An ever accumulating volume of scientific and preclinical data is suggesting that e-cigarettes are at least as harmful as regular smoking, i.e. combustible cigarettes you light up, and not a safe alternative. Understandably, most of the focus has been on the effects on the lungs, cardiovascular disease, and addiction. But recently, a growing body of scientific studies are starting to show the serious potential negative effects e-cigarette use may have on the brain.

Electronic-cigerettes (e-cigarettes), and more broadly electric vaporizers, have a history that goes back almost 100 years. The modern commercial version of the e-cigarette is usually attributed to the Chinese pharmacist Hon Lik, although numerous patents and related technologies developed by others were prevalent throughout the 1980’s and 90’s.

The immediate urgency in attempting to understand the health effects of e-cigarettes stems from their increasing rate of use, most concerning among young people. The challenge though is that they are simply too new, and not enough time has passed to understand and really appreciate their potential long term clinical effects due to sustained or chronic use.

Among high school students, the use of tobacco products had been on the decline until 1998, attributed to aggressive anti-smoking campaigns through the 90’s. But this changed that year, with an increase in tobacco use due exclusively to the use of e-cigarettes. By 2014 e-cigarettes overtook all other tobacco products among this population. Even more concerning is the rate at which their use is increasing. According to the Centers for Disease Control and Prevention (CDC) e-cigarette use among high schoolers increased 77.8% in 2018 over 2017, with similar trends observed internationally.

Among adults there seems to be a larger degree of variability across different studies, but was roughly between 15-20% between 2015 and 2016.

And while it is possible to find e-cigarette pods and inserts that do not have nicotine, the vast majority do. What’s worse, the trend has been to increase the concentration of nicotine delivered by these products. In the case of the popular Juul brand, the average concentration of nicotine considerably exceeds the concentration in regular cigarettes.

To be fair, one potential positive use of these devices might be in helping long time smokers reduce the use of regular cigarettes. By triturating the chemical composition and rate of nicotine delivery, it may offer a new tool to assist these individuals. Getting a long time smoker to reduce their dependency on combustible cigarettes is a meaningful thing. However, the measurable degree of any such impact remains to be seen. And it isn’t clear how the long term (still unknown) risks of e-cigarettes balance out with any potential advantages.

What is Currently Known About How e-Cigarettes Affect the Brain

The dangerous effects e-cigarettes may have on the brain and their long term consequences stem from the well established effects nicotine in general has on the brain and brain development, the degree and concentration of nicotine e-cigarettes are capable of delivering, and the chemistry associated with how these devices deliver it. The microvascuature of the brain - the collection of specialized blood vessels that feed the brain and spinal cord and regulate their chemical environment - as well as the cells that make up the brain itself (neurons and other cells), are all vulnerable to damage.

The microvascuature of the brain and spinal cord consists of a vast collection of capillaries that provide brain cells with oxygen and nutrients. It also shuttles away cellular waste products. The brain’s microvascuature is unique compared to the rest of the body. The endothelial cells that make up these tiny blood vessels form a regulated barrier between the blood on one side (the lumen side of the blood vessels) and the chemical environment the brain and spinal cord float in on the other side. This barrier is called the blood brain barrier.

The normal compliment of molecules and immune cells capable of moving between the blood and the cellular spaces in the other tissues of the body cannot freely do so with the brain and spinal cord - which collectively form the central nervous system. The unique chemical environment of the central nervous system formed by the blood brain barrier is the cerebral spinal fluid.

There is a strong correlation between long term smoking, cognitive decline in the later decades of life, and disruption of the blood brain barrier and microvasculature of the brain. In fact, cognitive decline and microvascular dysfunction are essentially universal consequences of long term smoking for everyone. The exact pathophysiological mechanisms involved are still not completely clear though, warranting continued research. But the research to date - summarized in a recently published paper - seems to show that the negative physiological effects nicotine has on brain cells when delivered via e-cigarettes mirrors the effects observed with combustible cigarettes.

The endothelial cells that make up the microvasculature are particularly vulnerable. This means that the normal regulatory mechanisms responsible for maintaining the unique chemical environment of the cerebral spinal fluid via the blood brain barrier may slowly break down, contributing to cognitive decline.

And in at least one mouse model study, the authors suggest that e-cigarettes may also have short term disruptive effects on cognitive and memory functions. So there may be more immediate and acute concerns with e-cigarette use, in particular in younger populations where the brain is still developing.

In another study, scientists found that e-cigarettes produce a stress response in neural stem cells, which are populations of cells that eventually become neurons and other important cell types in the brain. Again, potential effects on the still developing brain of adolescents is of immediate concern.

At the moment there are more questions than answers when it comes to understanding the physiological and cellular effects e-cigarettes - and in particular high concentration nicotine delivery via these devices - has on the brain. The long term epidemiological and public health consequences of e-cigarettes will not be fully appreciated for years to come. Not just on the brain but also the cardiovascular system, lungs, and immune system, among others. But there seems to be every reason to anticipate that e-cigarette effects on brain function and cognition will likely be as bad as regular combustible cigarettes.