The Chemistry of Modern Marijuana

Is low-grade pot better for you than sinsemilla?

First published September 3, 2013.

Australia has one of the highest rates of marijuana use in the world, but until recently, nobody could say for certain what, exactly, Australians were smoking. Researchers at the University of Sydney and the University of New South Wales  analyzed hundreds of cannabis samples seized by Australian police, and put together comprehensive data on street-level marijuana potency across the country. They sampled police seizures and plants from crop eradication operations. The mean THC content of the samples was 14.88%, while absolute levels varied from less than 1% THC to almost 40%.  Writing in PLoS ONE, Wendy Swift and colleagues found that roughly ¾ of the samples contained at least 10% total THC. Half the samples contained levels of 15% or higher—“the level recommended by the Garretsen Commission as warranting classification of cannabis as a ‘hard’ drug in the Netherlands.”

In the U.S., recent studies have shown that THC levels in cannabis from 1993 averaged 3.4%, and then soared to THC levels in 2008 of almost 9%. THC loads more than doubled in 15 years, but that is still a far cry from news reports erroneously referring to organic THC increases of 10 times or more.

CBD, or cannabidiol, another constituent of cannabis, has garnered considerable attention in the research community as well as the medical marijuana constituency due to its anti-emetic properties. Like many other cannabinoids, CBD is non-psychoactive, and acts as a muscle relaxant as well. CBD levels in the U.S. have remained consistently low over the past 20 years, at 0.3-0.4%. In the Australian study, about 90% of cannabis samples contained less than 0.1% total CBD, based on chromatographic analysis, although some of the samples had levels as high as 6%.

The Australian samples also showed relatively high amounts of CBG, another common cannabinoid. CBG, known as cannabigerol, has been investigated for its pharmacological properties by biotech labs. It is non-psychoactive but useful for inducing sleep and lowering intra-ocular pressure in cases of glaucoma.

CBC, yet another cannabinoid, also acts as a sedative, and is reported to relieve pain, while also moderating the effects of THC. The Australian investigators believe that, as with CBD, “the trend for maximizing THC production may have led to marginalization of CBC as historically, CBC has sometimes been reported to be the second or third most abundant cannabinoid.”

Is today’s potent, very high-THC marijuana a different drug entirely, compared to the marijuana consumed up until the 21st Century? And does super-grass have an adverse effect on the mental health of users? The most obvious answer is, probably not. Recent attempts to link strong pot to the emergence of psychosis have not been definitive, or even terribly convincing. (However, the evidence for adverse cognitive effects in smokers who start young is more convincing).

It’s not terribly difficult to track how ordinary marijuana evolved into sinsemilla. Think Luther Burbank and global chemistry geeks. It is the historical result of several trends: 1) Selective breeding of cannabis strains with high THC/low CBD profiles, 2) near-universal preference for female plants (sinsemilla), 3) the rise of controlled-environment indoor cultivation, and 4) global availability of high-end hybrid seeds for commercial growing operations. And in the Australian sample, much of the marijuana came from areas like Byron Bay, Lismore, and Tweed Heads, where the concentration of specialist cultivators is similar to that of Humboldt County, California.

The investigators admit that “there is little research systematically addressing the public health impacts of use of different strengths and types of cannabis,” such as increases in cannabis addiction and mental health problems. The strongest evidence consistent with lab research is that “CBD may prevent or inhibit the psychotogenic and memory-impairing effects of THC. While the evidence for the ameliorating effects of CBD is not universal, it is thought that consumption of high THC/low CBD cannabis may predispose users towards adverse psychiatric effects….”

The THC rates in Australia are in line with or slightly higher than average values in several other countries. Can an increase in THC potency and corresponding reduction in other key cannabinoids be the reason for a concomitant increase in users seeking treatment for marijuana dependency? Not necessarily, say the investigators. Drug courts, coupled with greater treatment opportunities, might account for the rise. And schizophrenia? “Modelling research does not indicate increases in levels of schizophrenia commensurate with increases in cannabis use.”

One significant problem with surveys of this nature is the matter of determining marijuana’s effective potency—the amount of THC actually ingested by smokers. This may vary considerably, depending upon such factors as “natural variations in the cannabinoid content of plants, the part of the plant consumed, route of administration, and user titration of dose to compensate for differing levels of THC in different smoked material.”

Wendy Swift and her coworkers call for more research on cannabis users’ preferences, “which might shed light on whether cannabis containing a more balanced mix of THC and CBD would have value in the market, as well as potentially conferring reduced risks to mental wellbeing.”

Graphics Credit: http://www.ironlabsllc.co/view/learn.php

Swift W., Wong A., Li K.M., Arnold J.C. & McGregor I.S. (2013). Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile., PloS one, PMID: 23894589

Marijuana Dependence and Legalization

Making best guesses about pot.

One essential question about state marijuana legalization continues to dog the debate:  Namely, as marijuana becomes gradually legal, how do we estimate how many people will become dependent? How can we estimate the number of cannabis users who will become addicted under legalization, and who otherwise would not have succumbed?

Back in 2011, neuroscientist Michael Taffe of the Scripps Research Institute in San Diego, writing on the blog TL neuro, referenced this common question, noting that “the specific estimate of dependence rate will quite likely vary depending on what is used as the population of interest… Obviously, changing the size of the underlying population is going to change the estimated rate….”

But change it how, and by how much? The truth is, we don’t know. We can’t know in advance. There are sound arguments for both positions: Legal marijuana will lead to increased rates of cannabis addiction because of lower price and greater availability. On the other hand, almost everybody likely to become addicted to marijuana has probably already been exposed to it, including teens.

What we can start attempting to find out with greater rigor, however, is this: How many chronically addicted marijuana users are out there right now?

In The Pathophysiology of Addiction  by George Koob, Denise Kandel, and Nora Volkow (2008), the base rate of cannabis dependence was estimated to be 10.3% for male users and 8.7% for female users. Their data came from the National Survey on Drug Use and Health, and the rate is similar to common estimates for prescription stimulant addiction. The dependence rate for cigarettes is at least three times as high. However, an overall dependence rate of 9.7%, when men and women smokers are combined, is the origin of the highly contested figure of 10%.

Since then, other databases have been tapped for estimates of existing cannabis dependence. In October of 2013, using the Global Burden of Disease database maintained by the World Bank, British and Australian researchers, along with collaborators at the University of Washington in the U.S., published revised estimates in the open-access journal PLOS ONE, based on numbers from 2010.  The scientists culled and pooled a series of epidemiological estimates and concluded that roughly 11 million cases of cannabis dependence existed worldwide in 1990, compared to 13 million cases in 2010. This boost can be accounted for in part by population increases.

Are these dependent users distributed evenly across the globe? They are not. The PLOS ONE paper demonstrates that marijuana use is markedly more prevalent in certain regions: “Levels of cannabis dependence were significantly higher in a number of high income countries including Australia, New Zealand, the United States, Canada, and a number of Western European countries including the United Kingdom.” High income equals high marijuana usage and dependence—“Cannabis dependence in Australasia was about 8 times higher than prevalence in Sub-Saharan Africa West.” But there may be major holes in the epidemiological database: “This is particularly the case for low income countries, where there is typically limited information on use occurring, even less on levels of use, and usually no data on prevalence of dependence.”

In conclusion, the researchers found an age and sex-standardized cannabis addiction prevalence of 0.2%. “Prevalence was not estimated to have changed significantly from 1990, although increased population size produced an increase in the number of cases of cannabis dependence over the period.”

In another 2008 study, this one published in the Journal of Clinical Psychiatry, scientists at Columbia University and the New York State Psychiatric Institute looked at a set of 2,613 frequent cannabis users, using the development of significant withdrawal symptoms as the leading indicator. About 44% of regular dope smokers experienced two or more cannabis withdrawal symptoms, while about 35% reported three or more symptoms. The most prevalent symptoms in this study were fatigue, weakness, anxiety, and depressed mood. “Over two-thirds smoked more than 1 joint/day on days they smoked during their period of heaviest use; mean joints smoked/day was 3.9. About one-fifth had primary major depression….”

