Archive for the 'Drug Abuse Science' category

Hyperemesis associated with synthetic cannabinoid products

Mar 07 2014 Published by under Cannabis, Drug Abuse Science

As you know, Dear Reader, a cyclical vomiting syndrome is often associated with chronic cannabis smoking. I've written about it a few more times (here, here, here) and you can check out additional posts at Addiction Inbox (here, here). I urge you to read through the comments posted under all of these blog entries. The numbers definitely rival the published Case Reports in number of affected individuals. Clearly there continues to be many folks suffering who go initially undiagnosed.

A Reader sent me a link to a medical diagnosis challenge published in the Well section of the New York Times recently which returned my interest to the topic. Mostly due to the following comment in the solution column:

Sure enough, there it was – two recent case reports describing several regular synthetic marijuana users who developed a syndrome that was indistinguishable from cannabinoid hyperemesis caused by the real stuff.

I had not seen any such reports so I went looking and found one of them on PubMed.

Hopkins CY, Gilchrist BL. A case of cannabinoid hyperemesis syndrome caused by synthetic cannabinoids. J Emerg Med. 2013 Oct;45(4):544-6. doi: 10.1016/j.jemermed.2012.11.034. Epub 2013 Jul 26.

By now, the diagnosis sounds very familiar. A 30 year old man presented at the ED with nausea and vomiting. He reported a prior history of such episodes, including gastro-enterology workups, scans, endoscopies, etc. Nothing that would explain his symptoms was ever found. The patient had found that hot showers relieved his pain and took several showers per day.

Naturally the patient had started using cannabis at the age of 13 and had been smoking several times per day for years.

Up until this point, everything is very familiar.

This particular individual had been cannabis free for 6 months due to legal surveillance under parole. After cleverly determining with over-the-counter tests that synthetic marijuana products (brand names of K2 and Spice were popular early in the cycle and have come to be familiar as semi-generic terms) didn't trigger cannabinoid positives:

...he quickly resumed his daily smoking habits and in the month before presentation was often smoking synthetic marijuana hourly, including waking up several times at night to get high.

The patient claimed that in the 2 months prior to presentation he'd been using "Scooby Snacks (sic)*" brand exclusively and provided some to the research team. This is cool because the team identified the cannabinoids in the product. It contained several, "JWH-018, JWH-073, JWH-122, AM-
2201, and AM-694" and they also found the patient's urine to be positive for JWH-018, JWH-073 and AM-2201.

As a bit of a sidebar, I really don't know why particular combinations are included in various synthetic cannabis products. It is unclear if it is accident of supply, illicit manufacturers who just throw stuff together at random, the end of the batches or something more intentional. There is an interesting paper from the Fantegrossi group (Brents et al, 2013) that suggests the possibility of synergistic effects.

Returning to the case report, on three month followup it was found the patient manged to remain abstinent and reported remission of his symptoms after the first 2 weeks.

Okay, so typical story for cannabinoid hyperemesis syndrome and in this case the patient had been exposed to multiple cannabinoid full agonists instead of delta-9-tetrahydrocannabinol prior to current episode. Of course his history suggests strongly that it was cannabis smoking that created his liability for the episodes in the first place.

One take-away message over the past several years is that we've rapidly gone from a point where nobody knows cannabis can cause a vomiting syndrome to some reasonable awareness. This is fantastic. The greater awareness, the greater the chances of rapid and accurate diagnosis. If you read the case reports you will see extensive and expensive gastrointestinal testing and diagnostic work in the history of many individual patients. Realization on the part of the patients that they should mention their cannabis smoking helps. Realization on the part of medical staff that they should ask about cannabis helps.

Knowledge can be a powerful bit of assistance for health care.

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*more likely Scooby Snax?

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Drivers are unsafe at any Blood Alcohol Concentration?

Jan 22 2014 Published by under Alcohol, Drug Abuse Science, Drug Fatality

A reasonably provocative paper which suggests that automobile drivers are impaired at a blood alcohol concentration (BAC) as low as 0.01% has recently appeared.

Phillips DP, Sousa AL, Moshfegh RT. Official blame for drivers with very low blood alcohol content: there is no safe combination of drinking and driving.Inj Prev. 2014 Jan 7. doi: 10.1136/injuryprev-2013-040925. [Epub ahead of print][Pubmed][Publisher]

When I was first told of this finding, my initial curiosity was not so much about the findings but more about the design. It is incredibly difficult to come up with ways to compare drinking driver versus non-drinking driver stats in field studies or data mining retrospectives.

