A small amount of alcohol, for example, may usher in a more outgoing personality, cause us to behave irrationally, or sink into melancholy. Women’s moods may fluctuate with their menstrual cycle. Regular running can produce a high so pleasurable that aficionados become stressed and irritable if they are prevented from exercising. Adenosine, administered to control the heart rate, has the extraordinary side-effect of producing a transitory feeling of impending doom so severe that the patient may feel they are about to die. Parkinson’s disease is noteworthy for its high incidence of associated depression. Syphilis causes marked changes in temperament, most famously in King Henry VIII. Simply stimulating certain regions of the brain can produce euphoria, anger – even, it has been claimed, spiritual experiences. All human emotions have their origins in the electrochemistry of the brain, and an intricate tapestry of chemical and electrical signals governs our every thought and action.
This penultimate chapter considers how neurotransmitters influence our moods, our memories and our thoughts, and how drugs of abuse enhance or mimic their effects. It looks at how our personalities are shaped by the electrical activity of our brain and considers what happens to us during sleep and anaesthesia. And it addresses the question that has perplexed mankind for centuries – what is consciousness and who, exactly, am I?
What a Pleasure
We are pre-programmed to seek pleasure. Food, sex, drink, exercise – all produce feelings of enjoyment that drive us to seek more. But our impulse to do so is more than hedonism or sheer sensual delight; it is a way of ensuring that our species survives. All pleasurable experiences stimulate the reward centre of the brain. This consists of several distinct brain regions, including the nucleus accumbens, the amygdala and the ventral tegmental area, which are wired together by a group of nerve cells known as the median forebrain bundle. Dopamine, one of the most crucial neurotransmitters in the brain, is intimately involved in desire and addiction. Pleasurable experiences such as sex, love and food trigger the release of dopamine in the brain’s reward centre, which increases nerve cell electrical activity, reinforcing our sensation of pleasure and coercing us to have yet another chocolate or glass of wine – too much in some cases. Many drugs of addiction act by increasing the concentration of dopamine in the nucleus accumbens, thereby producing feelings of euphoria.
Long ago when I was just a teenager I went to see a film at the local cinema with a school friend and her family. The queue was enormous and it was clear that we were unlikely to get in. ‘Never mind’, said my friend’s mother, ‘let’s go home and try the cocaine.’ This was not as outrageous a suggestion as you might imagine. Her son had just returned from South America with a bag of coca leaves. These have been chewed by Peruvian Indians for over 8,000 years, mainly because alkaloids in the leaves act as an appetite suppressant and help keep them awake. I, however, did not find it a stimulating experience – all that happened was that my lips and tongue were slowly and mildly anaesthetized, rather as if I had been to the dentist. Nothing else. Perhaps this may have been because I was far too nervous to take more than the tiniest bite of a leaf or two: even then, cocaine, which originates from coca leaves, had a fearsome reputation as a drug of abuse.
Initially, however, it was widely lauded. Sigmund Freud regularly took cocaine while writing The Interpretation of Dreams, as he found that cocaine caused ‘exhilaration and lasting euphoria’ and had such a ‘wonderful stimulating effect’ that ‘long-lasting intensive mental or physical work can be performed without fatigue’. In the nineteenth century a cocaine-laced drink, Vin Mariani, hailed as a tonic for body and brain, was such a favourite of Pope Leo XIII that he awarded it a special gold medal and appeared on a poster extolling its virtues. A pinch of coca leaves was also added to the original brew of Coca-Cola, along with extracts of the kola plant (hence its name). The power of cocaine to banish tiredness was even exploited by explorers. Both Ernest Shackleton and Captain Robert Scott took ‘Forced March’ cocaine tablets with them to Antarctica and during World War I it was supplied to some British troops to enhance their endurance.