Age of onset was not predictive of withdrawal symptoms in this large study. The investigators suggest that “irritability and anxiety may receive great clinical consensus as regular features of cannabis withdrawal because they are subjectively and clinically striking compared to fatigue and related symptoms.” The researchers also speculate that somatic symptoms of weakness and fatigue might be attributed to varying levels of THC, compared to the presence of other cannabinoids such as CBD. The study is further evidence supporting an “association of primary panic disorder or major depression with cannabis depression/anxiety withdrawal symptoms,” suggesting a “possible common vulnerability, meriting further investigation.”

One of the reasons this matters is because of the very tight relationship between marijuana addiction and major depressive disorder. A 2008 study of young adults in the journal Addictive Behaviors  found that participants with comorbid cannabis dependence and major depressive disorder, the most commonly dependence symptom was withdrawal, reported by more than 90% of the subjects in the study. 73% of the subjects experienced four symptoms or more. After that, the most common symptoms were irritability (an underreported but significant behavioral problem), restlessness, anxiety, and a variety of somatic symptoms, including gastrointestinal problems, loss of appetite, and sleep disturbances, including night sweats and vivid dreaming. The authors, affiliated with University of Pittsburgh School of Medicine, concur with the conclusion of earlier researchers:  “Given the weight of evidence now supporting the clinical significance of a cannabis withdrawal syndrome, the burden of proof must rest with those who would exclude the syndrome….”

Clearly, cannabis does not contribute to the world disease burden in the same way that alcohol, nicotine, and opiods do. However, it’s fair to say that for a minority of users, cannabis dependence causes disabilities and liabilities that are not always trivial.

Mark A. R. Kleiman, a Professor of Public Policy at UCLA and a consultant to the state of Washington on marijuana legalization, told PBS:

The couple of million who stay stoned all day, every day, account for the vast bulk of the total marijuana consumed, and thus the total revenues of the illicit marijuana industry. That's typical. The money in any drug, including alcohol, is in the addicts, not the casual users. There was a big fuss during the 80s about how much casual middle-class drug use there was and how respectable folks were supporting the markets. It's certainly true that most people who are illicit drug users are employed, stable respectable citizens. But it doesn't follow that if we could get the employed, stable respectable citizens to stop using illicit drugs, the problem would mostly go away.

Does Strong Marijuana Cause Addiction?

Strong pot matters, but maybe not the way we think.

Colorado, Washington, and some 20 additional states have now made various provisions for legal transactions involving marijuana. And since time immemorial, there has been an illegal market for marijuana. But try getting your hands on some marijuana straightforwardly, through appropriate channels, for purposes of medical research, and, well, most researchers have just said forget it.

Because in the U.S., a bizarre system of drug classification has led to the ludicrous situation of a virtual government monopoly on cannabis for experimental purposes. Can’t researchers just walk around this roadblock and procure pot in some manner that is legal in their state? No, they cannot—not if they want any serious research grants, or publication in refereed journals. Without the federal government imprimatur, marijuana research isn’t kosher, and could put researchers at legal risk. Researchers who go through channels report frequent and unpredictable delays, and this has been true for decades. Yet millions of recreational marijuana users can secure a supply of the drug, often accompanied by specific genetic information, often with relatively little effort.

The Drug Enforcement Administration (DEA) has refused to budge on its opposition to petitions for reclassification of cannabis. A recent Washington Post article  attributed the problem to “stigma associated with the drug, lack of funding and legal issues…. Scientists say they are frustrated that the federal government has not made any efforts to speed the process of research.”

However, as almost everyone knows, things are different in The Netherlands. It isn’t a big problem for researchers at the University of Amsterdam and elsewhere in that country to engage in behavioral studies of actual marijuana smokers. Participants in a recent study, the results of which appear in Addiction, were even allowed to use their own weed. (Thanks to Ivan Oransky for bringing this study to my attention.) The thesis being tested by Peggy van der Pol and colleagues is a familiar one: Do marijuana smokers “titrate” very strong pot—that is, do they modify their smoking/dosing behavior accordingly, in order to reduce overall THC exposure? If so, just because a cannabis user is ingesting high-THC plant material doesn’t mean that his or her THC blood levels are that much higher than smokers of less potent weed. But if this is NOT true—if smokers of strong pot are boosting their THC exposure significantly, the results could conceivably include impaired driving and greater rates of marijuana addiction.

Most studies that attempt to estimate the risk of cannabis dependence in pot smokers rely on a familiar yardstick—the number of days a smoker smokes per month. Dosing behavior, and other behavioral aspects of marijuana smoking that affect THC exposure, are usually ignored. The Dutch researchers found that, in a group of 600 frequent cannabis users, some smokers did in fact show “shorter puff duration and inhaled lower smoke volumes when joints with a higher THC concentration were used.” So, yes, users did engage in partial titration when they smoked stronger marijuana. However, this did not translate into the expected results. In a final sample of 98 participants, the scientists discovered that “users of stronger cannabis generally used larger amounts of cannabis to prepare their regular joint.” (The study participants smoked marijuana European-style, mixing their marijuana with tobacco.) And even though subjects smoking joints with higher THC levels did inhale at slightly lower volumes and at a slower pace, the average user of pot with THC levels of 12% or higher definitely inhaled more liters of smoked THC per month than users of less potent pot. But just to confound matters, total THC exposure over a month’s time turned out to be “a weak predictor of dependence severity, and did not remain significant after adjustment for baseline dependence severity.”

Nonetheless, even with some degree of titration, “a positive association between total puff volume and withdrawal/craving was found, indicating that a larger inhaled volume may increase the THC exposure sufficiently to result in significant effects on clinical outcomes.” (Here is the UK National Health Service take on the research.) 

It is always difficult to say for certain in a prospective, cross-sectional study of behavior whether participants are acting the way they would act in “real life,” although efforts were made to allow smoking at home, or in Dutch coffee shops, as well as the laboratory. Interestingly, the one behavior that seemed to predict dependence in post-hoc analyses was a simple one. Smokers were allowed to mix a joint however they wished, and smoke however much of it they wanted to. Smokers who finished their joints, rather than leaving a portion of it for later, were the smokers more likely to be associated with dependence in the follow-up studies. In fact, “percentage of the joint smoked may be a simple proxy for risky smoking behavior.”

In addition, certain withdrawal symptoms correlated with dependence: “Increased somatic withdrawal symptoms are predictive of relapse, and…. increased physical tension is a significant predictor of relapse.”

As with alcohol, it seems that it is not necessarily how much you smoke or drink. It is how you smoke or drink. Strong marijuana doesn't cause addiction. The way certain people use strong pot can result in addiction, however.

Earlier research has shown that higher levels of cannabis dependence are associated with greater functional impairment, and that "the average level of impairment caused by cannabis, while mild for most users, can rise to the level of tobacco withdrawal which is of well established clinical significance.”

 Physical distress, a “somatic” variable, often matters more, in terms of relapse, than the amount of marijuana smoked, or any other symptom on the roster of functional impairments—including mood and other negative affect variables.  In an earlier study published in PLOS ONE,  investigators found that “cannabis withdrawal is clinically significant because it is associated with elevated functional impairment to normal daily activities, and the more severe the withdrawal is, the more severe the functional impairment is. Elevated functional impairment from a cluster of cannabis withdrawal symptoms is associated with relapse in more severely dependent users.”

van der Pol P., Liebregts N., Brunt T., van Amsterdam J., de Graaf R., Korf D.J., van den Brink W. & van Laar M. (2014). Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study, Addiction,   n/a-n/a. DOI: 10.1111/add.12508

Who Smokes Dope, And How Much?

Marijuana stats skew perceptions of use.

Most statistical surveys of marijuana focus on a single quantitative measurement: How many people are using? But there’s a problem: More marijuana use does not necessarily translate into more marijuana users. And that’s because a clear majority of the consumption, and black market dollars, come from the heaviest smokers.

Drug policy researchers at the RAND corporation decided that frequency of use and amount of consumption were valuable parameters gone missing in most policy discussions. So they put the focus not just on use, but also on “use-days,” and pulled a number of buried tidbits from a very big data pile. If you zero in on consumption, and not just consumers, they insist, you will find a wholly different set of inferences.

For example: “Although daily/near-daily users represented less than one-quarter of past-month cannabis users in 2002 and roughly one-third of past-month users in 2011, they account for the vast majority of use-days and are thus presumably responsible for the majority of consumption,” write Rachel M. Burns and her RAND colleagues in Frontiers of Psychiatry. As with alcohol, the majority of cannabis consumption can be accounted for by a minority of users. The heaviest users, the upper 20 percent, consume 88 percent of the U.S. marijuana supply, say the RAND researchers. “Furthermore, if over time there were no change in the number of cannabis users, but the ratio of light vs. heavy users switched from 80/20 to 20/80, then consumption would increase by 250% even though there was no change whatsoever in the number of users.”

The RAND group used two data sets on cannabis consumption—the National Survey on Drug Use and Health (NSDUH) in the U.S., and the EU Drugs Markets II (EUMII) in Europe. Data included figures for past-year and past-month use, past-month use days, and past-month purchases.

Other intriguing figures come to light when you study cannabis use, as opposed to cannabis users. The researchers declared that “only 14% of past-year cannabis users [primarily males] meet the criteria for cannabis abuse or dependence, but they account for 26% of past-month days of use and 37% of past-month purchases.”

Happen to smoke blunts? That turns out to be very telling, according to the RAND study. “Perhaps the most striking contrast concerns blunts. Only 27% of past-year cannabis users report using a blunt within the last month, but those individuals account for 73% of cannabis purchases.” Casual users, it seems, don’t do blunts.

Clearly, it takes a lot of casual users to smoke as much marijuana as one heavy user. But exactly how many? The RAND researchers ran the numbers and concluded that, in terms of grams consumed per month, it would take more than 40 casual smokers to equal the intake of a single heavy user. The share of the market represented by daily/near-daily users is clearly the motive force in their analysis.

The study in Frontiers in Psychiatry also found patterns of interest on the buy side. General use took an upswing beginning in 2007. While the probability of arrest per marijuana smoking episode hovers somewhere in the neighborhood of 1 in 3,000, everything changes if you are purchasing cannabis. RAND reported that young people collectively make more purchases per day of reported use than do older users. Therefore, “statistics indicating that the burden of arrest falls disproportionately on youth relative to their share of all users may not be prima facie evidence of discrimination if making more purchases per day of use increases the risk of arrests per year of use.” Once again, those aging Baby Boomer potheads get the best deal. They have more money with which to buy bigger amounts less often, thereby greatly lessening their chances of arrest and prosecution.

This also applies to minority arrests for marijuana offenses. “Non-Hispanic blacks represent 13% of past-year cannabis users vs. 23% of drug arrests reported by those users, but they report making 24% of the buys. Thus, some of their higher arrest rate may be a consequence of purchase patterns… African-Americans may not only make more buys but also make riskier buys (e.g., more likely to buy outdoors).”

The researchers were able to draw some conclusions about the growth in marijuana usage from 2002 through 2011, based on the NSDUH data. Their main conclusion, after exploring the demographics of this 10-year record of use, is that “consumption grew primarily because of an increase in the average frequency of use, not just because of an increase in the overall number of users.”  The driver of consumption turns out to be… greater consumption. And that increased consumption is coming from… older adults. Those older adults, it turns out, are smoking more weed.

The shift is dramatic: “In 2002, there were more than three times as many youth as older adults using cannabis on a daily/near-daily basis; in 2011 there were 2.5 times more older adults than youth using on a daily/near-daily basis.” The record of alcohol and cigarette use over the same period showed no such inversion of use patterns.  And the tweeners? “In 2002, 12-17-year-olds represented 13% of daily/near-daily users; in 2011, that had dwindled to 7%.” These trends are not just the obvious result of an increase in the proportion of older adults in the population at large. Increases in the proportion of older heavy cannabis users were much greater than the general population drift.

Among the questions raised by the RAND analysis:

— Are older marijuana smokers primarily recreational, or medicinal?

—Do increased use days among older, college-educated marijuana smokers indicate greater social acceptance, or something else?

—Are younger people replacing traditional cannabis use with other substances?

—Why did Hispanic use increase more over the study period than other ethnic groups?

Burns R.M., Caulkins J.P., Everingham S.S. & Kilmer B. (2013). Statistics on Cannabis Users Skew Perceptions of Cannabis Use, Frontiers in Psychiatry, 4   DOI: 10.3389/fpsyt.2013.00138

Photo Credit: http://www.sho.com/sho/weeds/home

A Chemical Peek at Modern Marijuana

Researchers ponder whether ditch weed is better for you than sinsemilla.

Australia has one of the highest rates of marijuana use in the world, but until recently, nobody could say for certain what, exactly, Australians were smoking. Researchers at the University of Sydney and the University of New South Wales recently analyzed hundreds of cannabis samples seized by Australian police, and put together comprehensive data on street-level marijuana potency across the country. They sampled police seizures and plants from crop eradication operations. The mean THC content of the samples was 14.88%, while absolute levels varied from less than 1% THC to almost 40%.  Writing in PLoS one, Wendy Swift and colleagues found that roughly ¾ of the samples contained at least 10% total THC. Half the samples contained levels of 15% or higher—“the level recommended by the Garretsen Commission as warranting classification of cannabis as a ‘hard’ drug in the Netherlands.”

In the U.S., recent studies have shown that THC levels in cannabis from 1993 averaged 3.4%, and then soared to THC levels in 2008 of almost 9%. THC loads more than doubled in 15 years, but that is still a far cry from news reports erroneously referring to organic THC increases of 10 times or more.

CBD, or cannabidiol, another constituent of cannabis, has garnered considerable attention in the research community as well as the medical marijuana constituency due to its anti-emetic properties. Like many other cannabinoids, CBD is non-psychoactive, and acts as a muscle relaxant as well. CBD levels in the U.S. have remained consistently low over the past 20 years, at 0.3-0.4%. In the Australian study, about 90% of cannabis samples contained less than 0.1% total CBD, based on chromatographic analysis, although some of the samples had levels as high as 6%.

The Australian samples also showed relatively high amounts of CBG, another common cannabinoid. CBG, known as cannabigerol, has been investigated for its pharmacological properties by biotech labs. It is non-psychoactive but useful for inducing sleep and lowering intra-ocular pressure in cases of glaucoma.

CBC, yet another cannabinoid, also acts as a sedative, and is reported to relieve pain, while also moderating the effects of THC. The Australian investigators believe that, as with CBD, “the trend for maximizing THC production may have led to marginalization of CBC as historically, CBC has sometimes been reported to be the second or third most abundant cannabinoid.”

Is today’s potent, very high-THC marijuana a different drug entirely, compared to the marijuana consumed up until the 21st Century? And does super-grass have an adverse effect on the mental health of users? The most obvious answer is, probably not. Recent attempts to link strong pot to the emergence of psychosis have not been definitive, or even terribly convincing. (However, the evidence for adverse cognitive effects in smokers who start young is more convincing).

It’s not terribly difficult to track how ditch weed evolved into sinsemilla. It is the historical result of several trends: 1) Selective breeding of cannabis strains with high THC/low CBD profiles, 2) near-universal preference for female plants (sinsemilla), 3) the rise of controlled-environment indoor cultivation, and 4) global availability of high-end hybrid seeds for commercial growing operations. And in the Australian sample, much of the marijuana came from areas like Byron Bay, Lismore, and Tweed Heads, where the concentration of specialist cultivators is similar to that of Humboldt County, California.

The investigators admit that “there is little research systematically addressing the public health impacts of use of different strengths and types of cannabis,” such as increases in cannabis addiction and mental health problems. The strongest evidence consistent with lab research is that “CBD may prevent or inhibit the psychotogenic and memory-impairing effects of THC. While the evidence for the ameliorating effects of CBD is not universal, it is thought that consumption of high THC/low CBD cannabis may predispose users towards adverse psychiatric effects….”

