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Authors: D. F. Swaab

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CANNABIS AND PSYCHOSES

Cannabis has lost its innocence.

Addictive substances have been around throughout humankind's history, but every society and every group has different views on which are permissible and which are beyond the pale. I remember how amazed I was in the 1960s when people would stand with a glass of wine in one hand and a cigarette in the other, complaining loudly about the pot-smoking habits of long-haired layabouts. Addictive substances affect the brain by mimicking its own chemical messengers. Brain cells themselves produce a whole range of opiates and cannabinoids. The nicotine in a cigarette has the same effect as the chemical messenger acetylcholine. Addictive substances also affect the availability or the action of natural chemical messengers. The drug ecstasy, for instance, increases levels of serotonin, oxytocin, and vasopressin. That's why your brain no longer functions optimally when you stop taking a particular addictive substance: You feel terrible and get frequent uncontrollable urges to take more of it. All such substances have a direct or indirect effect on the brain's dopamine reward system (
fig. 16
), whether or not via an opiate system. Both systems are crucial to the rewarding effect of many normal
stimuli, including that of sexual behavior. Not for nothing is the brief euphoria following an injection of opiates often described in sexual terms; after all, it activates the same reward system.

Cannabis has been used for recreational, religious, and medical purposes since time immemorial. The medicinal effects of marijuana were first described in China around five thousand years ago. Nor is its medicinal use in the West new. It is said that Queen Victoria used it as a remedy for menstrual pain. Cannabis has recently been rehabilitated, and medicines with its active ingredient Δ
9
-tetrahydrocannabinol (THC) can be obtained in the Netherlands with a prescription. Studies are being carried out on its potential efficacy against pain, fearfulness, sleep disorders, the nausea caused by chemotherapy, and glaucoma (because it reduces eye pressure). Marijuana is also thought to reduce spasticity among patients with MS, although a controlled experiment with THC couldn't confirm such an effect.

Cannabis affects the brain because brain cells themselves produce cannabis-like neurotransmitters. The first such compound to be identified was christened anandamide,
ananda
being Sanskrit for “bliss.” The proteins that transmit anandamide's message to the brain, the receptors, are mainly located in the striatum (hence the blissful feeling) and in the cerebellum (hence the unsteady gait after taking marijuana), in the cerebral cortex (hence the problems with association, the fragmented thoughts and confusion), and in the hippocampus (hence the memory impairment). But there are no receptors in the brain stem areas that regulate blood pressure and breathing. That's why it's impossible to take an overdose of cannabis, as opposed to opiates.

The quality of cannabis in the Netherlands has improved so much over the years that it's rapidly changing from a soft drug into a hard drug. Daan Brühl was a nineteen-year-old boy from Amsterdam who was a champion rower. Returning from a disappointing tournament, he was seized by heart palpitations. To calm down he smoked a couple of joints with his girlfriend. Suddenly his expression altered.
He walked to the kitchen, grabbed a knife, and stabbed himself in the heart. He died that evening. Suzanne, a twenty-year-old, became psychotic after smoking large amounts of cannabis. She began to hallucinate and in an extremely fearful state was taken to the hospital, where she was diagnosed with schizophrenia. Schizophrenia is a developmental brain disorder that begins in the womb (see
chapter 10
). However, the first psychosis doesn't usually occur until around the age of sixteen to twenty because the sex hormones that circulate after the onset of puberty place an enormous burden on the adolescent brain and can bring on the symptoms of schizophrenia. The same applies to cannabis. It's quite possible that teenagers who are admitted to the hospital with symptoms of schizophrenia after smoking cannabis would have suffered a psychosis a few months later anyway. On the other hand, studies show that cannabis users are twice as likely to develop schizophrenia. Patients who already have schizophrenia but are past the worst stage can suffer from a relapse if they use cannabis. The link between cannabis use and psychosis is all the more interesting in the light of the recent discovery that the brain's own cannabis system is activated in schizophrenic patients. Research is now being carried out to find out whether this system could be a new target for schizophrenia medication.

Adult males who smoke marijuana daily for a period of years have been found not only to have a smaller hippocampus (important for memory), a smaller amygdala (affecting fear, aggression, and sexual behavior), and damage to the fiber tracts of the corpus callosum (left-right connections) but also to be more likely to develop a psychosis. Again, though, these characteristics may have been present before using cannabis.

