Gravel: human sacrifice, dogs and cats living together...mass hysteria?

News reports surfaced over the past few days about a new drug named “gravel”.

Yes, gravel…what a great name.

A new drug! Worst drug I’ve seen in years! Most dangerous drug ever!

Oh, the hyperbole!

But, what is it?

This news article states that it is a combination drug of methamphetamine, Klonopin (clonazepam) and "bath salts".

And these YouTube videos (1 and 2) from November 2013 state it's a drug sweeping the nation...

"Last year we were dealing with bath salts...and this year, it's gravel..."

"Gravel is the new drug...it's like the new 'crack'...it's like 'crack' for my generation."

In all my dealings with emerging drugs and substances, I have heard the term "gravel" used in reference to one specific research chemical:  Alpha-PVP or alpha-pyrrolidinopentiophenone.

 

Alpha-PVP, patented in 1967, is a substituted cathinone that is structurally related to methylenedioxypyrovalerone (MDPV) and pyrovalerone with the main structural differences being a 3,4-methylendioxyl and methyl group respectively. MDPV and pyrovalerone have been shown to affect dopamine and norepinephrine in the body. The pharmacological mechanism of action for alpha-PVP is thought to be similar, but it is unknown at this time as no published data is available regarding in vivo or in vitro activity. It has a molecular formula C15H21NO and a molecular weight equal to 231.3 g/mol. Alternative names for this substance are PVP and desmethylpyrovalerone. On January 28, 2014, the US federal government filed a notice of intent to use its emergency scheduling powers to place alpha-PVP, along with 9 other cathinones into Schedule I of the Controlled Substances Act.

There are some earlier news articles that seem to corroborate that "gravel" is alpha-PVP.

From August 2013, this article states that common names for alpha-PVP are "gravel" and "ice".

From October 2013, this article states that the substance is alpha-PVP and it is often mixed with other substances such as methamphetamine and Klonopin (the same previously mentioned substances again?)

From November 2013, this article states “gravel” is a street term used to describe a substance containing the compound alpha-PVP…”

Another article from November 2013 states "approximately 64 grams of what was thought to be “gravel” was found. “Gravel” is a synthetic drug that contains the chemical Pyrrolidinopentiophenone (Alpha-PVP)."

A new article from January 27, 2014 states that lab results show that confiscated material was positive for alpha-PVP. This article also shows a rather graphic picture of a user's arm who was supposedly injecting the "gravel" material. I have seen this picture floating around Facebook and Twitter today along with a story of a user who had been injecting the "gravel" substance.

.....

So, if this "new" drug "gravel" is truly alpha-PVP, then it is not new at all and honestly not worthy of such hysteria.  Alpha-PVP has been commonly found in "bath salt" powders, tablets, and associated products since 2011 when it became an MDPV replacement after MDPV's placement into Schedule I. Much like other synthetic stimulants and cathinone substances, it has been associated with death or contributing to cause of death. It is commonly monitored in cathinone, stimulant, or "bath salt" laboratory assays. And as with any street product or "bath salt" concoction, one can never be sure if the drug is cut with an agent or if it is undiluted active ingredient or if it even contains a drug substance at all.

In conclusion:

1. "Gravel" is the name for a drug substance that contains Alpha-PVP.
2. "Gravel" may or may not contain other substances.
3. "Gravel" has been in existence for a few years.

I'm hoping to head this one off at the pass unlike the krokodil hysteria that was perpetuated by the media at the end of 2013. With the pictures that I have seen on social media and the recent news article proliferation, it may be difficult, but let's hope we can...

Cheers,
 

ForensicToxGuy


"Believe half of what you see and none of what you hear."

Notice of Intent: 10 more cathinones are being placed into Schedule I

Previously, three substituted cathinones found in "bath salts" and related stimulant products were considered Federal Schedule I substances. These were MDPV, mephedrone (4-methylmethcathinone), and methylone.

 

On January 28, 2014, the Federal government filed its notice of intent to use its emergency scheduling powers to temporarily place ten more substituted cathinones into Schedule I of the Controlled Substances Act (CSA) for the next two years. The ten substances are 3-fluoromethcathinone, 4-fluoromethcathinone, 4-methylethcathinone, 4-MePPP, alpha-PBP, alpha-PVP, butylone, naphyrone, pentedrone, and pentylone.

 

The filing in the Federal Register can be found here along with the supplemental information. The final order of placement of these substances into Schedule I will not be official until at least February 28, 2014.

I'm honestly surprised it took this long to emergency schedule some of these substances.

Now there will be 13 of these "bath salt" substances explicitly scheduled at the Federal level in the USA.

And the beat goes on...

Cheers,

ForensicToxGuy

News: Synthetic Cannabinoid Products Pulled From New Zealand Market

Five products have been pulled from the New Zealand new psychoactive product market. The product revokation was reported here and the specific license revokation information can be found on the NZ Ministry of Health New Psychoactive Substances website. These have the names: AK47, Anarchy, Karma, Northern Lights Primo, and Voodoo.  The active ingredients were listed as the quinolinyl carboxylate cannabinoids 5F-PB-22 and PB-22, as well as a fluorinated version of JWH-398, also known as CL-2201.

