A case of death caused by abuse of a synthetic cannabinoid N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide
Sasaki C, Saito T, Shinozuka T, Irie W, Murakami C, Maeda K, Nakamura N, Oishi M, Nakamura S, Kurihara K
Forensic Toxicology (2014) DOI 10.1007/S11419-014-0246-5
This case was
reported out of the Department of Legal Medicine, Kitasato University School of
Medicine; the Department of Emergency and Critical Care Medicine, Tokai University
School of Medicine; and the Department of Pathophysiology, Yokohama College of
Pharmacy in Japan. The report describes a death associated with the synthetic
cannabinoid is also known as NNEI and is an indole carboxamide structural
variant. NNEI is compared to other synthetic cannabinoid structures
A male (age was
described as “in his twenties”) was found deceased on the floor in his bedroom.
A package of “Fairy Evolution” herbal product was found in the vicinity. No
medical history was known.
The Fairy Evolution herbal
product was tested and NNEI was the only substance detected.
analyses were undertaken. Plasma, whole blood, urine, brain, heart, lung,
liver, kidney, hair, and adipose tissue were analyzed. Femoral blood
concentrations were 0.99 and 0.84 ng/mL (right and left vein respectively).
NNEI was detected in all specimens analyzed, except urine. No other drugs or
metabolites were detected in any biological specimens. Disposition of drug is discussed in the paper.
was detected at autopsy. The total weight of the lungs was 1,750 grams. Organs
showed considerable congestion.
Arteriolar wall hypertrophy, slight
interstitial fibrosis and contraction bands were detected in the heart.
congestion and alveolar macrophage infiltrations were observed in the lungs.
Slight lymphocytic infiltrations were observed in liver.
hyalinization and severe splenic congestion was observed.
were observed in the corpus callosum in the brain.
No other remarkable findings
determined cause of death to be associated NNEI and concluded that the acute
circulatory disturbance to be induced by “NNEI poisoning”. Manner of death was not disclosed in the
paper, but my assumption is that it would be accidental or undetermined.
It is interesting to note that New Zealand preemptively banned NNEI from the market in 2012 due to the hypothesized formation of possible carcinogenic metabolites. It was hypothesized that the amide linkage could be hydrolyzed by carboxylesterases resulting in formation of 1-aminonaphthalene, a known carcinogenic substance. This was previously covered here. It has now been shown in in vitro experiments published by Thomsen et al. that carboxylesterase 1 (CES1) is the major hepatic and pulmonary enzyme that is responsible for the amide hydrolysis during metabolism of the indazole carboxamide synthetic cannabinoids AB-FUBINACA and AB-PINACA. As you can see from the structure representation above, AB-PINACA and NNEI share this same amide linkage. It is logical that NNEI would be metabolized via the same pathway.
Ultimately, I am ecstatic that we have seen a few papers published lately that describe case history + pathology/physical findings at autopsy + toxicology findings and analytical confirmation of substance.