The THC rates in Australia are in line with or slightly higher than average values in several other countries. Can an increase in THC potency and corresponding reduction in other key cannabinoids be the reason for a concomitant increase in users seeking treatment for marijuana dependency? Not necessarily, say the investigators. Drug courts, coupled with greater treatment opportunities, might account for the rise. And schizophrenia? “Modelling research does not indicate increases in levels of schizophrenia commensurate with increases in cannabis use.”

One significant problem with surveys of this nature is the matter of determining marijuana’s effective potency—the amount of THC actually ingested by smokers. This may vary considerably, depending upon such factors as “natural variations in the cannabinoid content of plants, the part of the plant consumed, route of administration, and user titration of dose to compensate for differing levels of THC in different smoked material.”

Wendy Swift and her coworkers call for more research on cannabis users’ preferences, “which might shed light on whether cannabis containing a more balanced mix of THC and CBD would have value in the market, as well as potentially conferring reduced risks to mental wellbeing.”

Swift W., Wong A., Li K.M., Arnold J.C. & McGregor I.S. (2013). Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile., PloS one, PMID: 23894589

Graphics Credit: http://420tribune.com

Marijuana and Diabetes: Does Pot Make You Thin?

Teasing out the insulin effect.

On the face of it, the study seems to come out of left field: A group of researchers claimed that marijuana smokers showed 16 per cent lower fasting insulin levels than non-smokers. The study, called “The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults,”  is in press for The American Journal of Medicine. The authors are a diverse group of medical researchers from Harvard, Beth Israel Deaconess Medical Center, and the University of Nebraska College of Medicine. The study concluded: “We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR [a measure of insulin resistance], and smaller waist circumference.”

Of course, it was that last tidbit about waist circumference that was picked up by the media. “Why Pot Smokers Are Skinnier,” headlined the Atlantic. However, the important implications are not so much for weight control, or the discovery of some built-in offsetting mechanism for the marijuana munchies, but rather for insulin control and the treatment of diabetes.

But in a clinical study, remarkable observations require remarkable documentation. What does the research actually say?

There are problems with the study worth noting. While researchers took blood samples after a 9-hour fast to determine insulin and glucose levels, they relied on self-reporting for marijuana use data. And self-reporting for alcohol and drug use has its limitations as an investigative tool. Namely, lack of honesty. But let’s get beyond that for a moment: From a database of 4,657 men and women who participated in the National Health and Nutrition Examination Survey, the researchers determined that 579 were current marijuana users, while 1,975 were pot smokers in the past.

The marijuana-smoking cohort tended to be young males who also smoked cigarettes. After running everything through a series of complicated multivariable-adjusted models, marijuana came out associated with lower insulin levels, and “lower waist circumference” than those who reported never using marijuana. And the results didn’t change much after adjusting for BMI numbers and excluding participants who actually had diabetes. Furthermore, the association was strongest in current smokers, “suggesting that the impact of marijuana use on insulin and insulin resistance exists during periods of recent use.” (It should also be noted that other health habits can affect glucose and insulin activity, including cigarettes, alcohol, and lack of physical activity.)

The investigators don’t offer a solution to the increased appetite/decreased waistline conundrum they claim to have identified. “We did not find any significant associations between marijuana use, and triglyceride levels, systolic blood pressure, or diastolic blood pressure,” they concluded.

We know marijuana has a complicated relationship with appetite mechanisms, as evidenced by its use with chemotherapy patients who need to eat. The theory is that the metabolic effects are mediated by a complex mix of cannabinoid type 1 and type 2 receptor interactions, since type 1 receptor antagonists like rimonabant improve insulin resistance in humans, and type 1 knockout mice also show resistance to diet-induced obesity.

Does marijuana smoking protect against diabetes? Wisely, the researchers don’t go that far, on the basis of this one uncontrolled study.  The researchers’ conclusions neatly hedge the bets, suggesting that with recent trends in the direction of marijuana legalization, “physicians will increasingly encounter patients who use marijuana and should therefore be aware of the effects it can have on common disease processes, such as diabetes mellitus.”

As it happens, the findings aren’t entirely new. Anecdotal reports abound. Back in 2010, on the Diabetes Daily support board, there was a long discussion of marijuana’s effect on blood glucose levels in diabetics. And there are several mouse models showing the same effects. In a prepared statement, lead investigator Murray A. Mittleman of Beth Israel Deaconess Medical Center in Boston conceded that previous epidemiological studies have found “lower prevalence rates of obesity and diabetes mellitus in marijuana users compared to people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes.” However, he believes that “ours is the first study to investigate the relationship between marijuana use and fasting insulin, glucose, and insulin resistance.”

Perhaps so. A 2011 study in the American Journal of Epidemiology concluded that “the prevalence of obesity is lower in cannabis users than in nonusers.” And the British Medical Journal featured a finding in 2012 by Los Angeles researchers that marijuana use was “independently associated with a lower prevalence of diabetes mellitus.” But the online patient guide for marijuana offered by Mayo Clinic  says without equivocation that “cannabis may lower blood sugar. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar.” In fact, Mayo Clinic advises that patients may want to monitor their blood glucose levels if they smoke medical marijuana.

Regarding the current study, the editor-in-chief of the American Journal of Medicine said in a statement that there is a need for “a great deal more basic and clinical research into the short- and long-term effects of marijuana in a variety of clinical settings such as cancer, diabetes, and frailty of the elderly.” Editor Joseph S. Alpert also called on the National Institutes of Health (NIH) and the Drug Enforcement Administration (DEA) to collaborate in “developing policies to implement solid scientific investigations that would lead to information assisting physicians in the proper use and prescription of THC in its synthetic or herbal form.”

Penner E.A., Buettner H. & Mittleman M.A. (2013). The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults, The American Journal of Medicine,    DOI: 10.1016/j.amjmed.2013.03.002

Photo Credit: http://www.herbalmission.org/

The Pot President

Hendrik Hertzberg on the hypocrisy of the hip.

In a blog post at the New Yorker last week, Hendrik Hertzberg spotlighted a recent joke made by the President of the United States at the White House Correspondents dinner. In reference to the rapidly changing media landscape, Obama said: “You can’t keep up with it. I mean, I remember when BuzzFeed was just something I did in college around two A.M. (Laughter.) It’s true! (Laughter.)”

The days of expressing a cringing contrition for your “youthful experimentation,” or claiming that you didn’t inhale, or clearly over.

But of course, the president’s joke wasn’t really that funny. Hertzberg cites statistics from Ethan Nadelmann of the Drug Policy Alliance, suggesting that “from fifty to a hundred thousand Americans are behind bars for pot, and only pot, on any given night.” The Office of National Drug Control Policy (ONDCP) disputes those figures, but the point is not so much whose numbers are closer to the truth, but rather the simple fact that while the president made his joke, too many people are locked up in federal and state prisons for an offense that a growing number of states are backing away from enforcing.

As Hertzberg put it, the subtext of the president’s pot joke was that it “allowed the tuxedoed, evening-gowned, middle-aged audience at the Washington Hilton to feel, for a precious moment, hip. The subtext was that smoking pot, whether a lot or a little, is just a normal part of growing up…. Nor has it done much to blight the lives of the other people in the Hilton ballroom, most of whom, like the rest of the media, political, and Hollywood elites, have smoked pot, too.”

Obama, they say, was a champ stoner in school. He was, writes David Maraniss in his biography of Obama, skilled at “interceptions”—sneaking an extra hit off the joint when it hadn’t gotten all the way around yet.  Obama, writes Hertzberg, really ought to feel “a smidgen of shame that the government he heads treats people who do exactly what he used to do, and now casually jokes about, as criminals.”

We haven’t heard much lately about the Boomer hypocrisy inherent in such roomfuls of high achievers who used to get high. (Some of them still do.) Jobs and reputations and bank loans are not endangered by these sly references and knowing winks. What hurts jobs and reputations is a stretch in federal prison—the unwilling route taken by many less fortunate Americans.

Hertzberg is wrong when he says that “marijuana-associated suffering enters the picture only when prohibition does.” Like most pro-legalization commentators, he does not mention addiction liability, or lasting cognitive effects on younger smokers.  But it is true that a disproportionate amount of suffering is caused by marijuana prohibition laws. The farthest corners of the debate are staked out, but decriminalization—the missing middle ground—still offers society a more balanced starting point than full-tilt legalization. Merriam-Webster says that to decriminalize is “to repeal a strict ban on, while keeping under some form of regulation.” State policy makers, although they don’t use the term very often, are pursuing what amounts to decriminalization. Nobody other than world-peace-through-weed zealots is arguing for a repeat of the track record with cigarettes (a drug in the process of being re-criminalized). And the regulation of alcohol does not offer a compelling model for marijuana’s future as a semi-legal drug. Happily, marijuana is not nearly as dangerous as alcohol or nicotine, so that helps.

It might surprise some readers to know that a majority of the Dutch aren’t interested in legalizing marijuana. They are concerned about keeping it out of the hands of minors. They’re not very happy with the trend towards higher and higher levels of THC. This is expressed in the fact that marijuana is, and likely will remain, illegal in The Netherlands. The narrow coffee shop exception is misleading in this regard. It was not designed to make marijuana more acceptable, but to deal creatively with the problem of street sales. You almost never see a drug deal going down on the streets of Amsterdam. That’s because a) It’s stupid, you can just waltz into a coffee shop if you’re over 21. b) Dealers have a hard time beating coffee shop prices. c) Dutch police come down heavily on street dealers.  Why? See a) above. The Dutch are no freer to wander their canal-lined streets with a joint in hand than Americans are free to wander Capitol Mall Boulevard with an open bottle of Jack.

Now that’s decriminalization. And an unfair comparison, of course, since the Dutch nation is so much smaller and more homogenous than the U.S. But lately, the talk has been about states, not the country at large. And at the state level, some of the Dutch lessons may apply.

What should our president do about all of this? Hertzberg has three proposals:

—Tell the Justice Department to “end the absurd classification of marijuana as a supremely dangerous Schedule I drug, like heroin.” Alcohol, let us recall, does not have a drug classification because it is not a scheduled substance at all. This American ambivalence is reflected by the names of the country’s premier drug research groups, the National Institute on Drug Abuse (NIDA), and the Monty Pythonesque National Institute on Alcohol Abuse and Alcoholism (NIAAA).

—Promise to “avoid making life unnecessarily difficult” for the states that have made provisions for medical marijuana or legalization.

—Change the name of the Drug Czar’s Office of National Drug Control Policy to something like the “Office of National Harm Reduction Drug Policy.”

Adopting any or all of these changes would be a useful step toward a decriminalized future for marijuana. Here’s the essential point: We have to make a space for marijuana use in American culture. I mean above the ground, and unassociated with jail time. While still murky from a medical point of view, there is just no doubting that millions of Americans prefer pot to alcohol as a recreational drug. Given alcohol’s role in the American death toll, and the lack of any such grim trail of the dead in marijuana’s case, there’s no shame in that decision, from my point of view.

Graphics Credit: http://www.anonymousartofrevolution.com/

Praising Marijuana Prohibition

The view from the White House.

As regular readers of Addiction Inbox will know, I am on record as favoring some form of decriminalization for marijuana. But I also write regularly about the difficulties of marijuana addiction and withdrawal. And I have been critical of the operational strategies employed by the medical marijuana movement in the several states in which it now operates. What I have not done, to date, is offer up the official view of a drug policy analyst from the Obama administration who straightforwardly favors a continuation of the legal prohibition against marijuana. 

One of the architects of the current federal resistance to marijuana legalization is Kevin Sabet, an assistant professor and the director of the Drug Policy Institute at the University of Florida College of Medicine. Sabet served from 2009 to 2011 in the Obama Administration as Senior Advisor for the White House Office of National Drug Control Policy (ONDCP) under Drug Czar Gil Kerlikowske, and was influential in shaping federal marijuana policy. Sabet consults with governments and NGOs on a wide range of drug policy prevention issues, and recently debated legalization advocate Ethan Nadelmann on CNN. He is also a regular columnist for thefix.com  and Huffington Post. He agreed to participate in a frank and lengthy 5-question interview with Addiction Inbox. (Be sure to check out the comments below).

1. In his new book, Too High to Fail, journalist Doug Fine argues that "the Drug War is as unconscionably wrong for America as segregation or DDT." Would you comment on this sweeping condemnation?

First, I think it is interesting to note that only people who want to condemn all of our current drug policies use the term "drug war." No one in serious policy circles uses that term anymore, and that is because it is woefully inadequate and vague as a way to describe a whole slew of policies designed to both reduce drug prevalence and drug consequences. I think his comparison is clumsy and unfair. Do some drug policies hurt disadvantaged groups? Of course they do. Is it a moral imperative to fix those policies, learn from our past mistakes and make our policies better? Of course it is. There's no reason to think that those policies can't be changed—in the White House in 2009, for example, we drastically reduced the penalty for crack cocaine. But what makes Mr. Fine's comparison even more wrong-headed and backwards is that we know that if we scale-up—not eliminate, as he would—the policies we know do work in reducing drug use and its consequences, all communities in America would benefit. A handful include:

(a) community-based prevention that not only focuses on stopping drug use among school kids, but in changing bad local laws and ordinances that promote underage drinking, smoking, and marijuana use (so-called "environmental policies");

(b) early intervention and detection of drug use in health settings;

(c) evidence-based treatment, including methadone and buprenorphine, as well as 12-step programs;

(d) recovery-based policies that don't penalize people for past drug use and instead facilitate recovery;

(e) law enforcement based on credible threats and modest sanctions.

2. The Drug War is an industry—the DEA alone has a budget of 2 1/2 billion and employs almost 10,000 people. If we add in profits from the private prison industry, and the money-laundering banks, the money is staggering. Wouldn't it make sense to recoup those historical costs by legalizing and taxing marijuana?

That phrase assumes two things: (a) criminal justice and regulation costs would be drastically reduced, or eliminated, with marijuana legalization; and (b) the underground market would be eliminated with marijuana legalization. Both of those assumptions are huge leaps that don't stand up to our experience with our already two legal drugs—alcohol and tobacco.

First, we know that legalization means more consumption. More consumption means more regulation. Today we have liquor laws, laws against drinking and driving, laws against public drunkenness, etc. With regards to legal alcohol, we make 2.6 million arrests every year for the violation of those laws. Meanwhile, we arrest a million fewer times for illegal drugs (1.6 million/year). Legal alcohol costs us money with regards to crime and regulation. I think that is a big consideration in this whole debate that we rarely hear about. So that means we'd have to have more prisons, more police, and more regulation costs under legalization—especially since few people are in prison or jail solely for marijuana use.

And I'm not so sure the underground market would be eliminated with marijuana legalization. Especially if it is taxed heavily, the incentive for the underground market—having been painstakingly established for decades by multinational corporate structures (cartels)—is very little. We'll still need a black market for underage marijuana, for marijuana to be sold to repeat offenders, etc. I just don't see the cartels throwing up their hands and saying "OK, it's legalized. We're out of the game now. Let's get into the ice cream business."

3. A "Pax Cannabis" would require rescheduling marijuana at the federal level, with an overt recognition that marijuana has some redeeming medical value. What's the argument for maintaining cannabis as a Schedule 1 drug along with heroin, a drug with which it has almost nothing in common? Could you comment on the upcoming U.S. Appeals Court consideration of medical marijuana?

Rescheduling marijuana is one of the biggest red herrings I can think of in this debate. If rescheduled tomorrow, it would do nothing to allow marijuana to be sold legally. Rather, it would be a huge symbolic victory for marijuana advocates -- but it would be wholly wrong on the science. Placing a drug in schedule 1 simply means the drug has no medical use and a high potential for abuse. It has nothing to do with the other drugs in that category (e.g. heroin). If it were a drug, a telephone would also need to be in Schedule 1 - I'm addicted to my cell phone and I know it has no medical use. That doesn't mean a phone is as dangerous as a syringe of heroin.  Today, cocaine is Schedule 2 because it has some very limited hospital use. Can a 21-year-old kid with no medical knowledge sell cocaine from a "dispensary" called "Happy Clinic" legally? Of course not, though that is what is happening [with marijuana] in California.

In order to be used for medical use, a specific product needs to be approved by FDA. Marijuana's specific product, so far, is Marinol, a Schedule 3 drug which has been approved by FDA and is used by people throughout the world. Crude, raw marijuana is not a specific product. The best way I can put it is this: We don't smoke opium to get the effects of morphine, so why do we think we need to smoke marijuana to get its potential medical effects? We have non-inhaled medications that are approved and we have others on the way. For a lot more on this, you can check out an article I wrote for Join Together. I think the District court opinion will rest on the science and agree with the Department of Health and Human Services that raw, crude marijuana is not medicine.

4. Alaska decriminalized marijuana in 1975, and only recriminalized after lengthy pressure from the Reagan administration. Isn't cultivation of this flowering weed for personal use the most obvious and straightforward solution?

The Reagan Administration could have cared less about Alaska, frankly. Alaska recriminalized because voters there wanted that to happen. They didn't like the effect of decriminalization on their state. That said, I don't think many people are in favor—and I am not—of locking up people smoking small amounts of marijuana. That isn't happening anywhere. One notable exception is New York City where they impose 24-hour detentions for public use and selling as part of their broken windows approach to crime control.

Indeed, in the 1970s, twelve states formally decriminalized marijuana. This meant that persons found to have a small amount of marijuana were not subject to jail time, but rather they would receive a civil penalty, such as a fine. The discussion in the United States is highly complex because even in jurisdictions without a formal decriminalization law, persons are rarely jailed for possessing small amounts of cannabis. A rigorous government analyses of who is in jail or prison for marijuana found that less than 0.7% of all state inmates were behind bars for marijuana possession only (with many of them pleading down from more serious crimes).[1] Other independent research has shown that the risk of arrest for each “joint,” or cannabis cigarette, smoked is about 1 arrest for every 12,000 joints.[2] This probably explains the fact that the literature on early decriminalization effects on use has been mixed. Some studies found no increase in use in the so-called “depenalization” states, whereas others found a positive relationship between greater use and formal changes in the law.[3]

The more recent discussion about state-level legalization may provide more insights. Two RAND Corporation reports concluded that legalization would result in lower cannabis prices, and thus increases in use (though by how much is highly uncertain), and that “legalizing cannabis in California would not dramatically reduce the drug revenues collected by Mexican drug trafficking organizations from sales to the United States.”[4]

5. Marijuana advocates don't like to hear it, but pot is addictive for some users. Where do you stand on this controversial issue?

Science tells us that marijuana is addictive—about 1 in 11 people who ever smoke marijuana are addicted; but if you start in adolescence that number climbs to 1 in 6. That's not anyone's opinion but rather the result of rigorous scientific research done by the National Institutes of Health and confirmed by other international scientific bodies. Is marijuana as addictive as tobacco cigarettes? No. The addiction rate for tobacco is about 1 in 3; for heroin it is lower, about 1 in 4. Users who try to quit experience withdrawal symptoms that include irritability, anxiety, insomnia, appetite disturbance, and depression.

A United States study that dissected the National Longitudinal Alcohol Epidemiologic Survey (conducted from 1991 to 1992 with 42,862 participants) and the National Epidemiologic Survey on Alcohol and Related Conditions (conducted from 2001 through 2002 with more than 43,000 participants) found that the number of cannabis users stayed the same while the number dependent on the drug rose 20 percent ­ from 2.2 million to 3 million.[5]Authors speculated that higher potency marijuana may have been to blame for this increase. As I've heard said many times by experienced tokers, "this isn't your Grandfather's Woodstock Weed."

[1] “Substance Abuse and Treatment, State and Federal Prisoners, 1997.” BJS Special Report, January 1999, NCJ 172871. http://www.ojp.usdoj.gov/bjs/pub/pdf/satsfp97.pdf

[2] Beau Kilmer, Jonathan P. Caulkins, Rosalie Liccardo Pacula, Robert J. MacCoun, Peter H. Reuter, Altered State? Assessing How Cannabis Legalization in California Could Influence Cannabis Consumption and Public Budgets, RAND, 2010.

[3] For a discussion see MacCoun, R., Pacula, R. L., Reuter, P., Chriqui, J., Harris, K. (2009). Do citizens know whether they live in a decriminalization state? State cannabis laws and perceptions. Review of Law & Economics, 5(1), 347-371.

[4] Beau Kilmer, Jonathan P. Caulkins, Rosalie Liccardo Pacula, Robert J. MacCoun, Peter H. Reuter, Altered State? Assessing How Cannabis Legalization in California Could Influence Cannabis Consumption and Public Budgets, RAND, 2010. And see Kilmer, Beau , Jonathan P. Caulkins, Brittany M. Bond and Peter H. Reuter. Reducing Drug Trafficking Revenues and Violence in Mexico: Would Legalizing Cannabis in California Help?.Santa Monica, CA: RAND Corporation, 2010. http://www.rand.org/pubs/occasional_papers/OP325. Also available in print form.

[5] ]Compton, W., Grant, B., Colliver, J., Glantz, M., Stinson, F. Prevalence of Cannabis Use Disorders in the United States: 1991-1992 and 2001-2002Journal of the American Medical Association.. 291:2114-2121.

Photo Credit:http://article.wn.com/

Synthetic Drugs: Collected Posts

Catching up with bath salts and spice.


The Low Down on the New Highs: Not all bath salts are alike.

“You’re 16 hours into your 24-hour shift on the medic unit, and you find yourself responding to an “unknown problem” call.... Walking up to the patient, you note a slender male sitting wide-eyed on the sidewalk. His skin is noticeably flushed and diaphoretic, and he appears extremely tense. You notice slight tremors in his upper body, a clenched jaw and a vacant look in his eyes.... As you begin to apply the blood pressure cuff, the patient begins violently resisting and thrashing about on the sidewalk—still handcuffed. Nothing seems to calm him, and he simultaneously bangs his head on the sidewalk and tries to kick you...” [Go here]


The New Highs: Are Bath Salts Addictive? What we know and don’t know about synthetic speed.

Call bath salts a new trend, if you insist. Do they cause psychosis? Are they “super-LSD?” The truth is, they are a continuation of a 70-year old trend: speed. Lately, we’ve been fretting about the Adderall Generation, but every population cohort has had its own confrontation with the pleasures and perils of speed: Ritalin, ice, Methedrine, crystal meth, IV meth, amphetamine, Dexedrine, Benzedrine… and so it goes. For addicts: Speed kills. Those two words were found all over posters in the Haight Ashbury district of San Francisco, a few years too late to do the residents much good…. [Go here]


“Bath Salts” and Ecstasy Implicated in Kidney Injuries: “A potentially life-threatening situation.”

Earlier this month, state officials became alarmed by a cluster of puzzling health problems that had suddenly popped up in Casper, Wyoming, population 55,000. Three young people had been hospitalized with kidney injuries, and dozens of others were allegedly suffering from vomiting and back pain after smoking or snorting an herbal product sold as “blueberry spice.” The Poison Review reported that the outbreak was presently under investigation by state medical officials.  “At this point we are viewing use of this drug as a potentially life-threatening situation,” said Tracy Murphy, Wyoming state epidemiologist…. [Go here]


The Triumph of Synthetics: Designer stimulants surpass heroin and cocaine.

A troubling report by the United Nations Office on Drugs and Crime (UNODC) shows that amphetamine-type stimulants (ATS) have, for the first time, become more popular around the world than heroin and cocaine. Marijuana remains the most popular illegal drug in the world, and the use of amphetamines has fallen sharply in the U.S., but the world trend represents the worldwide triumph of synthetic drug design over the plant-based “hard drugs” of the past…. [Go here]

Marijuana: The New Generation: What’s in that “Spice” packet?

They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills. Unlike the stimulants known as mephedrone or M-Cat, or the several variations on the formula for MDMA—both of which have also been marketed as Spice and “bath salts”—the bulk of the new products in the Spice line were synthetic versions of cannabis…. [Go here]


An Interview with Pharmacologist David Kroll: On synthetic marijuana, organic medicines, and drugs of the future.

Herewith, a 5-question interview with pharmacologist David Kroll, Ph.D., Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, and a well-known blogger in the online science community. A cancer pharmacologist whose field is natural products—he’s currently involved in a project to explore the potential anticancer action of chemicals found in milk thistle and various sorts of fungi—Dr. Kroll received his Ph.D. from the University of Florida, and completed his postdoctoral fellowship in Medical Oncology and Molecular Endocrinology at the University of Colorado School of Medicine. He went on to spend the first nine years of his independent research and teaching career at the University of Colorado School of Pharmacy, where he taught all aspects of pharmacology, from central nervous system-active drugs, to anticancer and antiviral medications…. [Go here]


Mephedrone, the New Drug in Town: Bull market for quasi-legal designer highs.

Most people in the United States have never heard of it. Very few have ever tried it. But if Europe is any kind of leading indicator for synthetic drugs (and it is), then America will shortly have a chance to get acquainted with mephedrone, a.k.a. Drone, MCAT, 4-methylmethcathinone (4-MMC), and Meow Meow--the latter nickname presumably in honor of its membership in the cathinone family, making it chemically similar in some ways to amphetamine and ephedrine. But its users often refer to effects more commonly associated with Ecstasy (MDMA), both the good (euphoria, empathy, talkativeness) and the bad (blood pressure spikes, delusions, drastic changes in body temperature)…. [Go here]


Tracking Synthetic Highs: UN office monitors designer drug trade.

Produced by the United Nations Office on Drugs and Crime (UNODC), the Global SMART Update  (PDF) for October provides interim reports of emerging trends in synthetic drug use. The report does not concern itself with cocaine, heroin, marijuana, alcohol, or tobacco. “Unlike plant-based drugs,” says the report, “synthetic drugs are quickly evolving with new designer drugs appearing on the market each year.” The update deals primarily with amphetamine-type stimulants, but also includes newer designer drugs such as mephedrone, atypical synthetics like ketamine, synthetic opioids like fentanyl, and old standbys like LSD…. [Go here]


The New Cannabinoids: Army fears influx of synthetic marijuana.

It’s a common rumor: Spice, as the new synthetic cannabis-like products are usually called, will get you high--but will allow you to pass a drug urinalysis. And for this reason, rumor has it, Spice is becoming very popular in exactly the places it might be least welcomed: Police stations, fire departments—and army bases. What the hell is this stuff? [Go here]

Photo credit: http://gizmodo.com/

photo credit 2: http://www.clemson.edu/

Status of Medical Marijuana to be Tested in U.S. Appeals Court

Ten-year old petition could change everything.

Medical marijuana advocates will finally have their day in federal court, after the United States Court of Appeals for D.C. ended ten years of rebuffs by agreeing to hear oral arguments on the government’s classification of marijuana as a dangerous drug.

A decision in the case could either finish off medical marijuana for good, or else upend the fed’s rationale for its stepped-up war against the medical marijuana industry. Americans for Safe Access v. Drug Enforcement Administration asks that the federal government review the scientific evidence regarding marijuana’s therapeutic value. The D.C. Circuit Court of Appeals has agreed to do so in October.

The original petition, filed by the Coalition for Rescheduling Cannabis (CRC) in 2002, has languished in obscurity, but recent moves to have marijuana rescheduled from its status as a Schedule 1 drug—a class that includes heroin—have increased in the wake of America’s Civil War over medical marijuana.  “This is a rare opportunity for patients to confront politically motivated decision-making with scientific evidence of marijuana’s med efficacy,” said Joe Elford, chief council for Americans for Safe Access, the group that successfully challenged the denial of the original CRC petition. “What’s at stake in this case is nothing less than our country’s scientific integrity and the imminent needs of millions of patients.”

The Controlled Substance Act reserves Schedule 1 for drugs that “have a high potential for abuse, have no currently accepted medical use in treatment in the United States, and there is lack of accepted safety for use of the drug or other substance under medical supervision.”

Recently, an article by Dr. Igor Grant in the Open Neurology Journal argued that marijuana’s Schedule 1 classification and surrounding political controversy were “obstacles to medical progress in this area.”

Seventeen states have now adopted some form of medical marijuana law, but the nascent field remains in limbo due to federal regulations about the illegality of marijuana use. Over the past year, the U.S. Justice Department has stepped up its pressure on medical marijuana purveyors, culminating in dozens of indictments, seizures, and shutdowns. Most recently, the Los Angeles City Council simply threw up its hands and banned most marijuana dispensaries in the city. But it’s not even clear if the ban on state-legal dispensaries is itself legal. A pot collective in Covina recently won its challenge to a blanket ban on pot sales in unincorporated areas of Los Angeles County in the state’s 2nd District Court of Appeal. As a Los Angeles Times editorial aptly put it, “we’re confused about how to legally restrict a quasi-legal business.”

According to Chris Roberts, writing in the SF Weekly, “the court hearing would be the first time the medical merits of cannabis would be examined in a federal courtroom since 1994.” At the core of the argument is the federal government’s contention that the marijuana plant has no redeeming medical value, as opposed to the mountain of scientific studies suggesting that marijuana may be applicable in the treatment of glaucoma, cancer, chronic pain, and possibly other conditions, such as multiple sclerosis.

Graphics Credit:   http://en.wikipedia.org/

A Look at the Recent Study of Cannabis and Multiple Sclerosis

Smoked marijuana reduced spasticity in a small trial of MS patients.

The leading wedge of the medical marijuana movement has traditionally been centered on pot as medicine for the effects of chemotherapy, for the treatment of glaucoma, and for certain kinds of neuropathic pain. From there, the evidence for conditions treatable with marijuana quickly becomes either anecdotal or based on limited studies. But pharmacologists have always been intrigued by the notion of treating certain neurologic conditions with cannabis. Sativex, which is sprayed under the tongue as a cannabis mist, has been approved for use against multiple sclerosis, or MS, in Canada, the UK, and some European countries. (In the U.S., parent company GW Pharma is seeking FDA approval for the use of Sativex to treat cancer pain).

There is accumulating evidence that cannabinoid receptors may be involved in controlling spasticity, and that anandamide, the brain’s endogenous form of cannabis, is a specific antispasticity agent.

Additional evidence that researchers may be on to something appeared recently in the Canadian Medical Association Journal. Dr. Jody Corey-Bloom and coworkers at the University of California in San Diego conducted a small, placebo-controlled trial with adult patients suffering from poorly controlled spasticity. Thirty participants were randomly divided into two groups. Those in the first group were given a daily joint, and those in the second group received “identical placebo cigarettes.” After three days, the investigators found that smoked marijuana resulted in a reduction in treatment-resistant spasticity, compared to placebo.

Clearly, it’s hard for a study of this sort to be truly blind: Participants, one presumes, had little trouble distinguishing the medicine from the placebo. And in fact, an appendix to the study shows this to be true: “Seventeen participants correctly guessed their treatment phase for all six visits… For the remaining participants, cannabis was correctly guessed on 33/35 visits.” This raises the question of various kinds of self-selection bias and expectancy effects, and the study authors themselves write that the results “might not be generalizable to patients who are cannabis-naïve.” On the other hand, cannabis-naïve patients were in the minority. The average age of the participants was 50, and fully 80% of them admitted to previous “recreational experience” with cannabis. (I don’t have a good Baby Boomer joke for the occasion, but if I did, this is where it would go).

