How doth the little crocodile...

How doth the little crocodile
improve his shining tail,
And pour the waters of the Nile
On every golden scale

How cheerfully he seems to grin
How neatly spreads his claws,
And welcomes little fishes in,
With gently smiling jaws!

- from Lewis Carroll's "Alice's Adventures in Wonderland"
 
After a small hiatus, for some unknown reason, krokodil is back in the news. The UK’s Metro is reporting that krokodil could be tempting to drug users in the area. No, really…the headline reads:

“Flesh-eating drug krokodil ‘could sink its teeth intoBritish addicts’, health workers warned”

Um. OK. Quite alarmist. The article also states that the drug has made its way to the US. Oy vey!

The International Business Times has countered with a sensible article. They simply concluded that there is no evidence that it has arrived in the UK.

And I’m not even sure why this story describing worries over an increase in drugged driving out of the Bangor (Maine) Daily News even mentions krokodil…

So, again for the record, there still exists no credible evidence to support the idea that krokodil exists in the USA, Canada, or the UK.

Cheers,

ForensicToxGuy

Curiouser and curiouser...

Nebraska is currently updating its controlled substance legislation and adding many synthetic cannabinoids to the list of banned compounds. Nebraska legislative bill 811 is still pending, but is on the fast track to getting signed into law.

From review of the bill, it effectively controls the older generations of cannabinoids such as naphthoylindoles (JWH-018, AM-2201, etc.), naphthoylmethylindoles (JWH-175, JWH-184, etc.), naphthoylpyrroles (JWH-307), naphthylideneindenes (JWH-176), benzoylindoles (RCS-4, AM694, etc.), cyclohexylphenols (CP47,497 and variants), phenylacetylindoles (JWH-203, JWH-250, etc.), adamantoylindoles (AB-001, AM-1248, etc.), and tetramethylcyclopropanoylindoles (UR-144, XLR-11, etc.). It also includes some of the newest generation compounds, such as the indole carboxamides (AB-001, STS-135, etc.) and indole carboxylates (PB-22, 5F-PB-22, etc.).

 

 

Interesting note on the indole carboxamide classification is that the indazole carboxamides are included, but I don’t see how they fit under this umbrella. These indazole carboxamides include STS-135, ABk48 and its fluorinated derivative, AB-PINACA and its fluorinated derivative, ADB-PINACA and its fluorinated derivative, AB-FUBINACA, and ADB-FUBINACA. Semantics matters here. An indole group is not the same thing as an indazole group.

Also listed on Page 24, section M is something curious…

“Any other compound, not specifically listed in these schedules or approved by the federal Food and Drug Administration, that is identified by chemical, medical, or pharmacological means as a cannabinoid receptor agonist which mimics or is intended to mimic the pharmacological effect of naturally occurring cannabinoids.”

Hmmmm…so, if any substance not scheduled in the CSA can be shown to be a “cannabinoid receptor  agonist”, then it will be considered a controlled substance.

Now, here is where it gets curiouser…

In the updated legislation, “cannabinoid receptor agonist” is explicitly defined as:

“…any chemical compound or substance that, according to scientific or medical research, study, testing, or analysis, demonstrates the presence of binding activity at one or more of the CB1 or CB2 cell membranes receptors located within the human body.”

The definition “cannabinoid receptor agonist” has nothing to do with actual activity at the binding site. As it is written, it has everything to do with binding affinity at the receptor. So, if a substance can be shown to bind to either cannabinoid receptor 1 or cannabinoid receptor 2, then it is considered a controlled substance.

Also noteworthy from the pending legislation…

In the amendments (AM2400 and AM2567), there is a definition for “imitation controlled substance”.

“Imitation controlled substance shall mean a substance which is not a controlled substance or controlled substance analogue but which, by way of express or implied representations and consideration of other relevant factors including those specified in section 28-445, would lead a reasonable person to believe the substance is a controlled substance or controlled substance analogue.”

