Saturday, August 29, 2015

Unintentional exposure to AB-PINACA and more...

This case report from Thornton et al. published in the Annals of Emergency Medicine's most recent issue describes an 10 month old child's unintentional exposure to a synthetic cannabinoid substance.

Thornton, S.L., Akpunonu, P., Glauner, K., Sarah Hoehn, K., Gerona, R. (2015) Unintentional pediatric exposure to a synthetic cannabinoid (AB-PINACA) resulting in coma and intubation, Annals of Emergency Medicine, 66, 343-344.

In summary:
A 10 month old female chewed on a synthetic cannabinoid-containing cigarette and was taken to the emergency department by her mother within thirty minutes of being found. Body temperature was 97.9 F.
Pulse rate 132 beats/minute
Blood pressure was 106/69 mm Hg
Respiratory rate was 34 breaths/minute
Oxygen saturation was 97% on room air.
Normal mental status was documented.

Within 90 minutes, the child's response to verbal and physical stimuli stopped.
The child developed respiratory depression which required intubation.

The child was admitted to the hospital and later tested positive for influenza A.

The child was intubated for 36 hours but recovered fully.

Serum was collected at hospital admission and was analyzed for the presence of drugs  by liquid chromatography with quadrupole time of flight mass spectrometry (LC/qToF). Analysis was positive for the synthetic cannabinoid AB-PINACA (42 ng/mL) and its metabolite AB-PINACA  N-pentanoic acid (345 ng/mL). No other compounds were detected in the toxicological analyses.

In addition to this Annals of Emergency Medicine report, this case appeared in Clinical Toxicology (Philadelphia) journal as part of the proceedings of the annual meeting of the North American Congress on Clinical Toxicology (NACCT). Here is the citation and link:

Thornton et al. (2015) Severe symptoms from an unintentional pediatric exposure to AB-PINACA with laboratory confirmation. Clinical Toxicology, 53, 7: Abstract 184.

We covered a little bit about AB-PINACA here at TDMTP when it was originally placed into Schedule I in December 2014, but as with most new psychoactive substances, at emergence, very little is known about a substance's pharmacological or toxicological profile. But now we do know a little more about AB-PINACA.
In a 2015 paper, Wiley et al. reported that AB-PINACA had binding affinity (Ki) equal to 2.87 nM at the CB1 receptor and 0.88 nM at the CB2 receptor.  EC50 was 71 nM at CB1 and 14.9 nM at CB2 (1). AB-PINACA is considered a high efficacy CB1 and CB2 receptor agonist.
The National Forensic Laboratory Information System (NFLIS) midyear report for 2014 listed AB-PINACA as the 3rd most commonly detected synthetic cannabinoid in drug seizures in the USA. The United States Federal government officially placed AB-PINACA into Schedule I of the Controlled Substances Act in January 2015 (2).
1. Wiley, JL, Marusich, JA, Lefever TW, Antonazzo KG, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: Affinity and potency of novel synthetic cannabinoids in producing delta-9-tetrahydrocannabinoil like effects in mice. Journal of Pharmacology and Experimental Therapeutics. Article in Press, doi: 10.1124/jpet.115.225326
2. Drug Enforcement Administration (2015) Schedules of controlled substances: temporary placement of three synthetic cannabinoids into Schedule I. Final Order. Federal Register. Vol. 80, 5042-5047.

Tuesday, August 4, 2015


Cocaine is a song written by J.J.  Cale in 1976 but made famous when Eric Clapton covered it in 1977 and put it on his 1980 Slowhand album. I enjoy the JJ Cale version better that Clapton's. It's a little more relaxed and chill. But, my favorite cover of the song is from the Canadian glam-rock band Brighton Rock (off their Love Machine album). I'd love to see Halestorm cover this song sometime.

The song is supposedly an anti-drug song. Looking at the lyrics (below), I definitely see that. What do you think?

 J.J. Cale's version of Cocaine from 1976

Eric Clapton's version of Cocaine from 1980
Brighton Rock's version of Cocaine from 1991
If you wanna hang out you've got to take her out.
If you wanna get down, down on the ground.

She don't lie, she don't lie, she don't lie; Cocaine.

If you got bad news, you wanna kick them blues.
When your day is done and you wanna run.

She don't lie, she don't lie, she don't lie; Cocaine.

If your thing is gone and you wanna ride on.
Don't forget this fact, you can't get it back.

She don't lie, she don't lie, she don't lie; Cocaine.
She don't lie, she don't lie, she don't lie; Cocaine.

- Cocaine by J.J. Cale

Sunday, August 2, 2015

Sandra Bland's Toxicology Report: THC

Sandra Bland’s toxicology report was released several days ago. The toxicology laboratory ran a basic "drugs of abuse panel" for several drug classes. The only results reported were blood THC concentration (18±4 ng/mL) and blood THC-COOH concentration (120±27 ng/mL). On a side note, the lab used GC/MS/MS to quantify THC, which is pretty cool to me. We don't see much gas chromatography tandem mass spectrometry in forensic toxicology.

