Nicotine promotes focus and, unfortunately, cardiovascular stress. A recent study discovered that a terpene known as beta-caryophyllene prevents aortic damage caused by nicotine. And it did so by activating a cannabinoid receptor. Nature provides solutions, but that doesn’t necessarily mean you should roll a spliff.
The study exposed mice to vaporized nicotine. (1) Researchers sacrificed the rodents to analyze the aortic wall after vapour sessions because sacrificing humans is unethical. But further research can confirm the current results.
The aorta is the largest artery, and its wall comprises three layers. Situated behind the heart in the shape of a cane, the aorta delivers oxygen-rich blood throughout the body. But a weakened aorta can balloon in the chest and cause an aneurysm or worse, a rupture or dissection.
Stable side effects: shortness of breath, sore back or abdominal pain, difficulty swallowing, and hoarseness.
Rupture side effects: ripping sensation in the chest, pain in the back, difficulty walking/speaking, and dizziness.
Nicotine and b-caryophyllene were featured in prior addiction studies, including a study by the National Institute on Drug Abuse in Maryland, USA. Nicotine is addictive due to selectively agonizing ACH receptors. To combat this, vaporized beta-caryophyllene uses CB2 receptors to turn down dopamine in the reward pathway. (2)
Nicotine selectively picks up acetylcholine, which releases dopamine, driving the reward response — the hook that grabs people. In contrast, CB2 receptor agonists, including caryophyllene, inhibit dopamine receptors in the midbrain. Beta-caryophyllene, therefore, helps remove nicotine’s hook.
Risk versus reward
Tobacco (Nicotiana) is still a traditional and spiritual medicine Indigenous to the Americas. (3) Regardless, claims that nicotine is non-toxic ignore risk versus reward. (4) The harms of smoking are apparent, given the CDC stated that tobacco smoking is the number one cause of preventable death in 2021.
That said, one study noted a reduction in Alzheimer’s disease in smokers compared to non-smokers. Nicotine likely reduces the risk for Alzheimer’s and Parkinson’s Disease by eliminating plaque in the brain, or more specifically, beta-amyloid proteins. But the reduction is not dramatic and comes with other side effects. (5)
Nicotine — first isolated in 1828 (6) — is physically addictive and can be lethal in doses over 500 milligrams depending on absorption. (7) Furthermore, it can strain the aorta wall by inducing an enzyme known as MMP-2. (8) Research from Japan — which analyzed beta-caryophyllene’s role — confirmed nicotine’s function on MMP-2 from a previous study. (1)
Preventing aortic damage
As it turns out, beta-caryophyllene idles damage to the artery’s wall by inhibiting MMP-2 (matrix metalloproteinase-2.) Yet, the terpene depends on (mouse) CB2 receptors to reduce the enzyme and aortic damage caused by nicotine. Mice treated with beta-caryophyllene and nicotine vapour were less susceptible to artery rupture compared to mice only given nicotine.
Beta-caryophyllene did not affect the artery wall’s thickness, despite reducing the risk for rupture. Instead, the terpene attenuated a reduction in elasticity. Researchers used Gas Mass Spectrometry to determine beta-caryophyllene levels in aorta tissue after sacrificing the mice. Their results confirm that terpenes saturate blood and arterial tissues.
Smoking but also vaporizing nicotine induces Reactive Oxygen Species (ROS.) And MMP-2 — the enzyme that weakens the aorta — is released by reactive oxygen species. In contrast, cannabinoids are potent antioxidants. Cannabinoid receptor agonists, including the terpene beta-caryophyllene, quell ROS which prevents aortic damage caused by nicotine.
Beyond reactive species and enzymes, nicotine agonizes specific metabolic processes. And CB2 receptor agonists regulate the same mechanisms.
Body weight and water intake, which were lower in the nicotine group, were also unaffected by caryophyllene vapour. The terpene did restore a nicotine-induced drop in glucose, though. Interestingly, Vitamin B3 activates similar parts of the ACH receptor as nicotine but with some key differences. Remember, Vitamin B3 — also known as nicotinic acid — causes redness and tingling and is even toxic in extreme doses.
Another reminder — terpene vapour should not contain toxins. But combusting aromatic hydrocarbons, especially the terpene limonene, can emit toxins that cause more damage than pure nicotine.
Sources analyzing terpene affect on preventing damage from nicotine
Inhaled volatile β-caryophyllene is incorporated into the aortic wall and attenuates nicotine-induced aorta degeneration via a CB2 receptor-dependent pathway. Biomedicine & Pharmacotherapy. 2022;153:113423.
He Y, Galaj E, Bi GH, Wang XF, Gardner E, Xi ZX. β-Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents. Br J Pharmacol. 2020;177(9):2058-2072. doi:10.1111/bph.14969
Pollan, M. 2022. How to Change Your Mind. Ep.1. Netflix.
van Duijn CM, Hofman A. Relation between nicotine intake and Alzheimer’s disease. BMJ. 1991;302(6791):1491-1494. doi:10.1136/bmj.302.6791.1491
Posselt W, Reimann L. Chemische Untersuchungen des Tabaks und Darstellung des eigenhumlichen wirksamen Principes dieser Pflanze. Geigers Magazin der Pharmazie 1828;24: 138-61
Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88(1):5-7. doi:10.1007/s00204-013-1127-0
Wang, S., Zhang, C., Zhang, M. et al. Activation of AMP-activated protein kinase α2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo. Nat Med18, 902–910 (2012).