Cannabis sativa vs. Cannabis indica: Science or Folklore?

Golden Goat or  Sour Diesel?

The bland assurances from medical marijuana dispensaries about the physical and psychological effects of the bewildering array of hybrid plant strains on offer is mostly bunk, claim a growing number of cannabis scientists.

Ethan Russo, a neurologist and pharmacology researcher, as well as the medical director of a biotechnology company, author of numerous books about herbal medicine, and a former faculty member at the University of Washington and the University of Montana, has something to say to marijuana connoisseurs: “There are biochemically distinct strains of Cannabis, but the sativa/indica distinction as commonly applied in the lay literature is total nonsense and an exercise in futility.”

How’s that again? The much-vaunted divide between the cerebral sativa strains, and the sedating, body-oriented effects of indica, are an integral part of marijuana lore and legend. Cannabis growers and biologists endlessly debate the hybridization of new strains. Extolling the virtues of a sativa plant crossed with a plant redolent of indica is a common sales pitch.

In an interview with Dr. Daniele Piomelli for the January 2016 issue of the journal Cannabis and Cannabinoid Research, Russo detailed his disagreement with the assumption that hard evidence exists for this distinction. Dr. Piomelli notes that “sativa is often described as being uplifting and energetic, whereas indica as being relaxing and calming.” Folklore, says Russo. Of course different strains have different effects. But in recent years, says Russo, almost all marijuana has been coming from high-THC strains, with a slight increase in CBD-predominant strains:

"The differences in observed effects in Cannabis are due to their terpenoid content, which is rarely assayed, let alone reported to potential consumers. The sedation of the so-called indica strains is falsely attributed to CBD content when, in fact, CBD is stimulating in low and moderate doses. Rather, sedation in most common Cannabis strains is attributable to their myrcene content, a monoterpene with a strongly sedative couch-lock effect that resembles a narcotic."

And, as for sativa strains: “A high limonene content (common to citrus peels) will be uplifting on mood, while the presence of the relatively rare terpene in Cannabis, alpha-pinene, can effectively reduce or eliminate the short-term memory impairment classically induced by THC.”

Well. I for one do not wish to be caught in the firing line between Dr. Russo and the legions of growers who will beg to differ with his conclusions. For years, it has been accepted wisdom that cannabis comes in two different forms, essentially considered two different species even though they readily interbreed. Even Jean-Baptiste Lamarck, the legendary naturalist of the 18th Century, agreed with the indica and sativa concepts.

But Russo will have none of it: “To paraphrase and expropriate an old Yiddish expression: 12 botanical taxonomists, 25 different opinions…. One cannot in any way currently guess the biochemical content of a given Cannabis plant based on its height, branching, or leaf morphology. The degree of interbreeding/hybridization is such that only a biochemical assay tells a potential consumer or scientist what is really in the plant.”

And finally: “I would strongly encourage the scientific community, the press, and the public to abandon the sativa/indica nomenclature and rather insist that accurate biochemical assays on cannabinoid and terpenoid profiles be available for cannabis in both the medical and recreational markets. Scientific accuracy and the public health demand no less than this.”

Russo’s interview is strong evidence of a viewpoint brought to public attention a few years ago by several others, including the controversial cannabis chemist Jeffrey Raber.

Raber told the L.A. Weekly in 2013 that there was no compelling scientific evidence for the claims routinely made by cannabis dispensaries about the effects of a given colorfully named strain of marijuana. “We took a popular [strain] name, Jack Herer, and found that most didn’t even look like each other. OG whatever, Kush whatever, and the marketing that goes along with it—it’s not really medically designed.”

And the difference between sativa and indica? The cerebral, bracing “mental” high vs. the sleepy, couch-lock “body” high? Forget it, said Raber. The two sub-species are distinguished by morphology only—different structures and appearance, but no hard and fast rules about the quality of the smoking experience. They look different, but that’s no guide to the distribution of THC, CBD, and numerous terpenes that determine the actual quality of the marijuana experience. Moreover, extensive crossbreeding by growers and dealers has helped to obliterate any consistent, meaningful distinctions between sativa and indica highs. (The so-called “skunk” varieties are simply high quality female plants that are prevented from going to seed, which dramatically pushes up the THC content. Almost all of the high-quality weed sold in the U.S., Canada, and the U.K. is skunkweed, so the definition is virtually useless.)

Sativa plants are characteristically tall and rangy, with long branches and long, thin leaves. They evolved, scientists believe, in humid jungle climates. Indica plants are shorter, more compact, and stubbier-looking, with shorter branches and fatter leaves designed for a hot, desert-like climate. It has been assumed that sativas originally came from India, and indicas from Afghanistan. However, indica is the term meant to indicate a plant from India, so right away we find that the situation is all muddled up: the plant from Afghanistan is known by the name of the plant from India. Blame this one on esteemed plant drug investigator Richard Evans Schultes, who apparently mislabeled the plants grown in Afghanistan as C. indica when he drew up the first cannabis taxonomy in the 1970s.

