# Investigating the role of THC in mediating pain signaling in the BLA

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $45,685

## Abstract

PROJECT SUMMARY
Chronic pain affects between 40 to 100 million people in the US and managing this pain with opioids has
increased the incidence of opioid substance abuse and death from overdose. There is an urgent and unmet
need for effective chronic pain medications with lower misuse potential. Δ9-tetrahydrocannabinol (THC) is the
most abundant pharmacological agent found within Cannabis and acts via the endocannabinoid (eCB) signaling
system to produce analgesia. Thirty-eight US states have approved legal medical Cannabis for the
pharmacological treatment of pain and anxiety, alongside recreational use in many cases. However, the precise
neuropharmacological and physiological mechanisms of THC use for pain treatment, and the circuit mechanisms
that underlie the pain-relieving properties of THC are unknown. The basolateral amygdala (BLA) is a critical brain
region important for encoding affective information from incoming stimuli and is a key component in pain
processing. The BLA has increased neuronal activity during chronic pain, and glutamatergic neuronal ensembles
detect and report noxious stimuli to cortical structures that impact pain perception. The BLA has enriched
expression of the receptor sensitive to eCBs and THC, cannabinoid 1 receptor (CB1R). The central hypothesis
of this proposal is that THC acts as a partial agonist at CB1R to decrease excitatory BLA neuronal activity and
pain behaviors during chronic pain. This proposal directly addresses the 2022-2026 NIDA Strategic Plan Goal
1.1 to, “Expand our understanding of the biological mechanisms underlying drug use, addiction, diverse
treatment responses…” and the NINDS 2021-2026 Strategic Plan to“… extend progress in prevention for
neurological diseases beyond stroke, building on basic research advances in epilepsy, TBI, neurodegenerative
diseases, chronic pain...” Aim 1 will determine whether THC acts within the BLA at CB1Rs to alter glutamatergic
neuronal activity to promote analgesia during chronic pain. In this aim, we will multiplex classic
neuropharmacology and dual-color fiber photometry with a machine learning-based behavioral tracking platform
to directly correlate local THC-action and neural activity with naturalistic chronic pain behaviors. We then propose
in Aim 2 to decode how and where THC alters specific BLAglu neuronal ensemble activity during chronic pain.
We will use in vivo 2-photon calcium imaging, a CRISPR site-specific CB1R deletion strategy, and a head-fixed
behavioral paradigm to observe glutamatergic BLA neuronal ensembles during pain. These findings will provide
foundational knowledge informing the cannabinoid, substance abuse, neuropharmacology, and pain fields. For
this proposal, I will gain training and expertise in the use of pharmacological, novel biological and high resolution
computational techniques and learn valuable career development skills through a wide variety of scientific,
intellectual, and mentored opportunities. This F31 proposal is specifi...

## Key facts

- **NIH application ID:** 10995720
- **Project number:** 1F31DA061576-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kaylin Ellioff
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,685
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995720

## Citation

> US National Institutes of Health, RePORTER application 10995720, Investigating the role of THC in mediating pain signaling in the BLA (1F31DA061576-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995720. Licensed CC0.

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