A study by Rachel Thayer and colleagues from the Universities of Boulder, Colorado and Portland, Oregon, published recently in the journal Addiction revealed some fascinating differences between the impact of recreational alcohol and cannabis use on the structure of the human brain.

It was known from previous research that the more alcohol an adult regularly drinks the greater the degree of shrinkage of the brain’s grey matter. The grey matter is the folded outer surface of the brain that makes it look a bit like a walnut. This is where neurons interface with each other by means of synaptic connections at which one neuron can exert an influence on another. It is the networks of neurons bringing information together within the grey matter that allows computations to be performed so that we can perceive the world via the senses, feel emotions based on our interactions with other people and execute purposeful behaviours like decision making, problem solving and voluntary movements. So, as a rule of thumb, the lower the volume of space occupied by a person’s grey matter, the greater the reduction in computational power.

This new study looked at not just the link between boozing and grey matter but also investigated whether it had any impact on the white matter too. White matter is the neuronal cabling along which electrical messages are ferried to and from different patches of grey matter in different parts of the brain’s cortex. Grey matter in the occipital lobe at the back of the brain, which crunches sensory information coming in through our eyes, can send messages to the prefrontal cortex via white matter pathways, and vice versa. Grey matter in the left side of the brain can send information to and receive information from right hemisphere cortical areas via white matter connections that run through the corpus callosum (this is a thick bundle of white matter connecting the left and right halves of the brain).

These white matter pathways contain the neuronal axons, which is the cabling through which electrical pulses (called action potentials) are passed between neurons. These axons are wrapped in electrically insulating myelin fibre which speeds up the transmission of action potentials. Damage to this insulating layer can be detected with a certain type of MRI scan and is formally described as ‘reduced white matter integrity’. Thayer and colleagues’ findings showed that the more alcohol people routinely drank the greater the impact on grey and white matter. High alcohol consumption is associated with reduced grey matter volume AND white matter integrity.

That’s not all. They also looked at the differences between adult brains (20-55 years old) and adolescent brains (14-19). While high alcohol intake way associated with reduced grey matter volume in the adolescent brains, they didn’t find any evidence of reductions in white matter integrity. Presumably if those teens carried on their high alcohol intake, they would end up damaging their white matter like their older counterparts.

Perhaps the most surprising thing about this study is that, across over 400 teens and more than 800 adults, they found no evidence of any link between the amount of cannabis consumed in the 30 days prior to brain scanning and the grey matter volume or white matter integrity. This suggests that despite alcohol being legal in the UK and cannabis being illegal, from the perspective of the impact of these commonly used recreational drugs on two different important aspects of brain structure, the relevant laws may well be working in direct opposition to the degree of harm caused, both to the individual and society as a whole.

If you enjoy these blogs then you’ll love my 2 series of Secrets of the Brain in Ultra High Definition (www.insight.tv / Sky Channel 564). This story was covered on episode 90 of my fortnightly Geek Chic’s Weird Science podcast available on iTunes, Acast, Libsyn and Podbay. I dig around on the internet on a daily basis for articles on the very latest breakthroughs in neuroscience research and, when I find something interesting, well-written and relevant, I post it on Twitter (@drjacklewis). Most excitingly of all, from the 12^th July 2018, my new book – The Science of Sin: Why We Do The Things We Know We Shouldn’t – will be available in all good bookshops.

Room For One More?

In the Smart Drugs chapter of the book I wrote with Adrian Webster “Sort Your Brain Out” we argued that of the various nootropics available in this day and age it makes sense to give preference to substances that have been around for eons rather than the new kids on the block. This really is the only way you can enjoy the benefits without having to worry about the potential unknown long term problems and side effects.

The brain benefits of regular coffee drinking were described, but due to space limitations we were only able to discuss a few other substances. This month’s blog highlights some of the many published studies that have indicated a wide variety of health benefits associated with regularly imbibing green tea – something that people have indeed been doing for hundreds of years.

Green & Black

Camellia sinensis is the name of the plant that gives us white, yellow, green, black and oolong teas. Black tea has more than twice the amount of caffeine as green tea, whilst green tea has more polyphenols (the very antioxidant substances that mop up all those dangerous free radicals). The difference in concentrations of these substances can be accounted for by the fact that black tea requires fermentation before preparation – which increases the caffeine content and decreases the polyphenol content – whilst green tea is prepared from unfermented leaves.

