[R01] Investigating the cannabinoid receptor type 1 (CB1R) availability in individuals with opioid use disorder (OUD)
Ente: National Institute on Drug Abuse
Scadenza: 2031-03-31
Importo max: 659.834 EUR
Paese: US
Descrizione
Project Summary/Abstract
The opioid epidemic continues to pose a major public health challenge, with relapse rates remaining high
despite the effectiveness of opioid agonist therapy (OAT). Relapse is particularly common during the early
phase of treatment and is strongly associated with negative emotional states such as stress, anxiety, and
dysphoria. Current treatments target the opioid system but fail to adequately address these emotional drivers
of relapse. The endocannabinoid (eCB) system, which modulates stress and emotional regulation and closely
interacts with the opioid system, represents a promising non-opioid target for intervention. Preclinical studies
consistently demonstrate dysregulation of the eCB system in animal models of opioid use disorder (OUD),
including low cannabinoid receptor type 1 (CB1R) levels, but its role in humans with OUD, particularly during
early abstinence, remains poorly understood.
The proposed study aims to fill this critical gap by investigating whether CB1R availability is lower in early
abstinent individuals with OUD on OAT, compared to healthy controls (HCs), and whether lower CB1R
availability is associated with high emotional distress and risk of relapse. Preliminary data from our NIDA-
funded R21 study show lower CB1R availability in individuals with OUD maintained on OAT and significant
associations between low CB1R availability and negative emotional states.
Using [11C]OMAR PET imaging, we will assess CB1R availability in 55 early abstinent individuals with OUD
(following inpatient buprenorphine stabilization) and 55 matched HCs (N=110). Individuals with OUD will be
followed for 90 days to assess mood, anxiety, perceived stress, opioid craving, and opioid use outcomes (e.g.,
time to first illicit opioid use, total days and amount used). This study will provide the first in vivo evidence of
CB1R availability during early OAT and test its utility as a predictive biomarker of relapse risk.
If successful, this research will advance our understanding of the neurobiological mechanisms underlying
relapse, and inform the development of novel adjunctive treatments targeting the eCB system during the high-
risk, early phase of recovery in OUD.
Istituzione: YALE UNIVERSITY
PI: Anahita Bassir Nia
Progetto: 1R01DA063712-01A1
Settori: National Institute on Drug Abuse
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