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CBD, nicotine metabolism, and cigarette consumption

Updated: Jan 17, 2023

A first-of-its-kind study found that cannabinoids affect nicotine. It was already known that individuals who do not use nicotine more often express a natural deficiency in metabolic processes impacted by cannabinoids. One cannabinoid, cannabidiol (CBD), was found to increase the bioavailability of nicotine by delaying its metabolism, which in turn may reduce cigarette consumption.

Researchers from the College of Pharmacy and Pharmaceutical Sciences at Washington State University alongside Dr. Joshua Muscat from Penn State University exposed nicotine to CBD in a substrate of cells acutely expressing two select enzymes. The study used cells from mouse and human tissue, analyzing nicotine metabolites with Ultra Performance Liquid Chromatography and Mass Spectrometry.

CBD, nicotine, and drug digestion

Drug interactions with CBD are a crucial topic since CBD can block enzymes used by the body to break down molecules, which include certain drugs, THC, and terpenes. Additionally, CBD can also inhibit its own enzymatic degradation. Before the recent in vitro study, however, it was currently not known if CBD or other cannabinoids block the enzymes responsible for metabolizing nicotine.

Special enzymes, known as Cytochrome P450, convert CBD to 7-OH-CBD. The CYP family is a group of metabolic enzymes, each with a unique shape and property that allows them to bind to and break down different molecules. CBD can inhibit the activity of various members of the CYP family.

The Cytochrome P450 superfamily contains two enzymes that play a major role in the metabolism of nicotine. CBD can inhibit these enzymes and reduce the conversion of nicotine into several metabolites by over 50% depending on the dose. Unique enzymes not affected by CBD are, however, still able to break down nicotine.

CBD blocks a route in nicotine’s metabolic path

Nicotine metabolism (left) and CBD metabolism (right) Photo courtesy of ACS by Nasrin et al. 2023.

Nicotine quantities decrease by half in one to two hours following oral consumption without interruption by CBD. Cotinine forms once the body exposes nicotine to two CYP enzymes known as 2A6 and 2B6. CBD and 7-OH-CBD block cotinine formation by approximately half.

CBD did not prevent nicotine’s metabolism to nicotine-N′-oxide because cannabinoids do not affect flavin monooxygenases (FMO1 and FMO3), which endogenously oxidize nicotine. The cannabinoid does, however, prevent nornictotine metabolism.

On the other side, the cannabinoid does not block the gut from converting nicotine or its metabolite cotinine into glucuronides (Gluc) through the process of glucuronidation. This process is mediated by the enzyme UGT. However, CBD may alter the ratio of 3HC:cotinine in smokers by inhibiting a specific form of UGT that metabolizes 3-hydroxycotinine into 3HC-Gluc.

Are nicotine metabolites active?

Nicotine primarily activates the nicotinic receptors that normally respond to the neurotransmitter — acetylcholine (ACH). Nornicotine, its metabolite, also agonizes these receptors, but with about half the efficacy. Previous studies in mice have shown that rodents self-administered nornicotine more than saline, implying that it may be addictive in humans.

Cotinine, on the other hand, is inactive. Likewise, Nic-gluc and Cot-gluc are neutral at nicotinic receptors and do not lead to known addictive habits or dependence. This means that CBD increases nicotine metabolism, while at the same time, it encourages the active ingredient in cigarettes to convert to substances that do not increase consumption patterns.

Essentially, the cannabinoid inhibits specific pathways in nicotine metabolism, which unintentionally encourages glucuronidation to inactive end products.

Let us know in the comments if you use CBD and nicotine products. Do you notice an effect from the cannabinoid?

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