An update on K2/Spice, JWH-018 and synthetic cannabis

June 23, 2011

The recent meeting of the College on Problems of Drug Dependence featured a very well attended session on the emerging recreational drugs that are best described generically as synthetic cannabis. Popularly these are frequently referred to as K2 or Spice as these seem to be the best known of the initial market branding. One of the first identified and most frequently observed active compounds in these products was JWH-018, so you may see this term as well.
The past year or two has seen an explosion in the use and supply of synthetic cannabinoid “incense” products in the US and worldwide. The basic nature of the product is well established- Small packets (typically 3g in the US) of dried plant material marketed as “incense” and marked “not for human consumption” that are priced well above what you might expect. In the range of $60 at my local fine inhalation glassware establishments, last I checked. Upon analysis, these products are typically found to have a variety of plant materials, but also to be adulturated with a host of drug compounds that have agonist effects at the CB1 receptor.
As you are aware the most-active psychotropic compound to be found in cannabis, Δ9-tetrahydrocannabinol (THC) confers the majority of its effects through partial agonist activity at CB1 receptors.
In short, these “incense” products are a constructed, synthetic mimic of cannabis. Since the active ingredients are, in many cases, full agonists this means that the maximum CB1 activation can potentially be higher than you could achieve with any dose of the partial agonist THC.

As my readers are aware, these products are capable of producing dependence with a profile, including withdrawal effects, that are typical of cannabis dependence.
The symposium was organized and chaired by a rising star in drug abuse research, William Fantegrossi, and a legend of cannabinoid behavioral pharmacology, Jenny Wiley. The latter had been involved with much of the characterization of the JWH- compounds when they were originally created.
The DEA reported continued surveillance of products and their scheduling action that placed 5 of the more-common cannabimimetic compunds on Schedule I in early 2011. Interesting tidbit was that the delay from the intended scheduling in late Dec 2010 (30 days after their initial notice of intent to schedule) was entirely due to putting out brushfire lawsuits from convenience store / head shop interests that were making serious bank from these products. He reported that a consortium of just four shops were reporting profits (might have been sales) in the neighborhood of $5M.
One of the more interesting parts of the symposium was the participation of three members of a four institution/agency consortium or task force that has been established in the state of Arkansas. It includes people from the state’s forensic crime laboratory, the poison control service, the University of Arkansas Medical Sciences campus and the state Children’s Health service (or Children’s Hospital, I’m not remembering precisely). It seems like an ideal response to an emerging health situation of this nature- involve the two areas of front line interface (poison control and law enforcement forensics) with scientists who have experience with the health condition in question.
What I learned that was of interest to me:
-Phone calls to all US poison hotlines for marijuana or cannabis amount to about 1,000 per year. Calls for synthetic cannabinoids were 2,800-2,900 in the past two years. Given that all available epidemiology suggests that marijuana use dwarfs use of synthetic products, we can tentatively infer a greater risk.
-40 of 48 calls to the Arkansas Poison Control Hotline were from/regarding individuals already in contact with Emergency Departments / Emergency Medical Services. (1 of 48 calls was from an individual calling to report the effects were just what he wanted and to tell the agency to stop denigrating these fine products.)
-Behavioral effects of the active compounds are opposed by CB1 antagonists, in general, so there is ongoing confirmation that this is indeed the most important pharmacological activity for a range of these compounds.
-While these compounds are more potent than THC (smaller amount leads to similar effect), there is some variability across those that have been studied in animal models. And for some of the compounds, such as JWH-073, there is some indication that it may actually be a partial agonist (like THC) rather than a full agonist.
-Certain cannabimimetic combinations are frequent. One lab reports never finding JWH-073 without JWH-018. Similarly, JWH-250 and JWH-081 were frequently found together. Samples are diverse enough that it suggests an intentional recipe being followed, rather than an accidental association.
In response to a query from Prof-like substance, the DEA guy mentioned that they were finding and rolling up domestic production labs. The compounds are being imported, the plant material locally sourced and the finished product being made and packaged.
The forensic scientist pointed out that since the method is to dissolve the compound in acetone and use a spray bottle to spritz the plant material the drug distribution should be uneven. And their analysis of packages shows what they call “hot spots” with some parts of it having up to 2X the drug content. So potency varies between and even within product units.
There was a distinct impression from both the DEA and the forensic side of things that there are/were many labs pumping out product, consistent with the highly diverse drug content, source material, branding/packaging, etc.
After the DEA scheduling action, apparently the packaging started using terms like “compliant” or “Does not include JWH-018, JWH-073….etc”. At least one sample that was so marked was analyzed and found to include JWH-018.

