Our brain is an extremely complex and delicate organ. Our body fiercely protects it by holding onto things that help it and keeping harmful things out, such as bugs that can cause infection and toxins.

It does that though a protective layer called the blood-brain barrier. Here’s how it works, and what it means for drug design.

First, let’s look at the circulatory system

Adults have roughly 30 trillion cells in their body. Every cell needs a variety of nutrients and oxygen, and they produce waste, which needs to be taken away.

Our circulatory system provides this service, delivering nutrients and removing waste.

Where the circulatory system meets your cells, it branches down to tiny tubes called capillaries. These tiny tubes, about one-tenth the width of a human hair, are also made of cells.

But in most capillaries, there are some special features (known as fenestrations) that allow relatively free exchange of nutrients and waste between the blood and the cells of your tissues.

It’s kind of like pizza delivery

One way to think about the way the circulation works is like a pizza delivery person in a big city. On the really big roads (vessels) there are walls and you can’t walk up to the door of the house and pass someone the pizza.

But once you get down to the little suburban streets (capillaries), the design of the streets means you can stop, get off your scooter and walk up to the door to deliver the pizza (nutrients).

We often think of the brain as a spongy mass without much blood in it. In reality, the average brain has about 600 kilometres of blood vessels.

The difference between the capillaries in most of the brain and those elsewhere is that these capillaries are made of specialised cells that are very tightly joined together and limit the free exchange of anything dissolved in your blood. These are sometimes called continuous capillaries.

This is the blood brain barrier. It’s not so much a bag around your brain stopping things from getting in and out but more like walls on all the streets, even the very small ones.

The only way pizza can get in is through special slots and these are just the right shape for the pizza box.

The blood brain barrier is set up so there are specialised transporters (like pizza box slots) for all the required nutrients. So mostly, the only things that can get in are things that there are transporters for or things that look very similar (on a molecular scale).

The analogy does fall down a little bit because the pizza box slot applies to nutrients that dissolve in water. Things that are highly soluble in fat can often bypass the slots in the wall.

Why do we have a blood-brain barrier?

The blood brain barrier is thought to exist for a few reasons.

First, it protects the brain from toxins you might eat (think chemicals that plants make) and viruses that often can infect the rest of your body but usually don’t make it to your brain.

It also provides protection by tightly regulating the movement of nutrients and waste in and out, providing a more stable environment than in the rest of the body.

Lastly, it serves to regulate passage of immune cells, preventing unnecessary inflammation which could damage cells in the brain.

What it means for medicines

One consequence of this tight regulation across the blood brain barrier is that if you want a medicine that gets to the brain, you need to consider how it will get in.

There are a few approaches. Highly fat-soluble molecules can often pass into the brain, so you might design your drug so it is a bit greasy.

Another option is to link your medicine to another molecule that is normally taken up into the brain so it can hitch a ride, or a “pro-drug”, which looks like a molecule that is normally transported.

Using it to our advantage

You can also take advantage of the blood brain barrier.

Opioids used for pain relief often cause constipation. They do this because their target (opioid receptors) are also present in the nervous system of the intestines, where they act to slow movement of the intestinal contents.

Imodium (Loperamide), which is used to treat diarrhoea, is actually an opioid, but it has been specifically designed so it can’t cross the blood brain barrier.

This design means it can act on opioid receptors in the gastrointestinal tract, slowing down the movement of contents, but does not act on brain opioid receptors.

In contrast to Imodium, Ozempic and Victoza (originally designed for type 2 diabetes, but now popular for weight-loss) both have a long fat attached, to improve the length of time they stay in the body.

A consequence of having this long fat attached is that they can cross the blood-brain barrier, where they act to suppress appetite. This is part of the reason they are so effective as weight-loss drugs.

So while the blood brain barrier is important for protecting the brain it presents both a challenge and an opportunity for development of new medicines.

Sebastian Furness, ARC Future Fellow, School of Biomedical Sciences, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Flavoured nicotine pouches are being promoted to young people on social media platforms such as TikTok and Instagram.

Although some viral videos have been taken down following a series of reports in The Guardian, clips featuring Australian influencers have claimed nicotine pouches are a safe and effective way to quit vaping. A number of the videos have included links to websites selling these products.

With the rapid rise in youth vaping and the subsequent implementation of several reforms to restrict access to vaping products, it’s not entirely surprising the tobacco industry is introducing more products to maintain its future revenue stream.

