# Preclinical assessment of a Sterol Carrier Protein-2 inhibitor in multidimensional opioid withdrawal.

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $256,490

## Abstract

The United States is still struggling with an opioid epidemic and high rates of opioid use disorder (OUD).
Medically supervised withdrawal is an important tool in management of OUD, where opioid discontinuation
occurs either directly from nonmedical opioid use or following agonist treatment. Abrupt discontinuation of
chronic opioid use results in a severe, multidimensional withdrawal syndrome that includes symptoms such as
aches/pain, tremors, gastrointestinal distress, diarrhea, restlessness, as well as increased pain sensitivity
(hyperalgesia), and negative emotional symptoms such as anxiety and irritability. Therefore, managing opioid
withdrawal is a primary treatment goal. There is compelling preclinical evidence supporting a link between opioid
dependence and the endocannabinoid (eCB) system, and delta-9-tetrahydrocannabinol (THC) and other
cannabinoid-1 receptor (CB1R) agonists can reduce opioid withdrawal symptoms. However, direct CB1R
agonist-based medications can produce adverse side effects and have demonstrated abuse liability. New
research suggests that indirect agonism of CB1R through increasing circulating eCBs is a promising strategy as
it confers similar benefits with fewer undesirable cannabimimetic effects. Recently, we determined sterol carrier
protein-2 (SCP-2) acts as a binding and transport protein for eCBs and we have synthesized an SCP-2 inhibitor
(SCPI-1) to block eCB transport and thereby increase eCB tone. This R21 Exploratory/Developmental
application will evaluate the effects of SCPI-1, a novel endocannabinoid transport inhibitor using a
multidimensional model of opioid withdrawal symptoms in rats. Our Primary Aim is to evaluate whether
SCPI-1 attenuates symptoms of spontaneous morphine withdrawal in male and female rats and determine
whether effects of SCPI-1 are via CB1R-dependent mechanisms. Opioid physical dependence will be induced
using a morphine dose escalation and maintenance procedure (opioid dependent group). A second group will
receive saline injections under the same schedule (non-dependent group). Following abrupt discontinuation of
morphine or saline dosing, we will inject SCPI-1 or vehicle under blinded conditions and then assess opioid
withdrawal symptoms that include: 1) somatic signs indicative of withdrawal (e.g., ptosis, wet-dog shakes,
grooms, hypophagia and weight loss) through timed behavioral observations and measures of home cage food
intake and body weights; 2) negative emotional symptoms of anxiety- and irritability- like behavior in the open
field, elevated plus maze, and bottle brush test; and 3) hyperalgesia using the von Frey test of mechanical pain
sensitivity. In addition, we will evaluate if effects of SCPI-1 on withdrawal-related behaviors are CB1R-dependent
through pretreatment with the CB1R antagonist rimonabant or its vehicle under blinded conditions. A Secondary
Aim of this proposal is to evaluate the metabolic stability of SCPI-1 in vitro, a key component of developing this
lea...

## Key facts

- **NIH application ID:** 10425572
- **Project number:** 1R21DA055790-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CHRISTOPHER W CUNNINGHAM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $256,490
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425572

## Citation

> US National Institutes of Health, RePORTER application 10425572, Preclinical assessment of a Sterol Carrier Protein-2 inhibitor in multidimensional opioid withdrawal. (1R21DA055790-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10425572. Licensed CC0.

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