neurologic complications
  • Seizure disorder
  • Demyelinating diseases or other non-HIV neurological disorders
  • Pregnancy
  • Acute or recent or previous clinically disabling stroke or previous cerebrovascular events
  • Lifetime history of schizophrenia or other psychotic disorders, or bipolar disorder.
  • Beck Depression Inventory-II (BDI-II) score is greater than or equal to 29 (severe depression) or suicidal ideas are endorsed on the BDI-II or a Center for Epidemiological Studies-Depression Scale (CES-D) subscale measuring suicidal ideation
  • Alcohol use disorder (moderate or severe) within the last 12 months
  • For other substances besides alcohol and cannabis, moderate or severe substance use disorder within the past five years or a mild substance use disorder within the past 12 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04883255


Contacts
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Contact: Arpi Minassian, Ph.D. 619-543-3422 aminassian@ucsd.edu

Sponsors and Collaborators
University of California, San Diego
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Arpi Minassian, Ph.D. UC San Diego
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Responsible Party: Arpi Minassian, Clinical Professor of Psychiatry, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04883255    
Other Study ID Numbers: 210323
R01DA051295 ( U.S. NIH Grant/Contract )
First Posted: May 12, 2021    Key Record Dates
Last Update Posted: May 19, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Arpi Minassian, University of California, San Diego:
cannabis
HIV
THC
cannabidiol
Additional relevant MeSH terms:
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Marijuana Abuse
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Dronabinol
Cannabidiol
Anticonvulsants
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists