Update on “legal” smoking highs

July 31, 2010, 1:20 pm


Spice drugs as a new trend: Mode of action, identification and legislation. Vardakou I et al. Toxicol Lett 2010:197:157-162.


Spice, like K2, is a mixture of herbs laced with various synthetic cannabinoids.  It is usually sold over the counter or via the internet, labelled as “incense” and “not for human consumption”.  Although it is not clear where these products originate, they appear to come from laboratories in Asia where analogs originally formulated for cannabinoid research are readily available. This paper, from Greece, reviews available clinical information about these products, as well as ongoing efforts to make them illegal.

Although numerous chemicals with agonist properties at the cannabinoid receptors have been discovered, analysis has shown that Spice most commonly contains the following:

JWH-018 – This potent activator of the cannabinoid CB1 receptor was synthesized in a laboratory a Clemson University in the 1990s, and was the first such chemical identified in Spice and K2 products.

CP-47,497 – This is another CB1 agonist, developed by Pfizer in the 1980s.  According to the authors, this chemical is more potent than Δ-9 THC in vivo, but does not have high affinity for the CB1 receptor.

HU-210 – This is a potent agonist of both the CB1 and CB2 receptors. Since HU-210 has a structure similar to that of THC, it is considered a Schedule 1 controlled substance in the United States.

The authors point out that these synthetic cannabinoids are more potent that natural cannabis, and considerably more expensive.  They are often used when cannabis itself is not available, or when the user wants his or her urine drug screen to remain negative for THC.  Efforts to regulate these products are made more complicated by the large number of synthetic cannabinoid agonists that are available; when one is outlawed, others can be substituted.

Typical effects of Spice and K2 included anxiety, agitation, and tachycardia.  Hallucinations are been reported.  The authors reference one German paper – in Journal of Mass Spectrometry of all places! – where two of the researchers conducted a “self-experiment” by smoking a cigarette containing “Spice Diamond”.  After 10 minutes they both experienced red conjunctiva, increased pulse rates, and dry mouth, as well as altered mood and perception.  Major effects lasted 6 hours.  (J Mass Spect 2009 May;44:832).


  1. precordialthump Says:

    Brave New World, eh.

    BTW, I find the Mass Spectrometry reference amusing – I never thought to do that when I was a mass spectrometrist (before I saw the light of medicine) – maybe I’d never have changed career paths!

  2. Leon Says:

    Yes, I have to admit that J Mass Spect is not one of my usual stops when making the rounds of medical publications. Never know where one will find interesting tidbits.

  3. Synchronium Says:

    To be fair, that J Mass Spec paper wasn’t just those two guys getting stoned. The bulk of the paper was their analysis of different products to determine what their contents.

  4. Leon Says:

    Synchronium, I agree, and I apologize if my post made it seem the “self-experiment” was the totality of the paper. That certainly wasn’t my intent. I did find, however, that the passage about the “experiment” was even more amusing occurring in the midst of all the GC-MS spikes and TLC plate smudges.

    BTW, for anyone interested in the fascinating history of self-experimentation in medicine, I highly recommend Lawrence Altman’s book “Who Goes First?”. There are some absolutely amazing stories in it.

  5. Synchronium Says:

    Don’t apologise, just wanted to point it out to everyone else.

    My first impression after reading your post was that it was amusing to find such a report in that journal. Of course, you obviously read the paper so knew of the other content, but most people don’t have access to the paper, let alone will have read it. Just wanted to clarify. 🙂

  6. precordialthump Says:

    I second the recommendation of Altman’s book – even though its missing Jack Barnes and the discovery that Carukia barnesi causes Irukandji syndrome…

  7. Leon Says:

    For the entire incredible story about Jack Barnes and Irukandji syndrome, see my 2005 column from “Emergency Medicine News”: