Saturday, September 3, 2016

Kratom into Schedule I

I’m sure you’ve heard by now that the DEA has filed a notice of intent to temporarily place kratom (active substances, mitragynine and 7-hydroxymitragynine) into Schedule I of the Controlled Substances Act.

What is kratom and why does the DEA think it needs to be banned?

Mitragyna speciosa is an tree that grows in Southeast Asia (primarily Thailand and Malaysia) and is known as kratom and biak-biak. The plant is in the Rubiaceae family, which famously includes the genera Coffea (caffeine). The leaves of the kratom tree contain many alkaloids, but the two primary ones are mitragynine (66% of total content) and 7-hydroxymitragynine (2% of total content). These two alkaloids are mu (μ) opioid receptor agonists similar to morphine and therefore, would exhibit similar pharmacological effects such as analgesia, sedation, central nervous system depression, and respiratory depression) From a potency aspect, mitragynine is considered to be 4 times less potent than morphine, while 7-hydroxymitragynine is said to be 10-20 times more potent. In lower dosages, kratom is said to have a cocaine-like (stimulant) effects.
Chemical structures drawn by ForensicToxGuy (2016)

Because of the opioid pharmacological activity, the kratom plant has been used for its medicinal properties (without the supervision of a physician or medical professional) in the management of chronic pain and treatment for opioid dependence/withdrawal. It has also been used as a recreational substance of abuse.  The raw leaf of the plant can be chewed or boiled into a tea. Kratom has been used for decades in Thai cultural traditions in this form. More recently it has been found in the form of capsules/pills, powders, and concentrated extracts.

Up until this notice of intent, the plant was considered a “drug and chemical of concern”, which is another name for the DEA’s watchlist of emerging substances. On February 28, 2014 and June 15, 2014 the US Food and Drug Administration (FDA) announced an import alert for kratom and issued multiple guidances that detailing that any shipments containing Mitragyna speciosa were to be seized without physical examination, especially those deemed dietary supplements and bulk dietary ingredients.

Data from the National Forensic Laboratory Information System (NFLIS) over 2012-2015 shows that mitragynine seizures in solid dose evidence has been relatively low. There were no reports of mitragynine in 2012. In 2013-2014, there were 181 and 137 detections of mitragynine respectively. The only data for 2015 available is through the midyear report and it listed 93 detections of mitragynine. To put this in perspective, propoxyphene (Darvon, Darvocet), a drug that was removed from the US market in 2010-2011, had 208 (2013), 143, (2014), and 53 (2015-midyear) detections reported in NFLIS.

Data from the CDC and National Poison Data System shows that from January 2010-December 2015 total 660 phone calls related to kratom exposure – 73.8% of calls reported intentional exposure to kratom and 90.2% reported ingestion of the substance.

Data from toxicology laboratories and coroner/medicalexaminer offices report a growing number of positive detections of mitragynine and/or 7-hydroxymitragynine.  There were 31 positive results reported from August 2012-July 2013; 274 positive results from July 2013-May 2014; 555 positive results from December 2014-March 2016. It is important to point out that without further case context, we cannot state much more about the toxicology results or detections of mitragynine other than they were simply detected in a biological fluid - the detections could have been associated with cause of death or they could have merely been incidental findings in postmortem toxicology; they could also be simple detection in probationary urine drug testing or even findings in urine drug testing for physicians prescribing medications and testing their patient's urine. for prescribed drug/illicit substance use. The Federal Register Notice of Intent states that 15 deaths have been associated with kratom from 2014-2016 – many of which have included the use of other central nervous system depressants or other drugs. Most notably, there were a cluster of nine deaths in Sweden associated with kratom use (Krypton brand) that was contaminated with the potent O-desmethyltramadol (active metabolite of the drug tramadol).

Because of these reasons, the DEA feels that scheduling kratom is necessary to avoid an imminent hazard to public safety. I look forward to observing the outcome of this action. I’m not so sure that the DEA has thought this one through completely. There has already been a petition created via the website - at the time of typing this sentence, there have been 49,965 signatures (100,000 signatures are needed) acquired in about 4 days. The American Kratom Association has also banded together for a Kratom March on Washington DC on September 13, 2016.

Some References of Interest

1.      Federal Register. Schedules of Controlled Substances: Temporary Placement of Mitragynine and 7-hydroxymitragynine Into Schedule I. Notice of Intent. August 31, 2016.

2.     Kroll. Forbes. The DEA is placing kratom and mitragynine into Schedule I. August 30, 2016.

3.     Boodman. STAT News. DEA will ban chemicals contained in kratom, a popular herbal supplement. August 30, 2016.

4.     Anson. DEA Banning All Sales of Kratom. August 30, 2016.

5.     Main. Newsweek. DEA to list kratom as Schedule I, effectively outlawing herbal supplement. September 1, 2016.

6.     Adkins et al. Mitragyna Speciosa, a psychoactive tree from southeast Asia with opioid activity. Current Topics in Medicinal Chemistry. PMID 21050173.

7.     National Forensic Laboratory Information System.

8.    Anwar et al. Notes from the field. Kratom (Mitragyna speciosa) exposures reported to poison centers – US, 2010-2015. MMWR Morb Mortal Wkly Rep. PMID 27466822.

9.     Holler et al. (2011) A drug toxicity death involving propylhexdrine and mitragynine. Journal of Analytical Toxicology. PMID 21218704.

10.  Kronstrand et al. (2011) Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. Journal of Analytical Toxicology. PMID 21513619.

11.  Rosenbaum et al. (2012) Here today, gone tomorrow…and back again? A review of herbal marijuana laternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. Journal of Medical Toxicology. PMID 22271566.

12.  Neerman et al. (2013) A drug fatality involving Kratom. Journal of Forensic Science. PMID 23082895.

13.  Karinen et al. (2014) An accidental poisoning with mitragynine. Forensic Science International. PMID 25453780.

Wednesday, August 17, 2016

Wait for the tox...

News broke the other day about a "face eater" and unprovoked attack that ended in two deaths in Florida. Of course the media jumped all over the possible drug angle. They've asked, could it be flakka? Some have said, yes, he was high on flakka.

Of course they did.

But let's wait for the toxicology analyses to come back. At this point, I seriously doubt any toxicology tests (outside of routine drug screens) have been completed. I'm sure tests will be run for cathinones such as MDPV and alpha-PVP (the supposed ingredient in flakka). Probably NBOMe hallucinogens as well. I'm sure an extensive and comprehensive toxicological analysis will be undertaken.

But, that takes time - this ain't CSI or NCIS.

Let's wait. Not speculate.

Remember the other famous (or infamous) "face eater" Rudy Eugene? Yeah, he wasn't on bath salts. And the media got that wrong from the initial reporting.

So again, let's just wait until the toxicology is reported.

But, if you do want to read more about alpha-PVP, gravel, or flakka, see these links:

5/26/15: Another day, another flakka story
4/14/15: On Flakka, Gravel, and Alpha-PVP
4/25/14: Gravel again
4/24/14: C'mon media, you have to do better...
1/29/2014: Gravel: human sacrifice, dogs and cats living together...mass hysteria?

Wednesday, June 22, 2016

It was only a matter of time...

News reports out of Arizona (12News) state that the DEA has raided a synthetic cannabinoid manufacturing laboratory.

Well, that's not news. It's happened quite a bit over the last several years.

Oh wait...

These folks were mixing synthetic cannabinoids with fentanyl.

This definitely is a way to cause serious harm.

It was only a matter of time.

According to the news report, they manufacturers were preparing the fentanyl and synthetic cannabinoid product in a cement mixer.


If I was in possession of a synthetic cannabinoid containing product in the state of Arizona, I'd throw it away. Now.

To all the people that come into contact with these substances (whether user, law enforcement, first responder, hospital staff, forensic chemists, etc.), be safe.

Officials prepare for the next big drug? It's U-47700.

Here is an article about the possible emergence of the opioid research chemical U-47700 in Iowa.

One quote to which you should pay attention...

"Weber says the new drug contains fentanyl which is a powerful medication."




Though they may be found together in illicitly produced products, U-47700 is not Fentanyl. Fentanyl is not U-47700.

They are two different compounds each with its own distinct chemical structure.

Let's make sure to accurately describe the situation.

Wednesday, June 1, 2016

W-18 is now controlled in Canada.

Health Canada has controlled W-18.

Link is here.

Though, they still say it is an opioid drug and it is 100 times more potent than fentanyl, which we know is not accurate.

Health Canada needs to do better. People, internally and externally, look to the organization for accurate information.

Saturday, May 21, 2016

More on W-18's pharmacology

Another update on Twitter by Dr. Bryan Roth from Roth Lab at UNC - Chapel Hill...

So, no predicted opioid activities again. Only histamine H3 receptor activity. And data will be posted on Bioarchivx sometime this coming week!

Ain't social media great?

Friday, May 20, 2016

W-18 Associated Fatality Reported in Calgary

It was reported today in the Calgary Herald that a 35 year old man was found deceased at a Calgary hotel on March 7, 2016. The death was believed to be drug-related at the time. Law enforcement found drugs, paraphernalia, and a naloxone kit (albeit unusued) on the scene.

The Herald reports that the individual had "heroin, W-18, and 3-methylfentanyl" in his system when he died.

The article gives some "fast facts on W-18". They include:

"The drug is said by police  to be 100 times more potent than fentanyl."

My thoughts?

First, I'm glad I'm not a forensic pathologist. And cause and manner of death is obviously the pathologist's responsibility. It is her call to make.

Second, from a toxicology perspective, I'd be more focused on 3-methylfentanyl (known potent mu opioid receptor agonist) and heroin (prodrug for 6-acetylmorphine and morphine) than the W-18 (at this point). Especially considering what we know about W-18 - that the 10,000 times more potent than morphine and 100 times more potent than fentanyl trope comes from a mouse model writhing assay - and what we officially unofficially know about W-18 - not an opioid receptor agonist.

Interesting article. Still we should be very, very careful on how we talk about W-18. Hysteria and hyperbole is not the way to go. Talk about what we do know. Talk about what we do not know. But misrepresenting facts in not ok. The headline of the article only includes W-18. That is misrepresenting the situation at hand. This is a death that was associated with all three compounds.


Medical examiner confirms city's first fatal W-18 overdose