Archive for the 'Drug Abuse Science' category

Marijuana Use, Abuse and Dependence Increased Over the Past Decade

Oct 23 2015 Published by under Cannabis, Drug Abuse Science

A new paper from Hasin and colleagues at JAMA Psychiatry reviews data:

from NESARC and from the National Institute on Alcohol Abuse and Alcoholism
2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions–III (NESARC-III), a survey of 36,309 new participants.
The NESARC field procedureswere similar to those in NESARC-III.

There are really three key observations, although the tables also break down the findings by sex, age, race/ethnicity, education level, etc.

First, past year use of marijuana went from 4.1% to 9.5% of the sampled populations. Interesting, but hey, could just be more people feeling free to try it out, right?

Second finding looked at prevalence of meeting DSM-IV criteria for a Marijuana Use Disorder (including Abuse and Dependence subcategories) in the past year. This measure went from 1.5% to 2.9% of the population.

The third finding is that if you condition only upon those individuals who have tried marijuana at least once in the past year, the rate of a Marijuana Use Disorder went from 35.6% to 30.6%.

This is all relevant to a few themes we've discussed before on the blog.

I don't see how you can view these data other than in a context of growing liberalization of medical marijuana laws and availability of marijuana. This refutes the occasional position struck by the pot fans that changes in legal status and attitude won't change use rates because everyone who wants to smoke marijuana already does. Clearly the US population undergoes significant changes in exposure to marijuana. In this case only over a decade.

My position has also been that, in general, as you increase the number of people who are exposed to a given drug you are going to see an increase in problems related to that drug. In the absence of other information, we must start our estimate of that rate from what we observe at a given time. The first two numbers in the study confirm this. As use rates increased, so did rates of meeting criteria for DSM-IV diagnosis of a MUD.

The conditional probability measure also addresses this phenomenon, perhaps in an even better way. I have mentioned before that it is really hard to assess conditional probability of dependence between drugs that feature significant base-rate exposure differences. You can't help but assume there is going to be a curve whereby the more democratic the exposure, the larger will be the occasional user population. That is, I assume some sort of nonlinearity is going to occur against the general estimation I mention above. I presume the lower the incidence of exposure to a given drug, perhaps the higher the conditional probability of dependence and the higher the incidence of exposure, the lower the conditional probability.

In this case, I'd say the change in conditional probability is not that significant. Something around a third of those who smoke marijuana in a given year are meeting criteria for a MUD across a doubling of the incidence of exposure. The curve is still pretty linear although I assume we will be getting another jump in a decade and can see how this curve shapes up.

This estimate of a MUD is really high to my eye, no doubt because it includes abuse and dependence together. Perhaps the data I usually think about (7-9% dependence rate) references dependence without abuse...I have to go check on that. In case you are wondering, the difference really boils down to symptoms of tolerance (diminished effect at same dose, increasing dose to get desired effect) and withdrawal, as well as some indicators of uncontrolled use relative to a person's intentions.

Now interestingly the authors reference another similar study (NSDUH) that didn't find an increase in prevalence that was so large- only 12% reported by Pacek et al, 2015. The present authors suggest more detailed questioning in the NESARC approach may explain the difference.

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Publisher wants to take journal Open Access

Someone forwarded me what appears to be credible evidence that Wiley is considering taking Addiction Biology Open Access.

To the tune of $2,500 per article.

At present this title has no page charges within their standard article size.

This is interesting because Wiley purchased this title quite a while ago at a JIF that was at or below my perception of my field's dump-journal level.

They managed to march the JIF up the ranks and get it into the top position in the ISI Substance Abuse category. This, IMO, then stoked a virtuous cycle in which people submit better and better work there.

At some point in the past few years the journal went from publishing four issues per year to six. And the JIF remains atop the category.

As a business, what would you do? You build up a service until it is in high demand and then you try to cash in, that's what.

Personally I think this will kill the golden goose. It will be a slow process, however, and Wiley will make some money in the mean time.

The question is, do most competitors choose to follow suit? If so, Wiley wins big because authors will eventually have no other option. If the timing is good, Addiction Biology makes money early and then keeps on going as the leader of the pack.

All y'all Open Access wackaloons believe this is inevitable and are solidly behind Wiley's move, no doubt.

I will be fascinated to see how this one plays out.

50 responses so far

Yes, it was the methylone that killed him

Jul 28 2015 Published by under Bath Salts, Cathinone, Drug Abuse Science, Methylone

StructureFig-mdma-vs-cathinones450A new Case Report verifies the lethal potential of methylone (PubMed). This drug is also known as beta-keto-MDMA (bk-MDMA; Wikipedia) or 3,4-methylenedioxycathinone. In short, this is the closest cathinone cousin to MDMA, aka Ecstasy.