Cocaine acts by preventing clearance of the neurotransmitter dopamine, released in response to nerve impulses, from the synaptic cleft. Consequently, dopamine hangs around longer and continues to stimulate its target cells. Amphetamine (speed) acts in a similar way. The addictive properties of both drugs come from the fact that dopamine stimulates the reward centre of the brain, so that pure cocaine produces feelings of exhilaration and euphoria, as Freud described. Providing that the body continues to be supplied with cocaine, dopamine levels in the brain remain elevated and the pleasurable sensation continues. When the drug wears off, however, the dopamine concentration plummets to below normal levels, producing depression, anxiety and a craving for more drug. Addiction, then, is an affliction of the brain and anything that stimulates the brain’s reward centres to excess has the potential to be addictive.
Hooked
Nicotine is one of the most addictive drugs known. It is found in the leaves of the tobacco plant, Nicotiana tabaccum, which is named after the sixteenth-century adventurer Jean Nicot who brought the plant to France and is said to have popularized its use as a treatment for headache. Tobacco was introduced into England by Sir John Hawkins in 1565 and at first was met with amazement and considerable opposition. There is a famous story, probably apocryphal, that Sir Walter Raleigh’s servant emptied a bucket of water over him in the mistaken belief that his master was on fire. Kings and papal bulls banned its use. King James I of England wrote a famous Counterblaste to Tobacco in 1604, calling it ‘a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs and in the black stinking fume thereof, nearest resembling the horrible Stygian smoke of the pit that is bottomless’. Gradually, however, tobacco use proliferated, becoming widespread by the middle of the last century.
Smoking is an expensive habit in every sense. Every hour, twelve people in the UK die from smoking-related diseases and many more in the United States, and billions of dollars are spent on smoking-related health costs – over 190 billion dollars per year in the USA alone. It is estimated that half of cigarette smokers will eventually be killed by their habit, for smoking dramatically increases the risk of lung cancer (85 per cent of lung cancer cases are due to smoking) and is also associated with heart disease, stroke, emphysema and a range of other cancers. The link between smoking and lung cancer was established by Sir Richard Doll in the early 1950s, but the idea initially met with considerable resistance. Concerted health campaigns over the past fifty years have led to a decline in tobacco use and a corresponding fall in lung cancer rates, but around 20 per cent of adults still smoke. As everyone knows, it is not the nicotine in cigarettes that causes cancer but a cocktail of carcinogens contained in tobacco smoke; nicotine is dangerous because it is highly addictive and its tenacious hold makes it difficult to quit smoking.
Nicotine acts on acetylcholine receptors found at the junctions between nerve and skeletal muscle and at certain nerve–nerve synapses in the brain. Like acetylcholine itself, binding of nicotine to acetylcholine receptors opens an ion channel that allows sodium ions to enter the nerve cell and so stimulates it to fire off an electrical impulse. It is the drug’s ability to activate certain brain neurones that accounts for its actions as a stimulant and, like caffeine, enables you to concentrate more effectively when tired. Its addictive properties stem from the fact that it also stimulates nerve cells in the reward pathways in the brain. Regular smokers adjust their smoking to maintain a constant concentration of nicotine in their blood and brain, and thus a steady level of neuronal stimulation. Some individuals have genetic differences in the liver enzyme that breaks down nicotine, so that the drug remains in their bloodstream for longer and they smoke fewer cigarettes to obtain the same effect.
Love, Love Me Do
‘Tell me where is fancy bred, Or in the heart, or in the head?’, asks Shakespeare in The Merchant of Venice. Romantic love has lon
g been a favourite topic for authors, artists and playwrights, but what does cause us to fall in love? To seek the perfect mate and stick with them forever – or to favour the fresher faces, being constant only to inconstancy? The lovesick have often wished for a simple means to make the object of their affection fall in love with them. This is the basis of many charms and potions, perhaps even our predilection for cosmetics, perfume and dressing up. In A Midsummer Night’s Dream, a love potion made from the juice of heartsease (the wild pansy) famously creates mayhem. It is administered to an unsuspecting Titania while she sleeps and compels her to fall in love with the first living thing she sees on waking. It happens to be Bottom, a most unprepossessing object of desire, since his head has been transformed into that of an ass. Yet although we may scoff at the idea of magical love potions, recent research suggests love is indeed no more than a chemical phenomenon.