It gets worse. In 2014, at a meeting of the International Cannabis Research Society, research John McPartland with GW Pharmaceuticals announced  the results of his study of genetic markers on the three subspecies of cannabis: C. sativa, C. indica, and a third wild variety, known as C. ruderalis, with very little THC. Any of the three subspecies can be bred as hemp or marijuana, said McPartland. Cannabis sativa should really be known as Cannabis indica, being the Indian variety, while the formerly misnamed indica subspecies should now be called Cannabis afghanica. The name of C. sativa, the high-end connoisseur favorite, would now go to the lowly C. ruderalis, otherwise known as ditch weed, under his new classification scheme.

Quite a lot of changes to a decades-old nomenclature, but it means we are finally getting some serious genetic information about one of the most popular drugs in the world. As Jeremy Daw of The Leaf Online writes: “Starbucks, for example, sources coffee beans from farmers spread across four continents…. In an astonishing feat of global supply chain logistics, Starbucks can now claim to have the ability to trace 94% of its coffee beans all the way back to the exact farm where they were produced.” The cannabis industry, he concludes, still has “a lot of growing up to do.”

Krymon deCesare, chief research director at Steep Hill Halent Lab in Oakland, California, a company developing more sophisticated tests for identifying the various compounds found in marijuana, told AlterNet  that “sativa and indica are only really valid for describing the physical characteristics of the cannabis strain in a given environment. They are not nearly as reliable as terms for making assumptions about energy versus couch lock.” To the extent that there is a grain of truth in the basic division between the mind high of sativa and the body high of indica, as traditionally classified, deCesare believes the culprit is myrcene. Based on the analysis of more than 100,000 samples, deCesare says that his team found “consistently elevated levels of the terpenoid myrcene in C. indica as compared to C. sativa. Myrcene is the major ingredient responsible for ‘flipping’ the normal energetic effect of THC….”

Ethan Russo invokes his notion of the “entourage effect,” in which the distinctive highs normally associated with indica and sativa are in fact the result of a complex combination of many different cannabinoids and terpenes working in harmony. Teasing that apart in the lab is not a cheap or easy affair. If you don’t know your terpene levels, says Russo, than you can’t compute your relative chances of full couch-lock. And even if terpene levels are known, the same pot plant, when smoked, can still cause one person to become energized and talkative, while another person may just fall asleep. Same chemicals, different metabolisms. One person’s happy, giggly high is another person’s paranoid bad trip.

The result of this recent research is to bolster the general suspicion about medical marijuana dispensaries: The names of various marijuana varieties are not only stupid and immature, but also completely misleading and unhelpful. Coherent labeling will require much more than listing relative THC percentages. We’ve only just begun.

Such Stuff As Dreams Are Made On: Marijuana and Sleeping

Study sheds potential light on indica vs. sativa debate.

[Thanks to Ivan Oransky (@ivanoransky) for alerting me to this study.]

Anyone who has smoked marijuana more than a couple of times knows that cannabis can alter how you sleep. The effect of cannabis on sleep is even part of the never-ending debate over Cannabis indica vs. Cannabis sativa, the two major species of the marijuana plant. Indica smokers typically report a marijuana high that is body-intensive and often soporific, sometimes leading to the condition aptly known as “couch lock.” Whereas sativa smokers, according to marijuana lore, experience a more cerebral, energetic “head high,” with fewer somatic effects. Not surprisingly, hybrid strains incorporating the alleged characteristics of both indica and sativa strains are popular in the medical marijuana community.

Although there is no official sanction for it in the medical community, marijuana is often dispensed medically for sleep problems. One piece of common wisdom holds that the higher the THC content of marijuana, the more helpful it will be in promoting sleep and improving poor sleep. The stronger the better, in other words. Similarly, indica strains are assumed to promote sleep more than sativa strains.

In an effort to clear the air, so to speak, a group of researchers, writing in Addictive Behaviors, sought to “document naturalistic choice of particular medical cannabis types among individuals who self-report using cannabis for the treatment of sleep problems…. Little research has documented species or cannabinoid concentration preferences among individuals who use medical cannabis for particular conditions…. We also evaluated the interaction between the type of cannabis used and diagnosis of cannabis use disorder among study participants.”

The researchers recruited participants from a medical cannabis dispensary in California under procedures approved by the VA and Stanford University review boards. 163 people with a mean age of 40, who used cannabis twice a day on average, provided self-reported information on their cannabis use for the study. 81 participants reported using cannabis for the management of insomnia, and another 14 reported using cannabis to reduce nightmares. (Frequent smokers insist they dream less. THC does appear to decrease the density of REM cycles, leading to more restful, dream-free sleep, according to some studies. )

So what did they find?

—“Individuals who reported using cannabis for nightmares, compared to those who did not, preferred sativa to indica.” (Small effect.)

Indica, considered the “heavier” high, might have seemed the likely choice here.

—"Individuals who self-report using cannabis to treat symptoms of insomnia and those with greater self-reported sleep latency reported using cannabis with significantly higher concentrations of CBD.” (Large effect.)

Again, a somewhat counterintuitive finding, since it is widely believed that CBD conduces toward a more wakeful state than THC alone.

—“Individuals who used sleep medication less than once/week used cannabis with higher THC concentrations than those who used sleep medication at least once a week.” (Large effect.) “There were no differences in THC concentration as a function of self-reported sleep quality, or use for insomnia or nightmares.”

Pretty straightforward finding: THC makes you sleepy. It is not clear, however, that above a certain threshold, more THC makes you even sleepier. In fact, some researchers would consider this finding unexpected, given that high THC concentrations have been shown to have a stimulating effect.

—“Older individuals were less likely to have cannabis use disorder compared to those younger….

No surprise about the older folks, since prior studies show a decrease in the prevalence of cannabis use disorders with age.

—“Individuals who preferred sativa or primary sativa hybrid strains were less likely to have cannabis use disorder compared to those who preferred indica or primary indica hybrid strains.” (Small effect.)

If replicated, this finding could have significant implications; both in strengthening programs to reduce marijuana smoking among the very young, and it warning consumers that some evidence suggests indica strains may be more addictive than sativa strains in plants with similar THC/CBD levels and ratios.

—“Neither concentration of THC nor CBD were associated with cannabis use disorder.”

Common sense, but useful to remember. In other addictive behaviors, such as heroin and alcohol abuse, the relative strength of the drug is not the primary determinant of its addictive potential.

Caveats and design limitations: The survey relied on retrospective reports of sleep quality and pot preferences. Also lacking is an examination of additional variables such as PTSD and co-occurring substance abuse.

Grab Bag of Addiction Links

Recent reading from around the net.

Can Medical Marijuana and Recreational Marijuana Coexist?

“The Washington State Liquor Control Board released recommendations for what to do with the state's medical marijuana system now that recreational marijuana is legal.” [Atlantic Cities]

Premature claims of a cannabis addiction "cure"

“Have scientists found a ‘cure’ for marijuana addiction? New treatment blocks the kick that users get from the drug,” reports the Mail Online. Based on the evidence presented in the study, which involved animals, the answer to the Mail’s question is 'not yet'. [NHS Choices]

Can Gambling Machines Prevent Addiction?

“Today's digital slot machines and poker screens in casinos and at online gambling sites are capable of amassing a wealth of behavioral data on individual players, and they are on the verge of altering game play on the fly.” [Scientific American Mind]

Food for thought: UF researcher’s book lays out evidence for food addiction

“For some, the famous potato chip slogan “Betcha can't eat just one” isn’t a wager — it’s a promise.” [University of Florida Health]

New Zealand’s bold experiment with regulating recreational drugs

“It’s been nearly a century since the United States began its experiment in prohibiting recreational drugs besides alcohol, caffeine and tobacco — and virtually no one sees the trillion dollar policy as a success.” [Reuters]

More Than 1,000 Meet in Denver to Develop Drug War Exit Strategy

“Which state will be next to legalize marijuana? What do the Obama administration's recent announcements about marijuana legalization and mandatory minimums really mean?” [Huffington Post]

This Is Why Social Media and Drinking Alcohol Don't Mix (Infographic)

“Engaging with peers and customers on social platforms can be dangerous. Doing so while you’re under the influence of alcohol is downright irresponsible. “ [Entrepreneur]

Economists Predict Marijuana Legalization Will Produce "Public-Health Benefits"

“In their 2012 book Marijuana Legalization: What Everyone Needs to Know, Jonathan Caulkins and three other drug policy scholars identify the impact of repealing pot prohibition on alcohol consumption as the most important thing no one knows.” [Forbes]

Photo Credit: http://lifeonthebalcony.com/

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/

Congress and the Civil War Over Marijuana

Two lawmakers take a stab at ending federal prohibition of pot.

Two new bills designed to end federal marijuana prohibition and let states set their own policies were introduced today in the U.S. Congress by Rep. Earl Blumenauer (Dem-OR) and Rep. Jared Polis (D-CO). Legislation introduced by Rep. Polis would formally end federal prohibition of pot, while establishing a state regulatory permitting process similar to frameworks used to regulate alcohol. Rep. Blumenauer’s bill would set up mechanisms for taxing marijuana at the federal level.

While President Obama has said that his administration has “bigger fish to fry” when asked about state marijuana crackdowns, the two U.S. congressmen contend that “too many United States Attorneys and drug enforcement personnel are still ‘frying those little fish.’ Only Congress has the power to unravel this mess.”

