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

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.

Happy 420 Dudes!

A little reading for marijuana fans from the blog’s Cannabis Archive
Yes, it does cause dependence, including symptoms of Withdrawal
A take on the conditional probability of cannabis dependence…wait, as many US folks are dependent on cannabis as have ever so much as tried…?
Oh, and that K2/Spice, synthetic marijuana stuff containing JWH-018 and other cannabimimetic full agonist drugs? Yeah that causes dependence too.

A peculiar phenomenon in some chronic marijuana users: Hyperemesis
The Pot Potency data
doc420
Parents want to know, “Did the pot make my kid lazy?“

Were “incense” products containing JWH-018 and other cannabimimetics ever “legal” in the US?

A comment over at Brayton’s blog drew my attention. A D. Johnson notes:

A few days ago, police arrested Eric Srack, a business owner in Salina. Srack had been selling an herbal potpourri which people were using as a legal alternative to marijuana.

The comment is apparently referring to so-called “incense” products being sold in head shops, cigar stores (like mine) and convenience stores that contain cannabimimetic compounds. The JWH series (JWH-018, JWH-250, JWH-073 seem to be common), CP_47,497 and a few other compounds are ligands for the endogenous cannabinoid receptor subtype 1 (CB₁) just like good old Δ⁹-tetrahydrocannabinol (THC). Natural products pharmacologist David Kroll has an excellent intro to these compounds at Terra Sigillata and dr_leigh has a two-parter on the pharmacology here and here. The summary version is that these compounds have the same basic pharmacological effect as that of THC which confers much of the psychoactive properties of cannabis, i.e., stimulation of the CB₁ receptor. In many cases these canabimimetic compounds are more potent than THC in their actions and they are what are referred to as full agonists, in contrast to the partial agonist actions of THC. Unsurprisingly, these “incense” products are capable of inducing dependence which looks reasonably similar to dependence produced by cannabis.
Back to our story…..

The stuff wasn’t illegal until around a month ago, when the police decided that it was chemically similar enough to something that was illegal to warrant an arrest.
In other words, the state government fiddled with the law until it enabled the police to arrest someone for doing something that wasn’t illegal when he started. Are these drug enforcement guys just bored?

As I responded at Brayton’s blog, this is inaccurate.

MtF 2010: Conditional probability of dependence on cannabis

The Monitoring the Future epidemiological survey of drug use in the US has announced some of their updated data today. As always, you can go to their website and look at the figures yourself. The monographs with expanded data tables and summaries can be found here, the current year’s data will be published in June, I think, so until then you’ll have to be satisfied with the selected figures on the website.

Why Pain Research Matters

Our good blogfriend JuniorProf has launched a campaign to explain why pain research matters. I am already learning lots of stuff from his older posts. Also from observations such as this one at Almost Diamonds and this one from Zuska.
The thing that caught my eye recently, though, was this post:
Drug discovery in academia and NIH, a new type of U01

This brings us to the bane of drug discovery: absorption, distribution, metabolism and excretion (ADME). This is something that industry does very well.
…
ADME in academia, well, let’s just say, not so much. The reasons for this are likely pretty simple: its an important area of drug development but not the most exciting, by any stretch of the imagination (sorry you ADME specialists), and it often requires all sorts of rather expensive testing in model organisms that aren’t used often in academic labs. Its also highly compound-specific and this makes grant writing very hard (or so I hear).

JuniorProf then goes on to make an argument for why drug development should be done in academia and how that might work best. He then describes a recent NIH initiative that is trying to support some academic drug development effort.
Go read. Follow @juniorprofblog on Twitter or perhaps just the #painresearchmatters hashtag.

Synthetic marijuana, K2, spice, JWH-018 searches..phew

The world wide web can be a random thing at times and so it is hard to make much out of a tiny pinhole of a window. Still, something really unique in my experience is the unbelievably sustained drumbeat of Google search hits which land on my post of Feb 17, 2010 entitled:

Synthetic marijuana, K2, Spice, JWH-018 and, you guessed it, dependence

Most of the time one of my blog posts enjoys traffic for a day or two and thereafter rapidly subsides into obscurity. I’ve never had, until now, a post that just keeps ticking away with a steady stream of daily hits from the Google like this one.
I’ve just looked at the past thousand or so hits that arrived at the blog via search word. Half of them are for this post on synthetic marijuana. This is atypical, as usually we see a much broader range of search terms landing on a variety of prior posts.
Where the search terms are elaborated, the major interests seem to be in side effects (generically), whether it is bad for you, how to make synthetic marijuana and whether a person can be tested for prior use of these items.
Anyway, like I said this is barely even a pinhole view. It would be an error to overinterpret. But it sure does represent a divergence from our usual experiences here at the blog.
Update: Abel Pharmboy reports he’s seeing the same thing on his post: What’s the buzz?: Synthetic marijuana, K2, Spice, JWH-018

#proofwaltdisneysmokedpot

I made the idle observation on Twitter yesterday that someone had found this blog by searching for the string “proof walt disney smoked pot“. My initial read:

search words finding the blog: “proof walt disney smoked pot”. Really people? Really?

Apparently some folks are amused by this concept.

Happy 420 Dudes!

Just ’cause you know I love you all pot heads….
Cannabis Archive
Hyperemesis
Withdrawal
The Pot Potency data
doc420

Meow-meow is dead, long live…ahhh, let’s just call it Monumental Dumb Ass, Inc

The UK has now made the 4-MMC (Meow-Meow, mephedrone) compound illegal to possess as of April 16, 2010. It will be interesting to see what pops up next as the latest waiting-to-be-criminalized recreational drug.
Apparently MDAI (5,6-Methylenedioxy-2-aminoindane; Wikipedia) is a hot prospect in the UK drug user stakes. I dunno, the go-to user forum thread on MDAI doesn’t make it look all that promising but who knows. It will be interesting to see how this plays out.
Legal sourcing has a way of trumping the actual quality of the high, as we’ve seen with mephedrone in the UK in the past year. My read on the user descriptions (such as they are) sure doesn’t make it seem as if mephedrone is as fun as MDMA. The primary draw seems to be that it was a reasonably good high but more importantly it was legal and available. Hmm, now where are those cannabis fans who claim that legality and ready availability of cannabis has nothing to do with use patterns?

