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Optimizing rodent models of drug discrimination and self-administration of vaporized cannabis extracts for medications development

Award Number: R21DA064845
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Optimizing rodent models of drug discrimination and self-administration of vaporized cannabis extracts for medications development - Summary The goal of this R21 NIH Exploratory/Developmental Research project is to advance development of rodent models of drug discrimination, drug-seeking and self-administration of vaporized cannabis extract to facilitate future medications development for cannabis use disorder (CUD). There are no FDA-approved medications for CUD, and development of effective pharmacotherapies is hindered the lack of appropriate rodent models demonstrating the reinforcing effects of cannabis (CAN) or its primary psychoactive cannabinoid, Δ-9- tetrahydrocannabinol (THC). The majority of studies in rodents examining IV self-administration of THC have failed to demonstrate reliable reinforcing effects. There is a critical need to continue development of reliable self- administration models in rodents to increase our understanding of CAN/THC reinforcement and to test novel pharmacotherapies for CUD. The primary route of use for CAN use in humans is via inhalation. Inhalation models using vaporization technology have been validated in rodents using combusted CAN and THC, and may be useful for advancing CAN/THC self-administration models. We will build on lessons learned from these prior studies and leverage our experience with cannabis and its phytocannabinoids to examine the discriminative stimulus effects and reinforcing effects of vaporized CANTHC. Aim 1 will utilize drug discrimination procedures to establish CANTHC vapor discrimination in comparison to intraperitoneally (IP) administered THC, including dose- and time course effects of discriminative stimulus effects. Importantly, we will then identify sufficient and optimal CANTHC vapor training doses for drug discrimination. The resulting data will inform optimal CANTHC vapor doses for self-administration under a second order schedule of reinforcement. We hypothesize that CANTHC vapor will produce discriminative stimulus effects in rats trained to discriminate IP THC and that rats will acquire CANTHC vapor discrimination from vehicle vapor. We expect that the time course of discriminative effects of CANTHC will be more rapid than IP injection and will be associated with plasma levels of THC and metabolites. We also expect the discriminative stimulus effects of CANTHC vapor will be blocked by administration of cannabinoid type-1 receptor antagonist. Aim 2 will evaluate the reinforcing efficacy of CANTHC vapor under a second order schedule of reinforcement in which responding is maintained not only by the CANTHC vapor delivery, but also by contingent presentation of drug-paired stimuli that serve as conditioned reinforcers. We hypothesize that CANTHC vapor will maintain seeking and self-administration responses greater than vehicle under a second order schedule of reinforcement and will result in significant levels of THC and its active metabolites. Development and validation of a translationally relevant CAN vapor drug discrimination and self-administration in rodents is critical to understanding the reinforcing and subjective effects of CAN. Establishing these models provides a necessary platform for the evaluation of novel pharmacotherapies for the treatment of CUD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $194,271 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Drug Use and Addiction Research Programs	000	1	4/28/2026	NEW	$194,271
														Subtotal = $194,271

Grand Total All Awards = $194,271

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Optimizing rodent models of drug discrimination and self-administration of vaporized cannabis extracts for medications development

Award Number: R21DA064845

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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