Rep. Polis’ legislation would also remove marijuana oversight from the Drug Enforcement Administration (DEA), and hand it over to a newly repositioned Bureau of Alcohol, Tobacco, Marijuana, and Firearms. Under the Polis bill, it would remain unlawful to move marijuana from states where it is legal to states where it is not. Meanwhile, Blumenauer’s piece of legislation would give the feds a healthy chunk of income in the form of a 50% excise tax on “first sales” between a grower and a processor/retailer, in addition to possible state sales taxes on a per ounce basis.

The congressional representatives also released a report in which they note that after “decades of failed policies and tremors of varying intensity, the tectonic plates of marijuana regulation abruptly shifted November 2012 as the citizens of Washington and Colorado voted to legalize the drug for personal, recreational use…. These developments have played out against a backdrop of the least effective, and arguably, most questionable front in America’s ‘War on Drugs.’”

Despite recent efforts to reclassify marijuana, pot remains a Schedule I Controlled Substance, along with heroin and LSD, meaning it is considered a drug with high abuse potential and no accepted medical applications. The report notes that more than 660,000 Americans were arrested for marijuana possession in 2011, despite the rapid adoption of medical marijuana laws in 18 states. “This situation has created a gray area,” the report notes, “where medical marijuana enterprises are operating in a patchwork of conflicting state, local, and federal regulations. Common sense suggests that these enterprises have the potential for abuse and other criminal activity.”

Using figures from the 2010 U.S. census, the report contends that more than 100 million people now live in jurisdictions where some aspect of marijuana use is now legally permitted under state regulations. The result? “Confusion, uncertainty, and conflicting government action.”

The congressmen conclude by warning that “no one should minimize the potential harmful effects of marijuana,” and challenged legislators, in their efforts to protect the health and safety of Americans, to “acknowledge when existing mechanisms don’t work, go too far, or cause more harm than good.”

Neither of the bills is likely to pass, although Senator Patrick Leahy (D-VT), who chairs the Senate Judiciary Committee, has said that he plans to hold a hearing on conflicting state and federal pot laws. The Justice Department remains mum on its strategy for dealing with state marijuana rebellions. Former White House drug policy advisor Kevin Sabet, a member of Project SAM, for “smart approaches to marijuana,” told Associated Press that he considered the bills to be “really extreme solutions to the marijuana problem we have in this country. The marijuana problem we have is a problem of addiction among kids, and stigma of people who have a criminal record for marijuana crimes. There are a lot more people in Congress who think that marijuana should be illegal but treated as a public health problem, than think it should be legal.”

Twelve Months of Addiction Box

(Inspired by Twelve Months of Drug Monkey)

Drug Monkey writes:

The rules for this blog meme are quite simple.
-Post the link and first sentence from the first blog entry for each month of the past year.
I originally did this meme, after seeing similar posted by Janet Stemwedel and John Lynch.

Okay, here we go:

January:

Say what you will about glutamate-gated chloride channels in the parasitic nematode Haemonchus contortus—but the one thing you probably wouldn’t say about the cellular channels in parasitic worms is that a drug capable of activating them may prove useful in the treatment of alcoholism and other addictions.

February:

Here’s a book I’m delighted to promote unabashedly.

March:

Mo Costandi at the UK Guardian expanded on his Nature article about the mechanisms that result in memory impairment when people smoke marijuana.

April:

Our latest participant in the “Five Question Interview” series is Dr. Keith Laws, professor of cognitive neuropsychology and head of research in the School of Psychology at the University of Hertfordshire, UK.

May:

I'm not a huge fan of infographics, mostly because they tend to overpromise and are often marred by factual errors.

June:

Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition.

July:

Dr. Tom McLellan, chief executive officer of the Treatment Research Institute, who served on President Obama’s healthcare reform task force, called the recent U. S. Supreme Court Decision on the Affordable Care Act “the beginning of a new era in prevention, early intervention, and office based care for patients who are not addicted—but whose drinking, smoking, and use of other substances is harming their health and compromising the effectiveness of the care they are receiving for other illnesses and conditions.

August:

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.

September:

Voters in The Netherlands may have lost their final chance to block the nationwide imposition of the wietpas, or so-called "weed pass," as the law of the land in The Netherlands next year.

October:

People who say they are addicted to marijuana tend to exhibit a characteristic withdrawal profile.

November:

Children with heavy alcohol exposure show decreased brain plasticity, according to recent research on fetal alcohol spectrum disorders (FAS) using magnetic resonance imaging (MRI) scans.

December:

When a stroke happens to anyone under the age of 55, a major suspect is drugs, specifically the stimulants—methamphetamine and cocaine.


Photo Credit: lotteryuniverse.com

Dutch Voters Leave Fate of “Weed Pass” Hanging

Clock Continues Ticking For Pot Tourists in The Netherlands.

AMSTERDAM—Voters in The Netherlands may have lost their final chance to block the nationwide imposition of the wietpas, or so-called "weed pass," as the law of the land in The Netherlands next year. On Wednesday, a crucial election in Holland determined the outline of a new coalition government under the narrowest of leads for the anti-immigration, anti-marijuana PVV party of Prime Minister Mark Rutte. The election featured a virtual tie with the center-left Labour Party (PvdA) upstart Diederik Samsom, who opposed the idea of closing marijuana shops to foreigners. 

 

But with 150 seats in the Dutch Parliament, experts say at least six parties will be involved in building a new coalition government. Cannabis advocates were hoping for a clear victory by the Labour Party and strong showings by other liberal parties.

Under legislation that came into effect in the south of the country in May, coffee shops effectively became private clubs, selling cannabis only to registered members, who must be Dutch, and able to prove it. The conservative government maintained that foreign drug criminals were replenishing inventory through the border shops, leading to violence and arrests.

As AP reported last week: “The center-left Labor Party [PvdA], which is surging in pre-election polls thanks to strong performances by its leader Diederik Samsom in televised debates, also advocates scrapping the pass and replacing it with legislation that would further enshrine tolerance of marijuana in Dutch law and regulate not only coffee shops but also growers. However, the coffee shops still have a fight on their hands – the conservative VVD party of outgoing Prime Minister Mark Rutte is topping polls and looks set to become the biggest single party.”

And that, more or less, is how it turned out. With a one-seat margin in various exit polls late Wednesday night in The Netherlands, the sitting VVD Prime Minister will want to stay the course and take marijuana out of the hands of foreigners, starting in January, 2013.

Dutch poll watchers had predicted a tight race between the conservative VVD and the liberal PvdA, with an additional dozen parties likely to land seats in a new coalition government. The VVD's election manifesto specifically supported the weed pass, as did other right-leaning parties in The Netherlands. 

"I don't want to apply for a pass because then everybody could see your personal information," one coffee shop owner told AP. "You don't have to do it in a bar to get alcohol, so why in a coffee shop?"

The only silver lining for pot tourists is a possible scenario in which a VVD-led coalition, having originally introduced the concept of the weed pass, winds up negotiating a centrist mashup in which all parties might be likely to barter away the weed pass in return for other policy favors. Moreover, the far-right PVV party led by Geert Wilders suffered heavy losses.

 

The Financieele Dagblad writes that in any case, voters will not be happy, "because any coalition is going to cause pain. The jigsaw that is a new cabinet will consist of many pieces. The results will be complex, just as in 2010."

Photo Credit: http://www.rnw.nl

Dawn or Dusk for Marijuana in the Emerald Triangle?

New book chronicles Mendocino’s “ganjapreneurs”

Every morning in California, thousands of marijuana growers wake up believing they are one day closer to becoming legitimate operators, like the state’s wine makers. Three generations ago, Northern California’s dope farmers dreamed the same dream—but it had nothing to do with “medical” marijuana. It had to do with a hilly, forested, secluded terrain with enough rain and sunshine to make it perfect for marijuana growing and utterly inhospitable to law enforcement without 4WD vehicles.

There are presently only a few disorders for which marijuana is clinically indicated (although that number is bound to go up.) These include glaucoma, HIV/AIDS-related nausea, certain forms of neuropathic pain, lack of appetite associated with chemotherapy, and some promising research having to do with the spasticity associated with Parkinson’s Disease and MS. But Doug Fine’s book, Too High to Fail: Cannabis and the New Green Economic Revolution, isn’t really about the medical specifics. It’s a paean by a true believer. “One tries not to sound like one of those ‘cannabis can do anything including bring about world peace and an end to Ring Around the Collar people,” he writes. But he does. Oh, how he does.  If you believe in cannabis legalization as the Higher Calling, this is the book for you.

Fine moves to Mendocino County to dwell among the ganjapreneurs and tell the tale of “horticultural civil disobedience” that is the hallmark of the Emerald Triangle of Mendocino, Humboldt, and Trinity counties in Northern California—a mythical adult Disneyland where juries tend to believe the assertion that “all 169 pounds of the marijuana on his property was medicinal in nature.” It is a land where the local sheriff acknowledges that “maybe five per cent” of medical cannabis claims are legit, but goes on to declare that “I’ve never seen a stoned man beat his wife.”

As a supporter of limited decriminalization, I tried hard to like Fine’s book. He has a breezy, colloquial style that makes for easy reading. And after all, the latest public opinion polls show American citizens poised 50-50 on the subject of cannabis legalization. The book has no source list, no back-of-the-book notes, and only the occasional footnote, but Fine does his journalistic part, following Lucille, his designated medical marijuana plant, from birth as a clone to death in the dope pipe of a cancer patient. But as his growing source, Fine picks a greenhorn grower whose poor planning and general lack of local knowledge give a Keystone Kops feel to the growing season. “Murphy’s Law rope-a-dope” is Fine’s description of his grower’s business strategy.  Fine’s Mendocino sometimes takes on aspects of a hip Lake Wobegon, where everybody is late for everything, and everybody thinks that’s fine.

In “Mendo,” organic cannabis growers envision a future in which arthritis-wracked senior citizens will go to their local pharmacy for insulin and amoxicillin, and to their local dispensary for an oh zee of Matanuska Valley Thunderfuck. Of course, Fine is correct to note that the vast majority of marijuana users do so without damage to their health and well-being. “What is the glass of red wine enjoyed by the fellow on his deck after a hard day of investment banking? I think that’s documented to be health maintenance. A long-term cost saver. An evening cannabis pipe… is the same thing for some people.”

If billions of dollars are poised to fall on our heads with the flick of a presidential pen, who would want to oppose legalization? The author has plenty of answers: Big Pharma, the private prison industry, law enforcement lobbies, and the banking industry (just too much profit laundering all that money from all those cartels).

Fine isn’t bothered by the menacing “Turn Around Now” signs, or the occasional shotgun volley over the tops of cars with an out-of-county look to them.  He doesn’t have much to say about booby-trapped fences, the county snitch line, the rampant foreclosures, or the stolen power from Pacific Gas & Electric. We don’t get many accounts of subpoenas for cannabis patient medical records, or opposition from the Mendocino County Board of Supervisors. To be fair, he does make note of all the young punks and career criminals drawn to tax-free grey markets like this one—“Real providers next to total thugs,” as one activist put it. There is no substantive discussion of other approaches, like Michigan’s medical cannabis model where there are no dispensaries, and cannabis patients either grow their own, or get it from a licensed grower. The in-your-face activism of growers and dispensary owners in California has led to a complete dispensary closure in Los Angeles (see below).

And there is the continuing “wet” and “dry” aspect to the California trade, reminiscent of the bootlegger era in the hills of Appalachia. To get their medicine to market, growers in the Emerald Triangle must run “The Gauntlet” south to San Francisco and Los Angeles, and the first hurdle—Sonoma County—has been the end of many “compassionate cannabis” deliveries. The situation is clearly untenable. Mendocino should have been a safe bet—all the arguments are settled, all the sheriffs are friendly, and the fix is generally in.

Except when it isn’t. Local constabulary may be green, and Fine delights in describing instances where growers called deputies to their aid when “rippers” show up at harvest time—but try going all green on the California Highway Patrol when they stop you on your merry way across Mendocino County with 50 pounds of pot in the trunk. Or even a pair of terpene-laced bud trimmer gloves in the back seat. Two words describe Fine’s book: bad timing. The “eye of Sauron,” as one grower described the federal presence in the Emerald Triangle, means that there are times when the habit of ignoring that pesky little federal cannabis scheduling problem can still land you in jail, official Mendocino yellow zip-tie program or not.

 On July 22, 2011, President Obama brought the Mendocino bubble in for a wobbly landing: “Am I willing to pursue a decriminalization strategy as an approach? No.” Federal authorities in the county seized a total of 725,000 plants in 2011. The Feds swooped down with “Operation Full Court Press” to clear growers out of Mendocino National Forest. Even the perennially optimistic Ethan Nadelman of the Drug Policy Alliance told Fine that “there’s only so much even a second-term Obama can do if the Republicans still control Congress.” This game, despite how it may look on the ground in Mendo, is still very much in the hands of the Feds. As an official for NORML admits, there could be “twenty years of this” yet to go.

To the DEA, local ordinances mean nothing. Shortly after Fine’s book ends, in early 2012, the cannabis market in the Emerald Triangle crashed after a series of raids and dispensary closures drastically limited medical outlets for their product.  By the end of the book, several of the growers have spent time in handcuffs—including the author himself, who didn’t care for the experience at all. It remains unclear whether he has written a celebratory book about the cannabis tipping point, or a eulogy for the death of the medical marijuana movement.

At this writing, cannabis activists appear to be genuinely baffled that Obama has not willingly adopted the mantle of “herb candidate” they wish to thrust upon him. But I do think Fine has at least a betting chance of being correct when he writes: “Like alcohol prohibition before it, commons sense, human desire, and economic inevitability will eventually prevail and the Drug War will end.”

Graphics Credit: http://humboldtherald.wordpress.com/

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/

Drug Links, Various

Pharmacology, Politics, and Recovery

* USA Today article on Opana abuse rivalling Oxy abuse.

* US Attorneys Crack Down on California Medical Marijuana Dispensaries.

* Downloadable reports from Alcohol Justice, an industry watchdog group.

* With regard to the approval of Lorcaserin as a diet pill, here's the saga of Phen-Fen--how a blockbuster diet pill died.

* Why the Dutch "weed pass" won't work.

* Cigars won't save you: Cigars cause your body similar problems as cigarettes.

* Playwright Sam Shepard on his stint in rehab: “I finally did AA down on Pico Boulevard. I said, 'Don’t put me in with Elton John or anything, just throw me to the lions.’”

* 4,848 and 390: number of medical marijuana providers in Montana in March 2011 and June 2012, respectively.