Not every psychosis after cannabis use is the first sign of schizophrenia. Gerard, a Dutch student, was mountain climbing in New Mexico. In the evening, when his group was sitting around the camp-fire, one of his fellow climbers offered him a joint. After four puffs he experienced hallucinations with flashes of light, became extremely hot, felt dehydrated, developed a burning spot in his heart region
along with cardiac arrhythmia, lost all power in his legs, and fainted twice. His friends took him to a hospital in El Paso, where he was told, not very helpfully, that he had had a “bad trip” and could go home again. Afterward he found out that the previous day, one of the other climbers had had a similar problem with that batch of cannabis, so they threw the rest away. The next day Gerard was left with the feeling that there was something odd about his sensory perceptions as well as the world in general (derealization), and he felt very tired. After a few days he had recovered sufficiently to join the next climbing trip. A month after the bad trip, after three days of climbing and considerable physical effort, he suddenly had the same symptoms as before, including the sensation of derealization, a feeling of acting on automatic pilot and observing himself from a distance (depersonalization), a tendency to faint, and serious difficulties in concentrating—something he found particularly worrying. Back in the Netherlands, doctors tried to get to the bottom of his extreme reaction to cannabis. Fortunately, he hadn't had the classic psychosis resembling a schizophrenic episode but had perhaps been intoxicated by a high dose of THC. In the Mexican border region, cannabis is said to be often far stronger than elsewhere. Someone put forward the theory that THC can remain in fat tissue for a very long time, to be released in response to intense physical effort. Moreover, Americans appear to smoke “pure” cannabis on the whole, unmixed with tobacco, causing a greater risk of adverse effects. (When on vacation in Amsterdam, they also put much too much THC in a single joint.) Another possible explanation was that the cannabis Gerard smoked had been sprayed with chemical agents or adulterated, possibly with a toxic weed killer or angel dust. None of these theories could be proven. Luckily, he made an excellent recovery. He's back at university and recently scored high grades on his exams.

Cannabis has lost its innocence. It's much stronger than it used to be and much less harmless than we all thought it was back in the 1960s. For some people, taking cannabis can have disastrous consequences. But compared to the enormous widespread damage that
alcohol and cigarettes cause in our society, the problem remains a proportionately small one.

ECSTASY: BRAIN DAMAGE AFTER PLEASURE

Take me, I am the drug; take me, I am hallucinogenic.

Salvador Dalí

Ecstasy is now known as the “love drug,” but it was originally patented as an appetite suppressant in 1914. Its recreational use can be extremely dangerous. A year ago, a trainee nurse decided to write a thesis on ecstasy. She didn't want to do so without any experience of the drug, so she tried it during the festival on Queen's Day, an important Dutch holiday. Just to make sure she wouldn't harm herself, she drank four liters of water. The experiment proved fateful. She lost consciousness, was in a coma for several days, and has been left with lasting brain damage, especially to the cerebral cortex.

When you take ecstasy, you make quite a lot happen in your brain, as a pioneer in this field, the radiologist Liesbeth Reneman, established many years ago, and the risks are considerable. Twenty minutes after swallowing ecstasy, increased amounts of the chemical messengers serotonin, oxytocin, and vasopressin are released. All tiredness vanishes and you feel happy and want to hug everyone. The pleasurable feelings of love and wonderful social interaction last for an hour. If you take a fair amount of ecstasy every weekend, you destroy the brain cells that make serotonin. Less of this messenger is produced, and you function less well. You also need more ecstasy each time in order to get the same pleasant effect. Users are more likely to develop psychiatric and neurological problems like mood disorders, aggression, impulsiveness, and memory impairment. Brain scans of ecstasy users indeed show permanently reduced activity in structures that would be involved in such problems, like the amygdala, hippocampus, thalamus, and cerebral cortex. A recent
follow-up study showed that even brief, extremely limited ecstasy use amounting to a couple of pills taken over an eighteen-month period impairs memory and blood flow in the thalamus and cerebral cortex. Scans have also shown that ecstasy can cause blood vessels to constrict or, conversely, to dilate on a long-term basis, depending on the brain region in question. The neurological consequences can include brain infarcts or bleeding on the outside of the brain, resulting in serious and lasting neurological damage.

