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What Happens When Mice Eat Edibles?

A story about mice who like to party

There’s this type of mouse that apparently likes to consume psychoactive drugs — at least that’s been demonstrated for morphine [1] and ethanol [2]. The latter was shown in an experiment that would have made The Boss happy, called Drinking in the Dark. But just because drunkard rodents can slug back some sauce doesn’t mean they would willingly eat delta-9-tetrahydrocannabinol (THC), does it? A recent study sought answers, not quite in regards to my inquiry, but rather to investigate edibles as a means of self-administering THC. [3]

Whereas there are several studies in the scientific literature that demonstrate cannabinoid self-administration in animals through intravenous (IV) delivery, this study sought to evaluate self-administration of THC in B6 mice using edibles. [3] The authors pointed out that IV delivery requires invasive surgery, and that it “often involves food deprivation, restraint, and/or prior exposure to experimenter-administered cannabinoids,” the latter of which has drawbacks, like increased stress in the animal (and maybe the experimenter), the use of administration routes “not used by humans,” and the perhaps more obvious fact that experimenter-administered and self-administered are indeed not the same, unless the experimenter is taking part in the experiment as well.

And so, the researchers whipped up a batch of rodent treats using a basic THC-spiked dough consisting of flour, sugar, salt, and glycerol. Individual servings were divvied up amongst the mice, and the mice were permitted to consume as much dough as they wanted over a defined period (30, 60, 90, or 180 minutes, depending on the experiment).

The researchers conducted three experiments. One considered the impact of gradually increasing the dose, versus providing a fixed dose, on locomotor activity. Locomotion is simply the ability to move, baby, fluidly, freely, without that improperly filled Jupiterian waterbed, or walking through an earthly bog feeling. These mice were kept in solitude.

A second experiment evaluated the impact of gradually increased doses on body temperature. Additionally, the researchers gauged pain relief (analgesia) in these mice, who were paired up with a friend. Experiment 3 investigated the effects of a fixed dose on the body temperature of solitary mice.

The mice enjoyed the dough, as the researchers noted that the “THC dough was well-consumed, with some reduction at higher doses.” Some mice knew their limit, but several mice consumed all the dough up to 10 mg/kg. The mice exhibited decreased locomotion in a dose-dependent fashion which lasted multiple hours in both females and males. This effect could be attenuated using the CB1 receptor antagonist called Rimonabant, which tried daylighting as an anorectic anti-obesity drug that was never actually approved in the United States.

Regardless of whether the mice were flying high in solo or partnered fashion, dough consumption was statistically similar.

When the females chronically ate the dough, their body temperature didn’t change, but when the dough was provided at a fixed dose, their body temperature slightly decreased. THC consumption caused the male mice to modestly chill.

The THC-infused dough didn’t lead to pain relief, but one of the most interesting and unsurprising conclusions pretty much envelopes the experiment with a flower-shaped bow. And I quote: “The simple fact that mice self-administered THC dough could be seen as evidence that it is rewarding.” Higher doses might have spooked the mice, but the researchers suggested that incorporating some cannabidiol (CBD) into their next batch of dough might lasso whatever thoughts or feelings were spiraling inside the little mice brains.

The thing is, though, that the mice also liked to eat the control dough, sans THC. The researchers questioned whether the mice tolerated THC to a certain point just to get at the dough. Perhaps a batch with zero sugar might provide some indication.

Another interesting aspect of the study was that females approached the control and THC-laden doughs more cautiously. Female mice also showed slowed locomotion at a lower dose (2 mg/kg) than the males, which interestingly was longer in duration than at higher doses. At 5 mg/kg, however, the males revealed a more pronounced and longer lasting response than the females, especially when they hadn’t a chance to acclimate themselves to lower doses.

Mice may and people do like edibles. They offer a familiar method of administration with long-lasting and pleasant effects despite the inefficiency of getting THC into the bloodstream — pleasant, that is, if the nascent consumer can get past not woofing down the whole candy bar in their indoctrinations to the form. But this study highlights that edibles can also be considered in scientific experiments meant to evaluate things like THC reward or reinforcement, and “consequences of oral THC use.” [3]

Some mice just like to party. I know, as I’ve had a couple traipse onto my land. But I’ve got cats, and they like to party too…

References

[1] Belknap, J. et al. “Voluntary Consumption of Morphine in 15 Inbred Mouse Strains,” Psychopharmacology (Berl.), volume 112, 1993, pp. 352-358. [journal impact factor = 3.875; cited by 84 (ResearchGate)]

 

[2] Rhodes, J. et al. “Mouse Inbred Strain Differences in Ethanol Drinking to Intoxication,” Genes Brain Behav., volume 6, 2007, pp. 1-18. [journal impact factor = 3.157; cited by 226 (ResearchGate)]

 

[3] Smoker, M. et al. “Self-Administration of Edible Δ9-Tetrahydrocannabinol and Associated Behavioral Effects in Mice,” Drug and Alcohol Dependence, volume 199, 2019, pp. 106-115. [journal impact factor = 3.466; cited by 0 (ResearchGate)]

 

Image Credit: cutestpaw.com

About the author

Jason S. Lupoi, Ph.D.

Jason S. Lupoi, Ph.D.

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