The National Institutes of Health seeks grant applications from small business concerns (SBCs) to develop psychoplastogenic compounds and new in vivo psychedelic behavioral pharmacology models for drug discovery and drug development for treating Substance Use Disorders (SUD), excluding alcohol use disorder.
Donor Name: National Institutes of Health
State: All States
County: All Counties
Type of Grant: Grant
Deadline: 11/18/2022
Size of the Grant: $2,500,000
Grant Duration: 3 years
Details:
Substance Use Disorders (SUD) are defined as a collection of chronic disorders initiated by the misuse of legal and illicit drugs, then potentially leading to an uncontrollable drug-seeking behavior. The neuroimaging studies of SUD patients have demonstrated abnormal prefrontal cortex (PFC) function. The PFC can regulate the ability of the limbic reward circuitry, modulate attention, and can apply top-down regulation over drug-seeking behavior. Improving PFC function, including non-pharmacological interventions, has led to some success in treating SUD. A promising new drug class of psychoplastogenic compounds (PC) includes a growing class of fast-acting and long-lasting therapeutics which promote structural and functional neural plasticity that extends beyond the acute effects of the treatment. The development of PC-based treatments will help identify the fundamental mechanisms of action for efficacy and eliminate unnecessary side effects which would address the pressing need for new and improved SUD pharmacotherapies.
Research Objectives
The National Institute on Drug Abuse (NIDA) seeks applications to validate PC-based pharmacotherapeutics or in vivo PSD behavioral model or PSD assay development or any combination of these activities in the context of SUD. Projects, proposing the development of PC therapeutics for a DSM5-defined SUD, will be considered equally responsive. Projects that focus on alcohol use disorder or pain as the primary indication will not be responsive and returned without review. Applications developing or utilizing natural or synthetic PC-based compounds entering at either target identification, target validation, assay development (AD), lead identification (LI), lead optimization (LO), or preclinical development (PCD) stages in the following areas for SUD are encouraged and may include:
- Target Identification and Validation Studies
- Investigation of bioactive natural products, related extracts, and the identification of essential active compounds for efficacy and toxicity in in vitro assays (e.g., on and off-target) and preclinical in vivo SUD models;
- Chemical synthesis of novel ligands as selective 5HT2A receptor agonists or other important tools for drug discovery of PC compounds (e.g., full or partial agonists, antagonists, allosteric modulators), purifying and testing synthetic PC candidates for efficacy and toxicity in in vitro assays (e.g., on and off-target) and preclinical in vivo SUD models;
- Drug repurposing and target deconvolution of the PC compounds including psychedelics (e.g., natural and synthetic 5HT2A agonists), non-psychedelics (e.g., 5HT2A agonists both new or known PCs {e.g., TBG, lisuride}), ketamine, and 3,4-Methylenedioxymethamphetamine (MDMA). Other potential PCs may also be considered responsive, if either preliminary data or cited publication evidence is provided (e.g., Salvinorin A, a κ-opioid receptor (KOR) agonist).
- Assay Development, hit-to-lead activities, and in vivo model development
- In vitro PSD and non-PSD assay development to identify phenotypes to triage compounds for PC drug development for subsequent in vivo research. Traditional hit confirmation and validation studies from target-based high content screens from chemical or virtual libraries.
- New In vivo model development (e.g., rodents, nonhuman primates) for PSD PC efficacy studies in comparison to the established models (e.g., head twitch model, drug discrimination model); new model development should include positive and negative control compounds (e.g., psychedelics and non-psychedelic drugs (e.g., lisuride, TBG) along with other controls, such as receptor antagonists (e.g., ketanserin or AAZ-134).
- Lead optimization (LO) studies
- For the LO stage, activities consisting of PC drug candidates demonstrating acceptable in vivo PK and toxicity, feasible formulation, in vivo preclinical efficacy (e.g., sufficiently powered) studies, dose range finding (DRF) pilot toxicology, process chemistry assessment of scale-up feasibility, and regulatory and marketing assessments.
- Preclinical (PCD) studies
- For the PCD stage, activities consisting of PC drug candidates demonstrating acceptable PK (with a validated bioanalytical method), absorption, distribution, metabolism, excretion (ADME) studies; demonstrating in vivo efficacy/activity, acceptable safety margin (e.g., toxicity in rodents or dogs, when appropriate), feasibility of GMP manufacture, acceptable drug interaction profile, and well-developed clinical endpoints.
Funding Information
- Total funding support (direct costs, indirect costs, fee) may not exceed $320,000 for Phase I awards and $2,500,000 for Phase II awards.
- Award periods may not exceed 1 year for Phase I and 3 years for Phase II. Applicants must propose a project duration period that is reasonable and appropriate for completion of the research project.
Eligibility Criteria
Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity.
For more information, visit Grants.gov.