* Andrea Mitchell talks to NIDA's Nora Volkow

* Listen to the talking urinal cake: Don’t drive drunk

* Feds say celebrity psychiatrist Dr. Drew was paid by Glaxo to talk up antidepressant on TV.

* Reactions to Marc Ambinder's GQ piece on Obama and the Drug War

* Lengthy interview with Drug Czar Kerlikowske by Mike Guy at The Fix:


Graphics Credit: http://tucsonvelo.com

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/

Decoding Dope

Why marijuana gets you high, and hemp doesn’t.

Cannabis sativa comes in two distinct flavors—smokeable weed, and headache-inducing hemp. The difference between hemp and smokeable marijuana is simple: Hemp, used for fiber and seed, contains only a tiny amount of THC, the primary active ingredient in the kind of cannabis that gets you high. I am old enough to recall the sad saga of California hippies driving through my natal state of Iowa, and filling their trunks with “ditch weed”—wild hemp that grows commonly along Iowa rural fencerows, and while it cannot get you high, it could, back then, get you arrested.

But the California hippies who ran afoul of the law in Iowa were not so stupid as it might seem. Even a marijuana connoisseur can have a hard time telling the difference between strong sinsemilla and wild hemp. Both varieties look similar, have similar growth patterns and flowering schedules, and a fresh bud of ditch hemp can look and smell enticingly like the real thing. Even the trichomes—the thousands of sticky, microscopic stalks that grow on the female flowers, each containing a bead of resin, like a crystal golf ball on a tee, containing mostly THC, in the case of pot, and mostly CBD, in the case of hemp—are also similar in appearance and growth behavior.

A study by a group of Canadian researchers, just published in Genome Biology, lays out the draft genome of marijuana, containing all of the plant’s hereditary information as encoded in DNA and RNA.In their article, Timothy Hughes, Jonathan Page and co-workers reported “a draft genome and transcriptome sequence of C. sativa Purple Kush.” (The genome and transcriptome can be browsed or downloaded at The Cannabis Genome Browser.) More than 20 plant genomes have now been sequenced, including corn and rice, but Cannabis sativa marks the first genomic sequencing of a traditional medicinal plant.

So how does it happen that one version of cannabis comes power packed, while the other version shoots blanks, so to speak? The researchers began with the modern facts of the matter: The THC content of medical and recreational marijuana is “remarkably high.” Research shows that median levels of THC in dried female flowers of Purple Kush (the strain used in the study) and other high-end variants now approach 11%, with some strains achieving a stratospheric 23% THC content by dry weight. Why can’t breeders pull any buzz out of ditch weed? How did cannabis split into two distinct subtypes? In an accompanying editorial entitled “how hemp got high,” Naomi Attar calls Cannabis sativa “a plant with a ‘split personality,' whose Dr. Jekyll, hemp, is an innocent source of textiles, but whose Mr. Hyde, marijuana, is chiefly used to alter the mind.” In brief, what are the biological reasons for the psychoactive differences between marijuana and hemp?

Co-lead author Jon Page, a plant biologist at the University of Saskatchewan, along with Tim Hughes of the Department of Molecular Genetics at the University of Toronto, compared the genomic information of Purple Kush, a medical marijuana favorite, with a Finnish strain of hemp called Finola, which was developed for oil seed production and contains less than 1% THC content. That is not enough THC to be mind-altering in any way. Instead, what Finola has in abundance is cannabidiol, or CBD, the other major ingredient in cannabis.

CBD isn’t considered psychoactive, but it does produce a host of pharmacological activity in the body. CBD shows less affinity for the two main types of cannabis receptors, CB1 and CB2, meaning that it attaches to receptors more weakly, and activates them less robustly, than THC.  The euphoric effects of marijuana are generally attributed to THC content, not CBD content. In fact, there appears to be an inverse ratio at work. According to a paper in Neuropsychopharmacology, "Delta-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of delta-9-THC."

The kind of cannabis people want to buy has a high THC/low CBD profile, while the hemp chemotype is just the reverse—low THC/high CBD. While the medical marijuana movement has concentrated on Purple Kush and other high-THC breeds, medical researchers have often tilted towards the CBD-heavy variants, since CBD seems to be directly involved with some of the purported medicinal effects of the plant. So, CBD specifically does not produce the usual marijuana high with accompanying euphoria and forgetfulness and munchies. What other researchers have discovered is that pot smokers who suffer the most memory impairment are the ones smoking cannabis low in cannabidiol, while people smoking cannabis high in cannabidiol—cheap, seedy, brown weed—show almost no memory impairment at all. THC content didn't seem to matter. It was the percentage of CBD that controlled the degree of memory impairment, the authors of earlier studies concluded.