After review of this bill, we can easily see that Nebraska government and law enforcement intends to cover these drug substances in many ways. As always, other states will follow suit. I already know of one state that has the imitation controlled substance language.

 

Cheers,

ForensicToxGuy

Synthetic Cannabinoids in Louisiana / Illnesses and Emergency Scheduling

It has been reported that over the last few weeks, hundreds of people have been treated after consuming synthetic cannabinoid containing products. Some of these patients have presented to the emergency department with "life threatening" symptoms. At this time, it is not known what exact symptoms or effects have been reported. It is also not known if any of these cases have been analytically confirmed via detection of drug or drug metabolite in a patient's blood, serum, plasma, or urine.

Today, Louisiana has emergency scheduled eight (8) synthetic cannabinoid compounds. The following compounds will now be considered Schedule I controlled substances in Louisiana. 

ADB-FUBINACA
N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1-H-indazole-3-carboxamide

ADBICA
N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1-H-indole-3-carboxamide

AB-FUBINACA
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide

5F-AB-PINACA 
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide

AB-PINACA
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-
carboxamide

FUBIMINA or AM-2201 benzimidazole derivative
(1-(5-fluoropentyl)-1H-benzimidazol-2-yl)(naphthalen-1-yl) methanone

Mepirapim
(4-methylpiperazin-1-yl)(1-pentyl-1H-indol-3-yl) methanone

FDU-PB-22
Naphthalen-1-yl-1-(4-fluorobenzyl)-1H-indole-3-carboxylate

LA House Bill 229 which is pending in Louisiana legislature already contained these compounds, as well as the designer opioid drug, Acetylfentanyl. 

AB-FUBINACA and ADB-PINACA were recently placed into Schedule I by the US Federal government. ADBICA and ADB-PINACA were also two compounds associated with the cluster of illnesses in Colorado in 2013. In late 2013, here at Dose Makes the Poison, the unknown nature of these "alphabet soup" compounds was also questioned.

If I see any updates on this story, I'll add to this post.

As always, stay safe.

Cheers,

FTG

"And now for something completely different..."

Forget explicitly banning drugs. Toss away the discussion of similar chemical structures and "analogue" acts. There is now new broad legislation pending in Minnesota that simply expands on the definition of the word "drug". Minnesota HF2446 has been referred to the MN House Health and Human Services Policy committee.

Previously, the word "drug" was defined as "all medicinal substances and preparations recognized by the United States Pharmacopoeia and National Formulary, or any revision
thereof, and all substances and preparations intended for external and internal use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals, and all substances and preparations, other than food, intended to affect the structure or any function of the bodies of humans or other animals."

The bill adds the following to the definition...

"Drug shall also mean any compound, substance, or derivative which is not regulated or approved for human consumption by the United States Food and Drug Administration or specifically permitted by Minnesota law, and when introduced into the body, induces an effect substantially similar to that of a Schedule I or Schedule II controlled substance listed in section 152.02, subdivisions 21.23 and 3; and Minnesota Rules, parts 6800.4210 and 6800.4220, regardless of whether the substance is marketed for the purpose of human consumption."

If passed and signed into law, it becomes effective on August 1, 2014. The bill also includes language on misbranding and adulteration. I recommend reading it completely if interested.

It'll be interesting to see how this plays out. I've been waiting for legislation similar to this piece to be written and introduced. It was only a matter of time. If this gains traction, then look for other state legislatures to move in a similar direction.

Cheers,

ForensicToxGuy

Synthetic Drugs - A Descriptive Phrase of No Value

I despise the descriptive phrase "synthetic drugs". Why? Because it serves no real purpose other than a media soundbite.

The definition of a "synthetic drug" is not simply a synthetic cannabinoid or a substituted cathinone or a "research chemical".

