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.

24 Comments

  1. mimac
    Posted December 2, 2009 at 6:45 pm | Permalink

    Hello!
    Quite an old story. But thanks! IMHO spice products are quite worse than cannabis. Here is an interesting study: http://www.aerzteblatt.de/int/article.asp?id=65284
    Another win for the drug war? Pushing users to use more dangerous (unresearched and without a long history) drugs.
    Greets!

  2. rageahol
    Posted December 3, 2009 at 1:36 am | Permalink

    The real situation is very likely much simpler than you’re making it out to be. All this actually requires to pull off is a basic knowledge of neuroscience, and a front company to purchase the drugs from a legitimate manufacturer. Basically, that means just having access to a catalog, although sometimes these companies put their catalogs online. Since the compounds generally aren’t watched or scheduled explicitly, the assumption is that you’re using it for legitimate research, and it’s up to the company to do the due diligence to ensure that.
    Speaking as a scientist who has in the past worked with Schedule I drugs and their analogues, I find it an incredible pain in the ass to deal with the regulatory regime in the US already. The more barriers you erect to legitimate research, the less research will get done, and we will all be poorer for it.

  3. gagoonies
    Posted August 23, 2010 at 9:15 pm | Permalink

    Why is getting high a crime?

    • mental health nurse
      Posted April 5, 2012 at 11:19 pm | Permalink

      I wouldn’t care if getting high was all that happened, but I have a young female patient in a psychiatric facility that has been damaged by smoking spice, and she may never be the same. She is unable to a make any decisions for herself. She is fearful, can’t eat, can’t focus, can hardly talk to us. She is terrified all of the time. That is what spice did to her. Gettng high is NOT what happened to her. Is it worth it? Jeez! I want to cry with her. She may never be the same. Her family has lost her for good, I fear, and, for what? Just to get high?

  4. Water Eyes
    Posted October 19, 2010 at 7:59 pm | Permalink

    People why would you put stuff into your body even if its legal. Get a grip people. Try to deal with life the right way. You didnt come into this world high,why do you want to die high.

  5. Denny B
    Posted October 26, 2010 at 1:10 am | Permalink

    @Water Eyes….We were born to learn and to explore. Some of us have been fortunate enough to experience, enjoy and appreciate what Mother Nature has to offer. Why do certain plants, such as, cannabis, peyote, and mushrooms, offer us the peace and tranquility after consuming them? These plants are hear for a reason and we as pioneers have the God given right to use them at our discretion.

    • john m
      Posted November 30, 2010 at 4:06 pm | Permalink

      I actually saw a new product called Wild Lotus that is not covered in the ban. Not to sure what the herb was, maybe marshmallow leaf… anyways, I agree with the above statement. In fact, the more we learn about quantum mechanics, the more we learn reality resemlbes the appitmy of a psychedlic “trip”

  6. BigEazy
    Posted December 21, 2010 at 3:25 am | Permalink

    I do not know where you all are located. I am in North Carolina, USA. There are two local stores that sell herbal incense. They don’t sell the Spice brand. They sell brands like K2, sugar sticks, greenies, red dragon, vice, kush, white widow, and the list goes on. It seems to me that these harsh effects are kindof magnified out of proportion. Some people are more sensitive to the cannabinoids than others. Nicotine is the same way. Should we ban cigarettes?? Hell no. The oversensitive should abstain. Plain and simple. By the way, I like the above question. Why, indeed, is getting high a crime. No one has every died from marijuana, but alcohol causes deaths everyday. Marijuana has no hangover. Marijuana has never caused suicide, and never given anyone I know, myself included, suicidal thoughts. Ban alcohol, and pass the blunt. :)

    • jim
      Posted January 24, 2011 at 3:48 am | Permalink

      you will know the problem in 10 years

  7. peaches
    Posted January 20, 2011 at 4:49 pm | Permalink

    i’m confused. what is this “spice” or k2 as some are calling it? what effects do u get out of smoking spice? if its not weed (that shows on a drug test) then what is it?

  8. jim
    Posted January 24, 2011 at 3:43 am | Permalink

    What does spice smell like?

  9. the
    Posted February 3, 2011 at 7:23 am | Permalink

    I live in Louisiana where these ‘legal highs’ are the most prominate in the country, outdoing every other state with 128 calls to poison control in 2010 regarding spice and other products like it.
    For everyone out there that uses these products, or is considering using this. Don’t, I’m not a concerned parent, or some bullshit law enforcer, I’m just a teen that made some seriously bad mistakes.
    I smoked ‘incense’ for just over a year, then quit after I had a seizure in early 2010. now, almost 9 months later; I am dealing with a myriad of medical problem. I have seizures almost once every 2 months and I have lost my drivers license because of it. My eyesight is dwindling into a foggy haze that glasses can’t fix and doctors can’t explain. The medical bills from my many hospitle trips since I quit continue to skyrocket. These destructive chemicals have left my life in shambles, and the horror storys caused by them are countless in my area. My cousins girl friend recently was diagnosed with a brain tumour from prolonged use of incense, and the newest line of legal highs called bath salts.
    I have nothing but regret from using these products to get a quick legal high… The moral of my story? Stay away from these posionious chemicals, if you want to get high. Stick with weed.

    BTW, I’ve seen this shit get made, and I will tell you that neuroscientists are not the people making it. Unless you call high schoolers and pill heads using spray bottles neuroscientists.

    • dg
      Posted February 25, 2011 at 5:14 pm | Permalink

      All the more reason to make safer altenatives like mj available. The govt is just making things worse. People will always find something to get high on like the much worse alcohol. Prohibition has never worked and never will. There ia just about a centuries worth of evidence: prohibition only leads to more death and criminals and crime.

  10. Posted February 14, 2011 at 5:47 pm | Permalink

    What does spice smell like?

  11. Posted March 3, 2011 at 1:59 pm | Permalink

    tight thread. like manu chao raps : too morality brings criminality brings hypocrisy and insanity. evidence in this post that someone’s trying to ban an idea — the cannabis meme. won’t work, no good. good luck to Mr the man. mimac and rageahol are right. Water Eyes may also be. what it think: there’s no good reason to give up on the market approach to mindfood/mindfun simply because the mind is involved. we need research, regulation, labeling and most of all competition. to “ban” something is to stick head in sand, turning the world over to mafia/mad science. but Spice is probably better than Mexican drug wars.

  12. terry blue
    Posted April 3, 2011 at 2:29 am | Permalink

    I personally think that all drugs should be legal. I myself do not abuse drugs at all I don’t like taking them. But I have many people around me slowly kill themselves by abusing drugs of all kinds. If they were legal and had total access to them. I think they might end up killing themselves much sooner. This would make the time they have to hurt the people around them much shorter. And best of all. It might kill them before they have time to reproduce. In days past both “stupid and lazy” did not survive very long. With modern medicine and all the protective laws our legislature pass. Dumb , lazy and stupid all survive and reproduce thus polluting the Gene pool. And worst of all. While they are alive they are endangering the liveS of the intelligent people and or end up killing a few of them with their stupid decisions or actions.

  13. PrettyPink
    Posted April 20, 2011 at 5:41 pm | Permalink

    Spice, K2, or K3 is what they make herbal incense with. You can get it from several different stores because it is legal. It can not be detected in drug test which is why it is smoke in the military. Spice has a chemical in it that gives you the same effects of THC in weed. You get the same high. Maybe higher or less high depending on what type u buy. There are different types of it just like different weed (regular, purp, etc. You get the same feeling just like when you smoke weed munches and smiles/laughter. Weed should be legal because they can not prove it does harm to the body after all these years, they have come up with nothing. Not even people overdosing off of it. Crack, meth, etc should be illegal just as it is because there are proven facts that it can harm you in so many ways. And even KILL U.

  14. Bobbi
    Posted November 28, 2011 at 4:23 am | Permalink

    this is to the young man from louisana…not even sure if you will ever get this post. My son IS very ill from that shit. He too has an array of medical conditions but somehow believes that spice has no bearing on his very unhealthy life these days. He is 17 by the way. I hope it is not too late for his body to start to heal. As I AM a concerned mother i am horrified for all you guys out there putting that shit into your bodies. Research it, the compounds, the articles, NMDA functions in your brains, your central nervous system etc… he vomits 3-4 times a night, headaches, shakes, it’s a nightmare…and thats an understatement.

  15. Tomas
    Posted November 30, 2011 at 6:59 am | Permalink

    Wow, you people have no idea what you are talking about. This stuff is VERY hard to make. To apply to an herb is very easy. It is damn hard to overdose on incense. Maybe something like pure am-2201 powder. But not an herbal blend. This is a full cb1 agonist guys, please be careful. And do not listen to anyone here (article is accurate, comments are not). Go to erowid, the shroomery, bluelight. Please educate yourselves. Enjoy :)

  16. LeeAnn
    Posted December 5, 2011 at 5:45 pm | Permalink

    If you know anyone doing this please tell them to stop! It is extremely bad for you. Unfortunaly my 28 year old cousin has been smoking spice for the last 2 years daily. She just recently had gotten committed to a mental hospital for testing. She seems to have completely fried her brain with all of the chemicals put into spice. She now thinks she is a 6 year old girl. Extremely sad and heart breaking for all involved. It is not something to mess with. If you want to smoke something just smoke pot.

  17. hennessy
    Posted May 30, 2012 at 7:30 am | Permalink

    Seems to me the government/CIA or whomever has all the guinea pigs it needs. How brilliant is that? Synthetics they need tested on vast numbers of people…. Let loose those chemicals into the general population and study the effects. And please, spare me the conspiracy theory accusations. Do you really need reminding that humans are beyond capable of such atrocities?

  18. hennessy
    Posted May 30, 2012 at 7:32 am | Permalink

    oh, and no, I’m not stoned lol. I don’t smoke pot, I do no drugs. Coffee is my only vice.

  19. Curry
    Posted September 12, 2012 at 2:51 am | Permalink

    I tried a spice called Rush Miracle last night. After 3 hits, my mind suddenly became empty, I didn’t know where I was. I got up because I was afraid to lose consciousness, I could hardly stand or think. At the same time I began to feel awful beatings through my whole body, I had to struggle not to collapse.
    This is the strongest thing I’ve ever taken, it’s not pot, it’s like a really bad medicine trying to mimic the pot, there is absolutely no point in it, I regretted instantly to smoke it.
    I was dumb to try it and now I only hope there won’t be any further conequences.

  20. Kim
    Posted April 23, 2013 at 1:22 am | Permalink

    I smoked spice on and off for a year, not everyday but i had short periods when i couldnt get a hold of marijuana and smoked spice instead.
    I now have agorafobia, suffering from a depression, hypokondria and my body shivers and get spasms every second of everyday. I dont know if this is with me for life, if i will ever get better cause it has been like this for 3 years straight. I wonder, can you rehabilitate from this ?


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