Posted by: leigh | June 6, 2010

Cannabinoid agonists and JWH-018- part 1

I’ve been noticing lots of talk of these “new” synthetic cannabinoids floating around out there lately, now that Spice and K2 have gotten a lot of media coverage. I also found a lot of hearsay and uninformed opinion floating around on the internet in various places, but not so much of the scientific information. Let’s remedy that, shall we? I’ll cover the basics over a couple of posts and more if there are remaining questions.

Spice and K2 are being floated as the new “legal marijuana” – a supposedly marijuana-like high without legal consequences. Abel Pharmboy kicked off the discussion with a Research Blogging post about synthetic cannabinoids that you should definitely check out. DrugMonkey brought up an interesting thought in his post on the topic: does the US Controlled Substance Analogue Enforcement Act of 1986 apply? This act states (I paraphrase here) that a compound that shares a similar chemical structure or pharmacological action and is intended for human consumption is treated as a Schedule I classified drug. According to some interpretations of people who know more about legal stuff than I do, that might be a negative. So let’s explore the chemistry of the cannabinoid agonists** to get started.

**Disclaimer: I am not an organic chemist. Don’t crucify me.

Delta-9 THC, the principal psychotropic ingredient in marijuana, is a terpenoid compound produced by the Cannabis sativa plant. You can examine its structure here:

Figure 1. THC chemical structure (via Pubchem)

THC acts through brain cannabinoid receptors to produce its typical effects. However, those receptors are involved in a whole lot more than just producing the psychotropic effects of cannabis intoxication. The pursuit of understanding the mechanism of action of cannabinoids, as well as further research to better understand the normal and abnormal physiology of the endogenous cannabinoid signaling system, has resulted in many novel synthetic drugs designed to target the cannabinoid receptors in experimental systems. They were devised to be used as tools to elucidate what happens when we probe the system- for instance, what molecular properties are required for a given drug-receptor interaction property (efficacy, affinity, what have you).

There are multiple classes of structurally distinct cannabinoid agonist drugs that emerged from these efforts. Given the topic under discussion here, I will focus on the aminoalkylindoles. They are structurally unrelated to delta-9 THC, as you can gather by the structure.

Figure 2. Aminoalkylindole cannabinoid agonist WIN55,212-2 structure (also via Pubchem)

Here’s where I bring in the so-called “legal marijuana” – one of the compounds that’s causing this stir, named JWH-018, is a derivative of the aminoalkylindole class of drugs. Take a look for yourself, and consider the similarities to the aminoalkylindole above.

Figure 3. JWH-018 structure. Rotated (imperfectly, but you get the idea) to demonstrate structural similarity to figure 2.  Pubchem may be a good start, but how about we get something that lets us rotate around bonds? Get on that, NCBI.

Note again that these are synthetic compounds- they are not analogs of THC and not produced by the Cannabis sativa plant. They are structurally unrelated, but act upon the same receptor as does THC. They have different pharmacological properties: efficacy and potency, which I will discuss in the next post. This does not make them “better” in some or any way compared to the plant-derived cannabinoid compound.

Now the curious thing is that while these synthetic classes of compounds may be structurally distinct from the original cannabinoid compound of interest, they do produce pharmacological effects that are classified as cannabimimetic. And yet, one does not need a DEA license to obtain some of these research chemicals.

Many of these “legal” products are distributed as plant matter soaked in JWH-018 and other compounds, and then marketed as incenses- covered with warnings about how they are not intended for human consumption. This is also curious. How long will this hold off the inevitable? I don’t have a guess.

[note: part 2 discussing pharmacological properties of JWH-018 can be found here.]


  1. […] This post was mentioned on Twitter by Drug Monkey, dr leigh. dr leigh said: cannabinoid agonists and JWH-018 (part 1) […]

  2. […] Dr. Leigh is at it again, this time on the new synthetic cannabinoid phenomenon. Head over there for some awesome pharamcology by one of the […]

  3. Tell me more as I light this bowl of it.

  4. […] at Clemson University. The compounds carry his initials followed by a number, such as JWH-018. The chemical structure of the compounds are different from the active constituents in marijuana but they bind to the same receptors in the […]

  5. Do these components cause any heath issues.Are we at risk for disaster?Without testing this product for human consumption what have we found out now?

  6. your perspicasity amazes me .

  7. […] at Clemson University. The compounds carry his initials followed by a number, such as JWH-018. The chemical structure of the compounds are different from the active constituents in marijuana but they bind to the same receptors in the […]

  8. Crystal, we’re not really in a position to know this for sure whether there are health risks, or how serious they may be. This is part of the reason for concern. All we have are anecdotes, and very little scientific data to go on.

  9. wow, well, i am flattered! thanks!

