Review: liquid nicotine toxicity

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Liquid Nicotine Toxicity. Kim JW, Baum CR. Pediatr Emer Care 2015;31:517-524.


This review of liquid nicotine toxicity is part of the continuing medical education series in Pediatric Emergency Care.

While there are a few good clinical nuggets buried in this review, they are surrounded by so many distracting and unnecessary epidemiological facts that the whole paper — though relatively short — is a chore to read. In addition, some of the “facts” are wrong. For example::

A study found that the proportion of calls that poison control centers received regarding e-cigarettes and cigarette exposures increased from 0.3% in September 2010 to 41.7% in February 2014, 51% of which were in children 0 to 5 years of age.

Anyone editing this piece should have questioned immediately whether it was even remotely possible that 41.7% of all poison center calls involved exposure to cigarettes or e-cigarettes. A quick review of the 2014 MMWR report that is the basis for this claim reveals that, in fact, this is not the case:

Calls about exposures to e-cigarettes . . . now account for 41.7% of combined monthly e-cigarettes and cigarette exposure calls to PCs.

Quite a different statement.

In addition, some of the statements relating to clinical toxicology are in error, or at least questionable. The authors say that “The estimated lethal dose of nicotine is 1 mg/kg.” As I explained in my Emergency Medicine News column on e-cigarette toxicity, that oft-repeated “fact” is based on an anecdotal report going back a century-and-a-half, and has been recently challenged in a paper by Mayer in Archives of Toxicology. Most likely the fatal dose is much higher.

Related posts:

Taste test: would a child find e-cigarette nicotine liquids appealing?

First case report of toxicity from ingestion of e-cigarette nicotine liquid

Calls to poison centers related to nicotine-containing e-cigarette liquid skyrocketing

E-cigarettes: risk of nicotine toxicity

Nicotine liquid fatality — but was it from intravenous injection?

Venlafaxine abuse

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Venlafaxine as the ‘baby ecstasy’? Literature overview and analysis of web-based misusers’ experiences. Francesconi G et al. Hum Psychopharmacol Clin Exp 2015 Jul;30:255-261. 


In 2003, Sattar et al published a case report of venlafaxine abuse in a 38-year-old man. The patient had been prescribed 225-mg extended-release venlafaxine daily. He found that increasing his dose by 50% — to 337.5-mg per day — initially produced a “sudden, amphetamine-like ‘high'” that he did not re-experience even after increasing the dose to 450-mg.

He subsequently discovered that crushing the pills produced greater effects, and he began ingesting up to 3600-mg daily (!) of crushed venlafaxine. After he ingested 4050-mg (!!) of crushed venlafaxine, he developed chest pain that required emergency department evaluation. He had tachycardia and hypertension on presentation, but these resolved and apparently no cardiac issues were identified.

This goal of this current paper was to investigate reports of venlafaxine abuse, both in the medical literature and as described anecdotally on the following websites:

Unfortunately, the 6 case reports the authors found in their literature search are described only vaguely, and the anecdotal reports were, well, anecdotal reports. However, there are some interesting points to be gleaned from the paper:

  • Venlafaxine blocks reuptake of serotonin (5-HT) at low doses (<150 mg/day), 5-HT and norepinephrine (NE) at moderate doses (150-300 mg/day), and 5-HT, NE and dopamine at high doses (>300 mg/day.)
  • The active metabolite desvenlafaxine inhibits the reuptake of NE more than that of 5-HT.
  • Venlafaxine can cause a false-positive test for phencyclidine.
  • Anecdotal online reports suggest that high-dose venlafaxine abuse is associated with manifestations similar to those of MDMA/ecstasy and methamphetamine.

To read my Emergency Medicine News  column on bupropion overdose, click here.

Case series: anxiety and agitation following exposure to the synthetic cannabinoid ADB-PINACA

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A Common Source Outbreak of Severe Delirium Associated with Exposure to the Novel Synthetic Cannabinoid ADB-PINACA. Schwartz MD et al. J Emerg Med 2015 May;48:573-80.


As noted in a recent survey of synthetic cannabinoid exposures in the New England Journal of Medicine, the synthetic cannabinoid (SC) ADB-PINACA was associated with outbreaks in August and September 2013, both in Brunswick GA (22 cases) and Denver CO (> 220 exposures).

This paper reports on 7 cases from the outbreak in Georgia. All patients tested positive for ADB-PINACA or its metabolic ADB-PINACA-5-Pentoic Acid in plasma and/or serum. All patients were agitated and/or anxious. Three patients needed to be intubated for control of these symptoms. One patient, a 30-year-old man,  suffered cardiac arrest but was resuscitated — in this patient, electrocardiogram showed an anterior STEMI. Cardiac catheterization showed total LAD occlusion that was treated with balloon angioplasty.

An additional patient experienced seizure activity :several days” after smoking a synthetic cannabinoid. Drug tests were not available, and because of the time interval between reported exposure and seizures, I was not convinced there was a clear connection. Unfortunately, including this case was confusion and impaired the clarity of the paper.

In one additional case, a 49-year-old DEA agent developed anxiety, chest discomfort, and irritability 1 day after handling a confiscated SC product. He had been wearing latex gloves but had no respiratory protection. His serum tested positive for a low level of ADB-PINACA-5-Pentoic Acid.

