Behavioral data for: A preclinical model of THC edibles that produces high-dose cannabimimetic responses

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 1 and 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. Acute acoustic startle responses were measured to
investigate THC-induced psychotomimetic behavior. When allowed access for
2 h to THC-E-gel on the second day of a three-day exposure paradigm, adult
mice consumed up to ≈30 mg/kg over 2 h which resulted in robust
cannabimimetic behavioral responses (hypolocomotion, analgesia and
hypothermia). Consumption of the same gelatin decreased on the following
3rd day of exposure. Pharmacokinetic analysis show that 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 THC intraperitoneal
(i.p.) injections. THC-E-gel consumption increased the acoustic startle
response in males but not in females, demonstrating a sex-dependent effect
of consumption. Thus, while voluntary consumption of THC-E-gel triggered
equivalent cannabimimetic responses in male and female mice, it
potentiated acoustic startle responses preferentially in males. We build a
dose-prediction model that included cannabimimetic behavioral responses
elicited by i.p. versus THC-E-gel to test the accuracy and
generalizability of this experimental approach and found that it closely
predicted the measured acoustic startle results in males and females. In
summary, THC-E-gel offers a robust preclinical experimental approach to
study cannabimimetic responses triggered by voluntary consumption in mice,
including sex-dependent psychotomimetic responses.