Skip to main content
OpenTrials
Completed

NCT Number: NCT04920539

In Vivo Study of THC-induced Immune-genome Changes at Single Cell Solution in HIV-infected Humans

In this study, the investigators hypothesize that THC alters the immunogenome in a cell type-specific fashion and alters cytokine production via epigenetic regulatory mechanisms and that these alterations differ between HIV-infected and HIV-uninfected host genomes.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Healthy Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

About this study

In this study, the investigators hypothesize that THC alters the immunogenome in a cell type-specific fashion and alters cytokine production via epigenetic regulatory mechanisms and that these alterations differ between HIV-infected and HIV-uninfected host genomes. To test these hypotheses, the investigators propose defining the epigenomic and transcriptomic alterations at single cell resolution in peripheral blood mononuclear cells by administering THC to humans with and without HIV infection. The THC-associated epigenomic/transcriptomic alterations will be linked to genomic variants to understand the causal effects of THC response in immune cells.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(HIV-infected group):

  • HIV-positive
  • Good medication adherence
  • Negative urine toxicology for drugs of abuse (including cannabis)
  • Good mental and physical health (other than HIV) as determined by history, psychiatric interview, collateral information, physical and laboratory examinations, ECG, and vital signs.

Inclusion criteria

(HIV-uninfected group):

  • HIV-negative
  • Negative urine toxicology for drugs of abuse (including cannabis)
  • Good mental and physical health as determined by history, psychiatric interview, collateral information, physical and laboratory examinations, ECG, and vital signs.

Exclusion criteria

(common to both groups):

  • Major medical conditions, e.g., myocardial infarction, hypertension, etc.
  • Positive pregnancy test and lactation;
  • Weight greater than 166 kg (365 lbs)

Treatment and study plan

Active Delta-9-THC

Drug

Active Delta-9-THC (0.03 mg/kg) administered intravenously.

Primary outcomes

  1. Change in Gene Expression Alteration

    Time frame: Blood samples will be collected to measure changes in gene expression altered by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.

    Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion will be identified as THC-induced gene expression alteration.

  2. Change in Cytokine Profile

    Time frame: Blood samples will be collected to measure changes in cytokine profile before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.

    Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.

  3. Change in Gene Expression Alteration by THC between HIV-positive and HIV-negative Groups

    Time frame: Blood samples will be collected to measure change in gene expression altered by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.

    Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion are identified as THC-induced gene expression alteration. Results will be compared between HIV-positive and HIV-negative subjects.

  4. Change in Cytokine Profile by THC between HIV-positive and HIV-negative Groups

    Time frame: Blood samples will be collected to measure changes in cytokine profile by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.

    Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. Results will be compared between HIV-positive and HIV-negative subjects. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.

Secondary outcomes

  1. Perceptual Alterations

    Time frame: Perceptual alterations will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.

    Perceptual alterations will be measured using scales such as the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.

  2. Cannabis Subjective Effects

    Time frame: Cannabis subjective effects will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.

    Various feeling states associated with cannabis intoxication will be measured using a self-reported visual analog scale of feeling states ("high", "calm and relaxed", and "tired") associated with cannabis effects. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 100 mm line (0 = not at all, 100 = extremely). These data will be captured to validate that the experiment is relevant to cannabis effects.

  3. Cannabinoid Relevant Molecules

    Time frame: Blood will be collected before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.

    Blood will be sampled for cannabinoid relevant molecules before and after study drug infusion. Cannabinoid relevant molecules will include THC and THC-COOH levels.

  4. Change in total immediate recall on the RAVLT.

    Time frame: The RAVLT will be administered prior to study drug administration at approximately 25 minutes after study drug administration.

    Memory, attention, and executive function will be measured before and after study drug administration using the Rey Auditory Verbal Learning Task (RAVLT).

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jun 10, 2021
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.