They affect serotonin and dopamine, and resemble ecstasy and speed



These pills are from a class of drugs known as piperazines. Piperazine, named because it is made from an extract of the pepper plant, has been used for a long time to treat worm infections in the gut. It kills parasitic worms through its effect on the neurotransmitter GABA. GABA is an inhibitory neurotransmitter; that is a chemical messenger which signals from one neurone to another that nerves should stop firing. It is found in the brain, where it is released to cause an overall dampening of activity in the neurons (brain cells) that it contacts, and is also found in the peripheral nervous system that is responsible for controlling the movement of muscles in the body. Piperazine is absorbed through the gut and does not easily enter the brain. By preventing activation of muscles it causes paralysis, and since it takes far less of the drug in the gut to paralyse a worm than a human it is able to kill the worms. In overdose piperazine can cause tiredness in the limbs, breathing difficulties and seizure. All of these effects are caused by its action on GABA.

Other drugs in the same class as piperazine include Viagra, and BZP, which is the drug most commonly found in legal party pills. These drugs do enter the brain and also effect neurons controlled by GABA, but in a different way which can lead to an increase in their activity. BZP and other closely related drugs in the same class are sold for recreational use because of their effect on the neurotransmitters 5-HT (serotonin) and dopamine, which resemble the effects of drugs such as ecstasy and amphetamine. This class of drugs has sometimes been given to people who have lost their sex drive due to treatment with antidepressants.

Research carried out at St George's Medical School into the contents of various party pills and capsules on sale legally in the UK found that despite labeling which occasionally suggested other ingredients, the vast majority contained a mixture of BZP and another piperazine, TFMPP. TFMPP is known for its hallucinogenic and euphoric effect, which is considered to be more like ecstasy than BZP. The study showed that there is a lack of accuracy in the labeling of these pills, which can be very misleading. It suggests that people taking these pills are unaware of what they are taking or how to use these drugs safely.

How come they are legal?

Laws controlling the classification of emerging drugs in the UK are among the strictest in the world but BZP and other piperazines remain legal. In the USA BZP was classified as a schedule 1 (illegal) drug in 2002. Australia and several European countries including Denmark have also banned the sale of BZP. Since then 'party pills' have been manufactured which do not contain BZP, presumably so that they can be sold in countries where BZP is illegal. In New Zealand, where most of these pills are made, BZP has been classified as a class D drug, and remains legal but with restrictions on its sale. The advisory group Transform has recommended that the UK should follow this model which is aimed at reducing the demand for black-market amphetamines by providing an alternative.

Do they work in the same way as ecstasy?

Many of the effects of ecstasy (MDMA) are due to its ability to release large amounts of the neurotransmitter 5-HT (serotonin) in certain parts of the brain. 5-HT plays a part in controlling mood, and is probably responsible for the euphoric effect of ecstasy. Many antidepressant drugs also affect 5-HT.

Although ecstasy is, in itself, able to activate the neurons affected by 5-HT, it also causes the neurons which contain 5-HT to pump it out into the brain in large amounts. This massive release of 5-HT is responsible for the common side effect of depression a few days after the drug has been taken. The release of 5-HT is also responsible for the release of two other neurotransmitters which contribute to the sensations caused by ecstasy as a knock-on effect. These are dopamine and (to a lesser extent) nor-adrenaline. Although it is an oversimplification, dopamine can be thought of as effecting perception (vision, sound etc.) and of giving a rewarding 'high' feeling, while nor-adrenaline gives a feeling of having energy.

BZP causes release of dopamine and 5-HT. While these are the same neurotransmitters released by ecstasy, low doses of BZP only cause release of dopamine, while higher doses also cause release of small amounts of 5-HT. This means that BZP bares more similarities to amphetamine, which causes release of nor-adrenaline and dopamine. A related point is that although it does not cause euphoria and direct changes in mood, both people and rats seem to enjoy dopamine release and it is thought to be the cause of the addictive 'rush' associated with cocaine and amphetamine use.

TFMPP, the other piperazine usually found in legal pills works in a similar way to ecstasy and activates neurons which respond to 5-HT. It also causes release of 5-HT, but not of dopamine since it does not fully activate the neurons responsible for this particular effect. This means TFMPP has a euphoric, mood-altering effect, but is not a stimulant, and will not keep users dancing all night long.

As BZP is not really a euphoric drug like ecstasy, and TFMPP is not really a stimulant, the two are often combined in 'legal high' capsules and pills. The combination of BZP and TFMPP together causes release of dopamine which is much greater than is expected for this combination, and far in excess of that induced by ecstasy. Excessive release of dopamine in a different part of the brain causes nausea, and this could be why people commonly report feeling sick as a side effect of these legal highs.

The effects of these drugs on GABA receptors have not yet been investigated. Most piperazines used by clubbers reduce the effects of GABA, so they should stimulate the nervous system, but some users have reported side-effects are similar to those of the original piperazine worming pills such as drowsiness, heavy limbs and difficulty breathing. Drugs which act on GABA receptors can potentially have harmful effects in overdose or in combination with other drugs, particularly depressants such as alcohol.

Are they safer than ecstasy?

The actions of these drugs are similar to ecstasy, but it should not be assumed that the contents of these pills are monitored or tested. They are currently less closely regulated than normal food products and can be misleadingly labeled. Where BZP and TFMPP are taken together they can cause seizures in rats at doses just three times those needed to induce release of dopamine and 5-HT. Piperazines are reported as having low potential for addiction due to the unpleasant effects experienced in overdose. However, a large overdose of these drugs could be dangerous, particularly if they are taken with or soon after alcohol. As BZP and TMFPP together cause excessive dopamine release they may lead to unpleasant hallucinations, paranoia and 'amphetamine psychosis'. These pills should not be taken by people who take antidepressants or any other psychiatric medication because of likely interactions between the drugs.

Anyone with a history of epilepsy, heart problems should not take piperazine based drugs. They should not be taken in combination with ecstasy, amphetamines. Some of the pills available for sale are strong and users should follow any guidelines for dosage given on the packaging, taking care not to take too many.

What should I do if someone experiences problems with these drugs?

The reported side-effects represent responses to a variety of different drugs and users are often unaware of the pill's contents. Toxic effects recorded by the emergency department of Christchurch hospital, New Zealand include: nausea, dehydration, insomnia, anxiety, blurred vision, palpitations, migraine, retention of urine, difficulty breathing. These effects can last for 24 hours after the drug has been taken.

A slight overdose of BZP or any of the related drugs is not usually serious. The effects can last for a long time so you should find a quiet space and anyone experiencing problems should not be left alone. Seek medical attention immediately if someone shows signs of serious overdose such as case of breathing difficulties, unconsciousness or seizures (fits).