# Microdosing Implant to Mitigate Depression Associated with Opioid Use Disorder

> **NIH NIH R41** · INTERVAL THERAPEUTICS LLC · 2024 · $306,556

## Abstract

Project Summary/Abstract
The opioid epidemic is one of the major crises of our time, causing over 80,000 opioid-related overdose deaths
per year in the United States and levying massive economic burden on our healthcare system. More than half of
the ~2 million individuals suffering from OUD have co-occurring mental illness, and it is well-established that
depression during withdrawal is a major cause of relapse. Therefore, therapeutic strategies to better address
depression associated with OUD are desperately needed. 5HT2A agonists (e.g. lysergic acid diethylamide (LSD)
and psilocybin) showed therapeutic promise for treatment-resistant depression (TRD) in early studies, but
research involving these psychedelic agents fell precipitously once they were categorized as Schedule I banned
substances in 1971. Although the benefits of 5HT2A agonists are being re-discovered – the FDA recently granted
“Breakthrough Therapy” designation to psilocybin in 2018 – patients must remain under observation with
psychological support during administration, and the therapeutic impact of a single dose eventually subsides. An
alternative treatment paradigm with promise of relieving mood disorder and lessening the likelihood of relapse
long-term is known as microdosing, where sub-perceptual doses of 5HT2A agonists are ingested every 3-7 days.
Those who microdose report a range of benefits including improved mood and decreased craving for addictive
substances, and scientifically rigorous trials and preclinical studies in animal models are beginning to corroborate
some, albeit not all, of the anecdotal claims. However, practical barriers such as low compliance, abuse and
diversion, access, medical cost, and placebo/expectancy effects from frequent interactions with the clinical staff
stymie further clinical investigation into this promising therapeutic modality. To overcome these practical
limitations, we have developed bioresorbable microdevices that deliver intermittent sub-perceptual 5HT2A agonist
microdoses. The innovation that makes intermittent microdosing possible is the use of a microfluidic “fuse" that
creates a pre-programmed delay for the desired pulsatile release profile. The fuses are fabricated from surface-
eroding cellulose acetate phthalate (CAP) and Pluronic® F-127 (P) polymer composites packed into
microchannels within a poly-𝜀-caprolactone (PCL) device body. A series of microfabricated drug reservoirs
beneath the CAPP fuse release their contents as the fuse dissolves. The current STTR proposal will move
these devices closer to clinical relevance by producing devices with highly tailored release profiles (Aim 1)
and demonstrating absorption and bioactivity of psilocybin upon release from the implants (Aim 2). Success of
this proposal will result in a disruptive new technology to enable microdosing as a therapeutic modality and offer
much-needed new options for patients suffering from OUD. After accomplishing our aims in Phase I, we will be
well-position...

## Key facts

- **NIH application ID:** 11067460
- **Project number:** 1R41EB036916-01A1
- **Recipient organization:** INTERVAL THERAPEUTICS LLC
- **Principal Investigator:** Katie Heath
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $306,556
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11067460

## Citation

> US National Institutes of Health, RePORTER application 11067460, Microdosing Implant to Mitigate Depression Associated with Opioid Use Disorder (1R41EB036916-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11067460. Licensed CC0.

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