All The Tea In China

Green Tea has been used in traditional Chinese and Indian medicine for thousands of years where it has been exploited for it’s stimulant, diuretic and astringent properties; not to mention improving heart health, flatulence and body temperature regulation. The stimulant effects are thanks to the alkaloids contained within the tea leaf including caffeine, theobromine and theophylline. As green tea contains about half the caffeine of black tea and MUCH less than a cup of coffee, dosing yourself with green tea throughout the day is much less likely to disrupt your sleep come bedtime than the other options.

Typing “green tea” into an internet search engine yields a huge number of websites dedicated to promoting the ubiquitous benefits of regular green tea ingestion to improve the effectiveness of exercise, improving weight loss and even helping to manage diabetes. Of course its always difficult to know which sources you can and can’t trust. Hard data is required to establish whether green tea really does help to ameliorate symptoms of the various complaints for which it has been traditionally recommended.

Is Green Tea Really Good For You?

Yes! When individual research studies are published in a peer-reviewed scientific journal they can provide evidence to support or reject any particular scientific hypothesis, but a single study cannot “prove” or “disprove” any given theory. Meta-analyses are much more powerful in this regard because they look at many different studies all investigating similar hypotheses. If, despite being conducted on a completely different group of subjects, often in a completely different location and undertaken by a different group of researchers, they all point towards the same conclusion this provides for a much more powerful argument to support, or refute, any given claim when the consensus points to a benefit. Just looking at the meta-analysis data it has been confirmed that green tea is effective at lowering blood pressure, reducing risk of several different cancers and improving cardiovascular/metabolic health, to name but a few.

Any Brain Benefits of Green Tea?

Drinking green tea has long been associated with relaxation and, indeed, scientific investigation has now backed this up. Epigallocatechine-3-gallate, the most active of the tea polyphenols (known collectively as “catechins”) is found in much higher quantities in green tea than other teas and is known to inhibit an enzyme that converts cortisone to cortisol. Cortisol is a so-called stress hormone and cortisone the inactive form. By preventing the enzyme in question – 11 beta-hydroxysteroid Dehydrogenase Type 1 – from doing its job, the active ingredient of green tea is able to reduce levels of the stress hormone. (In case you were wondering, the other 5 catechins are: catechin, gallaogatechin, epicatechin, epigallocatechin and epicatechin gallate).

Can Green Tea Can Improve Cognition?

Yes! Anecdotal accounts of the brain benefits of regular tea drinking in the elderly inspired research to establish whether green tea really could improve cognition. Over the last ten years huge amounts of data have been generated on this topic. The more green tea a person consumes, the lower prevalence of cognitive impairment (Full article available for free). Early research trying to ascertain the mechanism by which such benefits are realised demonstrated that spatial cognition was improved in rats that drank water infused with polyphenols from green tea (full article available for free).

In the last few years experiments dosing healthy, younger humans with green tea versus placebo have demonstrated an increase in functional connectivity between frontal and parietal brain areas during a working memory task (Full article available for free). Bearing in mind that improvements in working memory can translate into better fluid intelligence and therefore a higher score in the IQ test – swapping green tea into your daily hot drink regime might make sense for your brain’s sake as well as your body’s.

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What Does Caffeine Do To Your Brain?

 As a neuroscientist who spends much of his working life giving brain talks at events all around the country (at schools, conferences and science festivals) I’ve noticed that one theme catches public imagination over and over again: How does caffeine work? What does it do to my brain? How long does it stay in my system? Is it really that bad for me? This is one reason why it became one of the key topics in the “Smart” Drugs chapter of my book: Sort Your Brain Out. In this blog I’ll cover some of the most regularly asked questions.

How long caffeine takes to leave your system?

It depends what other drugs you’re on. If you’re on the contraceptive pill it can take up to twice as long for your liver to remove caffeine from your system. So people “on the pill” can find themselves particularly sensitive to its effects because consecutive doses stack up and are not cleared out as swiftly as in everyone else. But if you’re a smoker it is the other way around. Caffeine is removed from your system at double the speed of a non-smoker.
If you’re neither a smoker nor on the contraceptive pill the concentration of caffeine in your bloodstream is halved every 5-6 hours, but it really does depend on the individual as this “half-life” varies greatly from person-to-person.

Is it beneficial to have caffeine before a meeting / presentation / to improve concentration?

