Archive for the 'Cannabis' category

Transgenerational effects of exogenous cannabinoid exposure

Sep 11 2012 Published by under Cannabis

A paper in the October issue of the Journal of Psychopharmacology will be of interest to my readership. It looks at the consequences of exposure to an exogenous cannabinoid agonist

Byrnes JJ, Johnson NL, Schenk ME, Byrnes EM. Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring.J Psychopharmacol October 2012 26: 1348-1354, first published on April 19, 2012 doi:10.1177/0269881112443745 [ PubMed ]

In this study the authors exposed 23 day old (adolescent) female Sprague-Dawley rats to a three day, twice per day regimen of WIN 55,212-2 which is a full agonist at the CB1 receptor. The more familiar exogenous cannabinoid, Δ9-tetrahydrocannabinol (THC) is a partial agonist at the same site. The authors waited until the animals were adult (60 days), bred them and then examined the subsequent male off-spring of these mothers. They assay of interest was the Conditioned Place Preference test which is one common method to assess subjective drug liking in rats and mice.

The idea is to take a chamber which is divided into two or there sections by dividers and doors (in this case it was a three-chamber apparatus). The chambers are differentiated by salient stimuli such as the floor texture or type, wall stripes (horizontal vs vertical), etc. You let the subject explore at will in pre-conditioning baseline studies. Then, you conduct a series of conditioning sessions in which the animal is injected with a drug and then confined in one of the chambers. On other sessions the animal is injected with the drug vehicle only and confined to the other chamber. In this case, there were three active drug and saline conditioning sessions. Finally, on a later test day the animal is allowed once again to freely explore all of the chambers. The amount of time it spends in each chamber is recorded and the relative preference for the drug-paired chamber over the saline-paired chamber can be expressed, typically as a difference in amount of time, or the percentage of the total time, spent exploring the drug-paired chamber.

The figure presents Conditioned Place Preference data for the adult male offspring (WIN-F1) of mothers which were exposed to WIN 55,212-2 in adolescence and in the control group (VEH-F1) of adult male offspring of mothers treated twice a day for three days with the drug vehicle. There were three different place conditioning levels with groups of animals from the VEH and WIN treated dams place conditioned (in adulthood) with saline, 1 or 5 mg/kg of morphine. As expected, the chamber preferences of animals "conditioned" with vehicle were indistinguishable, i.e., they spent approximately equal time in each chamber. Animals conditioned with morphine, however, spent more time in the drug-paired chamber than in the vehicle-paired chamber.

Interestingly, there was a group difference which depended on the maternal treatment. The offspring of the WIN treated mothers appeared more sensitive to the rewarding effects of morphine because they expressed a conditioned place preference after 1 mg/kg training, unlike the adult offspring of VEH exposed dams. Although I'm not showing it here, the study also looked at adolescent male offspring and found a similar enhancement of morphine place-preference conditioning in the offspring of WIN exposed dams.

The translational take-away is pretty clear and fairly frightening. It suggests that one of the reasons for familial patterns of substance abuse may not simply be down to genetic legacy but may have something to do with drug exposures of the mother.

29 responses so far

More cannabis hyperemesis Cases emerge

Aug 15 2012 Published by under Cannabis, Drug Abuse Science

Just as our most fervent defender of pot posted the most scientifically offensive clause in the legalization initiative defeated by California voters:

5. Cannabis has fewer harmful effects than either alcohol or cigarettes, which are both legal for adult consumption. Cannabis is not physically addictive, does not have long term toxic effects on the body, and does not cause its consumers to become violent.[DM- policy statement, false, false, distraction]

a comment on an older post returned our attention to the cannabis hyperemesis syndrome.

The past year I started smoking a lot more than ever before.
I'm 21, and every single morning I wake up with the worst upset stomach. It gets all the way to the point where I'm running to the bathroom to throw up and nothing ever comes out. The doctors think its in my head. Awesome. When this first began happening I would just make myself throw up but once I began it wouldn't stop for hours and I had to be taken to the emergency room. I feel like I'm dying!! But of course I feel completely better when I go smoke. It's insane!