Barrios L, Grison-Hernando H, Boels D, Bouquie R, Monteil-Ganiere C, Clement R. Death following ingestion of methylone. Int J Legal Med. 2015 Jun 13. [Epub ahead of print]

The decedent was a 21 year old man reported to ingest methylone and cannabis. Friends placed him in a "nearby children's paddling pool" upon report of breathing difficulty and polypnea (rapid breathing, panting).

By the time emergency medical services made contact he was in cardiac arrest.

Investigators were able to procure a sample of the powder the decedent consumed, represented to him as ecstasy upon purchase.

The toxicological screening was negative for alcohol or "medication", opiates, cocaine and amphetamines (including MDMA, MDA, MBDB and MDEA). This individual was positive for THC. The screening for substances by GC/MS identified a substance with characteristics identical to the seized material which the decedent had ingested- methylone with a purity of 83.3%.

Now admittedly a cardiac arrest with labored breathing is not right down the main line of clinical findings in MDMA overdose cases. So this is a bit strange. However, "sudden collapse" or "found unresponsive" is not atypical as the triggering observation that the person on MDMA is in trouble. There are also numerous studies showing adverse effects on MDMA on aspects of cardiac function. Similarly, cardiac implications are common with methamphetamine-related deaths- both acutely and apparently as a consequence of longer term use.

So there is every reason to think that methylone might be cardiotoxic.

The finding of cardiac arrest triggered a vague memory and luckily these authors cited the paper I was remembering:

Carbone PN, Carbone DL, Carstairs SD, Luzi SA. Sudden cardiac death associated with methylone use. Am J Forensic Med Pathol. 2013 Mar;34(1):26-8. doi: 10.1097/PAF.0b013e31827ab5da.

Now in this case a 19 year old man collapsed while jogging and had a much lower blood level of methylone (0.007 mg/L) compared with the 6.64 mg/L blood levels in the Case reported by Barrios et al. No other drugs were detected, however:

No other drugs were detected in the urine or central blood, including pseudoephedrine, ephedrine, amphetamine, methamphetamine, MDMA, 3,4-methylenedioxyamphetamine, phenylpropanolamine, or cocaine and metabolites. Analysis was also negative for several other bath salts including flephedrone, n-ethylcathinone, mephedrone, methedrone, ethylone, butylone, MDPV, and naphyrone.

This was presumably not an effect of acute overdose intoxication but perhaps a lingering effect on heart function caused by the methylone consumed hours before. Hard to know without controlled studies, particularly given the exercise this person was engaged in.

Nevertheless, this new Case Report serves as a reminder that methylone, which is increasingly replacing MDMA in the US market, represents a risk for immediate and lasting adverse health consequences.
Related Reading:

It was the methylone that killed him.

Methylone, or beta-keto-MDMA, also causes fatality

Various posts on MDMA-related fatality and morbidity

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The Daily Show is just plain wrong on pot being non-addictive

Apr 21 2015 Published by under Alleged Profession, Cannabis, Drug Abuse Science

In the 420 bit from this week, Jessica Williams asserts that marijuana is "a non-addictive proven medical treatment".

Marijuana is most certainly addictive.

In 2012, 17.5% of all substance abuse treatment admissions had marijuana as their primary abused drug. Alcohol alone was 21.5%, heroin 16.3% and cocaine 6.9%.

Daily marijuana smokers use 3 times a day on average and have little variability from day to day.

Pregnant women are unwilling or unable to stop smoking pot almost daily. Increasing numbers of pregnant women are seeking help to discontinue pot use.

At least one woman found out her hyperemesis during pregnancy was the pot, not morning sickness.

Marijuana is addictive in adolescents.

When adolescents stop smoking weed, their memory gets better.

About six percent of High School seniors are smoking pot almost every day.

Clinical trials of medications to help people who are addicted to marijuana stop using are far from rare.

Francophones are addicted to pot.

Yes, Dutch people are addicted to pot.

Many Cases of cannabis hyperemesis syndrome are unable to stop smoking pot, even though it is severely incapacitating them.

Marijuana is addictive.

About 37% of frequent pot users will transition to dependence in three years.

Oh, and pot users are not awesome, friendly and mellow, actually nondependent users are impulsive and hostile on the day they use pot compared with nonsmoking days.

