LEGAL HIGHS ON THE RISE

Lying back, exhaling: usually the last thing a person does before
leaving this world. Only in this case it is the world that is leaving me.

A few minutes ago I smoked a pipe of Salvia divinorum, a powerful
hallucinogenic herb that I bought openly and legally from a shop near
my home. Of the UKP 25 I handed over, more than UKP 4 will find its
way into government coffers in the form of sales tax. And salvia was
just one of dozens of powerful but entirely legal psychoactive
substances that I could have chosen.

All that was far from my mind as the salvia took me on a
consciousness-expanding journey unlike any other I have ever
experienced. My body felt disconnected from "me" and objects and
people appeared cartoonish, surreal and marvellous. Then, as suddenly
as it had began, it was over. The visions vanished and I was back in
my bedroom. I spoke to my "sitter" - the friend who was watching over
me, as recommended on the packaging - but my mouth was awkward and
clumsy. When I attempted to stand my coordination was off. Within a
couple of minutes, however, I was fine and clear-headed, though
dripping with sweat. The whole experience had lasted less than 5 minutes.

My salvia trip was part of a journey into the world of "legal highs",
a new generation of powerful mind-altering substances that are
growing in popularity across the world. Accurate figures are hard to
come by, as these substances are rarely monitored by drug-enforcement
agencies. But the proliferation of online and high-street retailers
suggest they are an increasingly lucrative business, and one company
specialising in legal drugs recently reported an annual turnover of
$16 million.

The reasons for their rising popularity are not hard to fathom. Not
only are they legal and openly available in many countries, they
work. Whether or not they are a good thing, however, is more
difficult to decide. Supporters argue that legal highs are a bit of
fun with a social conscience - a harm-reduction measure that allows
people to experiment safely with psychoactive substances while
separating drug use from criminality. Others say no one should be
allowed to take such powerful drugs: the risks are too great. Some of
the disagreement is down to the dearth of information about the short
and long-term health effects of most of these substances, their
potential for abuse and their addictiveness. But legal highs are also
a battleground between those who see the use of mind-altering drugs
as a human right and those who think it is plain wrong.

Faced with growing use and an information vacuum, governments are
playing catch-up. Some, notably the US and Australia, are clamping
down on each new substance as soon as they encounter it. Some are
doing nothing. Others are commissioning research into the drugs and
their effects before deciding what action to take.

And this is just the beginning. With hundreds of synthetic drugs on
their way, not to mention traditional herbs that are being introduced
to western consumers for the first time, some believe that cheap,
easily available, legal highs could render the street drugs market
redundant. So what do we know - and not know - about legal drugs?

Legal highs are nothing new. Paul Anand, manager of Shiva, the shop
in Greenwich, London, where I bought my salvia, has been selling them
for 15 years, starting with a stall at the Glastonbury festival.
"Back then, I was selling guarana, damiana and wild lettuce," he
says, "basically poor imitators of cannabis." There was a small
market for the stuff, but among experienced drug users they were
regarded as a joke, with few discernable effects.

That all changed with the arrival of new, reliable and effective
substances, beginning in the UK at least with magic mushrooms. At the
end of the 1990s, vendors started taking advantage of a legal
loophole that permitted the sale of fresh mushrooms as long as they
were not prepared in any way. Business boomed. In the year to April
2004 the number of shops selling magic mushrooms in England and Wales
rose from a handful to over 400, according to the British Crime
Survey. In the same period 260,000 people bought mushrooms - an
increase of 40 per cent on the previous 12 months.

In July 2005, the government closed the loophole, outlawing the sale
of fresh mushrooms containing the hallucinogens psilocybin and
psilocin, but by then it was too late. The demand for legal highs had
been established, and high street and internet vendors rushed to fill
the void with an assortment of alternatives. These include another
type of magic mushroom, the fly agaric (Amanita muscaria), which does
not contain psilocybin or psilocin but is packed with other
hallucinogens including muscimol. Salvia is another. And then there
is an astonishing assortment of psychoactive herbs, pills and potions
designed to mimic the effect of pretty much every illegal drug going.

No Dodgy Dealers

Inside the shop, the cornucopia of offerings cannot be exaggerated.
Vials and bottles crammed with herbal extracts, tinctures, seeds and
powders jostle for attention with packets of "party pills". There are
hallucinogens, relaxants, aphrodisiacs, trippy highs, "loved-up"
pills and euphorics. All entirely legal, at least in the UK.

So why the sudden explosion? Anand says that his customers are
attracted by the safety and quality of his products. "People are
confident in what they're buying - that it's not cut with rat poison.
They enjoy coming into the shop. They're not forced to meet a dodgy
git in a UV-lit disco to buy an aspirin."