Our understanding of the chemistry of attraction has its origin in a somewhat unlikely source – a rather unappealing small rodent known as the prairie vole. Prairie voles are monogamous and bond for life. In contrast, their cousins the montane voles are highly promiscuous, preferring to confine themselves to one-night stands. The difference in their behaviour seems to be related to two specific brain chemicals, oxytocin and vasopressin, that are released during mating. Oxytocin is crucial for pair bonding because its injection into the nucleus accumbens is sufficient to cement a couple for life, even if they are prevented from having sex. Conversely, if oxytocin action is blocked the prairie vole is only interested in fleeting affairs. Injecting oxytocin into a montane vole, however, does not dissuade it from a life of promiscuity, because it lacks oxytocin receptors in the reward centres of its brain. Oxytocin induces the release of dopamine and both are thought to act in concert to make pair bonding a particularly pleasurable experience. Vasopressin is similarly important for pair bonding, especially in males, and also provokes the aggressive behaviour that male voles display towards potential rivals during courtship and when defending the nest. It has also been linked to aggression in humans.
Clearly, it would be injudicious to extrapolate directly from voles to humans, for both the human brain and our social interactions are far more complex and involve multiple transmitters and many brain regions. Nevertheless, oxytocin is also important for bonding in humans. It is released during sex and suckling and may help cement the links between lovers, and between mother and child. It also enhances trust between people, an essential component of any loving relationship. Dopamine, that arbiter of pleasure and addiction, also plays an important role in romantic love. When the brain activity of students who claimed to be madly in love was examined in a scanner, dopamine-rich regions lit up when they were shown an image of their beloved. Thus here, to answer Shakespeare’s question, is where fancy is bred, and in a very real sense, we may be addicted to the object of our love.
The (Un)Happiness Hormone
If pleasure is a construct of the brain, so too is misery. ‘A mark in every face I meet, Marks of weakness, marks of woe’ – as William Blake wrote, unhappiness is everywhere. So too is her more severe sister, clinical depression, for it is estimated that at some stage of our life almost 10 per cent of us will suffer from the ‘black dog’, as Winston Churchill termed it. In some people, it can be so severe that it is totally incapacitating.
Happiness and despair are the two faces of the neurotransmitter serotonin. Serotonin is produced by neurones of the raphe nucleus, whose processes ramify throughout the brain. Their targets include the nucleus accumbens and the ventral tegmental area, part of the brain’s reward system. Because serotonin is released in many brain regions and interacts with at least fourteen different kinds of receptor, it affects many types of behaviour, but one of its most important roles is mood control. Elevated levels of serotonin are associated with feelings of optimism, contentment and serenity. Too little brings despair, depression, anxiety, apathy, and feelings of inadequacy. One way of increasing your serotonin levels is by vigorous exercise, which is why a brisk walk or a game of squash (if you can drag yourself off the sofa) helps relieve the blues. Modern antidepressants such as Prozac also act by elevating serotonin concentrations. They do so by inhibiting the removal of serotonin from the synaptic cleft, so that the transmitter stimulates its receptors for longer.
Perhaps the most infamous of drugs that interact with serotonin receptors, however, is LSD. Its extraordinary effects on perception are poetically described in the Beatles’ song ‘Lucy in the Sky with Diamonds’. But not all trips are so pleasant. In the TV series Dr Who, the Time Lord is ‘regenerated’ every few years, enabling him to be played by a different actor. Papers in the BBC archive explain to producers that the experience of regeneration is horrifying – it is, they say, ‘as if he has had the LSD drug and instead of experiencing the kicks, he has the hell and dank horror which can be its effect’.
