# ICAL: Impact of Cannabinoids Across Lifespan

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $2,181,939

## Abstract

PROJECT SUMMARY: OVERVIEW
Teenagers use cannabis more than any other recreational drug. Their developing brains may also be
especially vulnerable to its effects, as epidemiological and experimental evidence suggests that
frequent cannabis use in adolescence may be associated with impairments in cognitive and affective
functioning that continue in adult life. Excessive stimulation of the endogenous cannabinoid (ECB)
system – the target of cannabis’s main psychoactive component, Δ9-tetrahydrocannabinol (THC) – is
a plausible but still poorly understood mechanism for the long-lasting consequences of cannabis use.
We propose the creation of a NIDA Center of Excellence, entitled Impact of Cannabinoids Across
Lifespan (ICAL), to test the hypothesis that non-physiological activation of the ECB system in
adolescence – caused by exposure to THC – initiates an epigenetically driven reprogramming of the
processes that govern the molecular structure, neuroanatomical architecture and synaptic functions of
this system, ultimately producing persistent abnormalities in cognition and motivated behavior. To test
this hypothesis, ICAL will deploy a vertically integrated strategy combining molecular,
neuroanatomical, electrophysiological and behavioral approaches. Specific mechanistic questions will
be addressed bringing to bear, as needed, current techniques such as chemogenetic (DREADD)
control of neural circuit activity. Synergistic integration within ICAL will be fostered by (a) a shared
Administrative Core that will ensure the seamless operation of the center; (b) Animal and Analytical
Cores, which will provide a consistent and well-characterized source of experimental subjects for all
projects; and (c) a Pilot Core, which will allow for the exploration of important new ideas arising inside
or outside the center. A structured set of measures (strict adherence to treatment protocols, animal
subject randomization, blind-testing) will ensure the rigor and reproducibility of our studies. A broad
program of outreach activities will target the scientific community (through undergraduate/graduate
student and faculty mentoring, a bimonthly seminar series and an international “state-of-the-field”
workshop, sponsored by the peer-reviewed journal Cannabis and Cannabinoid Research), health care
professionals and general public (through an annual Cannabis Awareness Day and a website
dedicated to the lay-term dissemination of new scientific discoveries in the field). In a context of
rapidly changing laws, social attitudes and economic interests, the enduring consequences of
adolescent cannabis use on brain development and mental function remain largely unknown. ICAL’s
mission is to fill this knowledge gap while enhancing our mechanistic understanding of the functions
serves by the ECB system in the brain, educating a new generation of cannabinoid researchers, and
disseminating scientific discoveries about cannabis and its effects.

## Key facts

- **NIH application ID:** 9934167
- **Project number:** 5P50DA044118-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Daniele Piomelli
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,181,939
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934167

## Citation

> US National Institutes of Health, RePORTER application 9934167, ICAL: Impact of Cannabinoids Across Lifespan (5P50DA044118-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934167. Licensed CC0.

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