I asked Dr. Corey-Bloom about this potential problem in an email exchange: “The primary outcome measure was the Ashworth Spasticity Scale, which is an objective measure, carried out by an independent rater,” she wrote. “Their job was just to come in and feel the tone around each joint (elbow, hip, knee), rate it, and leave.  That's why we think it was so important to have an objective measure, rather than just self-report.”

With all this in mind, the study found that “smoking cannabis reduced patient scores on the modified Ashworth scale by an average of 2.74 points.” The authors conclude: “We saw a beneficial effect of smoked cannabis on treatment-resistant spasticity and pain associated with multiple sclerosis among our participants.”

Other studies have found similar declines in spasticity from cannabinoids, but have tended not to use marijuana in smokable form.

Corey-Bloom, J., Wolfson, T., Gamst, A., Jin, S., Marcotte, T., Bentley, H., & Gouaux, B. (2012). Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial Canadian Medical Association Journal DOI: 10.1503/cmaj.110837

Photo Credit: http://blog.amsvans.com/

Marijuana: The New Generation

  

What’s in that “Spice” packet?

They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills. Unlike the stimulants known as mephedrone or M-Cat, or the several variations on the formula for MDMA—both of which have also been marketed as Spice and “bath salts”—the bulk of the new products in the Spice line were synthetic versions of cannabis.

The new forms of synthetic cannabis tickle the same brain receptors as THC does, and are sometimes capable of producing feelings of well-being, empathy, and euphoria—in other words, pretty much the same effects that draw people to pot. But along the way, users began turning up in the emergency room, something that very rarely happens in the case of smoked marijuana. The symptoms were similar to adverse effects some people experience with marijuana, but greatly exaggerated: extreme anxiety and paranoia, and heart palpitations.

As it turns out, there is a very real difference between smoking Purple Kush and snorting “Banana Cream Nuke” out of a metallic packet. The difference lies in the manner in which the brain’s receptors for cannabinoids are stimulated by the new cannabis compounds. When things goes wrong at the CB1 and CB2 receptors, and the mix isn’t right, the results may not be euphoria, giggles, short-term memory loss, and the munchies, but rather “nausea, anxiety, agitation/panic attacks, tachycardia, paranoid ideation, and hallucinations.” Furthermore, the Spice variants do not contain cannabidiol, a cannabis ingredient that has been shown to reduce anxiety in animal models, and reduces THC-induced anxiety in human volunteers. The authors of a recent study suggest that the “lack of this cannabinoid in Spice drugs may exacerbate the detrimental effects of these herbal mixtures on emotion and sociability.”

What concerned the researchers was that, in addition to reports of cognitive deficits and emotional alterations and gastrointestinal effects, emergency room physicians were reporting wildly elevated heart rates, extremely high blood pressure, chest pains, and fever. Fattore and Fratta report that “two adolescents died in the USA after ingestion of a Spice product called ‘K2,’” one due to a coronary ischemic event, and the other due to suicide. What’s going on?

In a paper for Frontiers in Behavioral Neuroscience called “Beyond THC: the new generation of cannabinoid designer drugs,” Liana Fattore and Walter Fratta of the University Of Cagliari in Monserrato, Italy, identified more than 140 different products marketed as Spice, and laid out the extreme variability found in composition and potency. Like a mutating virus, they came to the U.S., starting in early 2009, a new strain seemingly every week: Spice, K2, Spice Gold, Silver, Arctic Spice, Genie, Dream, and dozens of others, the naming and renaming suggesting nothing so much as the proliferating strains of high-end marijuana: Skunk, Haze, Silver Haze, Amnesia, AK-47. Synthetic marijuana comes mainly from manufacturers in Asia, and second generation chemicals have already been put on a to-be-banned list by the DEA. States have jumped all over the problem with duplicate legislation, despite the fact that experts believe a majority of sales take place over the Internet. A third generation of synthetic cannabis variants, which are sprinkled on an herbal base and meant to be snorted, are openly sold and touted as legal. And they are legal, depending upon which one you buy, and where you buy it. Synthetic cannabis is still readily available, affordably packaged, and right on the shelf, or ready for purchase online—unlike the frequently vague and sometimes shady process of scoring a bag of weed. In the beginning, at least, the new drugs were perceived by youthful users as safer than other drugs.

But the most crucial attribute of Spice and related products is that they are not detectable in urine and blood samples. You can cruise all night on Spice, and test clean the next day at work. The kind of cannabis in Spice doesn’t read out on anybody’s drug tests as marijuana. That requires the presence of THC—and the new synthetics don’t have any.

There are four different categories of chemicals used in the manufacture of “cannabimimetic” drugs. The first and best known is the so-called JWH series of “novel cannabinoids” synthesized by John W. Huffman at Clemson University in the 1980s. The most widely used variant is an extremely potent version known as JWH-018.  While JWH-018 is, chemically speaking, not structurally like THC at all, it snaps onto CB1 and CB2 receptors more fiercely than THC itself. The CP-compounds, the second class of synthetic compounds, were developed back in the 1970s by Pfizer, when that firm was actively engaged in testing cannabis-like compounds for commercial potential, a program they later dropped. The best-known example is CP-47,497. While CP-47,497 lacks the chemical structure of classic cannabinoids, it is anywhere from 3 to 28 times more potent than THC, and shows classic THC-like effects in animal studies. The next group is known as HU-compounds, because they originated at Hebrew University, where much of the early work on the mechanisms of THC took place. The last category consists of chemicals in the family of benzoylindoles, which also show an affinity for cannabinoid receptors.

JWH-018, the most common form of synthetic cannabis, and now widely illegal, is considerably more potent than THC—4 times stronger at the CB1 receptor, and 10 times stronger at the less familiar CB2 receptor. The CB2 receptor seems to have a lot to do with pain perception and inflammation, which is why researchers continue to investigate it. But CB2 receptors contribute only indirectly to the classic marijuana high, which is all about THC’s affinity for CB1 receptors, and the effects of using drugs with a very strong affinity for CB2 receptors is not well documented. And therein might lie the source of the problem—or, as Fattore and Fratta describe it, “the greater prevalence of adverse effects observed with JWH-018-containing products relative to marijuana.” A popular compound of the second kind, HU-210, has frequently been found in herbal mixtures available in the U.S. and U.K. According to the study, “the pharmacological effects of HU-210 in vivo are also exceptionally long lasting, and in animal models it has been shown to negatively affect learning and memory processes as well as sexual behavior.”

That, in a nutshell, is what the kids are smoking these days. But wait, there’s more: Besides synthetic cannabinoids, herbs and vitamins, researchers have found opioids like tramadol, opioid receptor-active compounds like Kratom (Mitragyna speciosa), and oleamide, a fatty acid derivative with psychoactive properties. (A combination of oleamide and JWH-018 has been sold as “Aroma.”) Indentifying which of these active ingredients is part of any particular packet of “legal highs” is further complicated by manufacturers’ tendency to mix the ingredients together with various organic compounds—everything from nicotine to masking agents like vitamin E. In fact, almost anything that might make it more difficult for forensic labs to pry it all apart: alfalfa, comfrey leaf, passionflower, horehound, etc. Banana Cream Nuke, which was purchased in an American smoke shop, and made two young girls very sick, contained 15 varieties of synthetic cannabis—but none of the herbal ingredients actually listed on the label.

Unlike the partial activation of CB1 receptors by THC, which takes place when people smoke marijuana, “synthetic cannabinoids identified so far in Spice products have been shown to act as full agonists with increased potency, thus leading to longer durations of action and an increased likelihood of adverse effects.” When it comes to cannabis, users are far better off smoking the real thing, from a harm reduction standpoint, and staying clear of these unpredictable synthetic substitutes.

Graphics Credit: http://www.cityblends.info/2011/10/beyond-thc.html

Fattore, L., & Fratta, W. (2011). Beyond THC: The New Generation of Cannabinoid Designer Drugs Frontiers in Behavioral Neuroscience, 5 DOI: 10.3389/fnbeh.2011.00060