Caffeine blocks the receptors of an inhibitory neurotransmitter called adenosine, which under normal circumstances reduces overall activity across the brain. By blocking these receptors and removing the dampening influence on brain activity, caffeine increases activity across brain pathways involved in alertness, focusing attention and initiating body movements. This why people dosed up on caffeine can get quite jittery.
Whether or not caffeine is beneficial for you in a meeting / presentation or to improve concentration whilst working depends on how much you’ve already had. There’s a sweet spot where you will feel more alert and switched on at moderate levels, but beyond that you can become so wound up that it has effects that are deleterious to performance (see description of caffeinism below).
However the increase in feelings of alertness and ability to focus attention only gets regular coffee drinkers up to levels enjoyed by non-caffeine drinkers everyday. This is because once you’re a caffeine addict the brain tends to increase the numbers of adenosine receptors to compensate for the fact that there’s loads of caffeine swimming around in your brain on a daily basis. This means that your average coffee drinker has more inhibitory receptors in their brain dampening activity levels to a greater degree – so they will feel more sluggish whenever they don’t have caffeine in their system.

Is caffeine good or bad for you in the long run?

There seem to be some long-term benefits to drinking caffeine even if the short-term benefits don’t amount to a whole hill of (coffee) beans. It has been observed that regular drinkers of moderate amounts of caffeine (3 cups / day) have a lower incidence of Parkinson’s, Alzheimer’s, liver and heart diseases. This may be due to the increased numbers of inhibitory receptors triggered by ever-present levels of caffeine dampening activity levels in body and brain. The decreased activity levels across the brain caused by the larger numbers of inhibitory receptors in the caffeine drinkers’ brains may relieve the pressure on dopamine neurons that are compromised in Parkinson’s disease and the acetyl choline neurons that get clogged up with various proteins in Alzheimer’s disease. In other words caffeine seems to slow down the process of cell death so that symptoms of these diseases kick in several years later than in your average non-caffeine drinker. At the moment this mechanism is purely speculative. The jury’s still out on the precise mechanism that might account for these observations, but the evidence supporting the concept of moderate amounts of caffeine having a neuroprotective influence on the brain is steadily increasing.

Is it important to control and monitor your caffeine intake?

A dose of 10g is deadly – 100 cups and a human may well find themselves popping their clogs as a typical cup of brewed coffee contains 100mg of caffeine. (NB you may notice that in the above video from the lovely people at ASAPscience they say 1 cup of coffee has 150mg – presumably they brew it stronger over in Canada 🙂 For the non-coffee drinkers out there here are some average caffeine contents of some other popular drinks. There are 80mg in a can of Red Bull, 75mg in a cup of instant coffee, 50mg in a cup of tea, 30mg in a can of Coca Cola.

Very high but not deadly doses can lead to a quite severe psychiatric condition known as caffeinism: “which is characterised by restlessness, agitation, excitement, rambling thought and speech, and insomnia.” (Winston et al, 2005). It is important to control and monitor caffeine intake because too much can interfere with appetite, make people anxious or depressed, not to mention the fact that anything that interferes with sleep will have a deleterious effect on the brain. Everyone’s sensitivity to caffeine is slightly different, but if you have trouble sleeping then you’d be well advised to avoid caffeine at least 5-6 hours before bedtime – for your brain’s sake.

3 cups of coffee per day is considered a “moderate dose” for most people. Get these in early enough to avoid any potential for them to interfere with sleep and you should get the apparent long-term brain benefits without the negative consequences associated with excessive consumption (DISCLAIMER: this should not be interpreted as medical advice – it is just the science-based opinion of the author who has a Ph.D. in neurobiology i.e. not a medical degree!).

I don’t like tea or coffee, are there any other sources of caffeine?

Caffeine is also found in kola nut (one of the original ingredients of coca cola) and guarana – a wonder berry from the Brazilian rainforest; it’s also found in low quantities in chocolate. Caffeine is also included as a stimulant in many cold and flu remedies – so beware what you reach for when you wake up in the middle of the night with a bunged up nose!

By the way: if you study the picture on the left very carefully you’ll find a face amongst the coffee beans – can you find it?

Keep looking… he’s definitely there and you’ll kick yourself for doubting me when you find him!!

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Tired doctors can feel a duty to neutralise fatigue by taking smart drugs (photo courtesy of photostock)

Cosmetic psychopharmacology, cognitive enhancement or simply smart drugs, call it what you will, the use of pharmaceutical agents like methylphenidate (Ritalin) and modafinil (Provigil) for performance enhancement and sleep avoidance is rife. Throughout big business, software development, academia, poker tournaments and – according to a recent academic paper – even the medical establishment itself, many healthy individuals are opting to optimise brain function with drugs specifically intended for the treatment of illnesses, simply to keep up with the breakneck pace of life in the 21st century.