The authors drew data from US traffic fatalities1 recorded in the National Center for Health Statistics database and the Fatality Analysis Reporting System database. The study sought to test the hypothesis that driver BAC would be related to the driver being determined to be solely and officially at blame for the crash. There are numerous factors that were coded for drivers including "under the influence of alcohol, drugs or medication" and "driving on wrong side of the road". The "under the influence..." factor was dropped from all analyses for the obvious reasons that it would contaminate their test of hypothesis.

This is important for the reader to grapple with his or her most obvious complaint about this design. If the police officer is determining the responsibility and can smell (or otherwise detect) alcohol on one driver, this puts a bias in the outcome measure (responsibility for the crash) that would tend to correlate with the thing being tested (BAC). So the authors focused on the factors that were seemingly unambiguous. Such as "running off road" or "driving wrong way on one-way" versus "unsafe speed for conditions" and other ambiguous factors that depend on a police judgement.

The authors calculated the Sole Official Blame (SOB) as the number of drivers officially and solely blamed for the crash divided by the number of drivers officially assigned no blame for the crash. They also calculated the percentage of drivers blamed solely and officially for the crash divided by the total number of drivers involved. Phillips14-traffic-F1Figure 1 from the paper presents the SOB by the BAC for both male and female drivers. The solid line is the "All Blame Factors" and the dotted line is for the unambiguous factors- the far better measure2, IMO. These data do make a case that fatal crash risk is an essentially linear function of BAC. Importantly, there is no inflection of the curve at either 0.08 or 0.1 BAC which have been the US legal limits during my driving lifetime. The error bars are 95% confidence intervals and they are using lack of overlap of the 95% CI as their inferential statistic indicating a significant difference (they also include a chi-square statistic for the 0.1 BAC vs sober bin). So far, so good. BAC is linearly correlated with the risk of being the sole and officially blamed driver for a fatal accident. [UPDATE: I didn't originally catch a bit of a dodge the authors are pulling here. The inferential analyses are conducted on the "all blame factors. Then they state "these patterns hold when one considered all blame factors or unambiguous factors". This "pattern" language is sometimes used to skip over the fact that the inferential analysis didn't hold up on the other variable(s). This is a big problem, given my questions about the contamination of the blame issue if the officer knows one driver had been drinking alcohol.]

An interesting side-analysis looked at the problem that BAC is not always measured which could introduce a bias. I'm assuming that the first analysis used only verified negative BAC "sober" drivers but it is hard to find this directly stated. Anyway, they looked at the correlation on a state-by-state basis between the SOB "buzzed", aka 0.1 BAC and SOB sober (which was 2.09 for the overall dataset), and the percent of unmeasured BACs in the fatal crash listing. The correlation was negative, showing that the lower the proportion of unmeasured BACs in a state, the larger the difference between sober and 0.1% BAC drivers in fatal crash responsibility. So if anything, I guess we have to assume that a lower percentage of blood testing results in an underestimate of the crash risk.

The authors next moved on to take a crack at the question of circumstances. In essence it addressed the question of whether people driving at 0.1% BAC are doing so under risky circumstances. At night, for example.
Phillips14-traffic-F3The third Figure from the paper depicts SOB ratio and the Percent Blamed for a subset of two-car crash pairings in which one driver was sober and the other was at a positive BAC. The beauty here is that nondriver circumstances are as identical as you can get for the sober and intoxicated drivers. The authors performed 16 chi-square tests but a quick multiple-comparisons adjustment to the listed p values shows they still survive as all of them being different, BAC vs sober, for SOB and P measures. Odds of being at fault are 60/40 for 0.1% BAC versus sober and about 80/20 by the time you reach two car crashes in which one driver was at 0.08% BAC. Interestingly this is the analysis that appears to show some categorical difference between BAC of 0.1-0.3% and BAC of 0.6-0.8%. They also did a cute little comparison of paired-crashes where one driver was at 0.08 and the other was 0.5-0.7 BAC. The SOB did not differ (95% CI overlap) in this analysis.

As a final note, a bunch of supplementary analyses were provided to try to rule in or out additional driver (sex, race), vehicle (speed and model year) and circumstantial (raining, time, location) factors. The relationship of SOB with BAC persisted.

Probably my largest question about traffic risks conferred by low levels of alcohol consumption is captured by the report of the relative effect size of the "most common driver factors" in Table 1. The "Driving too fast for conditions or in excess of the posted speed limit" factor is a large contributor to SOB ratio in the 0.1-0.7%BAC drivers as well as one of the larger differences from the sober drivers. This underlines a suspicion that those who are willing to drive after a low amount of alcohol consumed are perhaps innately different from those who are not. They might be somewhat more of a risk taker. Here, we'd really want to get at the population that is willing to drive after a drink or two and look at their driving crash risk when they are sober. Methodologically, this is asking for a lot, I realize.

This is only one study, of course. There may be other data out there that show a less continuous function of fatal crash risk to BAC in this range below the current US legal limit. But this is for sure an important study.