LSD is a psychedelic drug related to a natural compound, ergotamine, found in the purple-brown fruiting bodies of the ergot fungus, Claviceps purpurea. It grows wild on rye and in mediaeval times contaminated rye bread caused dramatic outbreaks of ergot poisoning. Whole communities were sometimes affected. In 1930 the active ingredient of ergot was isolated and named lysergic acid, and subsequently the Swiss chemist Albert Hoffman produced a derivative that he named lysergic acid diethylamide – or LSD-25 for short. Although he did nothing with it for the next five years, he never forgot that experimental animals became restless when given the drug and, in 1943, having decided to reinvestigate the drug, he synthesized some more. Despite taking considerable precautions (for he knew ergot was toxic), during the final step of the synthesis he was overcome by a string of strange sensations including ‘an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors’.
Thinking this astonishing experience must have come from the drug, in the time-honoured tradition of pharmaceutical scientists, Hoffman cautiously ingested a tiny amount in a self-experiment three days later. It had a most dramatic effect. His notebook records, ‘My surroundings had now transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness. The lady next door, whom I scarcely recognized, brought me milk – in the course of the evening I drank more than two liters. She was no longer Mrs. R., but rather a malevolent, insidious witch with a colored mask.’ Hoffman clearly had a bad trip, for he also remarks, ‘A demon had invaded me, had taken possession of my body, mind, and soul.’ He feared he was going to die, leaving his wife and three children bereft and his promising research work unfinished. Slowly, however, these horrors faded to be replaced by phantasmagorical visions of ‘circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux’, sounds that transformed themselves into optical images, and a sensation of renewed life.
LSD is one of the most powerful hallucinogens known. It has extraordinary effects on auditory and visual perception, producing a sparkling world in which colour, brightness and sounds are intensified, objects morph into strange shapes, and walls may ‘breathe’. But altered percept and hallucinatory visions are not its only effects. It also produces changes in time perception, the emotions and self-awareness. Some users claim it even leads to higher states of consciousness (whatever those might be), spiritual awareness, even enlightenment. More prosaically, what all these experiences boil down to is changes in the electrical activity of the brain. LSD and other hallucinogens produce their ‘magic’ effects by binding very tightly to a specific subset of serotonin receptors at brain synapses, known as 5HT-2A receptors. Why LSD causes such intense hallucinations and serotonin does not, given that they both bind to the same receptors, is far from clear, but one clue may be that they seem to trigger different signalling pathways in their target cells.
The Art of Memory
Our understanding of the physiological basis of emotions other than pleasure and despair – of anger, embarrassment, envy, grief, disgust, guilt and astonishment, to name but a few – is less clearly established. What is well recognized, however, is that our emotional reaction to a given situation is strongly influenced by our previous experience. Memory plays a key role in how we feel, and it is in the amygdala, two almond-shaped brain regions that lie on either side of the head, that memories are interwoven with emotions. Here, too, reward and fear memories are stored and recovered.
Memory – how to enhance it, and how memories are laid down, stored and retrieved – has perplexed and fascinated people for centuries. In the days before cheap paper, or computers, it was of particular importance. The Ancient Greeks and Romans were especially skilled in the art of memory, for lawyers and politicians were expected to speak for hours without notes. Consequently, methods of remembering were widely discussed. Quintilian tells of how the poet Simonides delivered the victory ode for his host, a champion boxer, at a magnificent banquet in Thessaly. As was traditional, his panegyric included a passage that lauded the twin gods Castor and Pollux. Annoyed at having to share the credit, and despite the price having been agreed beforehand, Simonides’ host withheld part of the fee, telling him he should claim the balance from Castor and Pollux. A little later, Simonides was summoned from the room by a message that two young men wished to see him urgently. Scarcely had he left the building before it collapsed and all inside were crushed to death beneath the rubble. The callers who had saved Simonides’s life had vanished, but were assumed to be Castor and Pollux. The message of this story was not, as one might imagine, the moral importance of paying one’s bills, but rather of what Simonides did next. So badly mutilated were the bodies of the dead that it was impossible to recognize any of them. However, Simonides was able to remember the precise positions in which all the diners had been sitting, thus enabling their bodies to be restored to their respective families. He had invented the ‘art of memory’.
The Spark of Life: Electricity in the Human Body Page 27