It is of note that the US Federal government filed a notice of intent to emergency schedule 4 synthetic cannabinoids, including 5F-PB-22 and PB-22, and at least five deaths in the USA have been associated with the use of 5F-PB-22.

According to the NZ Ministry of Health, the use of these products has resulted in reports of "nausea, vomiting, insomnia, acute psychotic reaction, and prolonged withdrawal". It should be of interest that eight products containing 5F-PB-22, five products containing PB-22, and five products containing CL-2201 remain on the NZ market.

What happens from here? We'll see.  As always, stay safe.

Cheers,

ForensicToxGuy

Notice of Intent - 4 Synthetic Cannabinoids Placed Into Schedule I

On January 10, 2014, the Federal government filed its notice of intent to use its emergency scheduling powers to temporarily place four synthetic cannabinoids into Schedule I of the Controlled Substances Act (CSA) for the next two years.  The four substances are PB-22, 5F-PB-22, AB-FUBINACA, and ADB-PINACA. The filing in the Federal Register can be found here along with the supplemental information. The final order of placement of these substances into Schedule I will not be official until at least February 10, 2014.

I have discussed some of these compounds in the past here, here, and here.

According to the notice of intent, 5F-PB-22 has been associated with the deaths of five individuals in the United States. In one case, it was determined that 5F-PB-22 intoxication was the sole cause of death. In a second case, it was determined that cause of death was cardiac arrhythmia and/or seizure in association with 5F-PB-22 consumption.

ADB-PINACA was implicated in the adverse events in George in August 2013. Its first identification was in a product named “Crazy Clown”.  The substance was also implicated in the adverse events in Colorado in September 2013 and identified in products named “Black Mamba”.

With these additional four synthetic cannabinoids added to Schedule I, the official count of controlled synthetic cannabinoids will be twenty-two.  These are:

5F-PB-22
AB-FUBINACA
ADB-PINACA
AKB48
AM-694
AM-2201
CP47,497
CP47,497-C8
JWH-018
JWH-019
JWH-073
JWH-081
JWH-122
JWH-200
JWH-203
JWH-250
JWH-398
PB-22
RCS-4
RCS-8
UR-144
XLR-11

Just another day with these synthetic cannabinoid compounds...

Cheers,

ForensicToxGuy

The ever elusive "krokodil"

Jacob Sullum (@jacobsullum) has written two fantastic articles about the krokodil hysteria. The articles can be found here at Forbes.com and Reason.com.

In summary, it has been several months since the first "krokodil cases" were reported by US doctors and media, and there still has been neither a nonbiological specimen test positive for desomorphine or derivative nor a biological specimen (blood or urine) test positive for desomorphine or derivative.

And the beat goes on...

Cheers,

ForensicToxGuy

More musings on the "krokodil" communication letter...

From a drug toxicology perspective, what compounds would I expect to be present in blood or urine in a true “krokodil” case?  Ultimately, the answer is I don’t know. I have never seen a confirmed “krokodil” case published with toxicology results. Grund et al. (2013) reviewed the reported synthetic pathways and manufacture of desomorphine and/or “krokodil”. Desomorphine may be the product that is sought, but with the different crude processes used, it may or may not be produced during the reaction. Savchuk et al. (2008) identified other desomorphine derivatives and codeine in actual “desomorphine” samples. In these samples, the desomorphine ranged from trace amounts to 75%. 

Are toxicology laboratory tests able to identify "krokodil"? This issue has been raised over at The Poison Review.  No. We wouldn't identify "krokodil", but the best that we can do (currently) is to attempt identification of desomorphine or codeine or possibly some other desomorphine derivatives in the samples.  My main criticism with the paper (or clarified as a "communication to the editor" by @infectiouschris) is that absolutely no toxicology was discussed AT ALL. Not a urine drug screen. Not a blood drug screen. No opiates analysis. No fentanyl analysis. Nothing. They had multiple patient visits over 5 months to interview the patient and collect biological samples.  And, as far as the reader knows, they did NOTHING.

When was the last administration of the drug in relation to the patient’s visits to the hospital? Opiates typically have a detection window of 1-4 days in urine post-administration. If drug use was recent, then biological samples could have been viable - at least it would have given more of an insight into the patient's substance use history. Was the patient not asked this question by the physicians? Is this not relevant to the case? It wasn't reported in the article.

Other than the patient's word, how do we know this case was or was not diacetylmorphine-related? We do not know. We have no toxicology results that show either the presence or absence of 6-acetylmorphine, morphine and/or codeine in the patient’s blood or urine.  How do we know this case was or was not fentanyl-related? We do not know. We have no toxicology results that show either the presence or absence of fentanyl and/or norfentanyl in the patient’s blood or urine.  How do we know this case was or was not “krokodil”-related? We do not know. We have no toxicology results that show either the presence or absence of desomorphine, desomorphine derivatives and/or codeine in the patient’s blood or urine. We also have no chemical analysis of any products used by the patient.