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1authors say that there is no sufficiently detailed database for nonfatal crashes, sady.

2Still trying to wrap my head around whether these "unambiguous" factors are in fact uncontaminated by the police officer's knowledge that one of the drivers had been drinking. Presumably they write up their reports somewhat after they have investigated. Maybe I'm searching for rigor where none is needed but it still bugs me.

4 responses so far

The Return of Does the Legal Status of Recreational Drugs Influence Your Use?

Dec 19 2013 Published by under Drug Abuse Science, Poll

I last did this poll in 2009 on the old Sb version of the blog. My readership has changed, medical marijuana has marched on and, most importantly, two US states have finally legalized recreational use of marijuana. A comment on a recent post reminded me of this.

Grumble asked:

I'm not sure why the "how much did usage change" question would be interesting at all. Can't we just say "of course usage will go up, duh?"

and I replied:

there is a species of denialist cannabis fan (we get them around here now and again) that insists that full legalization will do nothing to use rates. Their rationale is that pot is so easy to get that anyone who wants to smoke pot already does. I counter with the idea that they are biased by their subculture and proffer the counter example of *my* subcultures of interest in which there are tons of people for whom the only reason they do *not* smoke weed, on the odd occasion, is the legal status.

Well, what do you think?

Have at it peeps!

27 responses so far

Marijuana use rates in 12-17 year olds is highest in medical marijuana states

Dec 18 2013 Published by under Cannabis, Drug Abuse Science

The ONDCP twitter account just posted a very interesting graph on past-month marijuana use rates in the 12-17 year old adolescent population.
TeenMJbyState

This dovetails very nicely with a factoid being twittered today in the #MTF2013 hashtag which is covering the release of the mid-term data from the Monitoring the Future project.

this actually surprised me. That it was so low.

Of course, one's first suspicion is that states which are liberal enough to pass medical marijuana laws might have adolescent populations that are more likely to smoke marijuana anyway, i.e., regardless of the medical legalization. Be nice to see a workup on teen marijuana use in these states before and after they legalized medical marijuana.

8 responses so far

RIP Professor Nancy K. Mello, PhD

Dec 02 2013 Published by under CPDD, Drug Abuse Science, Obituary

Another legendary figure of substance abuse research has passed away.

Nancy K. Mello was a Professor of Psychology in the Department of Psychiatry at McLean Hospital. Her work spanned across a broad range of psychoactive and/or addictive substances with a focus on treatment medications in the recent years [PubMed].

According to the Obituary in the Boston Globe:

With her husband, Dr. Jack H. Mendelson, she cofounded the Alcohol and Drug Abuse Research Center at McLean Hospital in 1974, and they became leading researchers in the field of substance abuse.

“Their findings on loss of control and mood dysfunction as a result of drinking by alcoholics not only revolutionized scientific understanding of alcoholic drinking behavior, it also stimulated a new generation of behavioral and psychological researchers to apply experimental models to the study of alcoholism,” Dr. Roger Weiss, chief of McLean’s division of alcohol and drug abuse, said in a prepared statement.

Dr. Mello, who was director of McLean’s Alcohol and Drug Abuse Research Center and also taught at Harvard Medical School, died Monday, the hospital said. She was 78; other details, such as the cause of death, were not immediately available.

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Transitioning to cannabis dependence

Nov 04 2013 Published by under Cannabis, Drug Abuse Science

The conditional probability of dependence on a given drug is a question that is of substantial interest to users, parents of users, public policy makers and heath care providers. After all, if people simply stopped using a drug once a problem arises then many of the negative effects could be avoided. There is a fair degree of correlation between meeting diagnostic criteria for dependence and someone failing to stop using a drug despite clear and growing negative consequences. (Indeed this is one of the dependence criteria). Therefore, we must consider dependence to be a target of substantial interest.

It can be difficult to estimate the conditional probability of dependence in humans because we mostly have cross-sectional data to work with. And so we must infer conditional probability from dividing the currently dependent population by some denominator. Depending on what one uses for the denominator, this estimate can vary. Obviously you would like some population that uses the substance but what represents a level of "use" that is relevant? One time ever? Use in the past 12 months? Use in the past 30 days?

A new paper by van der Pol and colleagues uses a prospective design to provide additional data on this question.

The authors recruited 600 frequent cannabis users, aged 18-30, and assessed them for cannabis dependence at start, after 18 months and after 36 months using the:

Composite International Diagnostic Interview (CIDI) version 3.0 (Kessler and Ustun, 2004), and required the presence of three or more of seven symptoms within the 12-month period since the previous interview (without requiring the presence of all symptoms at the same time). It should be noted that the CIDI includes a withdrawal symptom, which is not included in the DSV-IV manual.

The study defined "frequent" use as 3 or more times per week for 12 months or more. This is important to remember when trying to assess the conditional probability. It all depends on what you construe as an at-risk population. Here, I'd say these were already rather confirmed cannabis fans.

The authors were interested in the very first incidence of dependence and so therefore excluded subjects who had ever met criteria, this left 269 subjects at intake (retention in the study left N=216 at 18 mo and N=199 at 36 mo). This is another point of interest to me and affects our estimation. Three or more times per week for 12 months or more and 45% of them had never previously met criteria for dependence. There are two ways to look at this. First, the fact that a lot of similarly screened users had already met criteria for dependence suggest that this remaining population was at high risk, merely waiting for the shoe to drop. Conversely it might be the case that these were the resistant individuals. The ones who were in some way buffered from the development of dependence. Can't really tell from this design....it would be nice to see similar studies with various levels of prior cannabis use.

There were 73 cases of cannabis dependence of the 199 individuals who were followed all the way to 36 months, representing a conditional probability of transitioning to dependence of 36.7% within 3 years.

Now, of course the authors were interested in far more than the mere probability of meeting dependence criteria. They assessed a number of predictor variables to find differences between the individuals that met criteria and those that did not. Significant variables included living alone, mean number of prior cannabis use disorder symptoms, a continual smoking pattern per episode, using [also] during the daytime, using cannabis to "cope", child abuse incidents, motor and attentional impulsivity and recent negative life events. For this latter, followup analysis identified major financial crisis and separation from someone important as driving events.

As the authors point out in the discussion, the predictors differ from those identified from a more general population. This makes sense if you consider that the range on numerous variables has been seriously restricted by their catchment criteria. The amount of cannabis exposure, for example, did not predict transition to dependence in this study--perhaps because it was well over the "necessary if not sufficient" threshold. This underlines my theme that the denominator matters a lot to our more colloquial estimates of the risks of dependence on cannabis.

Another issue identified in the discussion was the choice to start at 18 years of age for the captured population. Cannabis use frequently starts much earlier than this and many studies of epidemiology suggest that initiation of drug use in the early teens, mid teens, late teens and early twenties confers substantially different lifetime risk of dependence. "The earlier someone starts using, the more likely to become dependent" is the general findings. The authors cite a study showing that the mean age of meeting cannabis dependence criteria for the first time is 18. This is at least consistent with the fact that 65% of their collected sample had previously met criteria for dependence. No study is perfect or gives us the exact answer we are looking for, of course.

A final note on estimating the conditional probability of dependence in the population that uses cannabis 3 or more times per week for over a year. Of the original sample, 331 had already met dependence criteria and were excluded because the interest here was on the first time dependent. If we ignore those 70 people lost to followup during the study, and add the 73 to the 331 then we end up with 76% of those individuals smoking that much cannabis who have already, or will soon, meet dependence criteria.

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van der Pol P, Liebregts N, de Graaf R, Korf DJ, van den Brink W, van Laar M. Predicting the transition from frequent cannabis use to cannabis dependence: A three-year prospective study. Drug Alcohol Depend. 2013 Jul 22. pii: S0376-8716(13)00228-7. doi: 10.1016/j.drugalcdep.2013.06.009. [Epub ahead of print]. [Publisher, PubMed]

25 responses so far

NIH Appoints NIAAA Director, Closes Circle on Merger

Oct 31 2013 Published by under Alcohol, Drug Abuse Science

As you are aware, the National Institute on Alcohol Abuse and Alcoholism has been under the care of an Acting Director for years now as the attempt to merge the NIAAA with NIDA moved along before ultimately being axed by Francis Collins.

A Press Release today announces a new permanent Director has been appointed:

National Institutes of Health Director Francis S. Collins, M.D., Ph.D., announced today the selection of George F. Koob, Ph.D., as Director of the National Institute on Alcohol Abuse and Alcoholism. Dr. Koob is expected to join the NIH in January 2014.

“With his distinguished reputation and vision, I am confident that George will encourage innovative ideas in the basic neurobiology of addiction, and will be dedicated to bridging the gap between our understanding of alcohol abuse, alcoholism, and addiction and developing new, targeted treatments,” said Collins.

As NIAAA director, Dr. Koob will oversee the institute’s $458 million budget, which primarily funds alcohol-related research in a wide range of scientific areas including genetics, neuroscience, epidemiology, prevention, and treatment. The institute also coordinates and collaborates with other research institutes and federal programs on alcohol-related issues and national, state, and local institutions, organizations, agencies, and programs engaged in alcohol-related work.

Dr. Koob comes to the NIH from The Scripps Research Institute, California Campus, where he is Chairman, Committee on the Neurobiology of Addictive Disorders, and Director, Alcohol Research Center. He earned his Ph.D. in Behavioral Physiology at Johns Hopkins University.