I’m not going to interpret the blood concentration and offer an opinion on the matter because I do not have any additional information about the case. I do not have the facts and do not have a true context in which to place the toxicological findings. Currently, it is difficult to establish a relationship between a person’s THC blood concentration and impairing effects and it is not recommended to try and predict said effects based on blood THC concentrations alone.

But, I read a piece published by neuropsychopharmacologist Dr. Carl Hart, on the matter the other day and I found a few things that need clarified.

In his piece (found here), a few quotes were pretty bold. And a couple that were just wrong. I discuss these below. When I asked for a citation to the general Twitterati regarding Dr. Hart’s statements, Dr. Hart provided me with a citation to a paper by Cooper and Haney titled Comparison of Subjective, Pharmacokinetic, and Physiologic Effects of Marijuana Smoked as Joints and Blunts, published in the journal Drug and Alcohol Dependence. The full text paper can be found here open access.

The paper discusses plasma THC concentrations of subjects smoking marijuana. As mentioned before I’m not entertaining a discussion on actual concentrations or an opinion on the matter, but it is crucial to note the paper discusses THC plasma concentrations. The blood samples collected by the medical examiner were femoral and subclavian blood. They were not plasma. The reported blood to plasma ratio of THC is approximately 0.55 (range is 0.5-0.6). That is to say, blood concentrations should be approximately 55% of what plasma levels will be.

   A THC plasma level at 1 ng/mL is equivalent to 0.3 ng/mL in whole blood.
   A THC plasma level at 5 ng/mL is equivalent to 2.75 ng/mL in whole blood.
   A THC plasma level at 10 ng/mL is equivalent to 5.5 ng/mL in whole blood.
   A THC plasma level at 20 ng/mL is 11 ng/mL in whole blood.

Now, this is postmortem blood. It isn't antemortem blood. But taken at face value, a THC blood concentration of 18 ng/mL would equate to 32.8 ng/mL in plasma.

“Simply put, Waller County officials exaggerated Bland’s THC amounts.”

No, they did not exaggerate the amounts. They did [eventually] release the reports. They reported the correct values that were found. 18±4 ng/mL THC. Now, the interpretation of said results are a completely separate matter.

“Furthermore, the levels are far below the 150 nanograms per milliliter limit set by the World Anti-Doping Agency to indicate marijuana-induced performance alterations.”

The comparison of a postmortem whole blood THC concentration to the World Anti-Doping Agency’s (WADA) mandated THC-carboxylic acid metabolite concentration reporting threshold (150 ng/mL) is illogical and invalid. By doing this, one is not simply comparing apples to oranges. This is comparing apples to cats.

“It is disappointing that the county officials did not require him [Officer Encinia] to provide a urine sample for drug testing…”

It may or may not be protocol to do this. I do not know. But, even if it were, a urine drug test is negligible. It will more than likely provide little-to-no information about what was going on pharmacologically (if anything) in the officer’s body at the time of the traffic stop and eventual arrest. The detection of drugs in urine is typically measured in days. As an example, methamphetamine/amphetamine is detected in urine for approximately 1-5 days after administration. Heroin is detectable in urine as 6-acetylmorphine for up to 18-24 hours and as morphine for 1-4 days after administration. If you want more information on approximate drug detection windows, you can find it here. If one wanted to get a better picture or snapshot of what exactly was going on in the officer’s body at the time of the incident, then blood, not urine, would be the matrix to analyze.

One thing that wasn’t discussed in Dr. Hart’s piece, but I did see discussed in another article (with quotes from forensic toxicologists Dr. Bruce Goldberger and Dr. Nikolas Lemos) was postmortem redistribution (PMR).PMR is a phenomenon that occurs after death when drugs stored in tissues and organs diffuse back into the blood stream. This diffusion can falsely elevate the blood level at autopsy and may not be representative of the drug concentration at the actual time of death. THC can undergo PMR. In a series of 19 deaths, heart:femoral blood concentration ratios average 1.5 (range, 0.3-3.1) for THC. (Holland et al., 2010). In this case, femoral blood was analyzed, so PMR should be minimized, but it still can occur. If resuscitation was attempted (and I do not know if it was), then this could have also played a role in movement of blood from central to peripheral sites or even release of drug from tissues into blood creating a false elevation in blood drug concentration. Did PMR occur in this case? Unless a central blood sample was also analyzed (and quantified) for THC, we’ll never know. But it is something that must be taken into consideration when interpreting the postmortem blood THC concentration.
In postmortem toxicology, the entire case must be considered before offering an opinion on a matter. In the end, Sandra Bland did not die from a THC "overdose" or did not die from "THC intoxication". The blood THC findings do not change the ruled cause of death. All of this is just food for thought and things I thought should be clarified.