  10. this chemical does work better than thc, it opens the CB-1 and CB-2 receptors almost wide open in the brain causing way better feeling then marijuana. I have tried it, for me it has stopped me, over-night, from smoking marijuana, nor do I even want to smoke marijuana anymore. I have been offered marijuana, after the experimentation, and really don’t want marijuana, regardless of me being under the influence of the new compound. I prefer the compound 10-1, even over the hydroponically/pharmaceutical grade marijuana varieties. THC is not nearly as “clean” and “full-spectrum(if you will) as some of these compounds
    In my opinion, we will see this chemical outlawed soon, for it is bankrupting the marijuana industry in the U.S. Which makes politicians and law enforcement officials pay attention to it, they are no longer needed if marijuana isn’t being bought, and the economy will suffer greatly because of this. Fact, if the marijuana industry would stop over night, the United States would be bankrupt in less than a month. Do you realize how many law enforcement officials, probation officers, lawyers, and substance abuse counselors would lose work. Let alone all who profit from from its illegality. But, hey, like “they” tell marijuana-smokers after they take their future away, McDonald’s is hiring. Well on that note, maybe the extortion of marijuana-smokers will cease for a while, until these compounds are made illegal. But in the mean time we are seeing “the legalization of marijuana” not a taboo subject anymore. Can you put 2 and 2 together? Other good news, a lot of big time marijuana “pushers” have been keeping records for decades, linking politicians and law enforcement officials to the marijuana industry in the U.S. They are now threatening to expose these corrupted officials, because of the method they use to profit from them and the users. They take everything they “earned”, by “busting” them to bring in another “sucker”. That’s another reason why marijuana legalization is becoming a more excepted proposal in the federal and state governments.
    Well on that note, let your supreme being, bless us all!!! And don’t let them grind you down.

  11. […] For more reading, go to these posts by us, DrugMonkey, and Dr. Leigh. […]

  12. ha k2 is a great alternative and I’m a happy user, but today her in Wichita Falls TX i recieved a drug parephenalia ticket for having a pipe, the thing is there was no drugs or anything illegel in it. The officer even asked me why i didnt just rolled it in papers! ha so its not illegal to buy a pipe, its not illegal to buy k2, its not illegal to smoke k2 in a joint, but some how its illegal to smoke it out of a pipe or have it in a pipe. So yeah now theres a 300 dollar ticket that this broke college has to figure out how to pay just because I chose to smoke k2 instead of marijuana. So whats your legal view on that????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????

  13. life is rough, Todd. i suspect if you can afford the K2, you can manage to pay the ticket.

  14. ha that would be true elsewhere but k2 ia only $5.99 here

  15. I used traditional cannabis daily for 10 years. After a two year break for the purpose of gaining a legal lifestyle- I did experiment with a jwh herbal incense. The effects suit me better and the potency is better if compared to how much $ worth of local I’d need for a similiar effect. I find it worthwhile over all to spend 15 or 30 on a full weekend and not worry about the black market. As far as health risks- it seems we already know more about mode of action and short term effects than many psychiactric medications used frequently on a large scale. Weighing my options, I’m buying jwh products until something changes in legal statues.

  16. its poison! the shit made me go blind and deaf for about 5 mins the other day, and trust me, it was far from awesome. after my senses returned to normal, my muscles clenched up as if i was being electrocuted, also, not at all fun. i was very afraid that i was on the verge of dying. ban this crap and legalize marijuana. at least we know that pot wont make you blind, deaf, or dead!

  17. Spice is good. and all i now use, just easier to get, less worry, affordable, so what the hell? why not lol – and IT VAPORIZES WONDERFULLY, WHICH IS GOOD SINCE I STOPPED SMOKING MONTHS BACK AND WASNT GOING TO START NOW FOR SPICE. I agree has me not missing the real deal at all, man, I use to have a green thumb but not needed anymore, not worth it anymore, and seems crazy to do and kinda now, extreme even when there is Spice readily avail. LOCally for me at the same prices as hydro, BUT some places $10/a G or up to fukin $45 a G!! what is that but funny? u just cant be serious in pricing spice higher than nugs on the street… haa u cant price the “fake item” higher than the “real deal item” with any product…but i guess some people pay it? CHECK OUT THE VAPORIZER DISCUSSION BOARD (FORUMS) i administrate :) @

    join in the discussions on herb, marijuana, legal herbs, spice, e-ciggarettes, and all things related


  18. […] about for the past several months. I think leigh of the Neurodynamics blog (see posts on THC and cannabimimetic/JWH-018 pharmacology), may have been the first to report seeing these data at a meeting and then I ran […]

  19. I have used pot for twenty years and since using syth i dont wont pot ,nz has just ban it and I have a back injury that it was helping too deal with….
    Now i am looking at med’s that will have worse side effects and will have to be more careful about my pain relief
    Hope manufactures can rise up to the challange to create a safer legal substitute.
    Go hard….