Dr. Koob’s early research interests were directed at the neurobiology of emotion, with a focus on the theoretical constructs of reward and stress. His contributions have led to the understanding of the anatomical connections of emotional systems and the neurochemistry of emotional function. Dr. Koob also is one of the world’s authorities on alcohol and drug addiction. He has contributed to the understanding of the neurocircuitry associated with the acute reinforcing effects of drugs of abuse and more recently on the neuroadaptations of these reward circuits associated with the transition to dependence.

A quick search of PubMed pulls up some 650 articles including many reviews staking out his "dark side of addiction" orientation to substance dependence.

His wikipedia page indicates that Dr. Koob is on the ISI Highly Cited list and a quick trip to Web of Knowledge shows an h-index of 123.

I think this selection by the NIH indicates a degree of seriousness in the recent RFAs and Supplements designed to advance the"functional integration" of research on alcohol and other drugs. While Koob has had a very substantial amount of work in alcohol over the past years, he has also maintained programs with psychomotor stimulants and opioids.

So any investigators* who were a little suspicious that this "functional integration" stuff was just to soothe feelings over all the wasted time, money and stress of the attempted merger have to walk that cynicism back a bit. The NIH could have easily appointed a pure alcohol type of researcher, even an alcoholism clinician. But the choice of a pre-clinical scientist who has research feet planted across many different substances of abuse sends the signal that there is meat behind the idea of integration.

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*I'll raise my hand on that one.

8 responses so far

More cannabis hyperemesis Cases

Oct 28 2013 Published by under Cannabis, Drug Abuse Science

There was a twitt from Dirk Hansen today

which pointed to Chen and McCarron in Current Psychiatry. This paper seems to be a set of diagnostic and therapy recommendations and contains an example Case Report.

This triggered a bunch of the usual incredulity, in this case from @drogoteca.

those two are but the tip of this person's denialist iceberg on cannabis hyperemesis. He or she is quite convinced that this cannot be a real outcome of chronic pot smoking.

It can and is.

For background, I've discussed the evidence for a cyclical vomiting syndrome associated with cannabis use here, here and here. Also see Dirk's post.

For grins I thought I'd see if there were any new Case reports and found several I had not seen before.

Hickey and colleagues (2013) report a Case of Cannabis Hyperemesis Syndrome that was treated with haloperidol:

A 34-year-old man well known to our ED arrived with epigastric pain, nausea, and vomiting for 4 days. He had been unable to tolerate anything orally but reported temporary relief only with long hot showers. He came to the ED that night to be admitted because he knew his symptoms would not improve, and he was always admitted in the past when his symptoms were so severe. He denied fevers, chills, diarrhea, hematemesis, melena, or hematochezia.

The patient's history was significant for similar symptoms every 2 to 3 months for approximately 10 years. He reported daily cannabis use since 1992, with only short intervals of abstinence resulting in complete resolution of his vomiting. He has been admitted to our hospital from the ED 7 times and had multiple unremarkable diagnostic tests including 3 computed tomographic scans, an esophagogastroduodenoscopy, and several specialty consults. He has also been admitted to several other local hospitals for cyclical vomiting. Other than substance abuse, he has no known psychiatric history. A diagnosis of CHS was finally made in 2012, a few months before this ED arrival.

Mohammed and colleagues (2013) reported a Case (which they are at pains to point out is from the Caribbean) that resolved with abstinence.

A 26-year-old Caucasian male presented to our center with a
1-week history of severe colicky epigastric pain heralded by significant nausea for 3 weeks. He had approximately 20 episodes of bilious vomiting daily with numerous bouts of retching. He admitted to smoking 4 “joints” or marijuana cigars every day for the last 2 years, and denied alcohol and tobacco use. He had 4 similar episodes over the last 6 months. During
these admissions, he was rehydrated and abdominal imaging revealed no abnormalities. His ongoing nausea was relieved
by taking hot showers, of which he took up to 15 times per day, sometimes for more than an hour.

...

The diagnosis of CHS was made and he was counseled on abstinence from marijuana. Though he refused to enter a substance
abuse program, he remained cannabis-free and on follow-up at 1, 3 and 6 months revealed no recurrence in symptomatology.


Enuh and colleagues (2013)
report a case from the US.

A 47-year-old African American male with a history of epilepsy and drug addiction presented to the hospital with a seizure complicated by nausea, vomiting, and severe abdominal pain. He was known to be diabetic, hypertensive, and addicted to marijuana for 30 years. He smoked two to three “blunts” (cigar hollowed out and filled with marijuana) most days and occasionally up to eight blunts daily. The drug was last taken on the day of his admission.

