Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia
About This Grant
Project Abstract In recent years, the prevalence of depression has risen, and with it, the prescribing of serotonergic antidepressants. Approximately 13.2% of adults aged 18 and over report using antidepressant in the past 30 days. Anhedonia (loss of interest or pleasure in previously rewarding activities) is a common symptom of depression. First-line antidepressants, selective serotonin reuptake inhibitors (SSRIs), can effectively lift low mood, but often come at the cost of further blunting emotion and reward-processing. In contrast, psilocybin (a 5HT-2A psychedelic) has shown promise in alleviating anhedonia and improving emotional range, even outperforming SSRIs in head-to-head trials. Emerging clinical research supports the safety and efficacy psilocybin in individuals currently taking an SSRI, offering a promising new adjunctive treatment option for those experiencing residual anhedonia. Despite this potential, the neural mechanisms underlying psilocybin's therapeutic effects on anhedonia remain poorly understood. Parallel fronto-limbic circuits—connections between the medial prefrontal cortex (mPFC) and limbic system—regulate motivation and emotional response. One crucial circuit, connecting the pregenual anterior cingulate cortex (pgACC) and the nucleus accumbens (NAcc), forms the core of the brain’s reward system and is implicated in anhedonia. In anhedonia, activity and connectivity in this pgACC-NAcc circuit is suppressed. SSRIs may further suppress this circuit, leading to residual deficits in motivation and pleasure. This study will use a clinical trial to assess the effects of a single dose of psilocybin (25 mg single dose) or control (psilocybin 1mg) in individuals experiencing SSRI-induced anhedonia. We will utilize Precision Functional Mapping (PFM), a novel fMRI technique enabling individual-specific brain mapping, to investigate how psilocybin modulates fronto-limbic circuitry in individuals with SSRI-induced anhedonia. In addition to PFM, we will use well-validated task-fMRI (emotional processing, monetary incentive delay) to probe key fronto-limbic circuits. Then we will test the ability of psilocybin to engage reward circuitry relevant to anhedonia. This work will advance our mechanistic understanding of anhedonia, identify biomarkers for targeted treatment, and potentially lead to more effective therapies.
Grant Summary
Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia is a NIMH - National Institute of Mental Health grant providing up to $871K for university, nonprofit, healthcare org. Applications are due 2030-11-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $871K
2030-11-30
- 1Confirm your organization is eligible for Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia from NIMH - National Institute of Mental Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIMH - National Institute of Mental Health before the deadline.
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Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia: Frequently Asked Questions
Who is eligible for the Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia?
Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia is offered by NIMH - National Institute of Mental Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia provide?
Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia provides up to $871K per award from NIMH - National Institute of Mental Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia deadline?
Applications for Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia are due 2030-11-30 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia?
To apply for Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIMH - National Institute of Mental Health.