Marijuana Can Make You Vomit, and Other Stories

Short subjects, various.

First, a recap of an earlier story, and a very strange story at that. Cannabinoid hyperemesis, as it's known, was not documented in the medical literature until 2004, and was first brought to wider attention earlier this year by the biomedical researcher who blogs as Drugmonkey. Episodes of serial vomiting appear to be a very rare side effect of regular marijuana use. Posting on his eponymous blog, Drugmonkey documented cases of hyperemesis that had been reported in Australia and New Zealand, as well as Omaha and Boston in the U.S.

As Drugmonkey reported, “patients had discovered on their own that taking a hot bath or shower alleviated their symptoms. So afflicted individuals were taking multiple hot showers or baths per day to obtain symptom relief.”

A year ago, I published a post on this topic, titled "Marijuana, Vomiting, and Hot Baths." Sure enough, a number of people left comments about their own experiences with this unusual and unpleasant effect. Recently, one of my commenters caught drugmonkey’s eye, and he noted it in his new blog post on the phenomenon:

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

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….

Drugmonkey writes: “I reviewed several case reports back in 2010.... 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…. 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… 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. “
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In a story I think of as vaguely related, in the sense that it is a rare drug phenomenon unrecognized by the public, I recently wrote an article  for The Dana Foundation on the subject of “Smoking’s Ties to Schizophrenia.” In addition, check out a story about plans by the Air Force to make their hospitals and clinics smoke-free HERE. In brief: Smoke-free clinics pose major problems for heavy smokers with mental health disorders.
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Speaking of hospitals, Michelle Andrews reports in Kaiser Health News that about half of the patients undergoing treatment in hospital emergency rooms are under the influence of booze. Alcohol screening and counseling can be effective in this context—but there’s a catch. “Regardless of state law, self-insured companies that pay their employee’s health care costs directly can refuse to cover employees for alcohol-related claims.”

Even though the National association of Insurance Commissioners does not recommend it, dozens of states have passed laws allowing health insurers to deny payment for a patient’s injuries if they were incurred while he or she was under the influence of alcohol. About as many states have passed laws prohibiting such exclusions due to alcohol. The result is one big mess, and confusion reigns. As a professor of health law put it: “There’s no reason to think that insurers, eager to hold down costs, wouldn’t continue” to deny payment for alcohol-related injuries.
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And finally, some news about Chantix (varenicline), the drug both patients and doctors love to hate. It often works very well as an anti-craving medication for smoking cessation. But it can also, in some cases, present patients with a bewildering array of psychological side effects, including rare cases of suicidal ideation. A new study  by researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, suggests that Chantix may have application in the treatment of alcoholism as well. Participants in the study reduced the average number of drinker per week on Chantix, compared to placebo. The study was funded by the National Institutes of Health and the State of California. Pfizer, the company that markets Chantix, did not fund or participate in the study.

Graphics Credit: http://teesdiary.files.wordpress.com/

Researchers Eye a Cheap, Organic Alternative to Chantix for Smokers

Meet cytisine, available in Bulgaria for 25 cents a pill.

A clear majority of American smokers say they want to quit. But each year, only a small percentage of them manage to do it. For individual smokers, the will is there, but what’s sometimes missing is the money.

For many smokers, cessation aids like nicotine patches and anti-craving medication are effective. But they are relatively costly, and insurance coverage for such products varies widely. Chantix, the top-of-the-line smoking cessation aid introduced by Pfizer five years ago as a very expensive prescription drug, was discovered by modifying the chemical attributes of an existing plant substance called cytisine.

But what if cytisine itself, found in various plants, including the golden rain tree, a small shrub native to the Alps—worked almost as well as Chantix, but for only pennies a day? Cytisine, packaged as Tabex and marketed by a Bulgarian firm, has already been on the market in Central Europe and Russia for more than 40 years. In Russia, a four-week course of Tabex costs $6.  Chantix will cost smokers about $250 for a 12-week run, or about $3-$4 per pill. In Poland, Tabex sells for about 25 cents per pill.

Moreover, as David Biello pointed out in Scientific American, when Chantix (known as Champix in the U.K.) was first approved for use against cigarettes, “the leaves of Cytisus laburnum, or the golden rain acacia tree, were used as a tobacco substitute by soldiers in World War II.” Later, clinicians in the U.S. paid scant attention to reports of a cheap Bulgarian plant-based supplement that smokers in Russia and Central Europe were using to help break their nicotine addiction. Instead, researchers structurally modified cytisine to produce varenicline, or Chantix. It makes for a more effective drug, but there are always tradeoffs: It is expensive and time-consuming to produce drugs through a process of total syntheses, and they will always come at a considerable cost premium relative to their organic originals. That is partly how pharmacology works, and it’s a good thing, providing you have the money or the health insurance to be able to afford the finished product.

Recently, a group of researchers at a smoking cessation clinic in Poland studied the effect of cytisine, a “partial nicotine agonist,” in a clinical trial published
 in the New England Journal of Medicine. The double-blind trial showed that cytisine was not as effective as Chantix, but significantly more effective than a placebo. Dr. Robert West of University College, London, and lead author of the study, said the “net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4.”

“It wasn't compared head-to-head against the Rx drugs, but its reasonable efficacy makes it sound like a cheaper alternative,” said Dr. David Kroll, Professor and Chair of Pharmaceutical Science at North Carolina Central University. “Like nicotine, it can cause side effects like headaches and nausea,” he added.

So is cytisine an eventual possibility in the U.S., where it is not currently licensed and available? Is it something that the National Institute on Drug Abuse is interested in? When I asked NIDA director Nora Volkow that question in an interview last week, the answer was yes. “The data look very interesting,” Volkow said, referring to the New England Journal of Medicine Study.  “The beauty of cytisine is that it’s not just inexpensive, you can also get a response in three weeks.” She added that “we don’t know yet whether we can improve it,” by, for example, combining it with other cessation aids. “The main side effect of cytisine is nausea, but not suicidal ideation,” she said.

An earlier survey in the Archives of Internal Medicine of the admittedly sparse research showed similar results in several placebo-controlled double-blind studies. Cytisine, the Marxist-Socialist answer to cigarette addiction, works about as well as standard nicotine replacement therapy, like patches and gums.

“I hope this drug will be available throughout the world at a cost that every smoker can afford,” said West. And that might be a problem. Cytisine is not currently legal in the U.S. or Canada. Tabex itself was withdrawn from some of the European countries in which it was formerly available, after several Central and Eastern European countries joined the European Union and began adhering to stricter licensing rules.

Meanwhile, a third of the world is still out there smoking tobacco. It seems sensible to have some modest help available for smokers in poverty who want to quit and financially need to quit. “I have long been concerned that effective treatments to help smokers to stop are not affordable by the majority of smokers in the world,” West said. “There are still regulatory hoops to go through, but I hope that before long this drug will be available throughout the world at a cost that every smoker can afford. It should be cheaper to take this drug than to smoke, wherever you are in the world. It is not a magic cure by any means; stopping is still extremely difficult for many people. But it could save many hundreds of thousands of lives, if not millions, which is quite a thought.”

As Dr. Volkow put it: “We urgently need medications for smoking. Five million people die per year” from smoking-related causes in the U.S.

West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, & Stapleton J (2011). Placebo-controlled trial of cytisine for smoking cessation. The New England journal of medicine, 365 (13), 1193-200 PMID: 21991893

Coffee and Cigarettes

Recovering alcoholics and their drugs.

It's no secret that alcohol and cigarettes go together. And it is common knowledge--and an AA truism--that recovering alcoholics take to strong black coffee like ducks to water.

Now comes a study of Alcoholics Anonymous participants in Nashville, to be published in the October issue of Alcoholism: Clinical and Experimental Research, which verifies the obvious, with a twist. Of 289 AA members interviewed by Dr. Peter R. Martin and coworkers at the Vanderbilt Addiction Center, 56.9% of respondents were cigarette smokers (approximately 20% of all adult Americans smoke cigarettes).

When it came to coffee, however, 88.5% of AA attendees were coffee drinkers, and a third of them drank more than 4 cups a day. "The most important finding," said Dr. Martin in a Vanderbilt University press release, "was that not all recovering alcoholics smoke cigarettes while almost all drink coffee."

Does all that coffee guzzling and cigarette smoking help or hinder recovering alcoholics in their quest for sobriety? The answer is: nobody quite knows. Dr. Martin, professor of psychiatry and pharmacology at Vanderbilt and lead investigator of the study, entitled "Coffee and Cigarette Consumption and Perceived Effects in Recovering Alcoholics Participating in Alcoholics Anonymous in Nashville, TN," put it this way in Science Daily: "Is this behavior simply a way to bond or connect in AA meetings, analogous to the peace pipe among North American Indians, or do constituents of these natural compounds result in pharmacological actions that affect the brain?"

"It's possible that coffee is even a gateway drug, with coffee drinking beginning at about the time persons begin using alcohol," said Robert Swift of the Brown University Medical School. "In addition, a potential negative interaction is coffee's known negative effects on sleep."

Selena Bartlett of the Ernest Gallo Clinic and Research Center of the University of California, San Francisco, offers the same concerns about cigarettes. A reliance on smoking by recovering alcoholics has a biological basis, she believes, and may increase the odds of relapse. In a HealthDay article by Steven Reinberg, Bartlett said: "My prediction would be that the relapse rates among smokers is higher." Since nicotine and alcohol addiction are so often found together, Bartlett thinks they should also be treated together, and is studying the anti-smoking drug Chantix for this purpose. "The drug inhibits the effect of nicotine, and by doing that, you may also reduce the euphoric effects of alcohol at the same time," she said. "We already have some evidence that it may work."

Varenicline, currently marketed by Pfizer for smoking cessation under the trade name Chantix, caught the attention of alcohol researchers when it dramatically curbed drinking in alcohol-preferring rats. The synthetic drug was modeled after a cytosine compound from the European Labumum tree, combined with an alkaloid from the poppy plant. An estimated 85 per cent of alcoholics are also cigarette smokers. (Chantix has lately been implicated, along with a dozen other anti-seizure medications, in suicidal ideation in some patients).

"I think it is important for alcohol researchers and clinicians to know that alcoholics, even those who do not use other illicit drugs, are not just addicted to alcohol, but use other psychotropic drugs like caffeine and nicotine," said Professor Swift of Brown University. "A second important aspect is the finding that rates of smoking are much higher in alcoholics in recovery than in the general population.... Yet, AA tolerates or otherwise does not address smoking in its members."

Dr. Martin said that more detailed analyses of the results will help determine "whether these changes in coffee and cigarette use are predictive of recovery from alcoholism per se."

Photo credit: AA-Carolina.org


alcoholics anonymous smoking nicotine

Chantix and Suicide

Anti-smoking pill joins the list—but is the risk real?

The U.S. Food and Drug Administration fired both barrels last week, announcing that a variety of anti-seizure medications—as well as the anti-smoking pill, Chantix—may increase the risk of suicidal thoughts in patients who take them. The FDA will require new label warnings for a total of 11 drugs used for epilepsy.

New label warnings are also in the works for Chantix, the nicotine cessation aid being widely used by people attempting to quit smoking cigarettes. In a public health advisory issued last Friday, the FDA declared it “increasing likely” that Chantix may be associated with psychiatric problems. A month earlier, the FDA had advised that Chantix users should be monitored for the onset of suicidal urges, but backed off from making a strict cause-and-effect connection.

The FDA reviewed clinical data on anti-epileptic medications, including Pfizer’s Neurontin and Ortho-MacNeil’s Topamax, and concluded that “patients who are currently taking or starting on any anti-epileptic drug should be closely monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.” Topamax has shown additional promise as an anti-craving medication for alcoholism.

This follows on the heels of earlier warnings about increased suicide risk in adolescents taking SSRI antidepressants.

In the case of Chantix, the FDA’s Bob Rappaport, in a conference call with reporters, said the agency had “no definitive evidence there is a causal relationship here, they are just strongly appearing to be related.” Rappaport, quoted at WSJ.com, also said that “Chantix has proven to be effective in smokers motivated to quit,” and that the new warnings would help doctors and patients “make an informed decision regarding whether or not to use this product.”

A spokesman for Pfizer, quoted at Bloomberg.com, said that “no causal relationship has been established. There are some post-marketing reports and you cannot exclude those. We go by our scientific data, and from our clinical trial data we have not seen this.”

Discussions about a possible link between Chantix and suicide were fueled by the death last year of New Bohemians lead singer Carter Albrecht, who was shot while attempting to break into a house in Dallas. His girlfriend told authorities that his behavior had been erratic since he began taking Chantix in an effort to stop smoking.

In no case are the numbers of suicides linked to any of the drugs alarmingly high. The FDA study of epilepsy medications appears to demonstrate, as summed up by the San Francisco Chronicle’s Bernadette Tansey, “2.1 more people for every 1,000 on the medications exhibited suicidal thoughts or behavior, compared with every 1,000 on placebo.”

Note that the FDA is not discussing an increased risk of suicide, but rather an increased risk of suicidal thoughts or feelings. This is called “suicidal ideation.” The FDA usually refers to it as “suicidality.” Unlike an actual suicide attempt, suicidal ideation is the act of contemplating the act—a sort of “what if.” It is the difference, as a mental patient once put it, between buying the rope, and contemplating buying the rope

Persistent suicidal ideation is obviously not a desirable state of mind. But it does not downplay this behavior to note that it is, by nature, often fleeting and difficult to quantify. Moreover, the act of going cold turkey itself can cause heavily addicted people to feel temporarily suicidal—to ideate about killing themselves without killing themselves. These and other factors make it difficult to reach firm statistical conclusions about such risks.

For a Chantix user's point of view on the debate, visit www.stopsmokingcigs.com

Photo Credit: eNews 2.0
nicotine smoking

Nicotine Vaccine Doubles Quit Rate in Human Trials

NicVax still showing promise against cigarette addiction

Nabi Biopharmaceutical announced this week that an experimental vaccine it has been testing against nicotine addiction had shown itself to be effective in human trials. Volunteers were more than twice as likely to quit, compared to a control group whose members were injected with a placebo.

The company-funded study gave volunteers five injections of NicVax, Nabi’s proprietary drug, or else a placebo. In regulatory filings, the company claims that the vaccine triggers an antibody response, which prevents nicotine molecules from reaching the brain. The antibodies bind with the nicotine molecules, making nicotine too large to cross the exceedingly fine blood-brain barrier of the brain. Roughly 15 per cent of smokers who received injections of NicVax were nicotine-free after one year. For comparison, early studies of Chantix as an anti-smoking medication show a quit response rate in the range of 20 per cent for heavy smokers. Studies of NicVax undertaken last year were also positive. It is one of several nicotine vaccines currently under development, and while it is farthest along in the FDA pipeline, it is still a year or two away from any possible commercial introduction.

Vaccines for specific addictive drugs represent one of two different approaches to developing pharmaceuticals for addiction treatment. The other approach, represented by Chantix and Zyban, decreases drug craving by altering the neuroregulation of dopamine and other substances in the brain. In this respect, these two drugs, which are non-addictive, are related to nicotine gums and patches, which also attempt to diminish cravings for cigarettes.

A vaccine like NicVax, however, does not attack the craving for nicotine. It contains no nicotine and is non-addictive. Rather, the vaccine makes the attempt to assuage nicotine cravings an impossible task. And in this respect, NicVax resembles Antabuse for alcoholism--except that the vaccine does not cause the smoker to become seriously ill when he or she takes a puff. . (The company reported that side effects were “well tolerated.”) It simply (or not so simply) cancels out the nicotine high altogether, or at least that is the idea. It is unclear to what extent the antibody reaction prevents nicotine binding in other areas of the body where nicotine-type receptors are found, such as acetylcholine receptors in muscle tissue.

In addition, NicVax must be injected, while Chantix and Zyban or taken orally. “Some people prefer a shot and some people will do anything to avoid one,” Rennard said. “It’s important to have options.”

Stephen Rennard of the University of Nebraska Medical Center, one of the authors of the company’s study, which is funded by a grant from the National Institute on Drug Abuse (NIDA) and is now in midstage, said that when smokers “don’t get the hit they would normally get, it makes it easier for them to quit because smoking doesn’t really do it for them any more.”

The results were presented at the American Heart Association Scientific Sessions in Orlando, Florida. “This double-blind, placebo-controlled trial has demonstrated [that] there is a correlation between antibody level and the ability of patients to quit smoking and remain abstinent over long periods of time,” Rennard told the group. Leslie Hudson, CEO and Interim President of the company, said he was “excited and encouraged.” Nabi Biopharmaceutical, headquartered in Boca Raton, Florida, is traded on the NASDAQ stock market [NABI].

Smoking in New York City

A Borough-By-Borough Survey

New York City has 240,000 fewer smokers than it did in 2002, according to a recent report released by the city’s Department of Health and Mental Hygiene. City health official Jennifer Ellis told the New York Times that the data represent the sharpest fall-off in cigarette smoking since the department began the surveys in 1993.

The report cited bans on smoking in public places, higher taxes on tobacco products, and a multi-million dollar local advertising campaign as the ingredients that helped lead to the overall reduction in the number of smokers. Based on a citywide survey of adults, Who’s Still Smoking states that as many as 800,000 smokers attempted to quit in the past year, but less than one-fifth of them succeeded.

However, quit rates over the 5-year period varied markedly from borough to borough. Staten Island proved to be the home of the city’s most stubborn and recalcitrant smokers: While the citywide smoking rate dropped by almost 20 per cent, Staten Island’s smoking rate—27 per cent, according to the survey--has remained steady since 2002. Manhattan and the Bronx ended in a virtual tie for first place, with smoking reductions of about 24 per cent, while Queens trailed slightly. Brooklyn came in second to last, with a quit rate of only 13 per cent.

On August 21, the Health Department began a nicotine-replacement giveaway program aimed specifically at Staten Islanders. The 5-week giveaway and associated media campaign will run Tuesdays through Thursdays at the Staten Island Ferry’s Whitehall Terminal.

Men still lead women in smoking, 20 per cent to 15 per cent overall, but the report claims that quit rates are similar for both sexes. Low-income adults and adults without a high school education are more likely to attempt quitting by a slight margin, but less likely to be successful per attempt. One important side note: A separate analysis of survey data showed that only 11 per cent of heavy drinkers who smoke were able to quit in the past year.

The average pack-a-day smoker now spends $2,500 a year to support his or her habit. Health officials stressed that the use of nicotine replacement, either as patches or gum, along with anti-craving medications like Zyban and Chantix, can at least double a smoker’s chances of successfully getting free.

Information in the report was gathered through a random telephone survey of 10,000 adult New Yorkers.

Image courtesy of the National Library of Medicine.

smoking

European Tree Yields New Alcoholism Treatment in Early Tests

Anti-Smoking Drug Also Curbs Alcohol Craving

A drug approved last year for smoking cessation has also shown promise for use against alcoholism, researchers at the University of California, San Francisco (UCSF), announced yesterday.

Varenicline, currently marketed by Pfizer for smoking cessation under the trade name Chantix, dramatically curbed drinking in alcohol-preferring rats, according to the study, which will be published online this week by “The Proceedings of the National Academy of Sciences.”

The synthetic drug was modeled after a cytosine compound from the European Labumum tree, combined with an alkaloid from the poppy plant.

Since an estimated 85 per cent of alcoholics are also cigarette smokers, varenicline could have an immediate effect on this common dual addiction. The drug has already been approved by the Food and Drug Administration (FDA) for human use, so Pfizer is likely to be granted a speedy approval for the new indication, sources say. The drug is likely to join Antabuse (disulfiram), Revia (naltrexone), and Campral (acamprosate) as FDA-approved treatments for alcoholism.

Selena Bartlett of the UCSF-affiliated Gallo Clinic and Research Center, a co-author of the study, said that the drug works by disrupting the neuronal “reward pathway” of the brain. Specifically, the drug binds to acetylcholine receptors, a neurotransmitter involved in arousal and attention. Through a cascade effect, stimulating these receptors causes a release of dopamine, one of the primary pleasure chemicals in the brain. Varenicline prevents alcohol and nicotine from causing a release of dopamine at those sites.

“Treatments for alcoholism today are like those for schizophrenia in the ‘60s,” Bartlett said. “People don’t talk about it. There are very few treatments, and most drug companies are not interested in it.”

Bartlett said she hoped the research would spur additional studies of drugs for alcoholism. “It’s a disease. If you’ve inherited a gene variant, of if some other cause leads you to alcohol dependence, it should be treated--like any disease.”

Sources:

“Drug to curb smoking also cuts alcohol dependence.” University of California, San Francisco, News Office. 09 July 2007. http://pub.ucsf.edu/newsservices/releases/200707063/

“Need a Cigarette and a Cocktail? Just Pop a Pill Instead.” ScientificAmerican.com July 09, 2007

New Drug For Smokers

First there was Wellbutrin, an antidepressant which helped cut down on the cravings and nicotine withdrawal symptoms for many addicted smokers when it was marketed as the smoking cessation aid Zyban. In May, the Food and Drug Administration (FDA) okayed a second medication for the treatment of nicotine addiction. Chantix, the trade name for varenicline tartrate, works on the dopamine system to reduce withdrawal and craving symptoms, like Zyban. In randomized, placebo-controlled clinical studies involving more than 3,500 smokers, Chantix outperformed both placebos and Zyban. Common side effects included nausea, headache and vomiting. Two studies published in the Journal of the American Medical Association (JAMA) showed that about 22 per cent of smokers on Chantix were abstinent at the one-year mark, compared to 15 per cent for Zyban, and 9 per cent for placebos.

Zyban and Chantix are frequently used by doctors in combination with nicotine replacement therapy, such as gum or patches. Zyban was the first major success story in the burgeoning field of pharmacological treatments for addiction--fighting fire with fire.

According to the Centers of Disease Control and Prevention (CDC), more than 44 million American adults continue to smoke cigarettes, a fifth of whom suffer from smoking-related illnesses.

See more on anti-craving drugs at http://dirkhanson.org

Sources:

--”FDA Approves Novel Medication for Smoking Cessation.” U.S. Food and Drug Administration. www.fda.gov/bbs/topics/NEWS/2006/NEW1370.html. May 11, 2006.

Kotulak, Ronald. “New Drug Shows Promise in Helping Smokers Quit.” Chicago Tribune July 5 2006.