Spice flow: the new street drug pharmacology

Forensic Science International recently published an eye-opening study on a new generation of synthetic cannabinoids that have become popular as ‘legal highs’, provided by a highly organised neuroscience-savvy industry that is ready and waiting with new compounds before the law changes.

The study concerns several legal smoking mixtures, ‘Spice‘ being the most well-known (pictured), which were recently found to contain synthetic cannabinoids.

Cannabinoids are named for their abundance in the cannabis plant, but this class of substance also naturally occurs in the nervous system as part of the normal biological signalling system. In fact, the street drug cannabis has its effect because its various cannabinoids, the most famous being THC, target one or more of the brain’s cannabinoid receptors.

Marijuana and its derivatives are illegal in most countries but the brain’s cannabinoid system is complex and so it is possible to synthesise other types of drugs in the same class as the plant’s active ingredients, which target the same receptor sites, that have similar effects, but which are completely legal.

Although officially labelled as incense and not for human consumption, Spice was typically marketed as one of the many ‘herbal smoking mixtures’ which traditionally have been sold in head shops on the basis of their druggy associations despite having no psychoactive effects to speak of.

However, this brand became wildly popular and in 2008 scientific analysis found that it also contained the synthetic cannabinoids CP 47,497-C8 and JWH-018 which are structurally similar to THC.

I can’t imagine what it was like when this was first discovered. It reminds me of the hair bristling moment in movies when the scientists discover that some form of ultra-advanced technology is behind a spate of odd occurrences.

You see, drugs like speed, heroine, cocaine and ecstasy require legally controlled raw materials but the processing stage is low-tech. That’s why some types of speed are called ‘bathtub crank’, because some of it is literally synthesised in a bathtub, as images of meth lab busts illustrate.

But this is not the case with cannabinoids which require a complex and careful lab process with many stages and sometimes the separation of mirror image molecules (enantiomers) from each other as only one of the ‘reflections’ is desirable.

These are not trivial process. They can’t be done in back rooms and they can’t be done by amateurs.

What’s more, these aren’t just copy-cat syntheses done by your average underground lab who know the illicit process and just want to recreate it. These are new compounds, perhaps reported only a handful of times in the scientific literature and selected for their specific effect on the brain.

The authors of the Forensic Science International paper note “It is evident that the producers of these products have gone about in a very methodical manner to mine the scientific literature for promising psychoactive compounds. Most likely the published CB1 binding affinities were exploited as primary criterion.”

CB1 is a specific type of cannabinoid receptor and is the one most activated by THC, the principal active ingredient in marijuana, and it seems the producers were making their selections based on their knowledge of neuroscience and psychopharmacology.

Several countries have now banned, or are in the process of banning, the synthetic cannabinoids found in Spice and related products. In fact, Germany was particularly quick off the mark and outlawed the products in January 2009.

Now this is where it gets interesting because the researchers note that a new product appeared on the market, containing JWH-073 – another synthetic cannabinoid, within four weeks of the ban. JWH-073 has similar similar effects, but isn’t covered by the law and so remains legal.

The speed at which it appeared suggests that it had been selected and synthesised in advance, in anticipation of the ban:

Our analysis demonstrated that just 4 weeks after the prohibition took effect a multitude of second generation products were flooding the market. The speed of introduction of new products and the use of JWH-073 as a substitute for JWH-018 not only showed that the producers are well aware of the legal frameworks, but that they likely anticipated the prohibition and already had an array of replacement products on hand (JWH-073-positive products are still available on the German market; last checked: June 5th, 2009).

In other words, the legal high industry is packing neuroscientists and heavyweight lab pharmacologists. It is no longer just head-shop hippies repackaging obscure psychoactive and barely recreational plants as a poor substitute for street drugs. The legal high industry has become professionalised.

Seemingly based on the model of the pharmaceutical industry, it is becoming science-led, regulation savvy and is out-manoeuvring the authorities well before they catch up.

To use drug war terminology, it’s an interesting new front because the producers are not trying to evade capture, they’re using the agility of science of evade regulation.

Link to PubMed entry for Forensic Science International paper.
Link to .rar archive with pdf of full text inside (weird huh? via Google)
Link to good EMCDDA page on synthetic cannabinoids.

A trip to the Gothic tower

We’ve mentioned the famous 19th century neurologist Silas Weir Mitchell several time before on Mind Hacks, as he is well known for his early reports of phantom limbs and his creation of the ‘neurosis of modern life’ diagnosis ‘neuraesthenia’.

What I didn’t know was that in 1896 he also wrote an article in which he gives one of the first reports about the experience of tripping on peyote – a cactus that contains the hallucinogenic drug mescaline.

Weir reports that he became interested in the substance after learning about the traditional use of the plant by Native Americans in New Mexico and acquired some to try himself.

His article appeared in the British Medical Journal where he describes his experiences, and it’s quite an amazing document. This is a vivid part where he describes the experience of hallucinating a ‘Gothic tower’:

When I opened my eyes all was gone at once. Closing them I began after a long interval to see for the first time definite objects associated with colours. The stars sparkled and passed away. A white spear of grey stone grew up to huge height, and became a tall, richly finished Gothic tower of very elaborate and definite design, with many rather worn statues standing in the doorways or on stone brackets. As I gazed every projecting angle, cornice, and even the face of the stones at their joinings were by degrees covered or hung with clusters of what seemed to be huge precious stones, but uncut, some being more like masses of transparent fruit. These were green, purple, red, and orange; never clear yellow and never blue. All seemed to possess an interior light, and to give the faintest idea of the perfectly satisfying intensity and purity of these gorgeous colour-fruits is quite beyond my power. All the colours I have ever beheld are dull as compared to these.

As I looked, and it lasted long, the tower became of a fine mouse hue, and everywhere the vast pendant masses of emerald green, ruby reds, and orange began to drip a slow rain of colours. All this while nothing was at rest a moment. The balls of colour moved tremulously. The tints became dull, and then, at once, past belief vivid; the architectural lines were all active with shifting tints. The figures moving shook the long hanging lines of living light, and then, in an instant, all was dark.

The whole article is freely available online if you want to read the entire account which explores the hallucinatory state in some depth.

Link to ‘Remarks on the Effects of Anhelonium Lewinii (the Mescal Button)’.