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

NCT04920539 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2000030067R01DA052846
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Healthy

Outcome Measures

Primary Outcomes (4)

• Change in Gene Expression Alteration

  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.

  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.

• Change in Cytokine Profile

  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.

  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.

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

  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.

  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.

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

  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.

  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.

Secondary Outcomes (4)

• Perceptual Alterations

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

• Cannabis Subjective Effects

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

• Cannabinoid Relevant Molecules

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

• Change in total immediate recall on the RAVLT.

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

Study Arms (1)

Active Delta-9-THC

EXPERIMENTAL

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

Drug: Active Delta-9-THC

Interventions

Active Delta-9-THC DRUG

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

Active Delta-9-THC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• Yale University: lead

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• Deepak C D'Souza, MD

  Yale University Professor of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 10, 2021
• Study Start: February 8, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 30, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)