Vendors also make a selling point of legality. With drug testing
increasingly routine at workplaces, 30 and 40-somethings are
switching to highs that don't put them on the wrong side of the law,
Anand says. And with legality comes, if not official approval, then
at least an imprimatur of safety.

The majority of Anand's customers are aged between 20 and 30, he
says. Most have tried street drugs and are now looking for something
safer, more reliable, legal and affordable. And they're part of a
growing movement: one leading vendor of legal highs, Stargate of
Auckland, New Zealand, recently reported an annual turnover of NZ$24
million (approximately US$16 million).

Among the most popular legal highs are "party pills" made from
compounds called piperazines, which are chemically similar to Viagra
but with an amphetamine-like action. Known by various brand names
such as PEP and Bliss, their main active ingredient is BZP
(benzylpiperazine) - the "Z" pronounced US-style to rhyme with the
"B". Originally developed as a drug to treat parasites in livestock,
piperazines have been sporadically used on the dance scene for many
years but began to seriously take off about three years ago - though
not in the US, where they have been strictly illegal since 2002.
Anand started selling them in January 2006 and says that every month
they grow more popular.

The BZP story started in the late 1990s, when the drug was
"discovered" by New Zealand entrepreneur Matt Bowden. The former
musician and recreational drug user became hooked on illegal
amphetamines in the 1990s during an epidemic of methamphetamine -
"crystal meth" - addiction that swept the country. He had already
lost a family member to ecstasy when, in the mid-1990s, he witnessed
a friend on meth commit a horrific suicide - disembowelling himself
with a samurai sword - at a party.

Bowden became determined to kick the habit. His efforts to quit led
him to experiment with legal alternatives and he sought out a
professor of neuropharmacology to tutor him and work alongside him on
the project.
"I said, let's find something which is like methamphetamine but
non-addictive and has an extremely low risk of overdose or death,"
Bowden says. They searched through the scientific literature and came
across a piperazine which occasionally cropped up as an ecstasy
alternative called A2.

"We looked at a US study and found that one part of the molecule
caused liver damage in rats, but the other part appeared to be
perfectly safe. That part was BZP," he says.

In 2000, Bowden used the compound to break his addiction to
methamphetamine and then began giving it out for free to friends. By
2002, companies had begun making and selling BZP. The move led Bowden
to set up his own company, Stargate, to market safe, legal
alternatives to street drugs.

Stargate now produces and sells a range of pills based on piperazine
blends. BZP is often combined with another piperazine, TFMPP
(trifluorophenylmethylpiperazine), which gives the pills a relaxing,
euphoric effect that has been compared to ecstasy.

Both drugs activate the 5HT serotonin receptor in the brain - the
same receptor targeted by amphetamines and MDMA - and cause the
release of dopamine (Neuropsychopharmacology, vol 30, p 550). This is
responsible for the "high" associated with the pills, though it can
also lead to anxiety, overheating and dehydration. In one survey,
only half of people who had used BZP said they would describe its
effects as "good"; 16 per cent said it was "good early but bad
later", 10 per cent "bad" and 14 per cent "neither good nor bad". My
own experience of using BZP was mixed, with some enjoyable effects
but also a bout of paranoia, insomnia and a bad hangover the next day.

Worldwide, Bowden sells a million pills a year and, all told, New
Zealand's legal party pills industry is worth around NZ$50 million a
year. As these figures suggest, a lot of New Zealanders take BZP. In
June, researchers at Massey University in Auckland released the
results of a survey of more than 2000 people, commissioned by the New
Zealand government. "We expected that no more than 5 per cent of
those questioned would have tried BZP, but we actually found that 20
per cent of people had tried the drug, and 1 in 7 of 15 to
45-year-olds had used BZP in the past year," says study leader Chris Wilkins.

Wilkins says that the highest usage was by those in their 20s, as he
had expected, but he also discovered high levels of use by people in
their 30s and 40s.

A separate survey of around 1000 people carried out in Hamilton, New
Zealand's seventh-largest city, yielded similar figures. It found
that 12 per cent of the city's total population, and 30 per cent of
14 to 25-year-olds, had taken BZP at some point (Emergency Medicine
Australasia, vol 18, p 180).

The popularity of BZP, along with anecdotal reports of adverse
reactions, withdrawal symptoms and psychotic episodes, has led some
politicians and doctors to start campaigning for a ban. Bowden,
however, argues that his products are "harmless fun" and actually
reduce demand for street drugs and the damage they cause; the pills
are even labelled as "drug-harm minimisation solutions". He and other
vendors have an agreement to sell them only to adults and in outlets
where alcohol is not available.

