Study: Delta-8 THC May Dramatically Slow Nicotine Metabolism, Raising Smoking Cessation Potential

A new study published in Drug Metabolism and Disposition found that delta-8 THC can sharply inhibit the body’s ability to break down nicotine, suggesting it may have potential as a smoking-cessation aid. Conducted by researchers from the University at Buffalo, the study examined how delta-8 THC affects CYP2A6, the primary enzyme responsible for metabolizing nicotine into cotinine. Tobacco use remains the leading cause of preventable death worldwide, and nicotine’s addictive effects are closely tied to how quickly it is processed by the body.

In this study, researchers found that delta-8 THC potently inhibited CYP2A6-mediated nicotine metabolism, while delta-9 THC showed no significant inhibition. According to the findings, delta-8 THC acted as an irreversible inhibitor, meaning its effects on the enzyme were not easily reversed once the interaction occurred. The strength of that inhibition varied somewhat depending on a person’s CYP2A6 genotype, indicating genetics may play a role in how strongly delta-8 THC alters nicotine metabolism.

Using static modeling, the researchers estimated that an oral 10 milligram dose of delta-8 THC could increase nicotine plasma exposure by 189%. Even larger increases were projected with 20 milligram and 40 milligram doses. The study also found potential interactions with inhaled delta-8 THC at doses of 70 milligrams or higher.

Researchers say the findings are the first to identify delta-8 THC as a potent and irreversible inhibitor of nicotine metabolism to cotinine. Because slower nicotine metabolism can in some cases reduce the urge to smoke by prolonging nicotine’s presence in the bloodstream, the results suggest delta-8 THC may warrant further study as a possible smoking cessation aid.

The researchers caution that more investigation is needed, particularly to better understand safety, dosing and how genetic differences may influence its effects. Still, the study points to a new and potentially important line of research involving delta-8 THC and nicotine dependence.

They conclude by stating:

In conclusion, the present study is, to our knowledge, the first to demonstrate the irreversible inhibition of nicotine metabolism by Δ8-THC in vitro, highlighting its potential as a smoking cessation agent. To optimize therapeutic outcomes while minimizing toxicity, genotype-informed approaches involving CYP2A6 will be essential. Ultimately, advancing Δ8-THC toward clinical application will require careful characterization of its pharmacokinetics, as well as the incorporation of hepatic uptake transporters into physiologically based pharmacokinetic DDI- pharmacodynamic models to refine dose recommendations across genetically diverse populations

You can find the full text of the study by clicking here.