The authors point out that previous evidence indicates that ADB-PINACA quickly disappears from the blood, although the metabolite can be present for a longer period of time. Therefore, in cases of significant toxicity following suspected SC exposure, in is important to obtain an early blood sample. The local poison center or public health department can advise of specific testing is needed for epidemiology purposes.

I’d note that the title of this paper appears to be somewhat misleading. Although 3 of the patients described could be said to have had “severe delirium”, it is not clear that the others had anything more than anxiety and mild agitation. Because of this, I marked its score down half a “skull-and-crossbones.”

Related posts:

5F-ADB-PINACA and other extremely potent new synthetic cannabinoids

Serious toxicity and fatalities from synthetic cannabinoids

Death after consuming a marijuana edible

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Death Following Ingestion of an Edible Marijuana Product — Colorado, March 2014. MMWR 2015 July 24;64:771-772.

Full Text

This report describes the investigation by the Colorado Department of Public Health and Environment (CDPHE) into a well-publicized fatality that occurred shortly after recreational marijuana became available in that state.

In March 2014, a 19-year-old man ingested one piece of a marijuana cookie purchased by his 23-year-old friend. (Note: at that time as well as now, the legal age for using marijuana in Colorado was 21.) When he felt no effects after 30-60 minutes, he ingested the remainder of the cookie:

“During the next 2 hours, he reportedly exhibited erratic speech and hostile behaviors. Approximately 3.5 hours after initial ingestion, and 2.5 hours after consuming the remainder of the cookie, he jumped off a fourth floor balcony and died from trauma.”

The CDPHE investigation of this case provides some interesting details that hadn’t been reported previously in media coverage:

  • The deceased teenager had no previous history of drug or alcohol abuse, or mental illness.
  • The cookie content was listed on the label as “65 mg THC/6.5 servings.” The victim initially followed instructions and ate one-sixth of a cookie, but ingested the rest of the total 65 mg shortly thereafter.
  • The victim’s THC level at autopsy (central blood) was 7.2 ng/ml.

There are several things to note in this report. The THC level of 7.2 ng/ml at autopsy (performed 29 hours after death) was surprisingly low — the (rather arbitrary) legal limit for driving in Colorado is 5.0 ng/ml. Since THC undergoes post-mortem redistribution, the level at the time of death might have been even lower than the legal limit. This finding shows that blood THC levels are not good indicators of clinical effect. In addition, when ingested, THC undergoes the hepatic first-pass effect, producing the active metabolite 11-OH-THC, which may be more potent and longer-lasting than THC itself. Because of this — and because when marijuana is ingested it has a prolonged time to peak effect (1-2 hours) and longer duration than when smoked — the effects of marijuana edibles may be substantially different from those experienced after smoking or vaping.

I covered these issues in my Emergency Medicine News column “Four Things Maureen Dowd Should Have Known About Cannabis Before Going to Denver.” To read the column, click here.

5F-ADB-PINACA and other extremely potent new synthetic cannabindoids


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Pharmacology of Indole and Indazole Synthetic Cannabinoid Designer Drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. Banister SD et al. ACS Chem Neurosci 2015 July 17 [Epub ahead of print]


As TPR noted in a recent post, many recently reported cases of severe toxicity or death associated with exposure to synthetic cannabinoids (SCs) involved relatively new and unfamiliar chemicals such as MAB-CHMINACA, AB-PINACA, and ADB-PINACA.

These new compounds incorporate either an indole or an indazole group, and have structured that can be altered seemingly ad infinitum by substituting various halide and organic groups at various sites in the molecules. They are all powerful agonists at CB1 receptors, with a least one agent being more than 1000 times more potent as a CB1 agonist than Δ9-THC itself.

Because not much is known or has been published about these agents, this paper is a welcome addition to the literature about SCs and novel designer drugs, although the material presented concerns issues of synthesis and structure more than clinical presentation and treatment.

I’d recommend this paper to chemical structure geeks, as well as clinicians who have recently seen reference to a number of new SCs with names ending in “ACA’ or “ICA” and want clarification as to exactly what these unfamiliar designer drugs are.

Related post:

Serious toxicity and fatalities from synthetic cannabinoids



Serious toxicity and fatalities from synthetic cannabinoids

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Synthetic Cannabinoid—Related Illnesses and Deaths. Trecki J et al. N Engl J Med 2015 Jul 9;373:103-107.


As the authors point out in this interesting article, there has been a recent surge in reports of fatalities and severe toxicity from synthetic cannabinoids (SCs). This is likely from a combination of increased incidence and more diligent surveillance.

The most interesting part of the paper is the Table, that lists recent cases involving severe toxic effects from SCs, including 20 deaths. The specific SCs involved in the fatal cases include MAB-CHMINACA, AB-PINACA, XLR-11, ADB-PINACA, and AM-2201.

the authors also highlight the difficulties involved in dealing with these new agents, especially the time required to develop specific laboratory tests and the rapidly changing mix of chemicals being marketed as SCs.  Worth reading.

Related posts:

Dramatic recent increase in cases and deaths associated with use of synthetic cannabinoids