Zopiclone, Zaleplon and Zolpidem

Description

The ‘Z-drugs’ are a group of non-benzodiazepine drugs with effects similar to benzodiazepines which were designed to be used in the treatment of insomnia. They are called ‘Z’ drugs as they are similar in action and begin with a common first letter.

The three Z-drugs include zaleplon (brand names: Sonata), zolpidem (brand names: Ambien, Stilnox), zopiclone (brand names: Zimovane, Imovane), and its active enantiomer eszopiclone (brand name: Lunesta).

Pharmacology

Zolpidem exerts its effects through targeting the same GABA-A receptor binding site as benzodiazepines (for more information, see Diazepam). Unlike benzodiazepines however, it shows marked selectivity for GABA-A receptors containing the alpha-1 subunit, leading to its effects being more hypnotic than anxiolytic or anti-convulsant.

Z-drugs in immediate release formulations have an onset time of 30–60 min, while slow release can increase this up to 3 hours. Zopiclone has the longest duration of the Z-drugs (half-life ≈ 5–7 hours, half life of zolpidem ≈ 2 hours and Zaleplon ≈ 1 hour), leading to more residual effects similar to short acting benzos.

Zopiclone and zolpidem are primarily broken down by the CYP3A4 enzyme, so it is recommended to avoid taking them in conjunction with CYP3A4 inhibitors (e.g. clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, and grapefruit juice), as they may increase unwanted side effects and risk of overdose.

As Z-drugs have a similar mechanism of action to benzos, taking them alongside opioids, alcohol, GHB/GBL, and/or gabapentinoids significantly increases the risk of overdose.

Harm Reduction

• Start low, go slow: Take a small amount and wait until you can feel the effects before taking more/anything else
• Try not to use alone: If something goes wrong, someone is there to get help
• Be careful mixing: Mixing Z-drugs with other depressants increases overdose risk – avoid if you can, otherwise take less of each, as they can increase the effects and risks
• Carry naloxone: There have been counterfeit z-drugs in the UK found to contain strong opioids
• Test your stuff: Some Z-drug pills tested in the UK didn’t contain what they were sold as, and you can’t see this by eye. Find out how to send a sample to WEDINOS for testing here: https://www.wedinos.wales or pick up some test strips at our Harm Reduction Hub
• If you’ve been prescribed a Z-drug and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor – don’t just start increasing your dose yourself.
• Don’t suddenly stop taking them, or you may start to experience symptoms of withdrawal: these can range from a return of your original symptoms (possibly even worse than before) to totally new symptoms.
• If you have become physically dependent on Z-drugs, the symptoms of abruptly stopping are likely to be even worse. It’s important to get proper medical advice on how to reduce your intake slowly.
• It’s also possible to become psychologically dependent on the drug (feeling like you need it all the time). If you think this is happening, see your doctor as soon as possible, but don’t suddenly stop taking it.

History

‘Z-drugs’ emerged in the last years of the 1980s and early 1990s, with zopiclone (Zimovane) approved by the NHS in 1989, followed by zolpidem (Ambien) manufactured by the Sanofi Group. By 1999, the last of the group, zaleplon, was introduced to the clinical pharmacopeia. As concern of the potential for dependence formation and management of chronic insomnia rose, the Z group became increasingly popular. As may have been anticipated by students of the history of hypnotics, a debate over the dependence liability of the ‘Z-drugs’ has also developed across the years. Despite being marketed as a ‘safer alternative’ to benzos, Z-drugs appear to produce similar rates of dependence and protracted withdrawals among individuals who take them long-term.

In 2020, researchers Hockenhull and colleagues found that the non-prescribed use of Z drugs was more common among people who use heroin, compared to benzos being more common among people who use stimulants. In recent years, some benzos including bromazolam and diazepam have been missold as Z-drugs (most commonly sold as zolpidem), likely due to their mode of action.

Law

• Class C
• Schedule 4 (1)

Possible offences

• Possession
  • Maximum sentence – 2 years/fine/both
• Possession With Intent To Supply
  • Maximum sentence – 14 years/fine/both
• Supply (including being concerned in supply, conspiracy to supply, aggravated supply and offer to supply)
  • Maximum sentence – 14 years/fine/both
• Production
  • Maximum sentence – 14 years/fine/both

In practice maximum sentences are rarely used, for more detailed and accurate information go to our sentencing page.