"If we accept that people have the right to experiment with their
minds, just as they try paragliding or drag racing, then it is the
responsibility of governments to ensure that they have access to
well-designed drugs," Bowden says.

There is some evidence in support of Bowden's argument that BZP
reduces the demand for street drugs. In the Hamilton survey, 44 per
cent of the 15 to 45-year-olds who had tried BZP said they had
stopped taking illegal drugs as a result. In 2005, the head of the
New Plymouth Criminal Investigation Branch, Grant Coward, said that
the use of ecstasy had dropped after BZP became available. It also
appears that the relatively low price of BZP diverts people away from
illegal drugs. An ecstasy pill in New Zealand costs up to NZ$80; the
same amount will buy you up to 12 BZP tablets. "Most users said that
they would rather take ecstasy than BZP because the effect is
preferable and the hangover not as bad, but they're priced out of
it," Wilkins says. What is not clear, however, is whether BZP acts as
a gateway to illegal drugs among people who would otherwise never
have taken them.

Wilkins also points out that the drug seems to have less abuse
potential than amphetamines. "It gives you quite a bad hangover, so
people tend to limit their usage of it," he says. Overall, however,
Wilkins says it is too early to conclude that BZP reduces harm.

Health Worries

Worries are also emerging about the health effects of the drug.
According to emergency doctor Paul Gee from Christchurch Hospital,
BZP-related admissions were almost unheard of two years ago but are
now commonplace. Between April and September 2005, his team dealt
with 80 users complaining of nausea, vomiting, anxiety and
palpitations. Some had seizures; two cases were life-threatening (The
New Zealand Medical Journal, vol 118, p U1784). And while there have
been no deaths directly attributed to BZP, in 2001 a woman died in
Zurich after taking it with MDMA.

One of the biggest worries is that, because BZP is advertised as a
"safer alternative", it fosters the belief that it is completely
harmless and encourages people to take more than the recommended dose
(about 200 milligrams). In the Hamilton survey, around a third of 14
to 25-year-olds who had taken BZP said they did not read the
instructions on the packaging. Nearly half took more than the
recommended number of pills, and 66 per cent drank alcohol at the
same time, which is not advisable as alcohol exacerbates the
dehydrating effects of BZP.

The non-addictiveness and limited abuse potential of BZP have also
been called into question with a study showing that rhesus monkeys
will intravenously self-administer the drug at rates as high as they
would for cocaine (Drug and Alcohol Dependence, vol 77, p 161).
What's more, work due to be published in the journal Neurotoxicology
and Teratology shows that adolescent rats given BZP grow up into
anxious adults.

With the doubts about BZP growing, it is no surprise that governments
are sitting up and taking notice. In 2002 the US temporarily placed
the drug on its schedule 1 rating, the same category as MDMA and
heroin, and confirmed this in 2004. BZP has recently been made
illegal in Japan, Denmark, Greece, Sweden and, as of 1 September,
Australia. In the UK, BZP remains legal but is on the agenda for
discussion at the government's advisory council on the misuse of
drugs meeting on 2 November, where a decision will be taken as to
whether BZP needs to be monitored further.

New Zealand, however, has taken a different and arguably more
enlightened approach. In 2001 Bowden approached the government to ask
for its help in regulating the new industry. In response the
government introduced a new class of drug called "non-traditional
designer substances", also known as class D. This class is a
repository for new and little-researched drugs, such as BZP, pending
further information. Class D drugs are legal, though there are some
restrictions on them; in BZP's case that means a ban on sales to
under-18s and in places that sell alcohol.

The government also commissioned three studies into BZP. One, the
Hamilton prevalence study, has already been published. The other two
concern the drug's health effects and are due out in November;
Wilkins expects both to be critical. The outcome of these studies
will heavily influence the legal status of BZP in New Zealand.

Whatever the fate of BZP, party pills won't be the last legal high to
occupy government time. Thanks to the efforts of Bowden and
like-minded individuals, new psychoactive substances - both natural
and synthetic - continue to enter the market.

The next craze is likely to be for a legal high called kratom. This
extract of a tree native to south-east Asia has been dubbed the
"herbal speedball" for its euphoric and energising properties.
Kratom's main active ingredient, mitragynine, binds to the same
opiate receptor (mu) as opium, heroin and cocaine. There are no
documented overdoses or fatalities and proponents claim it is
non-addictive, although last year a team from Josai International
University in Togane, Japan, published evidence to the contrary (Life
Sciences, vol 78, p 2). It is legal almost everywhere except Thailand
and Australia. In high doses it is supposed to produce hallucinogenic
effects. However, when I tried it - boiling the leaves to make a
nauseating tea - it merely made me sick and sleepy.

