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I commented about using any drug entails some finite risk of bad effects. The apparently common belief that "designer drugs" shouldn't be "illegal" is certainly not supported by the article.

I can see your line of thinking: X has risks, X should not be done, thus make X illegal and X will not be done and the risk will no longer exist.

But that's not the way the world works. Making X illegal does not prevent X being done. Instead, it creates incentives try and find people doing X and put them through the criminal system. That introduces a whole separate set of risks. And making X illegal reduces the probability that problems created by X will be treated in time. Another set of risks. Etc.

The question you should be asking is: are the risks of X greater than the risks of making X illegal?

While I agree that is the appropriate question to be asking, it's worth considering the length and complexity of the drug pipeline for creating new legal drugs, as a way of estimating the risk of new illegal drugs, which go through nothing like the same degree of testing: http://www.pacificbiolabs.com/drug_stages.asp

A new legal drug in its first iteration frequently through animal models frequently has a breakdown of 80% or more effectiveness, with the balance of the population mostly experiencing no effect and a small remaining fraction experiencing negative side-effects. The drug will then be tweaked and twisted to increase the size of the population it is effective on and drop the size of the negative side-effect population to as close to zero as possible.

This is a hugely expensive process. It is where a good fraction of the hundreds of millions of dollars that go into the development of legal drugs wind up, and it is necessary because biochemistry differs very significantly across individuals.

What the makers of illegal designer drugs appear to be doing is more like a developer who says "works on my machine" and then ships. No testing, no QA, no coverage... just ship based on a single working instance in a particular environment. That's a recipe for disaster, and while the disasters are mostly recoverable, the process is fraught with risk.

This does not mean that making it illegal will change anything, because near as we can tell from the data the law barely changes human behaviour. Making abortion illegal does not change it's rate but just makes it unsafe. Making murder legal would not result in a vast increase in the rate of murders--it would result in blood-feuds and other mechanisms that the codification of law was designed to prevent. People don't refrain from murder because it's illegal (for the most part) but because they believe it's morally wrong. The law follows from that widespread moral belief, not the other way around.

So legalization and regulation may well be the best way to go, but given the ordinary standards of drug development that might create an underground grey-market where things are almost as bad, safety-wise, as they are now. A carefully targeted criminalization, that focuses solely on drug makers rather than distributors or users, might be a better solution. So long as we keep in mind that the goal is to minimize harm, including the harm done by law enforcement.

On the other hand, plenty of really good legal drugs fail for reasons which might not be relevant to many people-- Strange metabolism in select ethnic groups, possible tox issues after chronic use, etc.

For example, plenty of people involved with developing Vioxx bought tons of it before it was removed from the market, because it was such a good nsaid. These people decided that their mode of use wasn't problematic, or that the benefits of using the drug far outweighed the possibility of adverse reaction. While the Market and the FDA decided the drug should be pulled, the people who stockpiled it are certainly more informed than most medical doctors.

If LSD were trialled for psychotherapy today, it would probably be rejected on the grounds that it could make crazy people experience severe adverse effects.

With most novel recreational drugs, there's plenty of "phase 4" anecdata which suggests safety, at least in the short term and at cautious doses. Really nasty adrs usually show up fairly quickly, albeit at the expense of a few lives. If "legal" (nonrecreational) drugs could be put directly into phase 4 testing, drug development would be so much easier-- Animal models are a really crappy substitute for humans, especially with CNS stuff.

I suppose it's a balance of Bad Big Pharma poisons us vs. Bad Big Pharma doesn't make cheap/new drugs...

There's also the unspoken "X has risks, and I don't want to do X, therefore X should be illegal".

I ride motorcycles. I have friends and family involved in scuba diving, paragliding, football, rock climbing, hell - even horse riding.

_All_ of those activities have "well known risks of serious injury or death" associated with them, and each of them I've heard recent stories of death in the extended circles of my family and friends.

I'm not sure whether the "designer drug" risk is anything like as high as some of those legal and "acceptable for your children" risks.

My approach is less "asking are the risks of X greater than the risks of making X illegal?", but closer to "Quantify the risks of X, work out which can be mitigated or reduced without needing to ban X, make sure participants are informed of the risks, and if needed ensure training/insurance/licencing is available if required".

