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Updated: Jul 5, 2026
Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Oral THC produces minimal behavioral alterations in preadolescent rats
1Department of Physiology/Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States. Diana.dow-edwards@downstate.edu
Insights
Oral administration of Delta-9-tetrahydrocannabinol (THC) in young rats showed minimal behavioral effects. Slow absorption via gavage may result in sub-psychoactive brain concentrations, unlike intraperitoneal THC administration.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Psychology
Background:
- Traditional THC administration during the perinatal period in rats is oral.
- Postnatal THC studies often use intraperitoneal (IP) administration.
- A consistent route of administration for prenatal and postnatal THC studies is lacking.
Purpose of the Study:
- To investigate the behavioral effects of orally administered Delta-9-tetrahydrocannabinol (THC) in rats during postnatal development.
- To compare oral THC administration with previously reported IP administration effects.
- To explore potential reasons for discrepancies in THC's behavioral impact.
Main Methods:
- Rats (male and female) received oral THC (in sesame oil) via gavage on postnatal days 22-40.
- Behavioral activity was quantified using the Accuscan activity monitor 40 minutes post-administration on days 22, 29, and 40.
- Active and passive avoidance behaviors were assessed in adulthood (up to 140 days of age).
Main Results:
- Acute oral THC administration produced subtle effects on activity during the treatment period.
- Minimal effects on active and passive avoidance behaviors were observed in adulthood.
- These findings contrast with studies using IP THC administration in periadolescent rats, which reported behavioral alterations.
Conclusions:
- Oral administration of THC in rats during late postnatal development (days 22-40) resulted in limited acute behavioral changes.
- The slow absorption rate of orally administered THC may lead to sub-psychoactive brain concentrations.
- This route of administration, especially with mild food deprivation, might explain the lack of significant behavioral findings compared to IP administration.
Abstract:
Although the oral route has traditionally been used for THC administration during the perinatal period in the rat, most studies administering THC during the postnatal period utilize intraperitoneal (ip) administration. In an effort to utilize the same route of administration in both prenatal and postnatal studies, we administered Delta-9-tetrahydrocannabinol (THC) in sesame oil by gavage during postnatal days 22-40 (equivalent to childhood to early adolescence) to male and female rats. We quantified behavior 40 min after administration in the Accuscan activity monitor on days 22, 29 and 40. In addition, we examined active and passive avoidance behaviors in treated adults. Acutely, THC had subtle effects on activity when measured during the period of drug administration and minimal effects on avoidance behaviors examined up to 140 days of age. Since several groups have found that lower doses of THC administered intraperitoneally to periadolescent rats do produce behavioral alterations, we suspect that the inordinately slow absorption of the drug via the oral route may be responsible for the paucity of significant findings in our study. Therefore, oral administration of THC, particularly under conditions of mild food deprivation, may lead to sub-psychoactive concentrations of the drug within the brain.
