Cannabis Extract Changed How Rat Livers Processed Other Drugs and Chemicals | Research

The takeaway

Chronic cannabis extract in rats selectively boosted certain liver enzymes that break down drugs and chemicals, including a three-fold increase in an enzyme that processes cancer-causing compounds, with most effects reversing within a week of stopping.

Read this if you take medications alongside cannabis and want to understand potential drug metabolism interactions.

Three-fold increase in carcinogen-activating enzyme AHH

What the researchers found

Rats fed cannabis extract for three weeks at escalating doses showed selective changes in liver enzyme activity. Several enzymes that break down drugs and chemicals (carboxylesterases and amidases) were significantly boosted, with increases ranging from 60% to 125%.

The most concerning finding involved aromatic hydrocarbon hydroxylase (AHH), which processes benzo(a)pyrene, a carcinogenic compound found in smoke. This enzyme was induced approximately three-fold. Since AHH activation of benzo(a)pyrene is a step in its cancer-causing pathway, increased AHH activity could theoretically increase cancer risk from smoke exposure.

Most enzyme changes reversed within seven days of stopping cannabis. However, one cytosolic enzyme (thiacetazone N-deacetylase) remained substantially elevated even after withdrawal, suggesting some metabolic changes persist longer.

Why it matters

This study demonstrated that chronic cannabis use could alter how the liver processes other substances, which has implications for drug interactions. The induction of AHH, which activates carcinogens, is particularly relevant to understanding cancer risk in cannabis smokers.

The numbers in context

Acetanilide N-deacetylase: +125%. NPA esterase: +64%. ASA esterase I: +82%. ASA esterase II: +60%. AHH: approximately 3-fold increase. Most effects reversed within 7 days of stopping. Thiacetazone N-deacetylase remained elevated at 62% after withdrawal.

How the study worked

Animal pharmacology study in rats. Petroleum ether extract of cannabis leaves was administered orally at escalating doses (158, 250, and 500 mg/kg over three weeks). Liver and kidney enzyme activities were measured during treatment and after withdrawal.

What this study cannot tell us

Rat metabolism may differ from human metabolism. The cannabis extract used is not equivalent to modern cannabis products. Doses were high and escalating. The relevance of in vitro enzyme activity changes to actual in vivo drug metabolism is uncertain.

How to read the evidence

An animal pharmacology study with detailed enzyme measurements. Rigorous methodology but limited to rats and high-dose cannabis extract.

When this study was published

Published in 1991. Understanding of cannabinoid-drug interactions has expanded substantially, though many questions remain.

The bigger picture

This study raised two important lines of inquiry that are still active today: whether cannabis alters the metabolism of co-administered medications (drug interactions), and whether cannabis smoke exposure increases cancer risk through carcinogen activation pathways similar to tobacco smoke.

Questions still open

Do human cannabis users show similar liver enzyme induction? Could these enzyme changes alter the effectiveness of medications? Does the AHH induction translate to measurably increased cancer risk?

Common questions

Could cannabis affect how other drugs work?

In rats, cannabis extract altered several liver enzymes that process drugs. If similar effects occur in humans, cannabis could potentially change how quickly medications are broken down.

Did the effects last after stopping cannabis?

Most enzyme changes reversed within 7 days. However, one enzyme (thiacetazone N-deacetylase) remained substantially elevated even after withdrawal.

Read the original research

Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic metabolism of xenobiotics in rat.

Biochemical pharmacology, 41(1), 109-13

View on PubMed ↗

Citation

Khanna, P; Gupta, M B; Gupta, G P; Sanwal, G G; Ali, B. (1991). Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic metabolism of xenobiotics in rat.. Biochemical pharmacology, 41(1), 109-13.