# In vitro and in vivo characterization of CB1 allosteric modulators

> **NIH NIH K01** · UPSTATE MEDICAL UNIVERSITY · 2022 · $159,535

## Abstract

PROJECT SUMMARY
The cannabinoid type-1 (CB1) receptor is a promising pharmacotherapeutic target for many diseases as
evidenced by a large body of preclinical and clinical data showing efficacy treating drug dependence/addiction,
pain, obesity/metabolic syndrome, and others. Unfortunately drugs developed that target the CB1 receptor either
directly or indirectly have had limited success, i.e. dronabinol produces undesired psychoactivity, rimonabant
produces depression/suicidal ideation, and PF-04457845 did not demonstrate efficacy. Important considerations
in the therapeutic vs. nontherapeutic effects of CB1 activation are the various signaling pathways that contribute
to either of these. Allosteric modulation provides an additional vector through which the CB1 receptor can be
manipulated for therapeutic gain. This study proposes to 1) examine novel structural analogs of established CB1
allosteric modulators for their ability to alter orthosteric ligand binding, function, and signaling bias; 2)
characterize G protein subtype-dependent coupling by orthosteric and allosteric ligands; and 3) assess the
effects of CB1 allosteric modulators in assays of cannabinoid activity. My goals for this career development
award are to build on my laboratory’s capabilities and prepare for independence as a principal investigator in the
behavioral and molecular pharmacology of drug abuse. Under this award I will receive training in grantsmanship,
laboratory management, budget management, and responsible conduct of research. These career development
activities will include one-on-one training with co-mentors as well as workshops to provide me with necessary
training to successfully compete for R01 funding and develop a highly productive and efficient independent
research program.

## Key facts

- **NIH application ID:** 10954461
- **Project number:** 7K01DA045752-06
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Thomas F Gamage
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,535
- **Award type:** 7
- **Project period:** 2023-11-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10954461

## Citation

> US National Institutes of Health, RePORTER application 10954461, In vitro and in vivo characterization of CB1 allosteric modulators (7K01DA045752-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10954461. Licensed CC0.

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