26 Responses to “An update on K2/Spice, JWH-018 and synthetic cannabis”

  1. joed Says:

    “As my readers are aware, these products are capable of producing dependence with a profile, including withdrawal effects, that are typical of cannabis dependence.”
    Let’s get real! A person that gets “dependent” on marijuana will get dependent on Pepsi Cola or french fries or anything just about.
    Marijuana does not create dependence.
    Unsure about the “incense” stuff.


  2. Samples are diverse enough that it suggests an intentional recipe being followed, rather than an accidental association.
    Is it clear where the product is coming from and how diverse the source is?


  3. Phillip IV Says:

    He reported that a consortium of just four shops were reporting profits (might have been sales) in the neighborhood of $5M.

    Now that it’s illegal, watch those profits soar! Ka-ching.


  4. Jesse Says:

    While I am hardly one of those who says marijuana is absolutely harmless, this strikes me as yet another attempt to criminalize something that wouldn’t have appeared in the first place if marijuana wasn’t criminalized also.
    I mean really, if we’re going to say that this stuff causes dependence, fine, but I want to know why alcohol is legal at all then. Or caffeine. (I’m pretty addicted to that, probably). Or nicotine which is really addictive.
    After all, everything can be a “gateway” drug. Most people who are drug dependent that I ever see are smokers as well, and likely have some other problem that leads to dependence than the particulars of the substance.
    This seems completely the wrong way to deal with this kind of thing.
    Did anyone even think for one second that by criminalizing the sale of these artificial cannabinoids, you have just handed every organized crime ring a gigantic source of profits? You have just made something with a market you aren’t going to eliminate more risky, and thus upped the violence levels?
    Sorry to get on like this. But for christs’ sake, why is the only solution “make it illegal?” Especially when the relative harm is pretty small, as these things go? I have never heard of anyone dying from a marijuana overdose — though I would say that if I took enough THC tablets I might be able to commit suicide, but I think it would be a poor method. (Would it mess up your liver like Tylenol and kill you that way?)
    And I have seen no evidence (even in the peer-reviewed studies I saw) that the effects of THC withdrawal are much worse (or better) than those from nicotine and they seem better than some really bad alcoholics I have seen.
    What was the DEA thinking? (Or not).


  5. DrugMonkey Says:

    I’m not sure I buy your argument when it comes to this drug, Jesse. The user reports don’t tend to suggest it is “better” than cannabis, in fact the opposite. Too easy to get into what look like really high dose THC effects. Until there is better evidence for a population that actually prefers these drugs, the best hypothesis is that legal status is driving consumption.
    Philip, the market shift away from the five newly-scheduled compounds suggests that the biggest profits come with the quasi-legal products.


  6. Jesse Says:

    @Drugmonkey — that’s exactly the problem tho — if marijuana were legal, there wouldn’t have been a market for this stuff in the first place! It would be too easy to use the real stuff — it grows wild all over the place, let alone the cultivated crops — and not try untested substitutes.
    Making it illegal makes it impossible to make the substitutes better. There is simply no logical reason for them not to be perhaps regulated in the same way lots of OTC drugs or booze is. We have all kinds of rules about making wine or beer to keep it from containing lead, say, as a sweetener (common in centuries past). The same could be applied to anything like this.
    Honestly, even with what you have described here, and assuming that the calls to the poison control centers ALL involved someone unconscious and needing immediate hospitalization, can you really with a straight face say that this is worse tan the number of hospital calls from the “Zoo Mass” Boston campus on Saturday night? I worked as a security guy at a university with a student population of 5,000 total. We had several alcohol calls a week in the winter, adding up to 20 or 30 a year that went to hospital. I bet the numbers are even higher at say, UW Madison or FSU.
    Per population that is a LOT more than what you have listed for artificial cannabinoids. So even making the very scariest assumptions about what this stuff does, it still seems patently illogical to me to outlaw it when there are plenty of other strategies to assess its relative safety and even mitigate the bad effects.
    I’m also not with the hypothesis that legality (or lack of same) is much of a driver. If that were so there would be no illegal drug market and alcohol would have not been consumed at all in the 20s. The driver, IMO, is that the stuff is fun to do. People like it.
    You can get into the reasons why (biochemical, social, psychological) but that’s the long and short of it. This is the reason that datura trips — while legal (what are they going to do, outlaw one of the most common weedy plants?) are less popular than pot or cocaine. Datura is not much fun even though it is far more readily accessible. (Most people describe it as really, really scary, leaving aside the toxicity issues).
    I’m not saying that we should let people buy coke OTC and that there are no problems with dependence. Just that the whole premise of outlawing this stuff because people are taking it as a substitute for marijuana (and it could be harmful) because it is legal seems a bit circular.