So I trotted over to PubMed to see what is new, if anything, with cannabis hyperemesis. I found three new CaseReport publications that I had not seen before including:

Nicolson SE, Denysenko L, Mulcare JL, Vito JP, Chabon B. Cannabinoid hyperemesis syndrome: a case series and review of previous reports. Psychosomatics. 2012 May;53(3):212-9. Epub 2012 Apr 4. PubMed

Luther V, Yap L.A hot bath to calm what ails you: the Cannabis Hyperemesis Syndrome. Acute Med. 2012;11(1):23-4. PubMed

Bagdure S, Smalligan RD, Sharifi H, Khandheria B. Waning effect of compulsive bathing in cannabinoid hyperemesis.Am J Addict. 2012 Mar-Apr;21(2):184-5. doi: 10.1111/j.1521-0391.2011.00209.x. Epub 2012 Feb 7. PubMed

There are a total of 6 individuals reported (20-27 yrs of age, 2 female), all of whom presented to medical services (New York, 4; London, 1; Amarillo, TX, 1) with repeated and severe vomiting. All Cases had been smoking marijuana for many years with at least daily smoking in recent months to years. Five of the cases identify multiple uses per day, the sixth just indicates daily smoking.

Medical workups for all six indicated no other detectable gastrointestinal causes. All six Cases include multiple episodes of repeated vomiting in the past which had resulted in emergency department visits or hospitalizations for that patient.

All six had been using hot showers to control their symptoms, selected quotes from different Cases are illustrative:

he persistently demanded to use our showering facilities...He continued to demand to use the showering facilities, and oddly seemed more settled after bathing.

Several times during the interview, he went to the bathroom to put his head under the hot shower, which he said improved his

Ms. B complained that the hospital showers were not warm enough because the best way to relieve her symptoms was to take extremely hot, hour-long showers four times daily.

Three of the cases have evidence that ceasing marijuana smoking prevented further episodes of cyclical vomiting. Three show evidence that returning to marijuana smoking after abstinence led to recurrence of symptoms. Two cases had no followup evidence.

As this evidence starts to accumulate, we need to remember one thing about the Case Reports which is that there is a severe publication/selection bias in this sort of thing. Physicians' motivations to publish are not like ours and what strikes one group of physicians to bother to publish a Report is entirely opaque to me. It is, however, likely only the tip of the iceberg. As a second caution, it may also be the case that their is a bias for the publication of "clean" Cases. For only bothering when the individual Case seems to fit this growing profile to a T. Thus, it may make things about this syndrome appear more clear cut, more severe, etc. This goes both ways but one thing I would be concerned about are those Cases that are indeed caused by chronic cannabis use but are not diagnosed because they don't seem to fit the Case Report literature.

Perhaps hot bathing/showers are not always involved? Perhaps the use history is not as severe as it was for this most recent set of six cases? Perhaps there are some cases in which marginal gastro-intestinal concerns have interacted with a lesser degree of chronic cannabis smoking to push an individual over the threshold to cyclic vomiting symptoms?

There is always the unknown factor. People have proposed unknown toxins in the past...contamination of the cannabis being used. Still not impossible, especially given the apparent rarity of the syndrome. But, I would argue, as the cases occur across time and geography this becomes less likely. You would think that contamination might surround particular drug supplies (in time and space) in a way that might turn up as a geographic patient cluster.

For now, however, the evidence is reasonably strong and it is most certainly growing. Obviously, I think it is well past time for scientists with models that are relevant to emesis to get cranking and start up some studies. Unfortunately rats don't vomit so it is going to require some specialized animal models, perhaps the ferret.

31 responses so far

Will Washington State leegalizeetmon?

Aug 10 2012 Published by under Cannabis

From here we learn that WA voters are to consider Initiative 502 which would legalize marijuana. For recreational purposes.

Seems to be the same deal as the initiative that failed to pass muster with voters in our dope smokingist, weed growingist and reputably most individual "thing" friendly state of California.

Perhaps the good folks of WA will see it differently.

In my estimation the hook for this (tax money to balance the state budget) poses the same Catch22 which hung the proposition in Cali. Dope smokers don't like the idea of Marlboro Green becoming the only provider. They fear "regulation and taxation" means corporate profits and no more home growing. Or perhaps that corporatizing and commodifying the product would leave them in a situation similar to the beer industry in the US before microbrews came roaring back. whichever way it went, I think it was a segment of *dope fans*, ironically enough, that doomed the California effort.