Thirty thousand people a year are killed in motor vehicle accidents in the USA. We don't react by saying "Make cars illegal" - we manage, mitigate, reduce the risks (quite successfully, that 30k is down from 40k 10 years ago, and over 50k back in '79 and '80) - then we declare 30 thousand dead people a year an "acceptable cost" for the benefits of private car ownership.

Why aren't we able to be that rational about "designer drugs"?

I wish so much to hear at least a semi-coherent response to this from the pro-prohibition crowd.

The most of pro-prohibition crowds are either not-so-bright people who grab all their wisdom from TV without any proper experience whatsoever beyond alcohol & cigarettes, or law-enforcement-related people. As in many other cases, I believe following money explains it nicely. Ignoring the former redneck case, the rest has actually good bussiness case for latter. Ie legalize weed US nationwide, and many prisons (let's not forget many are private owned by investors, who want only one thign - maximize their profits by having as many inmates as possible), DEA loses maybe 90% of the success claims they have, and maybe local police can have more time dealing with serious issues. For conservative politicians, its political ammo par exellence, since if they will go hardline on drugs, there are very few risks to their career, and they can always claim all the usual stuff (drugs are destroying families and young people, we care about them etc... ever heard that?). Ask yourself - what can a politician gain vs lose bybeing pro-weed in US?

Too lazy to look it up, but if I remember correctly that one of DEA chiefs was also head of some UN panel on drugs, which then enforce rules for all UN member states (read whole world maybe except North Korea). From first glance, it might make sense. But show me one career-oriented competitive guy (and being head of such an agency, you have to be at least that, and have a lot of political games skills), who would undermine his own little kingdom, and make his own subordinates lose job by declaring that some of most popular drugs shouldn't be banned. One real example - weed & hashish have thousand years of history in hindu culture (look up shiva day when almost all india is high), yet they had to ban it after they joined UN.

So, we can thank those guys for making policies that worldwide raise crime, help supporting organized crime on massive scale (brutal mexical cartels are a fine example, out of many, ie afghanistan)

It's like thinking, that in banking/trading/brokering, it's always the client's best interest that's primary drive. Well yes of course, unless the bussiness is funded mainly by operational fees. WHat do those brokers do? Make you do as many operations as possible, of course, without being too obvious :)

(*no references here :))

I have one friend in his late 60's who just bought a new motorcycle. His wife was displeased with his decision though might be tempted to ride along sometimes. Another friend decided to stop riding a few years back because he felt it was too risky for him to continue.

Point is with motorcycles, cars, scuba, yes, even horses, the risks are more or less known and probability of various outcomes, including harm, can be reasoned about.

With drugs the estimation of probable outcomes is orders of magnitude more difficult to compute. To say it again, all drugs have numerous effects which vary greatly among recipients, and even for established agents most drug effects have received little or no study. However we do have a systematic track record of the AEs encountered, and after millions of cases we have a pretty good idea of how to use the agent safely.

Legal status notwithstanding, a drug with potent enough effects to be interesting is asymptotically guaranteed to have adverse effects in some members of the population of potential users. It means effects of a new and arcane product are no more than a total crap shoot.

Since even low frequencies of AEs may disqualify a drug as "safe", regulatory bodies require testing sufficiently large number of subjects under tightly controlled conditions to show evidence that it's safe enough to justify its proposed uses.

Without such study it is impossible to evaluate the use of an unvetted drug in the same way as riding a motorcycle. The information about benefits and risks is just not known. There is simply no basis for making a rational decision.

As a clinician and scientist questions of prohibition are largely beside the point. People will continue to do stupid things laws aside. However, laws/rules exist as a benchmark, and optimally serve as a statement of our communal ethical stance. Not that it's going to stop people who are determined to use a prohibited drug anyway, but maybe it supports restraint in some people who are "on the edge".

In respect to designer drugs, I'm very reluctant to say let's have no regulations at all, that anything goes, because logically lack of safety data leaves us to assume the risk of harm is significant. The burden of proof ought to be on the shoulders of those who assert use of the drugs is just harmless diversion.

I think that where this falls apart is "laws and rules exist as a benchmark". That should be true, but the conduct of the US criminal justice system suggests it isn't.

Point is with motorcycles, cars, scuba, yes, even horses, the risks are more or less known and probability of various outcomes, including harm, can be reasoned about.

Which is why we should legalize and regulate the drugs that we do understand. The risks of cannabis and LSD are also more or less known, and the (remarkably low) probability of harm (particularly compared with motorcycles, cars, etc) can be reasoned about.