He immediately went to the bathroom and remained under a hot shower with the exception of two 15-minute breaks for the rest of the day. He believed that a warm shower could relieve his nausea and vomiting. He stated that it made him feel better than medication. Intravenous ondansetron was of limited benefit. It was difficult to persuade him to exit the shower for the rounds and physical examination. Receiving medication and eating were problems because of this compulsive showering. The same event of entrenching himself in the shower had happened 2 months prior to his hospitalization for a grand mal seizure. Abstinence from marijuana during the hospital stay made the patient’s nausea, vomiting, and obsessive warm showering resolve after 3 days.

Not as satisfying as it could be with respect to the workup and the post-hospitalization followup, of course. But interesting.

Sofka and Lerfald (2013) report a series of four Cases. All had histories of chronic cannabis use, all used hot showers to alleviate symptoms and all had negative GI scans and other clinical workups. One individual was reported to have ceased cannabis use and had remained symptom free. The other three were reported as continuing their cannabis use and continuing to have symptoms. Frustratingly, the authors do not specify the followup duration for any of the cases.

Gessford and colleagues (2012) report a Case that is significant for the comment on the efforts to find a cause prior to the identification of CHS:

A 42-year-old Caucasian female, who has routinely been seen at our institution for nausea, vomiting and abdominal pain since 2003, presented with the complaint of nausea, vomiting and abdominal pain. She stated that the symptoms occurred this time after eating four bites of ice cream. ...

Her physical exam was normal except for some mild epigastric tenderness which she attributed to her excessive vomiting. Laboratory studies including a comprehensive metabolic panel, amylase, lipase, and complete blood count were normal except for anemia, which had improved since her last admission. Urine studies, including urinalysis, were normal with a urine drug screen positive for delta-9-tetrohydrocannabinol (THC), benzodiazepines and opiates. Abdominal and chest x-rays were normal.

During the course of her admission, further investigation into her history revealed chronic marijuana use. She reported that long hot showers provided the only relief for her pain and nausea. She claimed that she took so many showers that her bathroom was growing excessive amounts of mold and mildew. Research into her medical records revealed an even more disturbing fact: excessive radiation exposure and medical cost. In total, she has had in excess of 97 abdominal x-rays, eight abdominal CT scans, two abdominal MRIs, an abdominal MRA, small bowel follow-through, three gastric emptying studies, four esophagogastroduodenoscopies (EGD), and three colonoscopies. Since 2003 these tests produced two abnormal findings: (1) the two most recent gastric emptying studies at 224 and 180 minutes (gastroparesis) and (2) gastritis/duodenitis on EGD. Throughout her complete sevenyear work-up, celiac sprue, peptic ulcer disease, Barrett's esophagus, porphyrias, ischemic bowel disease, appendicitis, ulcerative colitis, Crohn's disease and H. pylori infection have been excluded. The patient's medical record indicated that since 2005 she has had 97 emergency room visits. Additionally, since 2007 she has had 42 admissions.

Emphasis added. This is a feature of many of the clinical Case Reports that cannot be ignored. The lack of awareness of cannabis as the causal agent is costly. In terms of the dollar costs of diagnosis and care and in terms of the drugs and invasive diagnostic procedures administered to the patient.

I don't have access to Morris and Fisher (2013) which the Abstract states reports a single Case.

In trolling around on Google I ran across this comment in a pot user forum:

As far as symptoms are concerned, they began about 3 years ago when I would wake up feeling nauseated. Shortly after the nausea started, I'd vomit once and (after smoking) I would feel better. This continued off and on without me giving it much thought until February of this year, when I was floored by intractable vomiting for about 48 hours. I couldn't keep anything down (not even water), and the only time I felt like I didn't want to die was when I was in a hot shower. When the vomiting and nausea finally relented after that first episode, I chalked the experience up to acute gastroenteritis. However, about three days later, I woke up feeling nauseated. I went to work as usual, but by noon I was throwing up unstoppably again and had to go home. By the time evening came around, I could eat light food like white rice and slept. But as soon as I awoke the next morning, I had the same stomach pains and nausea. Again I went to work and again the unstoppable vomiting kicked in right around midday. The only thing that brought relief was a hot shower or bath. So long as I was under hot water, I felt alright.

This person details a history of medical workups and a bit of the recur/remit presentation before ending up with his conclusion:

At this point, I have been completely abstinent from ze herb for 5 days and I have already noticed improvement. Although I, too, was skeptical about CHS at first, I just do not know what else could be causing the problem. Although I absolutely love to get high, at my current weight/height (I am 6'1" and 129lbs now) I am quickly running out of options. If I can't find a solution to this problem soon, it will literally kill me. And I'll be damned if I gonna become the first known death directly related to marijuana consumption.