According to a US National Drug Intelligence Center report published
in 2005, kratom is cheap and widely available in the US and has "high
abuse potential", though up to now there have been no moves to ban
it. That is sure to change. Arguably, drugs such as kratom are legal
not because they have official approval but by default: they have yet
to become popular enough to attract the attention of lawmakers. Once
that happens - as with magic mushrooms in the UK - governments are
quick to clamp down.

Another high that appears to be on the brink of losing its legal
status is salvia. Also known as diviner's sage, "magic mint" or
"Sally D", Salvia divinorum is a white-and-blue-flowered sage plant
that grows in the Oaxaca mountains in Mexico. It has been used for
centuries by the Mazatec people in shamanistic rituals and in healing.

The first westerner to experience salvia's powerful hallucinogenic
effects was anthropologist Brett Blosser, now of Humboldt State
University in Arcata, California. In the late 1980s, he was invited
to take part in a Mazatec shamanic ceremony in which the participants
rolled up salvia leaves and chewed them. The effect was profoundly
psychedelic, Blosser reported.

Inspired by Blosser's account, Daniel Siebert, an independent
ethnobotanist from Los Angeles, distilled the plant's juices to
produce white, needle-shaped crystals which he called salvinorum A.
Just a tiny crumb of this on his tongue produced what he describes as
the most awesome and frightening experience of his life. "Suddenly I
lost all physical awareness. I felt as though I were completely
conscious and yet I had no body. I wondered if I had died," he says.

In 2002, with recreational use of salvia on the rise in the US and
elsewhere, Bryan Roth, director of the National Institute of Mental
Health's psychoactive drug screening programme at Case Western
Reserve University in Cleveland, Ohio, took an interest. He
discovered that salvinorum A is highly selective for the recently
discovered kappa opioid receptor in the brain (Proceedings of the
National Academy of Sciences, vol 99, p 11934). Like the other two
opioid receptors (mu and delta), kappa is involved in pain
sensations. But, unlike the other two, chemicals bound to it can
cause hallucinations.

It's still unclear why salvia produces hallucinations. "Some of the
experiences people have on salvia may be similar to the psychosis
that occurs in late-stage Alzheimer's," says Roth. "There is an
increase in the number of kappa receptors in the brains of people
with late-stage Alzheimer's."

All studies so far have shown salvia to be non-addictive. It also
appears to have limited potential for abuse. "Most people taking
drugs are not looking for an out-of-body experience, they want
something gentle," says Harry Shapiro from UK drugs information
charity DrugScope. "Salvia is so strong that people try it once and
never take it again."

Playing With Fire

Even so, possession of salvia has recently been made an offence in
four US states - Louisiana, Missouri, Tennessee and Delaware - and a
federal ban appears inevitable. Thomas Prisinzano of the University
of Iowa in Iowa City, who is studying salvia to research new methods
for treating substance abuse and pain, believes it is only a matter
of time. "If LSD is schedule 1, then salvia will almost certainly be
classed the same," he says.

Some researchers would welcome a ban on salvia and other new drugs.
One of these is pharmacologist and substance misuse researcher
Fabrizio Schifano of St George's Medical School in London. He says
that the main problem with psychoactive substances - and
hallucinogens in particular - is that they may incite psychosis. "How
do you know if someone will have a sensitivity to the drug?" he says.
"I am really worried by the prevalence of these drugs, and the fact
that most users get their information from the internet. It is not
peer-reviewed research, just people's opinions, and that is very dangerous."

Tim Kendall, deputy director of the Royal College of Psychiatrists
research unit, says: "When you take salvia you are playing with fire.
People can be very damaged in terms of their personal functioning.
They frequently have flashbacks that intrude into their life, which
can be almost like a post-traumatic stress problem after very bad experiences."

"My recommendation is that people should keep their minds clean," adds Roth.

Others believe that knee-jerk bans are the wrong approach. People
have a natural drive to enter alternative states of mind, argues
Richard Boire from the Center for Cognitive Liberty and Ethics in
Davis, California. "The role of governments is to prevent harm to
people and society from dangerous drug use. I think the government
has lost sight of this and now thinks its role is to stop people from
entering other mindsets."

For governments intent on pursuing prohibition at all costs, there is
a sobering thought. For every banned psychoactive substance there are
dozens more that remain legal. The legendary pharmacologist Alexander
Shulgin has synthesised more than 230 novel designer drugs, and
according to psychologist John Halpern, associate director of alcohol
and drug abuse research at Harvard University, there are dozens of
legal hallucinogenic herbs besides salvia that are already widely
available on the internet and growing in popularity (Life Sciences,
vol 78, p 519). What is more, there is clearly a demand for the
stuff, and plenty of people like Bowden willing to supply it. Salvia,
BZP and kratom may be on the way out, but others will take their place.