The harm in making these well-understood substances criminal is far greater than the harm in regulating them. Indeed, as the GP points out, the harm in making the well-understood substances illegal is exacerbated by the harm from designer analogs.

As a clinician and scientist questions of prohibition are largely beside the point.

You're simply pulling the wool over your eyes if you believe that to be true. Prohibition is a causal factor in the danger of substance abuse.

>"I can see your line of thinking: X has risks, X should not be done, thus make X illegal and X will not be done and the risk will no longer exist."

I've tried on numerous occasions to debate with individuals that hold such an opinion. Once you point out the obvious error in their reasoning, they quickly move the goal post. It then becomes more about "protecting" productive society, and the slippery slope argument that everyone will devolve into "addicted, unproductive and unhealthy junkies". Making out to seem like we want society to burn and be ruined, when in actual fact we just want to allow individuals to be free to do with their bodies as they please, because there is no moral right by others to prevent them from doing so.

I'd much rather take an illegal drug than a legal, 'under the radar' one. The personal risks of possibly getting thrown in jail are vastly dwarfed by the risks of ingesting an untested and completely unknown substance. The sad thing is that even the illegal ones often involve a terrible externalized human cost. Illegal drugs are consumed at scale, exploiting the producers and transporters, legal ones are consumed individually, personalizing the risk.

I've nothing against the yearning to alter one's consciousness, however temporary it might be. But alcohol might be the only way to do it without assuming either great personal risk or great moral hazard. And alcohol can be so, well, boring. One of the great sadnesses of the world we live in.

Alcohol:

• makes people vomit • makes people fight and argue with each other • is incredibly easy to take to excess • physical addiction entirely possible • damaging to liver + kidneys

Cannabis:

• makes people lazy • makes people hungry • makes people generally friendlier • capable of curing cancer as well as many major diseases • not physically addictive

So wait, what?

Alleviates symptoms of chemo, yes, but curing cancer? Is this a recent finding?

Yep. Not sure how good this particular source is but it was in the mainstream news recently. http://ibnlive.in.com/news/cannabis-helps-shrink-aggressive-...

Biology is hard and confusing. If it's just one experiment, I would hold off before drawing conclusions. There's a long history of studies and experiments that appear to show something which is then later discredited.

>> The personal risks of possibly getting thrown in jail are vastly dwarfed by the risks of ingesting an untested and completely unknown substance.

False dichotomy in the modern age, unfortunately. You have no way of knowing what's in that illegal drug. It might be (and often is) exactly the same stuff.

Synthesizing legal "designer drugs" is safer for the chemist than synthesizing illegal drugs, because they are very unlikely to get arrested, have their lab equipment confiscated, and lose their career. Similarly, taking legal "designer drugs" may be safer for the user than taking illegal drugs, despite the extra risk of serious side effects, not only because there's less risk of getting arrested, having your children taken away, etc., but also because if something goes wrong, you have recourse — you can sue the pharmacy if the drug is contaminated, they can refer you to a legal collection agency if you don't pay them rather than to the Mafia, etc.

Of course, we could eliminate this ridiculous dilemma between the risk of novel side effects with "designer drugs" and the risks of illegality with the better-known recreational drugs, simply by making those drugs legal, although that will increase usage. That also has the additional benefit that it removes much of the stigma and danger from things like hobby chemistry. So far, it seems to be working well in Colorado and the Netherlands.

'Designer' drugs are produced in well-equipped modern labs, for the most part in China. Most of them are more complex to synthesise than illegal drugs and aren't coming out of some kitchen chem lab, but a well equipped industrial setup. In their country of origin the business seems legal so they come under no scrutiny.

The problem is, that the same cultural stupidity that sees us pass new laws banning the newest designer drugs, is also the one that sees us banning relatively harmless and well-understood substances that have been used by humans for tens of thousands of years. And, I don't think it's possible to rhetorically separate the two in a way the public can digest.

That is not to say you can't draw a logical distinction between the two that supports banning or strictly regulating the production and sale of one, while leaving the other alone - in fact I would say you've got a good start on doing that already. However, the distinction is subtle, and will be totally lost on a population that has had anti-drug propaganda shoved down its throat by the state for the last four or five generations. Any nuance in your argument will be seized on by drug warriors to justify banning the sale of e.g. marijuana or peyote, etc., and bring offenders into to the ever-growing all-consuming all-powerful prison complex.