If I was the editor of the journal, what would I have required for calling this a confirmed “krokodil” case? I don’t know. But using common sense, I would have required the drug toxicology results be published along with the opinion that the reported case was “krokodil”. I find it highly dubious that either no attempt was made to run drug toxicology or no attempt was made to publish the drug toxicology results and expound on them (whether positive or negative). Maybe this is a difference of perspectives between clinical toxicology and forensic toxicology? I am looking at this from purely a forensic toxicology view, similar to the "reasonable degree of scientific certainty" that we testify to in a court of law and/or while rendering an expert opinion.

Ultimately, I'm not saying this is or is not a "krokodil" case.  No evidence exists to say it is or isn't.  We simply do not know.  And therein lies the rub.


Cheers,

ForensicToxGuy

PS. Thanks to The Poison Review for making this a discussion.  It is very much needed.



Related Posts:

Krokodil...not so fast my friends!

Krokodil, 7 Days Post-Withdrawal

Krokodil Redux

"He that can have patience can have what he will."

Being in the laboratory for 10+ years in a few different roles, one tends to hear many inane things…the trick is to minimize your exposure to the ridiculousness.

So, here are three of my favorite stupid exchanges of all-time and in no particular order…

 

Exchange # 1

When preparing a solution of acetonitrile and concentrated formic acid (80:20) for mass spectrometer part cleaning...

AH: “Why do we use formic acid and acetonitrile? Why don’t we use acetic acid?”

Me: “Why would we use acetic acid?”

AH: “Because when you mix formic acid and acetonitrile, the resulting product is acetic acid.”

Me: “Seriously? No, that is not correct. I’m going to walk away for a minute, but I’ll be back to explain why it isn’t correct.”

AH: “Ok.”

Exchange # 2

I’m sitting at a LC/ToF instrument one day fiddling with the MS source. AH approaches me from his spot in front of another LC/ToF.

AH: “I just had a thought.”

Me: “Yeah, what is it?”

AH: “You know the LC that we have in front of the ToF as a separation mechanism?”

Me: “Yeah, I’m familiar with what an LC is and does.”

AH: “Well, what if we completely removed it from the mass spec?”

Me: “We can do that, but we would have no separation mechanism prior to MS analysis and all of our validated analytical methods would be useless.”

AH: “Well, that was my thought.”

Me: “Ok. What part was your thought? Expound on that please.”

AH: “What if we removed the LC and turned the ToF mass spec on its side?”

Me: “Why would we do that? That’s absurd.”

AH: “Think about it…we could utilize gravity to separate our mixture in the MS. We wouldn't need to spend money on an LC any longer.”

Me: “Ok. How about I write this down and take this to the lab director for her approval?”

AH: “Really? Would you do that for me?”

Me:  “…No…”

AH: “Huh?”

Me: “Let me leave you for a while and let you ponder your chemistry education throughout the years. Think about it really hard. And if you don’t know why that’s a really ridiculous idea by the time I come back, then we can discuss.”

Exchange # 3

While loading a batch of specimens on a LC/ToF one day, in my peripheral vision I notice AH running around frantically near some LC/MS/MS instruments and tapping on various argon tanks.

AH: “I think my nitrogen tank is empty.”

Me: “Why do you say that?”

AH: “I’m infusing a sodium formate solution to calibrate the ToF and I’m getting very intermittent signal – it disappears and reappears. So, I was checking the gas tanks to see if they were empty.”

Me: “First, the ToF uses nitrogen and the tanks you were looking at are argon.”

AH: “Ok, so what’s the issue?"

Me: “You were tapping on argon tanks for the MS/MS instruments and the ToF doesn’t use argon.”

AH: “Ok, I understand. So, where are the nitrogen tanks?”

Me: “Second, are you sure you don’t have some sort of air bubble in the tubing or syringe you are using for infusion?”

AH: “No, I checked. No air bubbles. All clear.”

Me: “Let me check.”

We walk over to the LC/ToF on which he is actively infusing calibration solution.

Me: “AH! There is a visible air bubble in the syringe. I can see it from 5 feet away. That’s your issue.”

AH: “Where’s the nitrogen tanks? I still think that’s the issue.”

Me: “If you really want to know…we have one very large liquid nitrogen tank outside those doors in the rear of the building.”

I point to the doors.

AH takes off through the doors and outside.

I clear the air bubbles in the syringe and tubing and then go back to my business.

AH comes back ten minutes later.

AH: “I think I found the issue.”

Me: “The air bubble has been cleared…”

AH: “There’s an ice build-up on the outside of the nitrogen tank.”

Me: “…I also calibrated your MS for you….Wait, what did you say?”

AH: “There’s ice on the nitrogen tank!!!”

Me: “And why is that? THINK.”

AH: “…”

I walk away.

There you have it.  And all of these people have degrees in chemistry…

In all seriousness, in exchanges 1 and 2, in the end we talked about why the thoughts were incorrect and in exchange 3, he had an epiphany and figured it out on his own. So, all was good in the end. Teaching experiences galore in the lab!

Cheers,

ForensicToxGuy