  7. leigh Says:

    thanks for passing along the report! this was one of the big topics i knew i’d really miss out on.


  8. DrugMonkey Says:

    Jesse, it no doubt escaped your attention in your leegalize eet frothing but I take no position on public policy. My interest lies in learning what these compounds actually do, what effects they have, etc. Consequently that is what I blog about.
    Now it is true that the Spice era has been sort of informative about the Analog act and what it takes to control substances at the federal level but this discussion makes no judgment as to the wisdom of scheduling specific compounds.


  9. becca Says:

    Might people be more willing to call poison control centers for this stuff than marijuana? Either because it is legal (ergo safe to confess to authorities) or because they simply are more worried about the unknown quantity aspect (i.e. people might call for marijuana toxicity, except somebody is always around to reassure them that it isn’t anything to worry about and will resolve on its own)?
    Also, LOL on the one individual in Arkansas.


  10. Jesse Says:

    You may not take a position on public policy per se, but if you want to do controlled studies of what this stuff does making it schedule I doesn’t make it easier, does it? That’s part of what I am getting at.
    I it turned out there was some horrific side effect or as yet unknown issue with these things damn right I’d say don’t sell it. But the public policy bit gets squarely in the way of doing good science — as it has for other controlled substances. (Not that some should not be controlled — lord knows there is a reason doctors are an at risk group).


  11. DrugMonkey Says:

    And how does scheduling affect “good science” Jesse? How is the science for Schedule II drugs like methamphetamine or cocaine better than for THC or MDMA?


  12. Patel, CPhT Says:

    This post and study confirms what my friends and I have suspected for the longest time. We’re occasional marijuana smokers that have tried the “legal stuff” for curiosity’s sake. Datura (the bag says not for human consumption lol) is plain disgusting and takes ~2g to feel the slightest buzz. I think I still have it sitting out of sight on my porch since February. On the other hand, some formulations of spice give a better high than some weed strains (confirmed in this study), but the high is short and a headache usually follows. Moves by the DEA to throw the new substances under Schedule I is totally retarded in my opinion, but I’m happy to read about scientists conducting these studies.


  13. Patel, CPhT Says:

    And I agree with Jesse’s post. Throwing marijuana under the Schedule I bus surely has an effect on the funding for its research. The federal government would much rather fund research that confirms its illegality rather than fund research that looks at the medical benefits.


  14. DrugMonkey Says:

    Do you have any evidence for that, Patel? Given that the Congressional against using NIH funds to “promote” use of schedule I drugs comes with an explicit exemption for medicinal benefits?


  15. How much of this shitte would people be smoking if weed were legal and regulated, like nicotine, alcohol, and other drugs? My guess is *NONE*.


  16. DrugMonkey Says:

    Well, stimulants like caffeine and nicotine are legal and yet cocaine and methamphetamine are still used by lots of people. So I bet you are wrong on that, PP.


  17. mikeez2011 Says:

    Marijuana Marijuana I am disabled …53 years old: Medical Marijuana I am fanatical about meds and side effects.I do my best to take care of my health! degenerating discs in both my neck and back ! many ADHD problemsa significant amount of stress and anxiety ! schizophrenia chronic pain and fatigue, and depression all caused from years of working hard, and many auto accident and MS on top. Medical Marijuana the benifits are amazing! The ease of pain, and relaxed mood is unspeakable ! what up in SC ? I love USA Marijuana is a beauiful thing !!! supposed “War on Drugs”. C’mon people! Wake up!