Naturally, the other forum users express the usual incredulity we see from the leegalizeetmon crowd. It's worth a read.

I also ran across this blog post from a person claiming to be an ER doc:

Since I have become aware of this association between marijuana use and CVS type presentations it has been my “good fortune” to care for nearly a dozen patients in the emergency department who self-reported diagnosis of CVS. Curiously, of these patients about 10 admitted active marijuana use, and the 2 who denied it had positive urine screenings for marijuana. This does not exactly make a case series, but is certainly another interesting observation. Of course, since the prevalence of marijuana use in our Emergency Department seems to approach 100% sometimes, this also may not be a statistically significant association!

I conclude with points I made in prior posts. At the moment, this syndrome is clearly quite rare considering estimates for chronic cannabis users worldwide. Some of this is due to lack of diagnosis..the Case Reports make very clear that an extended history of diagnostic investigation of more usual gastric disorders is typical prior to the identification of cannabis as the causal agent. But even so, very likely this is a rare reaction. Given that, it is not impossible that there is some as-yet-undetermined source of the chronic vomiting that is merely correlated with cannabis use. [In the event your imagination fails you, people tend to suggest moldy weed, herbicide/pesticide and/or contamination from smoking devices as causes.] Nevertheless, it appears to me to be likely that as we accumulate more and more Cases separated by time and place, which involve individual users with a variety of phenotypes and environmental circumstances, which present similar clinical pictures and which seem to have chronic cannabis smoking (not synthetic marijuana products, for example) as the only commonality.... well it becomes very difficult to sustain any alternative hypothesis.

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Hickey JL, Witsil JC, Mycyk MB.Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013 Jun;31(6):1003.e5-6. doi: 10.1016/j.ajem.2013.02.021. Epub 2013 Apr 10. [link]

Mohammed F, Panchoo K, Bartholemew M, Maharaj D.Compulsive showering and marijuana use - the cannabis hyperemisis syndrome.Am J Case Rep. 2013 Aug 23;14:326-8. doi: 10.12659/AJCR.884001. [PMC link]

Enuh HA, Chin J, Nfonoyim J. Cannabinoid hyperemesis syndrome with extreme hydrophilia. Int J Gen Med. 2013 Aug 19;6:685-7. doi: 10.2147/IJGM.S49701. [OpenAccess link]

Sofka S, Lerfald N. Cannabinoid hyperemesis syndrome: A case series. W V Med J. 2013 May-Jun;109(3):20-3.
[link]

Gessford AK, John M, Nicholson B, Trout R. Marijuana induced hyperemesis: a case report. W V Med J. 2012 Nov-Dec;108(6):20-2. [link]

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It was the methylone that killed him

Sep 13 2013 Published by under Bath Salts, Cathinone, Drug Abuse Science, Drug Fatality

The Daily Mail is reporting followup toxicity findings in the June 17 death of one Matthew Rybarczyk the after attending a rave party.

The Daily Mail:

There are fears that a string of fatal overdoses this summer have been caused by the toxic substance bath salts after it was pushed to young festival-goers as the party drug 'Molly', officials said today.

The substance had been sold to at least one young person as 'molly' - a potent form of ecstasy - but was in fact the meth-like street drug bath salts.

Officially known as methylone, it can have similar effects to ecstasy or MDMA on the user.

It has been confirmed as cause of death of a 20-year-old man and is suspected in the deaths of others.

StructureFig-mdma-vs-cathinones450As you can see in this structural diagram, methylone is the cathinone cousin of 3,4-methylenedioxy-methamphetamine (MDMA) which is the canonical psychoactive of both Ecstasy and Molly.I am delighted to see some actual toxicity data followup reporting. Perhaps other sources will have more specifics with regard to the medical examiner's findings and the various drugs found in the decedent's blood. For now, however, at least we have something to go on.

And I covered one prior Case Report containing three methylone-related deaths. And as I noted there, we know perfectly well that MDMA itself is capable of killing people.

As we've also discussed, MDMA can result in significant medical emergency and death. Yes, really, it is the MDMA.

It would not be at all surprising if methylone deaths were via the same neuropharmacological triggers, see Baumann et al 2012 and Simmler et al, 2013. Certainly what one can glean from the symptoms is very familiar.