57 responses so far

FLAKKA! (and other failures of the alleged profession of journalism)

Apr 20 2015 Published by under alpha-PVP, Bath Salts, Cathinone, Drug Abuse Science

Flakka is just the latest in a long line of stimulant drugs that can, in some very rare cases, result in astonishing public behavior.

Such as running nude through the streets to escape "unknown people trying to kill him".

Such as trying to kick in the door of a police station to get IN so as to escape cars that were supposedly chasing him.

Such as trying to shoot oneself on a rooftop, naked.

Such as trying to have carnal relations with a tree after proclaiming oneself to be Thor.

These stories are like crack to the mainstream media. They have been telling these stories for years, encompassing public scares over PCP, crack cocaine and methamphetamine over the decades past. More recently we've seen these types of stories about synthetic cathinones, in particular under the generic term "bath salts".

Sprinkled amongst the stories about classical psychomotor stimulant effects, we have stories of overdose involving synthetic opioids, MDMA and/or Molly and stories of adverse psychotropic effects of synthetic cannabinoid products. I've addressed some of these issues in prior posts and for today I want to discuss the stimulants of more traditional effect.

My greatest frustration with the reporting is not actually the breathless sensationalism, although that runs a close second. The biggest problem is the lack of verification of the bizarre behavior (or overdose) being associated with ingestion of the drug that is alleged in the initial reporting. I have not see one single verification of alpha-PVP in the body tissues of these recent Florida cases where the subjects reported consuming Flakka. We still do not know exactly what drugs were consumed by the 11 Wesleyan University students who became ill enough to hospitalize. We don't know what caused the death of Kimchi Truong at last year's Coachella music festival.

Oftentimes there are multiple media reports which, to their credit, mention that toxicology testing will take some weeks to verify. And yet. Rarely is there ever a follow-up accounting. And when there is a followup, well, it gets very poor penetration and people often parrot the wrong information even years later.

The Florida Causeway Cannibal is a case in point. At the time of the initial event it was almost universally reported to be due to "bath salts", i.e. MDPV. Toxicology reporting found no sign of any synthetic cathinone in Mr. Eugene.

It is long past time for us to hold the media as accountable for accuracy and followup on drug-related stories as we do for, say, sports reporting.

Now, there are a couple of bright lights in this generally dismal area of news reporting. Here's a local story that reported MDA, not MDMA, was at blame for a death (although they still screw up, MDA is not a "parent" drug of MDMA). In 2013 there was followup in three music festival deaths in New York to confirm MDMA, methylone and the combination of the two caused the three fatalities. We need this kind of attention paid to all of these cases.

Getting back to the current media storm over "Flakka", which is alpha-pyrrolidinopentiophenone (alpha-PVP), I have a few links for you if you are interested in additional reading on this drug.

@forensictoxguy posted a list of scientific papers on alpha-PVP at The Dose Makes the Poison blog. It is not a very long list at present! (Marusich et al, 2014 is probably the place to start your reading.)

The Dose Makes the Poison discussed alpha-PVP back in early 2014....this is not a new 2015 drug by any means.

Michael Taffe from The Scripps Research Institute [PubMed; Lab Site] gives a preview of a paper in press showing alpha-PVP and MDPV are pretty similar to each other in rat self-administration.

There was also a post on the Taffe blog suggesting that alpha-PVP samples submitted to were more consistently pure than MDPV and some other street drugs.

Wikipedia, NIDA brief

Jacob Sullum has written a pretty good Opinion piece at Forbes Fear Of Flakka: Anti-Drug Hysteria Validates Itself.

Review of the above information will help you to assess claims in the media that Flakka is "[insert more addictive, more dangerous, more powerful, worse] than [insert bath salts, MDPV, methamphetamine, cocaine]".

tldr; It isn't.

It will also assist you in coming to an understanding that Flakka is likely to be just as addictive and problematic as these previously sensationalized stimulants.

tldr; It is.

In my view, the scope of the Flakka problem over the coming years will be dictated by user popularity and availability, and not by anything particularly unique about the molecular structure of alpha-PVP.

24 responses so far

Why PMA if dealers don't want to kill their clients?

Mar 13 2015 Published by under MDMA

There's an interesting piece on Ecstasy in Mixmag that addresses something that is a side issue of the MDMA overdose issue that I've talked about on the blog. These issues bubble up to our conscious consideration every time there is a mysterious Ecstasy-related cluster of adverse events such as at Wesleyan University. Until there is confirmation of the drug(s) involved from toxicological testing we can only speculate as to the cause of the events.