It will be interesting to see if the WA folks who like the kinde learn from the prior example and line up in support. (and can be bothered to vote, naturally)

45 responses so far

Cannabis hyperemesis: A brief update

Apr 28 2012 Published by under Cannabis

Dirk Hanson's post on cannabis hyperemesis garnered another pertinent user comment:

Anonymous said...

My son suffers from this cannabinoid hyperemesis. At this moment he is here at my home on the couch suffering. I have been up with him for 3 days with the vomiting and hot baths. He says this time its over for good. This is our third bout. The first two time we went to ER, they put him on a drip to hydrate him, and gave him some pain medicine and nausea medicine. After a few hours he went home and recovered. This time we went to Urgent Care, put him on a drip, pain med, Benadryl, and Zofran. He felt better. That was yesterday, today we are right back with the nausea, but the Zofran limits the vomiting. I'm hoping tomorrow will be much better. He hasn't eaten for 3 days. He let me take a video of him at Urgent Care before treatment, and in the video he was heaving and begging himself with tears never to smoke again. My son has smoked for 14 years.

I reviewed several case reports back in 2010. The comment thread was robust (this was originally posted at the Sb version of the blog) and there was considerable skepticism that the case report data was convincing. So I thought I'd do a PubMed search for cannabis hyperemesis and see if any additional case reports have been published. There seem to be at least 17 new items in Pubmed since the Soriano-Co et al 2010 that I referenced in the update.

One in particular struck my eye. Simonetto and colleagues (2012) performed a records review at the Mayo Clinic. They found 98 cases of unexplained, cyclic vomiting which appeared to match the cannabis hyperemesis profile out of 1571 patients with unexplained vomiting and at least some record of prior cannabis use. The profile/diagnosis was created from the prior Case Report literature that I reviewed but unfortunately I can't get access to this paper to tell you more.

The other thing to think about is the relative increase in case reports in the past year or two. As I think I commented at the time, this is typical of relatively rare and inexplicable health phenomena. The Case Reports originally trickle out...this makes the medical establishment more aware and so they may reconsider their prior stance vis a vis so-called "psychogenic" causes. A few more doctors may obtain a much better cannabis use history then they otherwise would have done. More cases turn up. More Case Reports are published. etc. It's a recursive process.

I think we're seeing this at work.

And as more cases emerge, separated in time and space, the denialist position of blaming a contaminated cannabis product (or bad bongs) gets harder and harder to sustain.

121 responses so far

Annual Use of Cannabimimetic (Spice/K2, etc) Products in 12th Graders

Dec 22 2011 Published by under Cannabis, Public Health, Uncategorized

The Monitoring the Future study has added the synthetic marijuana products (see here, here, here for additional) to their annual survey. Data on annual use rates are now available for the 12th grader segment. I have taken the liberty of graphing the annual use rates for a selection of the more common drugs in this 2011 dataset.
What you can see (click on the graph to see a bigger version) is that these products are more popular than a host of drugs that have a considerably longer history. These packets of plant material spritzed with one or more full endocannabinoid CB1 receptor agonists (see dr leigh here, here for details) only really appeared on the US market in 2010 in broad availability.

Not too shabby to already be beating these other drugs, eh?

Unfortunately the full monographs aren't available yet and the update tables for "lifetime" and "30 day" do not appear to include the synthetic marijuana category yet. Nevertheless, it's a good thing that this drug category has been added to the survey. As we go forward it will be interesting to see if popularity continues or if this was a brief flash in the pan related to broad quasi-licit availability of these products.

These data will also provide a nice comparison to more limited investigations such as this one. Hu et al (2011) report 8% cannabimimetic use in a sample of 852 college students collected in September of 2010.
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The Annual Prevalence table is here.

MtF 2011 update page

To the Maximus Foundation (@FakeWeed)

21 responses so far

Congress moves to control synthetic cannabimimetic (K2/Spice) and designer cathinone (mephedrone/MDPV) drugs

HR 1254 (pdf) has passed the House.

This Act would criminalize possession of a range of compounds which activate the endogenous cannabinoid CB1 receptor. The language covers several structural classes as well as an extended list of, e.g. the JWH-xxx compounds. In essence this is another attempt on the analog front in which the DEA is not able to move quickly enough on specific new drugs that emerge within a general neuropharmacological class.

