How Drugs Work: A Scientist Speaks

A scientist explains how drugs work and why you take them.
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A scientist explains how drugs work and why you take them.

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A while ago I asked my brother Ben, a PHD student at Cambridge, to write something about the way drugs work. Almost all the human population, whether it's in their morning coffee or a syringe, consume drugs daily, often unaware of the effect said substances have on their body. What follows is a scientists explanation for what said drugs do to us and why we're so hooked.

Caffeine

Caffeine is thought to be the most used drug in the world, with estimates suggesting anywhere between 10% and 70% of the population experience withdrawal symptoms if they abruptly stop consuming caffeine. Some patients are even known to need hospital treatment for caffeine addiction, or to have gained super powers, but that may have just been in that episode of Futurama.

Caffeine dissolves in both water and oil, this means that it can pass through most biological barriers, including the blood-brain barrier, allowing caffeine to enter the brain. The primary reason for most drugs having an effect on the human body is because they have a similar molecular structure to a naturally occurring signalling chemical. Caffeine has a similar structure to the molecule adenosine. Adenosine is a neurotransmitter, which means it messages in the brain.

Adenosine is thought to act as a suppressor of neural activity, it binds to receptors on neurons and tells them to stop firing. This is probably a natural 'stop signal' mechanism. Adenosine works by fitting into adenosine receptors, and activating them. Caffeine's similar structure to adenosine allows it to fit into the adenosine receptors, but without activating them.  This means that after a cup of coffee, receptors keep firing when they should have stopped, giving you that continued, ‘buzzing’ feeling.

Adenosine has been linked to many different aspects of human biology, including sleep cycles, muscle contraction and dopamine release (happy hormones). Caffeine screws all these up – blocking your ability to sleep, making you feel alert but irritable and also allowing you to contract muscles more easily (which improves athletic performance). Caffeine is broken down into other products in the liver, these are thought to increase heart rate and base metabolic rate, improving performance.

Hunger in Cannabis

The 'munchies' effect of cannabis is very well known, and the subject of copious amounts of research. There are two major hormones which control hunger: ghrelin, which causes hunger, and leptin which reduces it. Ghrelin is slowly released in increasing amounts of over time, thus increasing your food cravings. When food passes out of the stomach and into the intestines, a signal is sent to the brain which stops ghrelin release (ending hunger), stimulating leptin release (making you feel satiated). Leptin causes release of dopamine, rewarding you.

THC, found in cannabis, is a cannabinoid, which along with sounding like a character from ‘Clone Wars’ has a similar structure to the endocannabinoids – signalling molecules produced by the body. The exact role of endocannabinoids in hunger is not well known, but they are known to increase with ghrelin and decrease with leptin. For this reason, THC would act like an endocannabinoid, inducing feelings of hunger. Further it has been shown that THC causes increased dopamine release after eating. This means that not only should you feel hungrier, but you'll also feel more “rewarded” when you eat (in science this is known as the 'hedonic value' of food). This explains why eating an entire bag of cheesy puffs post-spliff feels so good.

Addictive properties of cocaine

Dopamine (remember the happy hormone thing?) Is a neurotransmitter aka a signalling molecule in the brain. Normally it is released as a ‘reward,’ like, as mentioned above, when we eat.  It has evolved to train animals (including humans) to behave in ways that are favourable to them. After performing self-preserving behaviour, such as eating calorific food or having sex, dopamine is released, which fires your neurons and sends a message to the reward centre in the brain. In this way it encourages you to eat and spread your genes, like good little animals should. After the dopamine is released it is immediately taken back in, so you get a short burst of pleasure and then back to normal. It is taken back by dopamine transporters, small proteins which pump the dopamine back into the cells where it is made. Cocaine blocks these transporters, so the dopamine continues to stimulate a reward signal, leading to the “high” feeling. In addition, this reward signal blocks depressive signals, so you'll feel more alert, less depressed and respond to pleasure-inducing activities (such as eating, sex and smoking) more strongly.

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The dopamine system evolved to encourage you to do rewarding things. Cocaine screws this up and trains your brain to want more cocaine, thus leading to addiction. For an addict, cocaine would seem as essential as eating and sex. After taking cocaine, dopamine levels are higher in your brain, and so your body compensates by making fewer dopamine receptors, lowering your sensitivity. This leads to tolerance, making an overdose more likely, but also feeling of tiredness, depression and irritability when not taking coke. Try going a few days without eating, sleeping and sex; that’s what cocaine withdrawal is like.

Absinthe 

Absinthe is made by soaking a solution with a high-alcohol content in wormwood barrels. The alcohol dissolves the inside of the barrel causing chemicals in the wood to leak into the drink. Two of these include chlorophyll, the green stuff that allows plants to capture light energy and gives absinthe that famous green hue, and thujone, a chemical that likely gives absinthe some of its interesting effects.

The major effects of absinthe are hallucinations, a sense of clarity (as if the mind has been opened up) and convulsions if consumed in very high amounts. Thujone is thought to cause these effects, along with, er the really high alcohol content. Thujone activates GABA receptors in the neurons, causing them to fire. GABA receptors are found in lots of different neurons, which may all be firing when you drink absinthe. People describe the effect of absinthe as being like your mind has finally been freed, new ideas coming easily and the ability to experience life from other people's perspectives, hence why it was probably the drink of choice for Parisian bohemians. The most likely reason for these symptoms is that thujone causes lots of neurons to fire over and over, all at once. This neurological mess is likely what people interpret as their mind being set free. Overactivation of GABA receptors is known to cause epilepsy and convulsions.

Thujone does not however cause hallucinations. It is difficult to work out what causes the famous hallucinations as the methods for making absinthe have changed since 19th century France. It is thought that a neurotoxin present in the orginal formula could be causing hallucinations by a mechanism similar to THC in cannabis. Several neurotoxins are known to inhibit the neurons connecting the eyes to the brain, leading to black and green dots across the vision. This is sometimes interpreted by people as seeing bats (when black) and fairies (when green).

Nicotine

One major signalling pathway in the brain is the neurotransmitter called acetylcholine binding to its receptor. This binding activates receptors causing a nervous signal. Nicotine binds to a subset of acetylcholine receptors called nicotinic acetylcholine receptors. This action increases dopamine in the brain, leading to a sense of euphoria and relaxation, as well as the 'reward' signal which makes it addictive.

This interaction also causes the release of many other neurotransmitters, including acetylcholine, adrenaline, noradrenaline and beta-endorphin. This cocktails of neurotransmitters causes a huge relay of different signals, mediating different effects. Among these are alertness (caused by acetylcholine and noradrenaline), pain reduction by acetycholine and beta-endorphin and reduced anxiety due to beta-endorphin.

Long term use of nicotine causes a reduction in nicotinic acetylcholine receptors. This means that the effects of nicotine decrease with long term use. It also means that when nicotine is not present, withdrawal symptoms are essentially a reverse of nicotine's effects: poor concentration, sensitivity to pain, anxiety, and depression.