Even though we know that MDMA itself is always a top suspect, PMA, (para-Methoxyamphetamine), is a fine Usual Suspect of a non-MDMA substance sold to users as "Ecstasy" but resulting in adverse consequences.

The Mixmag piece reminds us of the MDMA drought in the UK that launched mephedrone into the recreational pharmacopeia.

One of the easiest ways to make MDMA is to use an essential oil called safrole, which occurs naturally in the roots and bark of the yellow camphor tree, found in Cambodian rainforests and elsewhere. The UN has targeted the trade repeatedly in the last decade, with the noble aims of protecting the rainforest, which is being chopped down by the gangs that steam-distil the oil out of the bark in giant, bubbling cauldrons in jungle labs. The UN burned 33 tonnes of it in 2008, which caused a worldwide drought of MDMA and the emergence of mephedrone as both gangsters and clubbers looked for alternatives. In September 2010, 50 tonnes were burned in Thailand.

Yep, we recall.

However, this previous preferred-method for synthesizing MDMA leads on to the reason why PMA is sometimes pushed out on the market for consumers to use, unsuspectingly in many cases. Mixmag proposes this hypothesis:

PMA is made from an oil called anethole, which is legal, cheap, and easy to get hold of.

Professor David Nutt agrees that the likely scenario is that clandestine chemists use anethole in a trial run, to test new lab set-ups, and then sell the resulting PMA to unscrupulous pill pressers. Making PMA involves an identical set of chemical reactions to making MDMA – only the precursor is different. Think about it: if you had a limited amount of very expensive safrole or PMK, and you had a new lab, or a new chemist, you’d want to test your kit out. A trial run making PMA from anethole would help you practice the technique and avoid losing valuable precursors – and you’d make some money back.

They then ask any chemists reading to confirm so one must take this as speculation rather than journalistically confirmed with clandestine labs.

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Health report from Colorado: Recreational marijuana harms

Dec 15 2014 Published by under Cannabis, Drug Abuse Science

a Reader put me onto a new Viewpoint in JAMA:

Monte AA, Zane RD, Heard KJ. The Implications of Marijuana Legalization in Colorado.JAMA. 2014 Dec 8. doi: 10.1001/jama.2014.17057. [Epub ahead of print][JAMA; PubMed]

The authors are from the Department of Emergency Medicine, University of Colorado and the Rocky Mountain Poison and Drug Center. They set out to describe a few health stats from before and after the recreational legalization of marijuana.

Interesting tidbits:

However, there has been an increase in visits for pure marijuana intoxication. These were previously a rare occurrence, but even this increase is difficult to quantify. Patients may present to emergency departments (EDs) with anxiety, panic attacks, public intoxication, vomiting, or other nonspecific symptoms precipitated by marijuana use. The University of Colorado ED sees approximately 2000 patients per week; each week, an estimated 1 to 2 patients present solely for marijuana intoxication and another 10 to 15 for marijuana-associated illnesses.

This one is obviously frustratingly anecdotal in that there is no real measure of the rate before legalization.

The one on cyclic vomiting syndrome is better:

The frequent use of high THC concentration products can lead to a cyclic vomiting syndrome. Patients present with severe abdominal pain, vomiting, and diaphoresis; they often report relief with hot showers. A small study at 2 Denver-area hospitals revealed an increase in cyclic vomiting presentations from 41 per 113 262 ED visits to 87 per 125 095 ED visits (prevalence ratio, 1.92) after medical marijuana liberalization (A. A. Monte, MD, unpublished data, December 2014).

We've discussed the phenomenon of cannabis hyperemesis before on the blog. One thing we do have to be careful about is that since it has only been recently that the medical community has been alerted to the possibility of cannabis hyperemesis, we should expect the detection rate to increase. Thus, even against a stable rate of cannabis hyperemesis I would expect the reported rate to be increasing.

The University of Colorado burn center has experienced a substantial increase in the number of marijuana-related burns. In the past 2 years, the burn center has had 31 admissions for marijuana-related burns; some cases involve more than 70% of body surface area and 21 required skin grafting. The majority of these were flash burns that occurred during THC extraction from marijuana plants using butane as a solvent.

This is the e-cigarette and vape market at work people. In South Florida they apparently call it 'Budda'.

Apparently some basic pharmacology 101 would be of help to the good citizens of Colorado.

Edible products are responsible for the majority of health care visits due to marijuana intoxication for all ages. This is likely due to failure of adult users to appreciate the delayed effects of ingestion compared with inhalation. Prolonged absorption complicates dosing, manufacturing inconsistencies lead to dose variability

Interesting. I recall the language in the original initiative was very vague about product testing, labeling, etc. Looks like this is a problem.