The major trans-national tobacco companies, including Philip Morris International and British American Tobacco, all manufacture nicotine pouches. British American Tobacco’s brand of nicotine pouches, Velo, is a leading sponsor of the McLaren Formula 1 team.

But what are nicotine pouches, and are they even legal in Australia?

Like snus, but different

Nicotine pouches are available in many countries around the world, and their sales are increasing rapidly, especially among young people.

Nicotine pouches look a bit like small tea bags and are placed between the lip and gum. They’re typically sold in small, colourful tins of about 15 to 20 pouches. While the pouches don’t contain tobacco, they do contain nicotine that is either extracted from tobacco plants or made synthetically. The pouches come in a wide range of strengths.

As well as nicotine, the pouches commonly contain plant fibres (in place of tobacco, plant fibres serve as a filler and give the pouches shape), sweeteners and flavours. Just like for vaping products, there’s a vast array of pouch flavours available including different varieties of fruit, confectionery, spices and drinks.

The range of appealing flavours, as well as the fact they can be used discreetly, may make nicotine pouches particularity attractive to young people.

Users absorb the nicotine in their mouths and simply replace the pouch when all the nicotine has been absorbed. Tobacco-free nicotine pouches are a relatively recent product, but similar style products that do contain tobacco, known as snus, have been popular in Scandinavian countries, particularly Sweden, for decades.

Snus and nicotine pouches are however different products. And given snus contains tobacco and nicotine pouches don’t, the products are subject to quite different regulations in Australia.

What does the law say?

Pouches that contain tobacco, like snus, have been banned in Australia since 1991, as part of a consumer product ban on all forms of smokeless tobacco products. This means other smokeless tobacco products such as chewing tobacco, snuff, and dissolvable tobacco sticks or tablets, are also banned from sale in Australia.

Tobacco-free nicotine pouches cannot legally be sold by general retailers, like tobacconists and convenience stores, in Australia either. But the reasons for this are more complex.

In Australia, under the Poisons Standard, nicotine is a prescription-only medicine, with two exceptions. Nicotine can be used in tobacco prepared and packed for smoking, such as cigarettes, roll-your-own tobacco, and cigars, as well as in preparations for therapeutic use as a smoking cessation aid, such as nicotine patches, gum, mouth spray and lozenges.

If a nicotine-containing product does not meet either of these two exceptions, it cannot be legally sold by general retailers. No nicotine pouches have currently been approved by the Therapeutic Goods Administration as a therapeutic aid in smoking cessation, so in short they’re not legal to sell in Australia.

However, nicotine pouches can be legally imported for personal use only if users have a prescription from a medical professional who can assess if the product is appropriate for individual use.

We only have anecdotal reports of nicotine pouch use, not hard data, as these products are very new in Australia. But we do know authorities are increasingly seizing these products from retailers. It’s highly unlikely any young people using nicotine pouches are accessing them through legal channels.

Health concerns

Nicotine exposure may induce effects including dizziness, headache, nausea and abdominal cramps, especially among people who don’t normally smoke or vape.

Although we don’t yet have much evidence on the long term health effects of nicotine pouches, we know nicotine is addictive and harmful to health. For example, it can cause problems in the cardiovascular system (such as heart arrhythmia), particularly at high doses. It may also have negative effects on adolescent brain development.

The nicotine contents of some of the nicotine pouches on the market is alarmingly high. Certain brands offer pouches containing more than 10mg of nicotine, which is similar to a cigarette. According to a World Health Organization (WHO) report, pouches deliver enough nicotine to induce and sustain nicotine addiction.

Pouches are also being marketed as a product to use when it’s not possible to vape or smoke, such as on a plane. So instead of helping a person quit they may be used in addition to smoking and vaping. And importantly, there’s no clear evidence pouches are an effective smoking or vaping cessation aid.

Further, some nicotine pouches, despite being tobacco-free, still contain tobacco-specific nitrosamines. These compounds can damage DNA, and with long term exposure, can cause cancer.

Overall, there’s limited data on the harms of nicotine pouches because they’ve been on the market for only a short time. But the WHO recommends a cautious approach given their similarities to smokeless tobacco products.

For anyone wanting advice and support to quit smoking or vaping, it’s best to talk to your doctor or pharmacist, or access trusted sources such as Quitline or the iCanQuit website.

Becky Freeman, Associate Professor, School of Public Health, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.