Caffeine and Cannabis Both Alter Brain Chemistry in Young Rats, but in Different Ways | Research

The takeaway

Both caffeine and cannabis changed neurotransmitter and enzyme levels in adolescent rat brains after 21 days of exposure, with caffeine producing more pronounced metabolic effects.

Readers interested in how cannabis and caffeine interact in developing brains.

Combined low-dose caffeine + cannabis produced the most significant increase in metabolic enzyme G-6-PDH

What the researchers found

Juvenile rats given cannabis, caffeine, or both for 21 days showed increased levels of GABA, glutamate, and dopamine across all treatment groups compared to controls.

The metabolic enzyme G-6-PDH was elevated in all treated animals, but the combination of low-dose cannabis plus low-dose caffeine produced the most significant increase. Caffeine alone generated more pronounced neurochemical changes than cannabis alone at the doses tested.

The cytochrome C oxidase results indicated altered energy metabolism in the brain tissue of all treated groups, suggesting both substances affected how developing brain cells process energy.

Why it matters

Adolescence is a critical period for brain development. Understanding how commonly consumed psychoactive substances affect neurotransmitter systems during this window could inform public health approaches to youth substance use. The finding that combining caffeine and cannabis amplified certain metabolic changes raises questions about how these frequently co-used substances interact in developing brains.

The numbers in context

72 juvenile rats across 6 groups. Treatment lasted 21 days. Caffeine doses: 50 and 100 mg/kg. Cannabis doses: 200 and 500 mg/kg. GABA, glutamate, and dopamine were all elevated across treated groups. G-6-PDH was most significantly elevated in the combined low-dose group.

How the study worked

Researchers divided 72 juvenile Wistar rats (approximately 40 days old) into six groups. Controls received nothing; other groups received high-dose caffeine (100 mg/kg), low-dose caffeine (50 mg/kg), high-dose cannabis (500 mg/kg), low-dose cannabis (200 mg/kg), or a combination of low-dose cannabis plus low-dose caffeine. All substances were given orally for 21 days. Brain tissue was then analyzed for neurotransmitter levels (GABA, glutamate, dopamine) and metabolic enzymes (cytochrome C oxidase, G-6-PDH).

What this study cannot tell us

This was an animal study using oral gavage in rats, which does not perfectly replicate human patterns of consumption. The cannabis doses were high by human standards. The study measured tissue levels at a single time point (24 hours after last dose), so the trajectory of changes over time is unknown. Behavioral outcomes were not assessed, so the functional significance of the neurochemical changes remains unclear.

How to read the evidence

Preliminary evidence from a single animal study with a small sample size per group. Findings cannot be directly applied to humans.

When this study was published

Published in 2017. Animal model research on adolescent brain neurochemistry.

The bigger picture

Caffeine and cannabis are two of the most widely used psychoactive substances worldwide, and adolescents frequently consume both. Most research examines each substance in isolation, but this study looked at their combined effects on developing brain chemistry. The results suggest that even at lower individual doses, the combination may produce amplified neurochemical changes that neither substance causes alone.

Questions still open

Do the amplified metabolic effects of combining caffeine and cannabis persist after exposure stops? Would these neurochemical changes translate to measurable cognitive or behavioral differences? How do these findings apply to the much lower cannabis doses typical of human adolescent use?

Common questions

Does this study prove caffeine and cannabis together are dangerous for teenagers?

No. This was an animal study using doses much higher than typical human consumption. It shows that both substances change brain chemistry in young rats and that combining them may amplify certain effects, but translating these findings to human risk requires further research.

Which substance had more effect on the brain, caffeine or cannabis?

At the doses tested, caffeine produced more significant neurochemical changes than cannabis alone. However, combining low doses of both substances produced the largest effect on at least one metabolic enzyme.

Read the original research

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.

Annals of neurosciences, 24(2), 65-73

View on PubMed ↗Publisher’s paper ↗

Citation

Owolabi, J O; Olatunji, S Y; Olanrewaju, A J. (2017). Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.. Annals of neurosciences, 24(2), 65-73. https://doi.org/10.1159/000475895