  18. rork Says:

    “but I take no position on public policy”
    Want dumb laws? Have quiet scientists.


  19. DrugMonkey Says:

    Standing up for the clearest understanding of the facts as we know them is not the same as being “quiet”, rork.


  20. rork Says:

    Agreed, they are different things, and you can even do both.


  21. Dude, coke and meth are drastically stronger than caffeine and nicotine, which is why people use them. Based on what people have reported on the Internet about these cannabinoid mimetics, decent weed is much more enjoyable, and the overwhelmingly vast majority wouldn’t be using them if they could easily obtain some decent weed. (So, yeah, maybe “*NONE*” is a tad hyperbolic.)


  22. DrugMonkey Says:

    Based on the number of people who use them, caffeine would appear to be much more enjoyable than cocaine as a stimulant. And yet cocaine continues to be a significant health problem.
    DirkH has a post up which overviews some Dutch efforts to treat cannabis / marijuana products with THC content over a certain limit as significantly more risky than good old regular weed.
    I happen to be more skeptical about that (given the active constituent is the same) but it all falls on a spectrum of inquiry. Along with whether beer/wine are less risky than MFJ. There are legitimate questions here about how compulsive use and dependence are generated. Certainly the animal models are consistent with the idea that “stronger” hit to a given system might convey enhanced risk. Clearly the breadth of human use suggests that some are going to prefer stronger, and some more mild, psychoactives in a number of categories.
    So I see no reason that the use of full agonist cannabimimetics would magically disappear if cannabis was freely available. Less use, perhaps. But not zero. or “NONE” as you would have it….


  23. Avicenna Says:

    I think the key factor driving demand for cannabimimetics is not legality, but drug testing. My impression is that most mimetics users have legal status (e.g. probation) or employment that requires they be regularly drug tested, and they turn from the real stuff to synethetics to beat the tests. Novelty-seeking is a distant second, and legality or lack of other source is third. This is just my impression from comments to this and other blogs and discussion fora, not based on any kind of systematically collected data.
    The distinction between testing and legality as reasons for use is somewhat subtle, but I think it is important. Even if cannabis were legalized, many of these people would still probably be prohibited from use and tested, and would still turn to mimetics. Similarly, if all mimetics were made illegal, there would still be demand if a black market supply could meet it. And most importantly it means that a cheap and effective test for mimetics would probably have more effect on demand than any legal changes.


  24. Skip Says:

    The scary part about Synthetic Pot is its unpredictability. In one case (reported by NBC TV 6, Johnstown, PA) a Penn State male student took a SINGLE hit of K2 and ended up in the hospital for nearly 3 days. And, on the other hand, I personally know of a Penn State coed who smoked K2, Spice, and other brands (nearly every day) for 9 months until these products were taken off the shelves in the local head shops. And, although her grades have dropped a bit, she’s still passing her courses and is currently on track to graduate in Dec., 2011. However, when she first went off synthetic pot she did seem to go through a withdrawal phase (which resembled having the flu); and, a few months later, put on a significant amount of weight around the waist and under the chin, which could be Pseudo-Cushing’s Syndrome. But, the bottom line is that this person has smoked a massive amount of synthetic pot over a long period of time and is still capable of obtaining a 4 year college degree from a reputable university. So, it’s quite clear that the effects from these products varies greatly by the individual. I would say that the risk is not worth taking and we don’t yet know what the long-term effects might be.


  25. dt Says:

    DrugMonkey, you don’t have to take a position on public policy to write a non-infuriating blog post, but you do have to acknowledge this simple proposition: There would be no market for this stuff but for marijuana prohibition.


  26. dt Says:

    “Do you have any evidence for that, Patel? Given that the Congressional against using NIH funds to ‘promote’ use of schedule I drugs comes with an explicit exemption for medicinal benefits?”
    NIDA’s monopoly on the supply of legal marijuana hinders research, and the federal government has not funded a clinical study on marijuana since before the passage of the first state medical marijuana law. NIDA has a bias against studying the medical uses of marijuana, and the federal government appears uninterested in such research. Link:
    Think carefully before you dismiss legitimate public policy arguments as “legalize eet.” As an intelligent person, you should be more reluctant to give ammunition to freedom-taking thugs.


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