Ten to 30 mg of THC is recommended for intoxication depending on the experience of the user; each package, whether it is a single cookie or a package of gummy bears, theoretically contains 100 mg of THC. Because many find it difficult to eat a tenth of a cookie, unintentional overdosing is common. Furthermore, manufacturing practices for marijuana edible products are not standardized. This results in edible products with inconsistent THC concentrations, further complicating dosing for users. According to a report in the Denver Post, products described as containing 100 mg of THC actually contained from 0 to 146 mg of THC.8

Oh, and the children. Don't forget about the children.

The most concerning health effects have been among children. The number of children evaluated in the ED for unintentional marijuana ingestion at the Children’s Hospital of Colorado increased from 0 in the 5 years preceding liberalization to 14 in the 2 years after medical liberalization.3 This number has increased further since legalization; as of September 2014, 14 children had been admitted to the hospital this year, and 7 of these were admitted to the intensive care unit. The vast majority of intensive care admissions were related to ingestion of edible THC products.

This Viewpoint certainly draws attention to the edibles/consumables products as being a problem. Seems pretty clear that maturation of product regulation would be a start, so that people are informed about what they are getting. This should probably be supplemented with some sort of public information campaign on the pharmacokinetics of ingested products compared with smoking marijuana. And, you know, keep it away from your kids.

13 responses so far

Szalavitz on marijuana addiction

Oct 15 2014 Published by under Cannabis, Cocaine, Drug Abuse Science

If I'm going to bash a journalist when she writes something horrible about drug abuse, I must take pains to congratulate her when she writes something pretty good.

Maia Szalavitz' latest "Of course Marijuana addiction exists and it's (almost) all in your head" is actually not bad.
Continue Reading »

4 responses so far

Repost: The War on Drugs Didn't Work, Eh?

Sep 02 2014 Published by under Cannabis, Drug Abuse Science, Public Health

There's a strawman-tilting screed up over at from my current favorite anti-drug-war-warrior Maia Szalavitz. She's trying to assert that Trying to Scare Teens Away From Drugs Doesn’t Work.

In this she cites a few outcome studies of interventions that last over relatively short periods of time and address relatively small populations. I think the most truthful thing in her article is probably contained in this quote:

Another study, which used more reliable state data from the CDC’s Youth Risk Behavior Survey, concluded that “When accounting for a preexisting downward trend in meth use, effects [of the Montana Meth Project] on meth use are statistically indistinguishable from zero.”

This points out the difficulty in determining broad, population based outcomes from either personal introspection (where a lot of the suspicion about anti-drug messaging comes from, let's face it) or rather limited interventions. Our public policy goals are broad- we want to affect entire national populations...or at least state populations. In my view, we need to examine when broad national popular behavior shifted, if it did, if we want to understand how to affect it in the future.

The following originally appeared 21 July 2008.

If you are a reader of my posts on drug abuse science you will have noticed that it rarely takes long for a commenter or three to opine some version of "The (US) War on Drugs is a complete and utter failure". Similarly, while Big Eddie mostly comments on the liberty aspects (rather than the effectiveness) of the WoD himself, a commenter to his posts will usually weigh in, commenting to a similar effect.

Now I'm open to all the arguments about personal liberty trade offs, economic costs, sentencing disparities, violations of other sovereign nations and the like. Nevertheless, I'm most interested in the fundamental question of whether the War on Drugs worked. That is, to reduce drug use in the US. For those who believe it has not worked, I have a few figures I would like explained to me.

Continue Reading »

10 responses so far

Insinuations, misdirections, straw arguments and obsfucation in drug abuse journalism

Jul 18 2014 Published by under Drug Abuse Science, Public Health

Maia Szalavitz has penned a new article on addiction that has been circulated, credulously and uncritically, on social media by people who should know better. So, once more, into the breech, Dear Reader.

The article in question is Most of Us Still Don't Get It: Addiction is a Learning Disorder is posted at

We can start with the sub-header:

Addiction is not about our brains being "hijacked" by drugs or experiences—it's about learned patterns of behavior. Our inability to understand this leads to no end of absurdities.

From whence comes learning if not from experiences? And what is the ingestion of a psychoactive drug if not an experience? She is making no sense here. The second sentence is pure straw-man, particularly when you read the entire piece and see that her target is science, scientists and the informed public rather than the disengaged naive reader.

Academic scientists focused on drug abuse have talked about the learning aspect, of habits and of the lasting consequences of drug experiences since forever. This is not in the least little bit unknown or novel.
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