Impaired or improved driving in abstinent Ecstasy users?

A recent paper set out to examine automobile driving skills in people who had previously used Ecstasy (presumptively 3,4-methylenedioxymethamphetamine; MDMA) but were currently not using. Dastrup and colleagues (2010) used a driving simulator task in which the job was to maintain a set distance behind a lead vehicle (LV) displayed on the computer screen. The job was to stay abut two car lengths (given as 18 meters) behind the LV while accelerating to 55mph. My Google U conversion calculation makes 55 mph out to be about 25 meters / sec. I would therefore estimate the closing time between the cars as about 0.4-0.5 seconds, depending on car length and how much space you assume between these lengths. Thereafter the LV changed speed as depicted in the Figure 2 from the paper.
The horizontal line sits at the 55 mph point and you can see that the speed of the LV varies up to about 59 mph and down to about 51 mph with the maximum change taking place over about 18-20 seconds. .

breadcrumbs…

in case you were wondering where I’ve been lately, I’m talking about those ballot-happy Californicans and their upcoming attempt to legalize recreational dope smoking over at A Vote for Science.

RIP: Billy Ray Martin

An absolute lion, perhaps even the dean, of exogenous cannabinoid pharmacology has passed away.
The obituary from the Richmond (VA) Times-Dispatch is here.

MARTIN, Dr. Billy Ray, 65, of Richmond, died Sunday, June 8, 2008. He was Chairman of the Department of Pharmacology and Toxicology at VCU.

Billy Martin’s scientific output was prodigious, with a majority of it focused on the pharmacological properties of the cannabinoids. His interest dated at least back to 1975 with the publication of this paper:

Martin BR, Dewey WL, Harris LS, Beckner J. Marihuana-like activity of new synthetic tetrahydrocannabinols. Pharmacol Biochem Behav. 1975 Sep-Oct;3(5):849-53.

Conyers’ Letter to the DEA and Medical Marijuana Trojan Horses

Representative John Conyers, Chair of the House Committee on the Judiciary, sent a letter to the DEA inquiring about the “paramilitary style enforcement raids” conducted against medical marijuana distributors in California. In case anyone hasn’t been following this story the state of California permits the use of marijuana for medical purposes. Since the federal government does not and the current Federal apparatuses’ have chosen not to look the other way in respect of State’s rights, there have been Federally motivated enforcement actions against people and businesses that are legally permitted by the State but not the Federal government.
Ed Brayton observes:

All of this can be blamed entirely on the Supreme Court, which issued one of the most indefensible rulings in its history in Gonzales v Raich. And yes, this one you can lay directly at the feet of the liberals on the court. Stevens, Souter, Ginsburg and Breyer were all in the majority in ruling that the federal government has the authority to overrule state medical marijuana laws.

I ran across something specific related to this Conyers’ letter that ties back to some previous comments I had about drug advocates trying to Trojan Horse recreational use under cover of medicinal use.

Yeah, Yeah, College Kids Take Drugs (snore)….WHAT???!! 75 Arrests?

Perennial Playboy Magazine Top-Ten Party School San Diego State University is in the news following the arrest of some of its students on allegations of illicit drug dealing and drug possession. The San Diego Union Tribune is reporting:

Federal agents and SDSU police culminated a yearlong investigation into drug dealing around campus yesterday, …Ninety-six suspects, including 75 SDSU students, have been arrested on drug-related charges…The SDSU Police Department approached the DEA and county narcotics task-force officials for assistance in December, when it became clear that the trafficking was more widespread than it could handle.
Investigation seizures by the numbers (sidebar; SOURCE: SD County District Attorney’s Office)

• 50: Pounds of marijuana
• 4: Pounds of cocaine
• 3: Semiautomatic handguns
• 1: Shotgun
• 48: Marijuana plants
• 350: Ecstasy pills
• 30: Vials of hash oil
• $60,000: Cash

Sadly, the investigation was sparked by a drug-overdose fatality, albeit of an anonymous undergraduate rather than someone as famous as Heath Ledger or Len Bias. There is also another drug-overdose fatality caught up in this story.
I want to talk about Jennifer Poliakoff and Kurt Baker today.

NYC Bar Discusses Marijuana Arrest Policy

The Drug Law Blog notes that The Association of the Bar of the City of New York will be discussing Marijuana Arrest Policy tomorrow.

In 1977, New York State decriminalized possession of personal use amounts of marijuana. Nonetheless, researchers report that New York City is now the national leader in detaining individuals for possession of personal use amounts of marijuana. Beginning with the advent of quality of life policing, the New York City Police Department dramatically increased the number of arrests for marijuana possession: from 1997 to 2006 the Department arrested 362,000 people for possessing marijuana, in 2006 alone it arrested 33,000 people for marijuana possession. The Department also commonly holds marijuana possession arrestees in detention for up to 24 hours pending arraignment. Published research indicates that the marijuana possession arrests are not in central business districts, and that the police primarily make the arrests in Black and Hispanic neighborhoods.

Looks fascinating.
Drug Law Blog also has a post reviewing 2006 marijuana arrest stats for the entire US and ends with the following observation.

That’s more than 1.5 million people who were arrested in 2006 simply for possession.

The link to my other post today should be obvious.