This summer a paper was published in the Journal for Law, Medicine and Ethics discussing a pretty unusual moral dilemma. Some medical doctors have concluded that their “ethical duty to reduce error during periods of fatigue” extends to dosing themselves with smart drugs, such as modafinil, to improve concentration and alertness in circumstances where their punishing schedule leaves them feeling utterly exhausted. Medical physicians are also finding themselves under pressure from patients to dish out prescriptions for “smart drugs” to help them keep up with the incessant demand for increased efficiency and competitiveness placed on them by work, family and friends. It may sound reasonable upon first glance but the upshot is that, in either case, it is quite simply illegal for these drugs to be prescribed for such purposes and, irrespective of issues of jurisprudence, it places patient, physician and society “at risk for dangerous health and social consequences.”

In 2008, results of an online poll were published in the journal Nature, revealing that 20% of respondents (predominantly academics) had used such nootropic substances for non-medical purposes like improving concentration, memory or to counteract jetlag. This inspired a large number of newspaper and magazine articles and a flurry of scientific studies to further investigate this phenomenon.

Hollywood got in on the act earlier this year with the blockbuster film Limitless. It spun a typically high-octane tale of the meteoric rise (and inevitably crushing fall) of a failing author who temporarily manages to transform himself into a super-intelligent, ultra-motivated, overachieving writer, linguist and stock trader through regular doses of a transparent, fictitious and exceptionally effective smart drug. (Un?)Fortunately, in the real world, pharmaceutical neuroenhancement quite simply does not result in such dramatically transformative effects.

A businessperson hell-bent on performing to the best of their abilities in spite of jetlag may elect to emulate the example set by the military, which can actually require their staff to neutralise the debilitating cognitive consequences of fatigue under circumstances of “operational necessity,” by using modafinil to gain the competitive edge. Yet a recent meta-analysis of a large number of studies investigating the use of popular neuroenhancing drugs in healthy people highlighted the gap between people’s expectations and the actual effects of such substances. In sleep deprived individuals a single dose of modafinil does have a strong positive effect on executive function and improvement in memory – an effect that wears off during continued sleep deprivation. But were they to take a single dose when not sleep deprived, they would find it has the opposite effect; under these conditions it actually induces drowsiness. Furthermore, repeated doses of modafinil when not sleep deprived increases both positive and negative affect, which means you would simultaneously feel slightly happier and more anxious.

Methylphenidate (Ritalin) is a drug prescribed for people with ADHD which is also used by healthy people in an effort to improve concentration and alertness

As pressure to succeed continues to mount in higher education, business and medicine, a wide range of different people from all walks of life are beginning to find themselves under increasing pressure to jump on the smart drug bandwagon just to keep up with their peers. Given that the 2008 Nature poll also found that “one-third of respondents said they would feel pressure to give cognition-enhancing drugs to their children if other children at school were taking them” – it is perhaps unsurprising that the competitiveness epidemic may already be spilling over into the school system. Indeed, confidential sources (an ex-pupil) tell me that it has become common practice in many British public schools for those prescribed Ritalin for ADHD to sell it on to other pupils at extortionate rates. Interestingly, the market appears to be not the usual suspects – that inevitable group in every secondary school who become enamoured with with recreational drug experimentation –  but instead the conscientious geeky types who are hell bent on doing whatever they can to ace their exams. The sad thing is they are almost certainly wasting their money.

Methylphenidate, the drug branded as Ritalin, is a funny old drug. Much confusion has, quite understandably, arisen from the counterintuitive concept of using an amphetamine-derivative in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). A typical response to this revelation is: “Why would anyone want to give a hyperactive child speed?” The explanation is, in fact, reasonably straightforward. Methylphenidate has a very different effect on the brain to the other amphetamines. Whilst amphetamines generally elevate levels of neurotransmitters such as dopamine across the whole brain, a low dose of methylphenidate has a different impact on levels of these neurotransmitters in different brain areas. The trick with methylphenidate is that it slightly increases dopamine and noradrenaline in prefrontal brain areas involved  in maintaining attention and inhibiting impulsive behaviours, whilst having a minimal impact on levels of those same brain chemicals elsewhere in the brain that lead to the hyperexcitability usually associated with amphetamine drugs. But what effect do such drugs have on a healthy, normal brain? Overall there is minimal evidence to suggest any objective improvement on alertness, attention, mood or memory (apart from spatial memory) when healthy people take methylphenidate. So my message to school kids (or their parents for that matter) who are considering buying into the promise of Ritalin enhanced grades? Don’t believe the hype!

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Henry Solomon Wellcome was well ahead of the game when it came to the “Mo-vember” look for a charitable soul

With just one week to go before it closes (Sun 27th Feb 2011) I visited the “High Society” exhibition at the Wellcome Collection in London yesterday so that I could review it here in case you were curious.

