CPDD 2014: The XLR-11 synthetic cannabinoid is looking nastier by the day

XLR-11_structureA session on synthetic cannabinoids at the Experimental Biology meeting in April included a talk on nephrotoxicity consequent to use of synthetic cannabinoid products. I covered it in a post. As with a prior report of Cases in Wyoming, the scientist from Oregon reported being able to identify XLR-11 in two of the cases presented. There is not much available on PubMed at the moment regarding the effects of this cannabimimetic. (The XLR-11 structure at the right is courtesy of "meodipt" who submitted it to the Wikipedia page for free use.)

New data presented by Michael Gatch at the recent meeting of the College on Problems of Drug Dependence in San Juan, PR (lovely venue, btw) caught my eye because of an unusual property of XLR-11. Previously, Gatch has looked at a lengthy series of synthetic cathione ("bath salt") drugs in mouse locomotor and rat drug-discrimination assays. This new work is similar, save for the different drug class, so if you want some background reading, that prior paper would be a good complement.

The key, for me, was the drug-discrimination data. This is an assay in which animals are trained to discriminate saline from a reference drug, in this case good old Δ9Tetrahydrocannabinol (THC). In essence the rat is reinforced for responding on one lever if it has received saline just prior to the operant session and on the other lever if it has received THC. Then, on critical test days, you can substitute a dose of some other drug and determine the extent to which the rat responds on the drug-paired versus saline-paired lever. As I've mentioned before, this seems imprecise to the newcomer since seemingly any intoxicant would be scored as "drug" to a rat. Not so. They are actually highly specific in categorizing drugs of similar pharmacological activity.

The interesting thing in the presentation by Gatch was that he showed time-course with bins of about 5 minutes after the start of the session. One drug, XLR-11, popped out as having rapid onset of activity (i.e., full THC responding at 5 min when it takes maybe 10 or 15 for this to occur for THC itself) and a short duration of action (THC-lever responding disappeared after about 15 minutes). I say it popped out because out of a series of cannabimimetic drugs he presented, this one was the only one to have this profile (to my recollection).

This is interesting because in a general sense this tells me two things. First, this is the profile of a drug that is going to engender rapid on/off subjective effects and therefore very likely frequent re-dosing. From a comparative perspective this sounds like enhanced abuse liability to me...i.e., better chances of causing addiction.

The second aspect only hit me when I recalled that XLR-11 was the compound associated with nephrotoxicity. Now, admittedly, it may be the case that XLR-11 itself has a pyrolosis product produced during the smoking of plant matter containing it. But it also strikes me that this rapid on/off pharmacological profile might lead to recreational users simply using more of the products containing this compound than they ever would of products containing some longer acting synthetic cannabinoid. And that might get us back to thinking about what is contained in the various plants used in the products being sold to users.

9 responses so far

  • Natalie says:

    Great write-up of a topic in a field dissimilar to my own. I relayed the interesting tidbits to my (non-sciencey) husband over coffee this morning. Thanks DM.

  • Comradde PhysioProffe says:

    Sounds like good old weed is a lot safer than this shittio. I wonder if anyone would use this dangerous crappe if good old safe weed of known controlled potency were easily and legally available?

  • cat says:

    That ols safe weed sounds like fu
    on just to try once

  • drugmonkey says:

    I wonder if anyone would use this dangerous crappe if good old safe weed of known controlled potency were easily and legally available?

    Do people drink alcohol preparations of high concentration when good old safe 4.2% beer is readily available?

    Why do people bother to extract the cocaine out of good old safe coca leaves? Why have people altered the structure of cathinone, as provided by the good old safe delivery system khat, to make it into various types of "dangerous crappe"?

    Yeah...it's a real mystery, that one CPP. A puzzler.

  • There's a difference between the desire for higher potency preparations of known pharmacological agents at known concentrations whose manufacture, labeling, and sale are closley regulated and the desire for unknown shitte cooked uppe in some basement lab and provided at some unknown concentration with unknown purity and unknown contaminants.

    People may like to get high, but they also mostly have a decent instinct for self preservation. There's not much market anymore for bootleg moonshine tainted with methanol that makes people go blind, is there? I wonder why that might be???

  • Just some rambling on my end.

    I don't believe people use these synthetic cannabinoid products because cannabis is still illegal in most areas of the USA. I believe they simply use them to evade the routine drug test.

    Even in those areas where cannabis is legal, most (if not all) workplace drug testing programs still frown upon positive results for THC/THC-COOH.

    Look at Colorado and their perspective on cannabis and its eventual legality. Now, what happened in mid-to-late 2013? An outbreak of illnesses due to synthetic cannabinoid products. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6249a7.htm
    And this was in a place that decriminalized and eventually legalized recreational cannabis possession/use.

    I'd love to see how some of these INACA synthetic cannabinoids or even the PB-22/5F-PB-22 variants do in drug discrimination assays.

  • DrugMonkey says:

    Gatch had at least one of those FUBINACA I think, have to check my notes.

    I'll have a short comment wrt your speculation about use later today, also from CPDD presentations.

  • ForensicToxGuy says:

    If you can find the info about the INACA compounds, please share.

  • Bobby T says:

    Do you think XLR-11 is the synthetic cannabinoid that is behind the spike in of ODs in April-May of 2015 (in the US)?

    Your description of quick onset followed by fast crash/rinse/repeat sounds like many of the reports submitted to our website lately.

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