The bill also doubles the amount of time the DEA has to generate the support for a final rule, once an emergency action has been invoked.

The House Resolution next addresses 17 compounds in the likely stimulant/empathogen class, with most of them being cathinone derivatives. Readers of this blog will be familiar with the well known 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV) on this list.

One assumes that Chuck Schumer will be leading the charge on this in the Senate and that it will pass in short order...opposition to this sort of legislation is not usually robust among elected politicians.

8 responses so far

Because nothing is more compassionate and caring than half-nekkid chicks

Nov 28 2011 Published by under Cannabis, Medicine and Law

From the Sacramento Bee:

At the "Kush Expo Medical Marijuana Show" in Anaheim this month, the 420 Nurses were joined by the Ganja Juice girls and a bikini troupe for an Orange County dispensary sponsoring the Expo's "Hot Kush Girl" contest. A whooping, largely male throng cheered as 21 women competed for signature edition bongs and cash prizes.

"The marijuana industry is male-dominated, and dudes love to look at hot chicks," said Ngaio Bealum, Sacramento publisher of a marijuana lifestyle magazine called West Coast Cannabis.

And this, my friends, is yet more evidence that medical marijuana and compassionate care nonsense is 10% about legitimate treatment for health problems and 90% about schmokin' some weed.

In more ridiculousness, you too can try to be a "420 Nurse". Aka, Pot Pinup.
h/t: @Dirk57

76 responses so far

Jurors convict K2/Spice Synthetic Cannabis Seller Under Analog Provision

Sep 12 2011 Published by under Cannabis

Following up* on the case of Eric Srack who was prosecuted for selling a synthetic cannabis product containing the cannabimimetic compound JWH-081. The Salina Journal reports:

Jurors found Eric W. Srack guilty Tuesday morning of three felony counts of sale, delivery or distribution of JWH-081, an analog of an illegal substance.

As you will recall, this particular compound was not one of the ones listed (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) ) on the recent scheduling action by the DEA.

You will also recall that this whole blossoming retail market in cannabimimetic products showed quite clearly that the Federal Analog Law, despite having an "OR" between its two key provisions (acts like, looks like) was in fact being interpreted as having an "AND" between these two provisions in case law. The above mentioned compounds were clearly endocannabinoid CB1 receptor agonists, therefore they "act like" the Schedule I drug Δ9-tetrahydrocannabinol. They did not however look structurally like THC. So it appeared to be the case in summer-fall 2010 that DEA's "watching and evaluating" language was the same as saying "Yup, these are not currently illegal folks, go nuts!".

Putting at least one of the JWH-xxx compounds on the Schedule, however, had the potential to support the "AND" interpretation of the Federal Analog Act language. All that matters going forward from here is the case law.

This is the first successful conviction that I've heard of. If it holds up, it is a highly significant turning point for the legal status of these cannabimimetic, synthetic marijuana products.

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*hmm, actually that may be one of the posts I've failed to recover from Sb.

5 responses so far

CPDD Annual Meeting 2011!!!!!111111!!!!!

Did I mention I enjoy learning more about the neurobiological and behavioral effects of recreational drugs as well as the development and treatment of addictions?

The College on Problems of Drug Dependence will be holding their annual meeting in Hollywood Florida this upcoming week. I've been going through the Itinerary Planner and Program Book to get a preview. There are a few presentations that touch on topics that we've blogged about here at the DrugMonkey blog, including

-treating the hyponatremia associated with MDMA-induced medical emergency

-vaccination against drug abuse

-exercise as a potential therapy for, or antidote against, stimulant drug addiction

-JWH-018 and other synthetic cannabinoid constituents of Spice/K2 and similar "incense" products

-some preclinical studies on mephedrone / 4-methylmethcathinone

-presentations from the DEA on scheduling actions that are in progress

I'm certainly looking forward to seeing a lot of interesting new data over the next week.

3 responses so far

In the event all the discussion of representation is boring you...

Mar 17 2011 Published by under Cannabis, Drug Abuse Science

we're talking about cannabimimetic "incense" or "potpourri" products and the Analog provision of the Controlled Substances Act over at Scienceblogs.

No responses yet

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