1. chillinwill
    My field of natural products pharmacology was founded by indigenous cultures who recognized that plants and fungi contain compounds that produce altered states of consciousness, leading to their most common use in religious ceremonies.

    While we may most often associate these naturally-occurring drugs with hallucinogens, the arguably most common natural product in use today is marijuana or Cannabis sativa. Indigenous to India and China, Cannabis has been the subject of increasing decriminalization worldwide due in part to its clinical, medicinal effects in multiple sclerosis, cancer, and AIDS.

    Over the last few months, I've seen reports of a so-called "synthetic marijuana" being sold on the internet with stories most commonly coming from England and Germany and, in the US, from Kansas, Missouri, and Arizona. In fact, the St. Louis Post-Dispatch reports today that a bill has been brought before the Missouri House Public Safety Committee seeking to add this product to the state's list of illegal drugs.

    I became intrigued as to why anyone would go through the trouble of making a synthetic marijuana when it is so readily cultivated worldwide.

    So what is it?

    Synthetic marijuana, sold as K2 or Spice, is an herbal substance sold as an incense or smoking material that remains legal in the United States. The products contain one or more synthetic compounds that behave similarly to the primary psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol or THC.

    The compound most commonly found in these products is a chemical first synthesized by the well-known Clemson University organic chemist, Prof John W Huffman: the eponymous JWH-018. Another compound, found in Spice products sold in Germany, is an analog of CP-47,497, a cannabinoid developed by Pfizer over 20 years ago.

    Known as (1-pentyl-3-(1-naphthoyl)indole), or the more proper IUPAC name of Naphthalen-1-yl-(1-pentylindol-3-yl)methanone, JWH-018 is one of over 100 indoles, pyrroles, and indenes synthesized by the Huffman laboratory to develop cannabimimetics, drugs that mimic the effect of cannabinoids such as THC. The primary goal of these studies was to create pharmacological probes to 1) determine the structure-activity relationships of these compounds and 2) tease out the physiological function of subtypes of receptors we have for cannabinoids: the CB1 and CB2 receptors.

    Much of the biological assessment work of Dr. Huffman's compounds was carried out by the laboratory of Professor Billy R. Martin of the Medical College of Virginia. Dr. Martin, a native of North Carolina, was a giant in the field and sadly left us two summers ago at the all-too-young age of 65 (obituary).

    According to this 2000 paper in Drug and Alcohol Dependence from the Huffman and Martin groups, JWH-018 binds to the psychotropic CB1 receptor with approximately 4 times the potency of the naturally-occurring THC. Unlike THC, which binds with almost equal affinity to CB1 and CB2 receptors, JHW-018 exhibits a 3-fold preference for CB1 receptors.

    What does this mean? Well, the CB1 receptor is the primary means by which cannabinoids exert their psychotropic effects. The CB2 receptor, on the other hand, appears to be more involved in pain and inflammation and is therefore a very active area of research for new therapeutics.

    So while JWH-018 has four-fold greater potency for CB1 receptors than THC in an isolated receptor binding study, how its effect compares to plain-old marijuana depends on other factors such as the relative amount in the product, how stable it is to combustion, how it's metabolized in the body, among others.

    I'm not going out on a limb to say that the statement of Missouri Rep. Ward Frantz, "We don't know much about this, but it's going to end up killing somebody," might be a bit hysterical at this point, but I could be wrong. Human toxicology studies have not been done and the indole moiety of the drug raises the potential for it causing serotonin syndrome, a potentially fatal disorder.

    It's worth reading the backstory on Professor Huffman in this UK Guardian/The Observer article:

    JWH-018 was "nothing special", Dr Huffman remembered, "but it was one of the more potent compounds we made, and it was quite easy to make from commercially available materials. Probably the reason it has now caught on." [...]

    [...]"My biggest surprise was that this all hadn't happened sooner," he told me. "All it needed was somebody with a reasonable understanding of science to see the papers we had published and think, 'Aha!'"

    And with the perspective of a 77-year-old organic chemist:

    "I've lived around the world a long time," said Dr Huffman. "I've come to the conclusion that if an enterprising person wants to find a new way to get high, they're going to do it."

    JWH-018 is however already classified as illegal in several European and Scandinavian countries. So unless JWH-018 does something different from garden-variety marijuana, outlawing it in the US will just push folks back to God's own herb.

    Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, & Martin BR (2000). Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding. Drug and alcohol dependence, 60 (2), 133-40 PMID: 10940540

    February 9, 2010
    Science Blogs


  1. Arkero
    Till employers and governments have widespread urine testing for this it will continue to be popular weather legal or not. Governments banning it raise awareness of it and also legitimize it as a substance that works at getting someone high.
  2. BloodyMuffin
    Alas for silly comments such as this. there are many many drugs that have already killed people. Diphenhydramine, dextromethorphan, heroin, meth, acetaminophen, alcohol... note which of thos are illegal, only the ones with the strongest potential for pleasure. the use of these JWH chems has become extremely widespread and common yet there have been no reported deaths. the risk of death is not at all why people want stuff like this banned. they want it banned because they dont understand it and they fear it. i wish people wouldnt make claims like this, and that when they did they would have the sense to think through it and explain it.
  3. WhiteFox
    "I don't need to know what it is. If it makes you feel good, it's undoubtedly dangerous, addictive, and intended to be sold to your children" --Government spokesperson.

    Any substance which gets you high will eventually be banned once the authorities catch onto it. It's second nature to them by now. Tradition.
  4. Humanity
    No reported deaths, true, but it isn't known how the drug(s) affect the body when used over a longer period of time. I feel that raising a healthy amount of suspicion towards a substance that hasn't had due testing, is the way to go. 0 deaths is all good and well, but doesn't prove it's harmless.
    Banning something because it isn't understood, as a short-term plan, makes sense imo. At least until further research can be carried out (as if...).

    I'm all for decriminilisation (of cannabis), btw, it's not that at all :) Just as far as harm-reduction goes, maybe banning a new substance isn't that terrible of an idea.

    EDIT: Oh and thanks for a fascinating article! SWIM hates there's not much info to be had on all these smart-products going about. And before someone slaps me in the face, I do realise that not everything said in the media is pure gold nor should be taken as such! Cheers.
  5. WhiteFox
    The problem with that is, once a substance gets banned, it doesn't get un-banned. And, more than likely, the authorities won't go through the trouble of studying it.. in fact they're more likely to deny funding to study it. And even if they did study it, they would ignore the results unless the results showed harmful, addictive effects.
  6. Arkero
    My understanding is that most new drugs approved by the FDA have not been tested for long term effects. Unless your definition of long term is short. Wonder what clinical trail phase would be analogous to the real world use at this point.
To make a comment simply sign up and become a member!