Cannabis and Cancer

 
Canada considers the case.

The link between cigarette smoking and respiratory disease is irrefutable. But what about pot smoking? A long history of contentious argument and clinical inference has left the picture as fuzzy as ever. Despite strenuous efforts to prove the case, the evidence remains ambiguous.

The Canadian Centre on Substance Abuse in Ottawa recently released an analysis of current evidence, “Clearing the Smoke on Cannabis: Respiratory Effects of Cannabis Smoking.” (PDF). In the report, prepared in 2009 by the Centre for Criminal Justice Research at the University of the Fraser Valley, Jordan Diplock and Darryl Plecas assess the argument that cannabis poses similar risks to the airways as tobacco, primarily due to the tar content of cannabis. It is sometimes argued that cannabis is even more dangerous than tobacco, due to the deeper inhalations and breath-holding manner of smoking typical of pot smokers. The well-known style of high, tight exhalations, while tightening the abdomen, is meant to increase the absorption of THC in the lungs. It is similar to the so-called Valsalva Maneuver, which increases thoracic cavity pressure through forcible exhalation against a closed airway, such as holding one’s nose and attempting to “pop” one’s ears.

Earlier studies by Moore and others had confirmed that “common self-reported respiratory problems include coughing on most days, wheezing, shortness of breath after exercise, nocturnal chest tightness, chest sounds without a cold, early morning phlegm and mucus, and acute and chronic bronchitis. These symptoms were associated to cannabis smoking even when gender, age, tobacco smoking, and asthma were controlled.” Nonetheless, the majority of cannabis smokers in such self-reported results were frequently cigarette smokers as well, making it difficult to assess the health risk such negative respiratory symptoms represent.

A study by Aldington and colleagues in New Zealand in 2008 reported that the risk of lung cancer “increased by 8% for each joint-year of cannabis smoking after adjusting for various confounding variables, including tobacco smoking.”  However, a significant degree of what researchers call “recall bias” may be at work in retrospective studies of this kind. Other studies that found connections have been hospital-based, which can introduce selection bias and other problems.

A 1997 retrospective study of more than 64,000 people in California  found exactly the reverse: “Current and ever-cannabis use (defined as use of cannabis six or more times over a lifetime) was not associated with an increased risk of cancer overall,” after adjusting (or attempting to adjust) for the usual factors like drinking and smoking.  The problem here is that there is no way of knowing whether these studies manage to capture a sufficient number of heavy, long-term marijuana smokers.

Smoking aside, what about the contention that THC in the lungs can damage respiratory tissue? The idea that THC causes immune system deficiencies, which, in turn, hinder the ability of the lungs to fight off pathogens, has been around for some time. But again, the evidence remains inconclusive. In fact, some evidence points in the other direction entirely. By curbing a substance called epidermal growth factor (EGF), THC may in fact confer a protective effect, inhibiting the growth of certain tumors. THC “seems to have a suppressive effect on certain lines of cancer cells,” according to a pulmonary specialist at New York’s Lenox Hill Hospital, quoted in a HealthDay article by reporter Amanda Gardner.

The Canadian authors caution that these inhibitory effects “have been demonstrated using THC (not cannabis smoke) in preclinical models, and do not necessarily imply that exposure to cannabis smoke can prevent cancer occurrence in humans.”

The problem is that, over the past ten years, these conflicting studies suggest either that: a) There is no association between cannabis smoking and an increased risk of chronic obstructive pulmonary disease (COPD), or b) There is a serious risk of COPD in people who smoke both marijuana and tobacco. Unfortunately, there is no c) There is (or is not) evidence of elevated COPD risk among people who smoke pot but not tobacco. And while there is always reason to speculate that sustained pot smoking could put users at risk for pulmonary problems, the authors of the Canadian report concede that the state of the research “is too limited to provide estimates of the prevalence of these and other serious health threats.”

So, the picture remains out of focus. Does pot smoking raise the risk of respiratory diseases, including lung cancer? We still don’t know.  The limited research literature remains wholly inconclusive, and the current connection between lung cancer and cannabis smoking remains weak at best.

Common sense suggests that inhaling hot vegetable matter that has been dried for smoking can’t be a terrific idea on the long run. The Canadian authors make a pitch for vaporizers as a harm-reduction  approach to marijuana smoking. Vaporizers heat the active cannabinoids enough to produce vapors but do not produce enough heat for combustion of the plant material.

Cocaine Vaccine Hits Snag

Some addicts risk OD to overcome its effects.

The National Institute on Drug Abuse (NIDA) has increasingly placed its bets on treating cocaine addiction with a vaccine rather than an anti-craving medication. And there is reason for this: No prominent candidates for anti-craving drug treatments have yet emerged from the research on cocaine and methamphetamine addiction.

However, there’s a catch: Some cocaine addicts appear willing to risk overdose in order to defeat a new cocaine vaccine, a recent study has shown.

The study, which appeared in the Archives of General Psychiatry, demonstrated that the TA-CD vaccine could blunt the effects of cocaine in some, but not all, patients. The vaccine works by causing the production of antibodies, which attach themselves to cocaine molecules, making the molecules too big too pass effectively through the blood-brain barrier.

Of 115 addicts involved in the study, only 38 % produced sufficient antibodies to dull the effects of cocaine, Rachel Saslow of the Washington Post  reported. And among the high-antibodies group, only 53 % stayed free of cocaine 50 % of the time. “Immunization did not achieve complete abstinence from cocaine use,” said Thomas Kosten of Baylor college of Medicine, one of the authors of the paper.

Moreover, in some of the study participants for whom antibodies made cocaine a disappointing high, researchers found cocaine levels in the body to be as much as ten times higher than previous levels of usage—an obvious attempt to overcome the vaccine’s effectiveness. There were no overdoses, according to Kosten.

No researcher has claimed this as a complete breakthrough, in light of the fact that even those who responded well in the high-antibody group achieved a substantial reduction in cocaine use during the study period--but not abstinence. At this stage the work appears to be aimed more at dose reduction.

Despite the mixed results, NIDA director Nora Volkow characterized the work as “a promising step toward an effective medical treatment for cocaine addiction,” with the proviso that “larger follow-up studies confirm its safety and efficacy.” In an earlier interview with Addiction Inbox, Volkow also expressed excitement about another possible addiction vaccine: “Currently there are anti-nicotine vaccines in clinical testing, which are designed to capture the nicotine molecules while still in the bloodstream, thus blocking their entry in to the brain and inhibiting their behavioral effects. They appear to be effective in helping subjects who develop a high antibody response sustain abstinence over long periods of time. Even those people with a less robust antibody response to the vaccine, decreased their tobacco use. So this approach appears very promising.”

An earlier study by Margaret Haney and others at Columbian University Medical Center, published in Biological Psychiatry, had similar results: “The TA-CD vaccine substantially decreased smoked cocaine's intoxicating effects in those generating sufficient antibody.”

In both studies, roughly a quarter of participants made almost no antibodies at all in response to a vaccine injection.

A multi-site clinical trial of the vaccine, headed up by Kosten at Baylor, will begin sometime this spring.

Haney of Columbia told the Washington Post that people “have a mistaken view of how a vaccine might work, thinking of it as magic, where what it’s doing, at best, is blunting the effects. They get very excited, and it’s heartbreaking.” An earlier Addiction Inbox post on cocaine vaccination brought several emails from people asking where they could obtain the vaccine.

DrugMonkey at scienceblogs.com dissected the complicated study, particularly the different levels of antibodies generated in study participants, calling the vaccine “quite obviously not a silver bullet at present.” Furthermore: “Even for the high-responders the outcome was far from overwhelming, a 10 percentage improvement from 35% to 45% cocaine-free urines.” 

Given how intractable to treatment addiction to stimulants has proven, any promising results at all are cause for cautious optimism. DrugMonkey writes: “We need new approaches and this immunopharmacotherapy stuff has potential.”

Photo Credit: http://addictions.about.com/b/2009/10/10/new-cocaine-vaccine.htm

Leave E-Cigarettes Alone, Judge Tells FDA

Ruling halts FDA confiscations.