A "synthetic drug" is anything that was created or SYNTHESIZED. It is manufactured. It is cultivated. It is derived. It is fabricated. It is processed. It was made in a laboratory.

Oh, off the top of my head and in no particular order, here's just a tiny list of drugs that are considered "synthetic drugs":


 

Amphetamine
MDMA
Methamphetamine
Oxycodone
Oxymorphone
Hydrocodone
Hydromorphone
Fentanyl
Acetylfentanyl
Sufentanil
MDPV
Alpha-PVP
Naphyrone
Pentedrone
Methylone
JWH-018
AM-2201
UR-144
XLR11
AB-PINACA
PB-22
25I-NBOMe
2C-B
2C-I
LSD
Methoxetamine
Amobarbital
Secobarbital
Phenobarbital
Alprazolam
Flunitrazepam
Diazepam
Phenazepam
Chlordiazepoxide
Amitriptyline
Imipramine
Clomipramine
Fluoxetine
Sertraline
Quetiapine
Olanzapine
Mirtazapine
Duloxetine
Citalopram
Diphenhydramine
Chlorpheniramine
Doxylamine
Brompheniramine
Atenolol
Metoprolol
Labetalol
Verapamil
Methadone
Ropinirole
Sumatriptan
PCP
Propoxyphene
Zolpidem
Zaleplon
Zopiclone
Methylphenidate
Sildenafil
Tadalafil

Yeah, so there is a list of 63 random drugs that can be described using the phrase "synthetic drug". And we could keep listing substances, but there's no point. "Synthetic drug" means very little to nothing of value.

Media and legislators, please stop using the term.

Cheers,

ForensicToxGuy

The game is afoot!

Upon review of some literature , I ran across a few synthetic cannabinoids that I did not know existed. The existence of these substances (and pretty much any synthetic cannabinoid since 2011) simply shows that the chemistry games continue and as such, I see no real end game. These substances are not banned in any state of the USA that I know and they are not explicitly banned by the US Federal government, but the substances may fall under the Analogue Enforcement Act.

AB-CHMINACA is a cyclohexyl-substituted derivative of AB-FUBINACA.

XLR12 is trifluorobutyl derivative of the earlier generation XLR11, which consisted of a 5-fluorinated pentyl alkyl chain.

The remaining two compounds are interesting as they are a hodgepodge of moieties from earlier generation compounds.

JWH-018 8-quinolinyl carboxamide consists of a pentylindole structure of JWH-018, but with a replacement of the napthalene group with an 8-quinolinyl carboxamide subgroup. The carboxamide group can be found in recently scheduled substances, AB-FUBINACA and ADB-PINACA, as well as numerous other cannabinoids. The carboxamide group is designated by the CA lettering scheme. The 8-quinolinyl group can be found in the recently scheduled PB-22 and 5F-PB-22.

FUB-144 is a 4-fluorobenzyl derivative of the earlier generation UR-144. The fluorobenzyl group can also be seen in previously mentioned compounds, AB-FUBINACA, ADB-FUBINACA, FDU-PB-22, and FUB-PB-22. In each of those alphabet soup names, the fluorobenzyl group is designated by the FUB lettering scheme.

I have mentioned previously that while these structural changes are common sense from the manufacturer's perspective as they evade strict legislation banning compounds, they are a nightmare from the user's viewpoint. Pharmacological or toxicological properties of these substances are not known. Are the substances CB1 or CB2 agonists? Do they have downstream effects? What are the effects from acute consumption? What are the effects from chronic consumption? How is the substance metabolized? Are metabolites pharmacologically active? Are there any degradation products from the pyrolysis process during the act of smoking? Are those degradants pharmacologically active? How is the substance excreted? What is the dose of the cannabinoid being consumed? So many unknowns!

The variety of compounds also makes my job challenging and sometimes downright frustrating, but as Sherlock said, "The game is afoot!".

As always, stay safe out there.

Cheers,

ForensicToxGuy