Adolescent THC Edible Experience Made Alcohol's Stimulant Effects Stronger in Rats and Changed Brain Endocannabinoid Levels | Research

The takeaway

Rats given THC edibles during adolescence showed enhanced stimulant responses to alcohol as adults, and alcohol withdrawal reduced endocannabinoid levels in the frontal cortex, with interactive effects between prior THC and alcohol exposure on specific endocannabinoids.

Addiction researchers, adolescent health specialists, substance use prevention scientists.

Prior adolescent THC experience enhanced alcohol stimulant effects in rats

What the researchers found

Adolescent edible THC experience facilitated alcohol-induced increases in moving speed on a maze. Combined THC-alcohol exposure did not produce additive memory deficits on the Barnes maze. Alcohol abstinence significantly reduced endocannabinoid levels (OEA and SEA) in the frontal cortex. Reductions in OEA and SEA showed interactive effects with THC discontinuation. Little effect was observed in the hippocampus.

Why it matters

Cannabis and alcohol are the most commonly co-used substances among adolescents, yet how prior THC exposure changes the brain's response to alcohol is poorly understood. This study shows THC primes the brain to respond differently to alcohol.

The numbers in context

Adolescent THC via cookies. Post-THC alcohol dose: 3 g/kg. Increased moving speed on Barnes maze with combined exposure. OEA and SEA reduced in frontal cortex during alcohol abstinence. Interactive THC-alcohol effects on OEA and SEA.

How the study worked

Male Long Evans rats given daily dronabinol-laced cookies during adolescence. Three days after discontinuation, tested with oral alcohol (3 g/kg) on Barnes maze. Endocannabinoid levels measured in hippocampus and frontal cortex.

What this study cannot tell us

Male rats only. Single THC dose regimen. Barnes maze is one specific cognitive test. Endocannabinoid measurements at one timepoint only. Dronabinol (synthetic THC) may differ from whole-plant cannabis. Cannot extrapolate doses directly to human adolescents.

How to read the evidence

Animal study examining a relatively understudied question. Novel endocannabinoid findings but limited to male rats.

When this study was published

Published in 2023.

The bigger picture

The finding that THC experience enhanced alcohol's stimulant properties is concerning because stimulant effects of alcohol (increased energy, reduced sedation) are associated with greater drinking and higher risk for alcohol use disorder. Prior cannabis use during adolescence may set up the brain for riskier alcohol responses.

Questions still open

Does adolescent cannabis use in humans similarly enhance the stimulant effects of alcohol?
Could the OEA and SEA changes be biomarkers for vulnerability to alcohol problems after cannabis exposure?

Common questions

Does using cannabis as a teen change how alcohol affects you?

In this rat study, adolescent THC edible experience made alcohol's stimulant effects stronger in adulthood. Stimulant effects of alcohol are linked to heavier drinking patterns.

Did THC plus alcohol cause worse memory?

Surprisingly, combined exposure did not produce additive memory deficits on the maze test, though frontal cortex endocannabinoid levels were significantly affected.

Read the original research

Experience with dronabinol consumption facilitated a stimulant effect of alcohol and affected alcohol-related changes in frontal cortical endocannabinoid levels in male rats.

Behavioural brain research, 452, 114587

View on PubMed ↗Publisher’s paper ↗

Citation

Sangiamo, Daniel T; Weingarten, Michael J; Nelson, Nnamdi G; Choi, Chan Young; Das, Aditi; Liang, Nu-Chu. (2023). Experience with dronabinol consumption facilitated a stimulant effect of alcohol and affected alcohol-related changes in frontal cortical endocannabinoid levels in male rats.. Behavioural brain research, 452, 114587. https://doi.org/10.1016/j.bbr.2023.114587