If you take ecstasy when it's hot and you don't drink enough, you can dehydrate, resulting in organ failure. Some people develop palpitations or have a sudden fatal heart attack. Unity, a voluntary project sponsored by the Jelinek addiction treatment center in the Netherlands, therefore rightly advises ecstasy users to drink a glass of water or a sports drink every hour to prevent dehydration and overheating. But apparently people also need to be explicitly warned that drinking too much water in combination with ecstasy can also be dangerous. Ecstasy causes the pituitary gland to release much more vasopressin (the antidiuretic hormone; see
chapter 5
), so your kidneys retain all the liquid you drink. As a result, drinking too much can cause water poisoning and serious brain damage.

This is exactly what happened to the trainee nurse researching her thesis: She developed brain and vascular edema—essentially a swelling of the brain—causing serious brain damage. After three days she gradually emerged from the coma, suffering subsequent epileptic attacks. A scan showed severe swelling of the brain, mainly on the left-hand side. In the early weeks she couldn't talk (Broca's area, bottom left of the frontal cortex,
fig. 8
) or walk (motor cortex,
fig. 22
) and her sight was impaired on one side (visual cortex, at the rear of the brain,
fig. 22
). She's still recuperating with therapy. She can't yet read and finds writing difficult. When she speaks, she regularly struggles for words. Recovery is a slow, demanding process, and she's continually tired. It's not yet clear what permanent impairment will result from her brush with ecstasy, but an MRI scan shows damage to the cerebral cortex. Instead of writing a thesis on ecstasy, she now wants
to warn schoolchildren about its dangers, particularly in combination with a lot of water. Her own ecstasy party is over for good.

SUBSTANCE ABUSE BY POLITICIANS

Drunkenness is nothing more than voluntary madness.

Seneca

The terms
addiction
and
substance abuse
mainly conjure up images of neglected, homeless, and often schizophrenic people. But the former British cabinet minister David Owen, a neurologist by training, makes clear in his startling 2008 book
In Sickness and in Power: Illness in Heads of Government During the Last Hundred Years
that the problem of substance abuse can be found even in the highest government circles, with potentially dramatic consequences for the course of history.

Teenagers experiment with pills, magic mushrooms, marijuana, and other potentially dangerous substances. This seems to be a normal aspect of adolescent behavior (see
chapter 4
). Some world leaders have been forced to confess to similar youthful peccadilloes, which isn't always easy. During his 1992 campaign, Bill Clinton was forced to admit that he had smoked pot as a student, adding rather feebly, “But I didn't inhale.” But America has become more tolerant of these things in recent years. When Barack Obama sought the presidential nomination, he was questioned about his book
Dreams from My Father
, in which he wrote about smoking pot and drinking as a troubled teenager, and he owned up to the occasional hit. “I inhaled frequently—that was the point,” he said, poking fun at Bill Clinton. This open admission never worked against him.

Before his presidency, George W. Bush was an alcoholic, and certainly not just as an adolescent. At the age of thirty he was arrested for drunk driving and lost his driver's license for two years. During his 2000 campaign he stated that in 1986 he woke up with a hangover
after celebrating his fortieth birthday and that he had not drunk a drop since. That claim seems a little questionable. In 2002, Bush fell off a couch while watching a football game and was taken to the Johns Hopkins Hospital in Baltimore. A British doctor there told David Owen that Bush's blood contained significant amounts of alcohol. Bush has refused to answer any questions about his alleged past cocaine use.

There's no doubt at all, however, about Richard Nixon's alcoholism during his presidency. In 1969, when an American spy plane was shot down in North Korea, Nixon stormed about in a drunken rage, telling his national security advisor, Henry Kissinger, “Henry, we'll nuke 'em!” Tapes released after the Arab-Israeli conflict in 1973 also revealed that Nixon was too drunk to discuss the situation with his British counterpart. Russian president Boris Yeltsin suffered severe back pain after being in a Spanish plane that was forced to execute a crash landing. Beginning in 1994 he took more and more painkillers and drank increasingly. At an official ceremony that year in Berlin, in honor of the departure of the last Russian troops, he was clearly drunk. There was another incident that same year when his plane stopped over at Shannon International Airport. The entire Irish government stood ready to welcome him at the foot of the aircraft steps, but he was sleeping off the effects of a drinking bout and failed to appear.

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