# Effect of Cannabis Administration and Endocannabinoids on HIV Neuropathic Pain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $594,681

## Abstract

SUMMARY/ABSTRACT
HIV-associated neuropathic pain (HIV-NP) affects a significant proportion of people living with HIV (PLWH) and
has a major impact on everyday functioning and quality of life in this population. Over the past decade a
growing number of preclinical studies and clinical trials have indicated that cannabis administration and
manipulation of the endocannabinoid (EC) system may have therapeutic utility in addressing HIV-NP. EC CB2
receptor activation and inhibition of the EC deactivation enzymes fatty acid amide hydrolase (FAAH) and
monoacyglycerol lipase (MAGL) have been shown to decrease pain in rodent models of HIV-NP, while acute
exposure to cannabis reduces self-reported pain in PLWH with neuropathy. However, little work has been
conducted to elucidate the effects of the two primary cannabinoids (delta-9-tetrahydrocannabinol, THC and
cannabidiol, CBD) on the EC system or to assess EC function in PLWH. The objective of this application is to
address these fundamental gaps in our knowledge by: 1) examining the acute effect of administering NIDA-
prepared THC/CBD products on HIV-NP; 2) utilizing mHealth text messaging to monitor daily real-world self-
administered cannabis effects on pain; 3) assessing the relationship between cannabinoids and EC
biomarkers, including ligands, enzymes, and receptor expression; and 4) conducting exploratory analyses to
evaluate the effect of longitudinal cannabinoid use on changes in HIV-NP over time. We will examine the effect
of low (0.20%), medium (1.3%), and high (13%) CBD-containing cannabis on NP, the EC system (ligands AEA
and 2-AG, enzymes FAAH and MAGL, CB2 receptor expression), and heart rate variability (as a proposed
objective biological measure of pain) in 120 PLWH who use cannabis to treat neuropathic pain. We will
subsequently employ a mobile phone text messaging system, the Individual Monitoring of Pain And Cannabis
Taken (IMPACT), to track cannabis exposure, CBD and THC consumption, and pain over a period of 6 months
in these same PLWH participants. IMPACT will be used quantify the real-time effects of acute CBD/THC
exposure on pain before and after cannabis self-administration, the real-time relationship between self-
reported pain and changes in HRV, and to assess any longitudinal changes in NP, HIV clinical outcomes (viral
load, CD4) and cognition during the 6-month period. This plan allows us to acquire data and compare the
effects of cannabis product obtained from NIDA and self-administered cannabis obtained from local medicinal
dispensaries. The overarching hypothesis is that CBD exposure and a higher CBD/THC ratio will exert
beneficial effects both in the laboratory and during the observational study, including increasing EC biomarkers
and reducing NP. In summary, this approach will advance our understanding about several key issues,
including the interaction between cannabis constituents, the EC system and pain, the biological mechanisms
that underlie these effects (EC enzymes...

## Key facts

- **NIH application ID:** 9838198
- **Project number:** 5R01DA043430-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RONALD J. ELLIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $594,681
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838198

## Citation

> US National Institutes of Health, RePORTER application 9838198, Effect of Cannabis Administration and Endocannabinoids on HIV Neuropathic Pain (5R01DA043430-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838198. Licensed CC0.

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