  20. I started using it because it was legal, I did no research on it because my computer gets checked. It was found it in my purse after smelling a hint of smoke in the bathroom. I felt like a trust was broken by the inturder entering my purse. Yet relieved I no longer had to hide it. To make a long story short, i’ve decided to quit! Now that it’s out in open I can research and i’ve come to realize it”s addicive more so than pot. Knowing this I figured the best way was to cut down, in a matter of four days I am only smoking a third of what I was. Every two days adding a half hour wait time, between getting high. It is working well for me so far, i’ll be off it soon and will look ahead never to go back! I hope this post helps someone, somewhere. Know you can do it if you try, one day at a time.

  21. Does anyone still come to this site? I’ve been waiting on moderation approval for four days now.

  22. It seems that we just need to have a big party and get a room vaporizer going. That way everyone is immersed in the incense. Can’t we all just get a bong? Love you long time….

  23. After having dosed 13 individuals in a controlled setting here at the University I work for (with toxicologists, physicians and ER nurses present); I must say much of what has been said here is true about the synthetic cannabinoids. We dosed with single versions (JWH-108 for example) as well as “cocktails” (JWH-250 along with JWH-018 as well as other combinations) and found that some users very much enjoyed the “high” while others were extremely uncomfortable displaying high levels of anxiety and fear during their “ride”. Hypothesis: for those who have had a long history of stimulating the CB1/CB2 regions they seem to “enjoy” the synthetic experience…while those who have not (or rarely) used THC seem to be overwhelmed by it. My analogy is this: on a hot day of yard work, a cold stream of water over your head from the garden hose feels pretty good. But if the local fire department comes by and turns their pressured hose on you…it won’t be comfortable at all. We will continue our research as time and funding permits. What troubles me much more is the recent surge in synthetic stimulants (MDPV, Methylone, Mephedrone, Pentylone, Pentedrone and similar chemicals). They are simply far too dangerous to screw around with. Any “research chemical” use should remain in the lab until we know much more about them.

  24. My son had a “near death” experience from this crap….thinking since you only need to be 18 and its legal, he thought it would be smarter the smoking pot or drinking….he passed out, lost his pulse and saw angles and his whole life pass before him while passed out, he was taken by ambulance to ER…it was a very scary experience for him and his friends who thought they had witnessed their friend dying right in front of their eyes. This stuff needs to be illegal!!!!

  25. To: Concerned mom and other interested parties…

    Many States have moved to outlaw a number of these synthetic cannabinoids and the Federal government has finally moved to place them on their Schedule One list…however we have two major hurdles to overcome (1) each time a State or the federal government places a new chemical on the banned substances list, two more are rolled out from clandestine (and not so clandestine labs) normally originating in China and (2) we must fight the “analog” battle in court. Successfully convincing a local prosecutor (who has a limited budget) to spend money bringing in a chemist every time the defense attorney is shouting “If the molecule don’t fit, you must acquit!” is simply not going to happen. Adding to those issues is the issue of cannabinoid-mimetic substances (which may or may not be covered by any law anywhere) and you begin to see the problems we are facing.

    Finally, THC is a “partial agonist”. Many of these new chemicals are full agonists which mean they affect the cannabinoid receptors in the brain at a level many orders of magnitude more than marijuana does…which may help explain the bizarre, scary and downright dangerous behavior we have been seeing. We have dosed a dozen human subjects (in tightly controlled human subjects research) here at the University I work for and we are very concerned about these chemicals. They are clearly dangerous and should be eradicated from the public arena.

  26. Do you mind if I quote a couple of your posts as long as I provide
    credit and sources back to your webpage? My website is in
    the very same area of interest as yours and my visitors would truly benefit from some of the
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  27. that’s ok with me.

  28. I ha
    I have a stepson that has been smoking this. He is Ok while he is high but when it wares off he is very angry,violent and can not control his anger. He has broken things in my home and tried to hurt my husband. We have had to call and have him arrested and a restraining order. He acts completely out of his mind. This is a very dangerous substance and should be banned .

  29. […] there's some lovely bodily decor on display. Finally, Dr. Leigh is at it again, this time on the new synthetic cannabinoid phenomenon. Head over there for some awesome pharamcology by one of the best. Oh oh oh wait. One more thing. […]

  30. Many of the synthetic cannabinoids (SCs) are banned here in Missouri. However the chemists crafting/designing them are very clever (read diabolical) and are good at staying ahead of legislation and crime labs. Many of the SCs are designed specifically to trigger neurotransmitter response in the cannabinoid receptors. There is absolutely ZERO quality control and those mixing the herbal/botanical substances have not a whit of care as to the damage they inflict. This is profit driven. When we dosed 13 subjects with SCs (physicians, toxicologists, nurses present) here we found a range of reactions from mildly high to erratic/paranoia. They are not to be trifled with. Marijuana/THC is a partial agonist. Many of the SCs are full agonists and powerfully trigger receptor responses. They are responsible for heart attacks, strokes, injuries (self inflicted and accidental) and many deaths.

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