I take issue, however, with the Louise Boyle piece in the Daily Mail. We can start from the headline:

Did all these festival-goers die from taking BATH SALTS? One death confirmed as fears others were duped into buying toxic street drug while believing it was 'molly'

See that? Nice trick. Methylone is a "toxic street drug" while apparently 'molly' is no such thing. Bzzzt, wrong. Methylone and MDMA are the same category of thing. Recreational drugs obtained from sources of dubious quality. Trying to distinguish one as a "toxic street drug" as different from the other is silly and nonsensical.

next we have this whopper:

but was in fact the meth-like street drug bath salts

Another report from the NY Post goes down the same path of underinformed sensationalism:

New York club kids who use the party drug Molly ... are often being peddled deadly “bath salts” by ruthless dealers,...The dangerous narcotic — which causes a violent, meth-like high — has killed at least one reveler this year and is being eyed in the deaths of two partiers at the Electric Zoo festival on Randall’s Island two weeks ago...Known to drug regulators as methylone

The term "bath salts" is just a nickname. It is no different than Ecstasy, molly, crack, crystal, weed, smack. It has meaning in so far as there is a consensus use of it, but in the absence of consensus it is near meaningless. I would say that at this point in time "bath salts" in the US can mean any of the substituted cathinone drugs. There was a time when I might have said it was semi-uniquely referring to 3,4-methylenedioxypyrovalerone (MDPV) but given the diversity in the market this is no longer correct.

The above referenced papers from Baumann and Simmler, and this additional one from Baumann, should tell the tale about the "meth-like" charge as well. While some of the substituted cathinones could be argued to be "meth-like", methylone sure isn't one of them. In fact the neuropharmacology suggests "MDMA-like" if anything. And really, given the most popular cathinones being used to date, it is silly to say that bath salts are meth-like. Mephedrone and methylone are MDMA-like in many ways and MDPV is turning out to be more like cocaine in activity. That's neuropharmacology, for the most part. When we look at compulsive use and propensity for addiction it in fact looks like methylone (Watterson et al, 2012) and mephedrone (Hadlock et al, 2011; Aarde et al, 2013a; Motbey et al, 2013) might have more reinforcing effect in rodent models than would be expected for a MDMA-like drug (see Schenk 2009; de la Garza et al, 2007 for review). In some of these studies the authors show data suggesting* the "MDMA-like" cathinones might actually be more effective in self-administration than methamphetamine. MDPV appears to generate more compulsive use than does methamphetamine (Watterson et al, 2012; Aarde et al 2013b). So, I suppose if the journalists mean the compulsive-use or reinforcing value as indexed by rat self-administration studies then they might have some defense for the "meth-like" charge. Somehow I doubt they are so informed.

Nevertheless.

When we are talking the acute overdose profile, the symptoms sure sound like MDMA and the relative reinforcing properties are most likely not directly related.

Oh boy. As I was writing this, some tox reporting from the New York Electric Zoo overdoses (it also repeated the methylone finding for Mr. Rybarczyk). James C. McKinley Jr reports at an Arts Beat blog at the NYT:

Toxicology results showed Ms. Rotondo died from acute intoxication after taking pure MDMA, the euphoria-producing drug sold on the street in pill form as ecstasy and in powdered form as molly, said Ellen Borakove, a spokeswoman for the medical examiner’s office.

Mr. Russ had taken a fatal mix of MDMA and methylone, a closely related stimulant that is also often sold under the name molly.

Nice to see some confirmation since there are definitely other drugs to suspect, like PMA and PMMA, when it comes to rave-drug overdoses.

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*there are some methodological questions to be answered. I'd like to see a few more comparisons, myself.

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Repost: Musty Must-Read: "Mrs. Winslow's Soothing Syrup"

I originally posted this Jan 09, 2008 on the old blog and reposted it 12/12/2008 with small improvements over the prior version. It has been one of my more popular posts when it comes to Google hits. You might want to check out a personal recipe for opiate based cough remedy as well.


The US Food and Drug Administration (FDA) began sending warning letters to sellers of so called "bio-identical hormone replacement therapy" today according to an AP report. Apparently the claims for alleviating menopausal symptoms are

not supported by medical evidence and are considered false and misleading.

Needless to say, these "compounded" products are being sold without FDA approval. It's all a conspiracy man! Dang FDA is a tool of BigPharma trying to keep cheap and effective remedies from the public. Noted tool of TheMan(BigPharmaDivision) Abel Pharmboy has a recent post in which he touches on "cosmeceutical" marketing of drugs and the FDA's authority to regulate cosmetics under

their regulatory authority is in part ordered by the Federal Food, Drug, and Cosmetic Act of 1938 (and subsequent legislation).

soothingsyrup.jpg
source
This reminds me of the glory days of the quack remedy / patent medicine era and today, from the mouldering archives, we take up a Case Report published by A. B. Hirsch, M.D. ["Mrs. Winslow's Soothing Syrup. American Medical Journal, 1884, 12(11):504-506] which is available from Google Books here. A footnote indicates that this Abstract was read before the Philadelphia County Medical Society on Sept 17, 1884. Ahh, Mrs. Winslow's . Used for over 60 years by mothers for their teething children.

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