I would like to state for the record that I LOVE THE WELLCOME TRUST and would rate Henry Wellcome in my top 5 heroes of all time. His enormously generous philanthropic endowment has turned into a fantastic instution built on sound priniciples that have withstood the tests of time.

Not only does the WT fund an enormous amount of British scientific research (my PhD included – during which my scientific approach was gradually sculpted under the influence of many extraordinary neuroscientists; most of whom were also Wellcome Trust funded), but it also takes it’s role in public engagement with science, a subject very close to my heart, extremely seriously.

This commitment to spreading the good word of scientific innovation old and new is, I believe, deliciously exemplified by the special exhibitions that rotate through their space on the Euston Road a few times per year to showcase an interesting area of scientific enquiry. These exhibitions beautifully complement the tone set by the permanent collection upstairs: ancient medical tools, scientific relics and other treasures from the history of medicine; not to mention some outstanding fashion photography modelled by good old Henry himself.

In late 2010/early 2011 the show space addressed the issue of mind-altering substances. From the outset the visitor couldn’t help but be impressed upon that these chemicals have been popping up throughout history everywhere, for millenia. Drugs of various description have been consumed in one form or another across ALL cultures of the world. And the vehicle for explaining this was a lovely collection of drug paraphernalia from all over the globe and a whole bunch of amazing facts about the drug trade both medical, illicit and sometimes both.

Psilocybin is a hallucinogenic substance found in certain species of mushrooms

The free exhibition included a 6th century BC embossed tablets from the Middle East describing some of the medical uses of Cannabis sativa, ornately decorated tobacco pipes, ancient betel nut cutters, indian and chinese opium pipes right up to the modern day DIY crackpipe (comprising a small water bottle, a biro casing and some perforated tin foil).

These drug taking curiosities, collected from all corners of the earth, may well have encouraged spectators to consider why human beings everywhere are so keen to experiment with mind-stimulating (or mind-depressing) substances in spite of the potential dangers, for instance, picking the wrong mushroom and popping your clogs.

People expecting an exhilarating experience may have been disappointed. I personally believe it is always important to arrive at an event free of the burden of overly-high expectations. And it worked just fine for me as there were some real treasures within.

Shockingly heroin was once sold by Bayer pharmaceuticals as an everyday medicine

Highlights for me included some of the black and white footage documenting Andean Indians drinking the potently hallucinogenic ayahuasca extract (which immediately makes a person vomit and is deemed to be a good thing… helping to purify body and soul prior to entry into the “other” world) provided a fanastic account of how, why and where these indigenous tribespeople enter into this ritual.

Also the footage of a 1950’s experiment in which a “terribly posh” doctor tests a volunteer before and after consumption of the hallucinogenic drug mescaline. I thought it was very amusing that he was considerably better at counting down from 100 to zero in blocks of 7 (i.e. 100, 93, 86, 79 etc) when he was tripping compared to before he had taken any drug. Also amusing (to me at least) was the way he answered all questions from the battery of cognitive tests directly in a very authoritative manner, yet failed absolutely to find suitable words to describe the gorgous array colours that were hallucinogenically tinting his vision and no doubt also inducing his huge grin.

Scandalous: when our plentiful supplies of silver and gold were no longer worth what they were the British Empire got China hooked on opium so that we could trade that instead!

It was also very interesting to get an insight into some of the details of the Opium Wars in which the British used Afghani opium to get the whole of East Asia hooked on smack as a solution to plummeting gold and silver prices leaving them with no barganing chips with which to trade. An absolute scandal of which I had no prior knowledge. There was also an ingenious installation involving various projectors and light filters beaming amorphous colours and shapes onto a large screen that I could have watched for hours – very relaxing.

The sillhouettes are spectators standing in front of the projectors, not part of the trippy art installation – or are they?

And on the way out I found the large graphical representations of the relative yearly global turnover elicited from trading legal versus illegal drugs of recreation very interesting – as the relative size of the cannabis versus cocaine versus opiate markets are not as you might expect, particularly when compared to the computer game or pornography markets. Another large graph that effortlessly conveyed a lot of information in a very straightforward, user-friendly manner depicted the gradually declining purity and increasing costs of cocaine as goes from being picked and processed at source, moved from Andean regions to the Carribean, imported into the UK and then sold to the end consumer. It seems that the biggest jump in the cost per kilo occurs, not surprisingly if you think about it, when it enters the country in which it is to be sold, the suprise comes when it is revealed that the hike in cost from before to after is a whopping 600%.

This ball of opium is the size of my fist!!

In conclusion it was an eye-opening and fascinating excursion into the world of illicit drugs through the ages showing how our interest in them across all cultures has always been there and will probably always remain.

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