The Secret History of Ambien

Ambien is the world’s most popular sleeping tablet. Side effects include; sleep driving, night terrors and sexting.

 THE NATURAL WORLD

Your body’s sleep cycle is governed by your hypothalamus, situated deep within the brain.

Each twenty-four-hour period contains several phases of wakefulness and sleepiness, collectively known as the ‘Circadian Rhythm’. Circadian Rhythms are present in humans, most animals, and even trees and other plants.

Living things are designed for a cyclical existence.

The hypothalamus governs this cycle with hormones, which raise or lower neural activity, and so make the body feel more or less alert. But disorders of this system are common.

According to the National Institute of Neurological Disorders, in the United States alone, 50 million people experience difficulty sleeping.

Sleeping tablets are not new science.

Barbituic acid, a combination of urea from animal urine and diethyl malonate from apples, was first synthesized in Germany, in 1864. By accident it was given to some laboratory dogs, and it was discovered that the compound put animals to sleep.

In 1903, pharmaceutical company Bayer created the first synthetic sleeping aid, for human use. The product was called ‘Veronal’; as Barbituic Acid was the active ingredient, this new class of drugs was called ‘Barbiturates’.

One high profile victim of barbituates

Barbiturates work by aiding one of the sleep-wake hormones produced by the hypothalamus.

GABA, gamma-aminobutyric acid, decreases neural activity in the brain, and so makes you feel calmer, and eventually, sleepy. Barbiturates stick to the brain’s neurons and make them more receptive to GABA, meaning the hormone is more likely to attach to the neuron and so is more effective.

While Barbiturates are very good at putting you to sleep, there is a downside; they are almost too good at what they do.

Their action disrupts the natural Circadian cycle, which makes them addictive. Once people start taking Barbiturates, they find it difficult to sleep without them.

They are also something of a blunt instrument, shutting the brain down so thoroughly that overdoses are common; Jimi Hendrix, Marilyn Monroe and Judy Garland all OD’d on Barbiturates.

GABA operating on neurons

Jean-Pierre Kaplan was a Paris born biochemist, who specialised in synthetic compounds.

In 1973, he took a job working for pharmaceutical company Synthélabo, and began developing a revolutionary new type of sleeping tablet. Called Zolpidem, it was to function in a similar way to existing Barbiturates, by assisting the efficacy of GABA, but in a subtler way.

GABA also plays a role in muscle relaxation, and memory, both of which are impacted by barbiturate use. This is why people taking these drugs often feel groggy the next day. But Zolpidem was able to target just the sleep inducing properties of GABA, reducing the unwanted side effects.

The molecular structure of LSD, with the 'tail' highlighted

Kaplan partnered with George Pascal, another young biochemist, and the two began designing molecular models out of wooden blocks

They began by creating models of existing sleeping agents - Valium, different Barbiturates – to see what molecular similarities they had. Then they transposed these onto the molecular design for Zolpidem.

They even borrowed a structure that they found when they modelled LSD; the psychedelic has a molecular ‘tail’ of oxygen, nitrogen and carbon, that causes it to linger in someone’s brain, which the two young scientists added on to their new compound.

Zolpidem goes on sale

In 1980, testing of the new drug commenced.

It was first trialled on animals, and was found to be remarkably effective, sending the test subjects to sleep within minutes. Later, at the beginning of human testing, a lab technician accidentally ingested some of the compound; he was found, five minutes later, asleep in his chair.

‘It was clear that it would be a great success. After the very first compound, I knew.’

 

- Jean-Pierre Kaplan

Zolpidem was launched as a commercial product in France in 1988. Five years later, it was launched in America under a new product name: Ambien.

Ad for Ambien

As predicted, it was hugely successful.

Viewed, and deliberately marketed, as safer than existing sleep medication, Ambien quickly overtook its competitors. By the year 2000, more Ambien prescriptions were written each year, then for all other sleep medication combined.

‘Everybody switched allegiance to Ambien, and then nothing came along that was any better. Everyone bought into it.’

 

- Jed Black, sleep specialist, Stanford University

But behind the success, something was not quite right.

While Ambien successfully quiets the brain, and usually induces sleep, its effects are not always predictable. Neurotransmitters are mercurial, and messing with their function, as Ambien does, can have unexpected consequences.

Many Ambien users have reported a sense of childlike wonder overtaking them as the drug kicks in.

Less happily, other users have reported stranger, more disturbing emotions; that they are being stalked, that strangers are in their house, that they are in sudden danger.

Even when the drug does send someone to sleep, strange business can still occur:

‘I took Ambien last night, and this is what I did in my sleep:

 

-Ordered 3 pairs of saddle shoes from eBay

-Sexted my best male friend who is married. I have a BF as well

-Played draw something w/my friend and drew penises and rainbows for every word

-Tried to legally change my name on the computer

 

- Anonymous Ambien user, medical discussion forum

Sleep driving on Ambien is common.

Patrick Kennedy, a US Congressman, crashed his car in 2006 while driving under the influence of Ambien; he had no memory of leaving his house, or getting behind the wheel.

Sleep cooking is another common side effect.

Other users have reported rearranging their cupboards, sending emails, cleaning, even knocking on their neighbour’s doors. None of them recall any of these activities, and have to be told they did them, when they wake up.

Rachel Uchitel and Tiger Woods

And then there are the recreational users.

While Ambien is a powerful sleep inducer, its effects can be resisted. And for anyone that can fight their way through the drug’s onset, they then find themselves in a weird, trippy twilight zone.

Fully awake, but still feeling the drug’s effects, makes users feel ‘de-personalised’, like having an out of body experience. Some recreational users also report vivid hallucinations, similar to taking LSD.

Rachel Uchitel, a former girlfriend of Tiger Woods, reported that she and the golf superstar used to take the drug, resist going to sleep, and then engage in ‘crazy Ambien sex’. Other people use it much the same as they would ecstasy or cocaine, as a party drug. Charlie Sheen called Ambien, 'The devil's aspirin.'

Ambien’s reputation is such that it has an established place in popular culture. In an episode of ’30 Rock’, Tina Fey’s character, Liz Lemon, reads the label of a bottle of Ambien she has been prescribed; ‘May cause dizziness, sexual nightmares, and sleep crime’.

While Ambien’s reputation has become a little muddied, in the ongoing absence of anything better, it remains pre-eminent.

In an interview in the New Yorker in 2013, Ambien’s inventor, Jean-Pierre Kaplan, was asked if he had ever used the drug.

‘Never!’ he yelled.

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