Reviewer #3 (Public Review): A preclinical model of THC edibles that produces high-dose cannabimimetic responses
Year: 2023
Type: peer-review
Abstract: No preclinical experimental approach enables the study of voluntary oral consumption of high-concentration Δ9-tetrahydrocannabinol (THC) and its intoxicating effects, mainly owing to the aversive response of rodents to THC that limits intake. Here we developed a palatable THC formulation and an optimized access paradigm in mice to drive voluntary consumption. THC was formulated in chocolate gelatin (THC-E-gel). Adult male and female mice were allowed ad libitum access for 2 h. Cannabimimetic responses (hypolocomotion, analgesia, and hypothermia) were measured following access. Levels of THC and its metabolites were measured in blood and brain tissue. Acoustic startle responses were measured to investigate THC-induced psychotomimetic behavior.Adult mice consumed high-dose THC-E-gel (≈30 mg/kg over 2 h) and exhibited robust CB1 receptor-dependent behavioral responses. High-dose THC-E-gel consumption led to parallel accumulation of THC and its psychoactive metabolite, 11-OH-THC, in brain, a profile that contrasts with the known rapid decline in brain 11-OH-THC levels following intraperitoneal THC injections. High-dose THC-E-gel consumption increased the acoustic startle response preferentially in males, and this psychotomimetic response was remarkably different from the response triggered by intraperitoneal contingent administration of THC. Comparing cannabimimetic responses elicited by intraperitoneal versus oral administration enabled a “predicted dose” model of THC triggered behavioral changes. Significantly, voluntary consumption of high-dose THC-E-gel triggered equivalent cannabimimetic responses in male and female mice but increased acoustic startle response preferentially in males. Thus, THC-E-gel offers a robust preclinical experimental approach to study cannabimimetic responses triggered by voluntary consumption in mice, including sex-dependent psychotomimetic responses.
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4387448286