Mind-altering drugs:

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 Mind-altering drugs: does legal mean safe?

     •      29 September 2006
     •      Exclusive from New Scientist Print Edition. Subscribe

 Legal highs: the facts

 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 
£25 I handed over, more than £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 (see Table). 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. ““<quote><quotetext>There are hallucinogens, 
relaxants, aphrodisiacs, trippy highs, 'loved-up' pills and euphorics.”

 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 
 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 
 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. 
““<quote><quotetext>I lost all physical awareness. I felt as though I were 
completely conscious and yet I had no body. I wond”

 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.

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