The Food and Drug Administration (FDA) lost its battle Thursday to keep electronic cigarette manufacturers from bringing e-cigarettes to America. According to a report in the Washington Post, U.S. District Judge Richard J. Leon “determined that electronic cigarettes are tobacco products and are not subject to such restrictions.” The FDA had been contending that e-cigarettes were in fact novel and untested drug delivery devices, and as such, had not been approved by the agency for sale to U.S. consumers.  "This case appears to be yet another example of FDA's aggressive efforts to regulate recreational tobacco products as drugs or devices," the judge wrote in his decision.

The FDA had been confiscating imports of e-cigarettes but had not put together an entirely coherent strategy with respect to the smokeless electronic cigarettes, which heat liquid nicotine into an inhalable vapor. Two suppliers of e-cigarettes brought suit against the agency for the confiscations.  According to the Washington Post article, the judge took a further slap at the FDA, callings its stance on e-cigarettes a “tenacious drive to maximize its regulatory power."

For its part, the FDA maintains that e-cigarettes are more akin to nicotine gum, which is subject to  FDA regulation. The agency also questions claims by e-cigarette manufactures that their products "alleviate nicotine withdrawal symptoms." Furthermore, the FDA has voiced health concerns, based on studies showing that electronic cigarettes contain carcinogens and toxic chemicals such as diethylene glycol. (See my earlier post). The e-cigarette makers had argued before the judge that their products are not substantially different than the Marlboros and Salems sold everywhere.

According to the Wall Street Journal: “Health groups including the American Lung Association have called for e-cigarettes to be removed from the market, saying their safety is unproven and children may be attracted to them.”

As a reader commented on another e-cigarette post here: “I think it will be interesting to see how this all plays out. Judge Leon just gave the FDA a slap for trying to stop the import of e-cigs, some places are allowing them because it doesn't violate the Clean Air act and some places, like NJ are restricting the sale and use. We'll see a lot of battles over the next year or two.”

Graphics Credit: http://topnews.net.nz/

The Addiction Inbox Top Ten

A rundown of the most popular posts.

What are readers of Addiction Inbox interested in? Although scarcely scientific, a look at the most-viewed posts here over the past couple of years is indicative of general interest—or at least indicative of the general drift of Google searches on topics related to addiction and drugs.

Ranked by overall page views, from most to least, here are the ten most-visited blog posts on Addiction Inbox:

1. Marijuana Withdrawal

The most popular post on Addicton Inbox by a considerable margin. With almost 700 reader comments, this post has evolved into a message board for people having problems related to marijuana dependence and withdrawal. Very interesting first-person stuff attached to a rather straightforward post. Continues to grow like Topsy.

2. Is Marijuana Addictive?

A continuation of the discussion of marijuana withdrawal, or, as the director of the National Institute on Drug Abuse (NIDA) Nora Volkow calls it, “cannabis withdrawal syndrome.” 100 reader comments thus far.

3. Serotonin and Dopamine: A Primer

Sometimes you just gotta get back to basics.  Inquiring readers want to know.

4. E-Cigarettes and Health

A lively debate on the new, smokeless nicotine delivery system. Electronic cigarettes use batteries to convert liquid nicotine into a heated mist that is absorbed by the lungs. The latest in harm reduction strategies, or starter kits for youngsters?

5. Topamax for Alcoholism: A Closer Look

Another good response to a medical post about a drug for seizure disorders and migraines that shows promise as an anti-craving drug for alcoholism. People are getting more accustomed to hearing about medications for addiction.

6. Bill to Legalize Marijuana Offered in U.S.

Not a big surprise.

7. Marijuana Withdrawal Rivals Nicotine

Another comment-heavy post concerning a controversial study of withdrawal effects from smoking cigarettes and pot.

8. Anandamide: The Brain’s Own Marijuana

Something of a merger here between two consistently popular topics--cannabis and brain science. After the Sanskrit “ananda,” meaning bliss.

9. Food Addiction and Dopamine

Readers seem to take seriously the notion that certain forms of overeating are substance addictions.  This post focused on sugar's drug-like effect on the nucleus accumbens, a dopamine-rich brain structure in the limbic system.

10. Coffee Addiction

Increased tolerance, craving, and verifiable withdrawal symptoms--the primary determinants of addiction--are easily demonstrated in victims of caffeinism.

Risky Drinking

 

The one-question questionnaire.

Answer: Once or twice.

Question: “How many times in the past year have you had 5 or more drinks (for men), or 4 or more drinks (for women) in a single day?"

A recent study published in the Journal of Internal Medicine strongly suggests that this simple question identifies those drinkers at risk for alcohol use disorders roughly 75 % of the time.  While the one-question screening test has been endorsed by both the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for several years, little clinical evidence existed for assuming that it worked. 

It seems weirdly unrealistic as a standard measure, leaving out, as it does, so many other telling features of active alcoholism. Nonetheless, the group at the Boston University School of Medicine that conducted the research concluded that “the single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in the sample of primary care patients.”

It seems safe to assume that the majority of people who occasionally overdrink are not alcoholics. Is the occasional binge or bender by recreational drinkers really that rare? In a research summary comment on the results, Dr. Peter D. Friedmann opens up the possibility of using the one-question screen to “facilitate more discussion of heavy episodic (binge) drinking, a major source of adverse consequences among nondependent drinkers.”

Five or more drinks, on a single occasion in the past year? Is that really sufficient data? Is a response of  >1 really a genuine cause for concern?

But it gets even stranger. In 2006, the Journal of Studies on Alcohol published a primary care validation study which showed that narrowing the criteria to one incident in three months did not significantly change the results. When the choices available were “within 3 months,” “within 12 months,” “ever,” or “never,” the 3 month and 12 month positive answers were predictive of risky consumption levels about 75% of the time in a study of 625 patients.

One conclusion to be considered is that “normal,” non-alcoholic drinking males rarely—if ever—consume more than 5 drinks in one evening (4 for women). For heavier drinkers, this seems an impossibly Puritan standard, and useless as a diagnostic tool.  As usual, more studies are needed. But the authors of the 2006 paper were confident enough to conclude: “A single question about the last episode of heavy drinking is a sensitive, time-efficient screening instrument that shows promise for increasing alcohol screening in primary care practices.”

Photo Credit: http://talesblog.com/2008/07/19/highlights-of-tales-so-far/

Serotonin Syndrome

Too much of a good thing.

Serotonin syndrome is a rare but potentially deadly condition that results from the combination of two or more serotonin-boosting drugs. Taken in sufficient quantities, the drugs can lead to a serotonin overdose. The symptoms of serotonin syndrome range from mild flushing, muscle jerks, and rapid pulse to fever, hypertension, disorientation, respiratory problems, destruction of red blood cells, seizures, and kidney failure. 

No one knows exactly how often it occurs, since most cases are thought to resolve without further problems within 24 hours after discontinuation of the serotonin-boosting drugs in question. Serotonin syndrome was characterized in animal models years ago, and is probably rare enough to merit little more than a passing notice if not for the variety of serotonin-boosting drugs and medicines continually coming to market. Demerol, the pain reliever, and dextromethorphan, the cough remedy, are another good example of a bad serotonin combination. There is also concern about combining serotonin drugs with over-the-counter diet suppressants. Large hits of Ecstasy or LSD are not recommended, either, although Prozac has long been used informally as a “morning after” drug following a long night on Ecstasy. (Self-prescribing of this kind is foolish and dangerous.) Other problematic combinations include SSRI antidepressants and any of the following: Selegiline (used for Parkinson’s), Linezolid, Risperidone, Haldol, the analgesic Tramadol, Hismanal, St. Johns Wort, certain forms of antiretroviral therapy, and Sumatriptan for migraine.

The most dangerous combination of all is an SSRI medication taken with a strong MAO inhibitor. There have been reports of fatal interactions between SSRIs and MAOIs. MAO inhibiting drugs themselves do not combine well with a long list of other drugs, and there are dietary restrictions that go with taking any monoamine oxidase inhibitor. Here again, prescribers and drug makers have not always taken sufficient care to explain these basic facts to users of prescription MAOIs like Marplan, Parnate, and Nardil. St. John’s Wort and Ecstasy also inhibit monoamine oxidase. Similar problems can occur when MAOIs are combined with stimulants like speed or cocaine.

Foods containing high levels of the amino acid tyramine stimulate the release of norepinephrine, and this buildup can lead to a form of norepinephrine overdose—a hypertensive reaction caused by interaction with MAOIs, which block the reabsorption of norepinephrine. The syndrome is marked by intense headache, nausea, and soaring blood pressure. Serious cases lead to cardiac failure, or intracranial hemorrhage. Foods on the danger list for users of MAO inhibitors include, but are not limited to, large amounts of the following: Chianti wine, vermouth, bean curd, dietary protein supplements, certain cheeses, smoked or aged fish and meat, sausages, sauerkraut, miso soup, and Brewer’s yeast. Drugs to be avoided, in addition to the aforementioned, include Ritalin, asthma inhalers, Tegretol, psuedoephedrine, ephedrine, and others. (As always, check with your doctor about drug combinations).

Not all physicians are familiar with the presenting symptoms of serotonin syndrome (or the details of the MAOI diet). In an emergency, cyproheptadine or propranolol, which are serotonin-blocking drugs, can be administered. Though rare, it is possible to cause serotonin syndrome in drug-sensitive people with high doses of a single serotonin-boosting drug.

From The Chemical Carousel By Dirk Hanson, pp. 281-283.  © Dirk Hanson, 2008.

          

Diurnal Drinking

Casting a light on circadian disruptions.

Scientists and laypeople alike have known for years that the consumption of alcohol interferes with the body’s biological ability to synchronize its daily activities with light. Disruptions of the body clock due to alcohol increase the risk of cancer, depression, and other health problems. Furthermore, a recent animal study showed that the effect of alcohol on sleeping patterns could be detected several days after the last drinking event.

Alcohol’s chronobiological effects grow more profound as steady consumption continues. Previous research has demonstrated the disruptive function of alcohol on melatonin rhythms, body temperature and glucocorticoid release.  Disturbingly, recent research suggests that such disruptions along the hypothalamic-pituitary-adrenal axis may predispose alcoholics to relapse—a vicious hormonal feedback cycle. In a study on hamsters published in the American Journal of Physiology, researchers at Kent State University and the University of Tennessee describe “a feedback cycle of circadian rhythm deterioration and reinforcing alcohol self administration” mediated by glutamate and NMDA-driven “phase resetting of the circadian clock.”

The study separated drinking from non-drinking hamsters, and subjected both groups to light exposure in order to break up the regular diurnal wake/sleep cycle of the animals.  Hamsters that drank only water during the test woke up 72 minutes earlier than normal, while hamsters drinking 20% alcohol did not reset their internal clocks as acutely, waking up only 18 minutes earlier.

However, as Christine Guilfoy wrote for Medical News Today, “When the hamsters were withdrawn from alcohol for 2-3 days and then exposed to the same light treatment again, they woke up much earlier than the animals that had drunk only water. The hamsters that were withdrawn from alcohol woke up 126 minutes sooner compared to the water drinking control group, which advanced 66 minutes. This exaggerated response persisted even up to three days later, when the experiment ended.”

Bearing in mind that drawing conclusions about human brain behavior from animal studies is unavoidably speculative, what possibilities emerge from this study? From the short-term perspective, the researchers note that people who drink alcohol late at night are probably less likely to respond appropriately to light cues, and therefore less likely to keep their biological clocks synchronized over the next 24 hours. Moreover, this circadian disruption from drinking may continue for several days, like jet lag, even after a complete abstention from alcohol.

The researchers also discovered that the drinking animals had fewer bouts of activity during normally active hours, leading to the suggestions that heavy drinkers may be less active during normally active daytime hours, and more active late at night, when chronobiological systems are signaling for sleep. The result: chronic daytime sleepiness.

The major point of the study may be that “brain systems involved with circadian regulation are closely and reciprocally tied to those underlying alcohol abuse,” and that this connection has been underscored “by recent studies showing a link between circadian clock genes and an increased drive for alcohol consumption.”