TL neuro

March 3, 2014

Misuse of Prescription Opioid Medications

Filed under: Drug Overdose, Opiates — mtaffe @ 11:50 am

CDC-allopioidODsThis post will initiate a new conversation on this blog about the detrimental health effects of the non-medical use and misuse of prescription opioid medications such as Oxycontin, Vicodin and Percocet. The overdose death of beloved US actor Phillip Seymour Hoffman recently re-focused attention on prescription drugs. Mr. Hoffman had reported in 2013 that he had relapsed to heroin use subsequent to a prescription drug use episode. This, after a 23 year interval of recovery from drug use in his 20s.
It isn’t made specifically clear that Mr. Hoffman’s 2013 relapse was with prescription opioid analgesics and the autopsy report after his death reported he was taking benzodiazepine medications in addition to heroin. Nevertheless, this case echos a recent trend for an increase in prescription opioid overdoses in the general US population. Data from the CDC (obtained in this case from a NIDA site) show the increase in unintentional overdose deaths from 1999-2008.

Subramaniam-teenadmissionsA meeting report by B.M. Kuehn (2010) illustrates data sourced to G. Subramaniam showing an increase in prescription opioid treatment admissions for adolescents over a similar interval. This trend for adolescents is reflected in broader data reported by the Treatment Episode Data Set for all people 12 and older. This post outlines and graphs the relative increase for prescription opioids which reached 8.6% of all admissions in 2010 following a steady increase from about 1999 onward. In contrast admissions for stimulant treatment were in decline from 2006-2010 and heroin-related admissions were approximately stable from 2000-2010.

There are other data sources available which point to a very clear picture. The extra-medical use and abuse of opioid medications has been growing for nearly 15 years in the US. This has led to clear implications for health, including dependence and overdose deaths. A recent paper by Cicero and colleagues indicates that medications that contain oxycodone and hydrocodone are highly preferred in individuals that are opioid dependent. Recent papers from Mars and colleagues and from Young and Havens show that most young users of heroin had a prior history of extra-medical use of prescription opioids. Thus the downstream impact of prescription opioid misuse may extend to individuals who are no longer using prescription medications as their primary substance of abuse.

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The lab has recently begun a new NIH funded project on prescription opioids: R01 DA035281

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September 5, 2012

A review of deaths associated with 4-methylmethcathinone (mephedrone).

Filed under: 4-MMC/Mephedrone, Cathinones, Drug Overdose — Tags: — mtaffe @ 10:10 am

A new paper reviews a series of fatal cases reported via coroners in the UK which involved suspicion of mephedrone / 4-methylmethcathinone (4-MMC) involvement.

Schifano F, Corkery J, Ghodse AH.J Suspected and Confirmed Fatalities Associated With Mephedrone (4-Methylmethcathinone, “Meow Meow”) in the United Kingdom. Clin Psychopharmacol. 2012 Aug 24. [Epub ahead of print] PubMed

The lead author is a familiar name from similar overviews of MDMA-associated fatalities.

In this new paper, out of 128 reported cases, there were 62 in which 4-MMC was confirmed (no 4-MMC in 25 cases, toxicology was still pending for 13 cases* and apparently inquest forms were unavailable for an additional 7 cases).

As with many surveys of human recreational drug-related fatality the data are messy. Recreational drug users have often been using multiple psychoactive substances that might be expected to be risky themselves, induce multi-drug interactions and to generally complicate interpretation. There is also the reality that the mechanism of death in “drug-related” fatality can vary. This report identifies acute drug toxicity (4-MMC alone or with other drugs) in 26 cases, self-inflicted harm (18 cases), at risk behavior (6 cases) and at-risk sexual behavior** (2 cases).

As best I can tell from the paper, 4-MMC was determined to be the sole cause of death in 8 cases. It is very unclear if this represents what we might view as straight-up drug overdose but this appears to be the case. I.e., this number doesn’t count the risky-behavior part although there is a case to be made that changes in behavior, behavioral inhibition and risky decision making are no less “straight-up overdose” than cardiovascular or other physiological regulatory events.

The paper also identifies 5 cases in which 4-MMC intake was followed by multiple days in the hospital and eventual death (3 cases of multi-organ/liver failure). A further 5 cases involved collapse while attending a party; interestingly high body temperature was confirmed in only one case.

These final observations sound very much like the overall picture for MDMA-related fatality and morbidity.

This is unsurprising given recent neurotoxicological and neurochemical studies indicating a similarity of 4-MMC to MDMA.

Nevertheless, we’ve been finding that the thermoregulatory effect of 4-MMC in rats differs from what would be expected for MDMA. Human fatalities related to MDMA often feature high body temperature (start with the Schifano papers linked above). In rat models, MDMA produces hyperthermia, including to a fatal degree, if the ambient temperature is above about 25 degrees Celsius. We have found no evidence of increased body temperature in rats when dosed with mephedrone at 30 degrees Celsius. This suggests that at least for this particular risk category, 4-MMC may have a lower impact than does MDMA.

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*I think peer review should have insisted they not include these 13, personally. Doesn’t really add to the paper.
**Not specified. At a guess, auto-erotic asphyxiation.

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