 The researchers found evidence in Purple Kush for “upregulation of cannabinoid ‘pathway genes’ and the exclusive presence of functional THCA synthase.” That means the reason hemp doesn’t get you high is because it is lacking the crucial enzyme—THCA synthase—that limits production of CBD and allows the production of THC to go wild. In contrast, cannabis strains producing high levels of THC—the Kushes and Hazes and White Widows and other seriously spendy variants—do have high levels of the enzyme that limits the production of CBD. Purple Kush gets you high because it has a built-in chemical brake on the production of CBD. Hemp doesn’t.

In a press release from the University of Saskatchewan, the researchers explain how they think this divergence came about: “Over thousands of years of cultivation, hemp farmers selectively bred Cannabis sativa into two distinct strains—one for fiber and seed, and one for medicine.” This intensive selective breeding resulted in changes in the essential enzyme for THC production, which “is turned on in marijuana, but switched of in hemp,” as Page put it. Furthermore, says co-leader Tim Hughes of the Department of Molecular Genetics at the University of Toronto, an additional enzyme responsible for removing materials required for THC production was “highly expressed in the hemp strain, but not the Purple Kush.” The loss of this enzyme in Purple Kush eliminated a substance “which would otherwise compete for the metabolites used as starting material” in THC production.

Without knowing the mechanics of it, underground growers and breeders have been steadily maximizing the cultivation of strains of cannabis high in THCA synthase, the result of which is a molecular blocking maneuver that maximizes THC production. This is great for getting high, but may not be the optimal breeding strategy for producing plants with medicinal properties.  Raphael Mechoulam, the scientist who first isolated and synthesized THC, has referred to plant-derived cannabinoids as a “neglected pharmacological treasure trove.”  The authors of this study agree, and have already identified some candidate genes that encode for a variety of cannabinoids with “interesting biological activities.” Such knowledge, they say, will “facilitate breeding of cannabis for medical and pharmaceutical applications.”

But cannabis of this kind may turn out to be low-THC weed. And that may be a good thing, some researchers believe. Marijuana expert Lester Grinspoon told Nature News: "Cannabis with high cannabidiol levels will make a more appealing option for anti-pain, anti-anxiety and anti-spasm treatments, because they can be delivered without causing disconcerting euphoria." (We’ll leave definitional issues about the effects of euphoria for another post.)

Finally, the authors strongly suggest that if it were not for “legal restrictions in most jurisdictions on growing cannabis, even for research purposes,” we would have known all of this stuff years ago, and would have been well on our way to developing “finer tailoring of cannabinoid content in new strains of marijuana,” as Nature News Blog describes it.

van Bakel H, Stout JM, Cote AG, Tallon CM, Sharpe AG, Hughes TR, & Page JE (2011). The draft genome and transcriptome of Cannabis sativa. Genome biology, 12 (10) PMID: 22014239
Photo Credit:http://www.medicinalgenomics.com/

Feds Go “Passive-Aggressive” in Fight Against Medical Marijuana

Sending in the IRS instead of knocking down doors.

It’s official: The Obama administration has thrown off the gloves, repudiating Attorney General Eric Holder’s vow of two years ago that the federal government was not interested in prosecuting “state-legal” cannabis activity. Instead, a flurry of action is underway, intended to signal that the DOE and DEA are out to put a stake through the heart of the medical marijuana industry as a whole. Marijuana, however it is used, remains wholly illegal under federal statutes, and federal law enforcement officials insist such laws trump any state laws aimed at allowing the sale and use of cannabis.

During the last 30 days:

-- The DEA raided medical marijuana clinics in Tempe, Arizona.

--The Rhode Island governor reneged on an earlier pledge to okay medical marijuana in his state, saying that any such activity would make the state a target for federal prosecution. 

-- Federal prosecutors seized the bank accounts of medical marijuana shops in Sacramento, claiming a series of “irregular deposits.”

--The IRS decreed that the biggest marijuana dispensary in California cannot deduct ordinary business expenses on its taxes.

--A study of marijuana for posttraumatic stress disordered descended into “regulatory limbo,” as Brian Vastag reported for the Washington Post, after the National Institute on Drug Abuse (NIDA), the only legal source of cannabis for researchers, refused to hand over government marijuana to the study authors because of “a number of concerns” about research protocol.

--A California Appellate Court ruled that the statute allowing  marijuana dispensaries in Long Beach is in violation of federal law, which will force a long and arduous rewrite of the permitting laws for that city, and presumably other cities as well.

 The irony is that California’s medical marijuana industry, the first in the nation, may have survived the SWAT team attacks of the Bush years, only to fall victim to renewed regulatory fervor under President Obama’s watch. And, as I reported earlier at The Fix: “Britain’s giant GW Pharmaceuticals received U.S. patent approval for the use of Sativex, its nasal spray for treatment of advanced cancer pain composed of—yes, that’s right—a combination of the two primary chemicals found in cannabis. Since then, Sativex has made it all the way to Phase III clinical testing in a bid for FDA approval. At the moment, the company’s chances of producing a cannabis based pill are looking very good.” Meanwhile, so-called “whole-plant” marijuana research is getting squeezed out.

And now comes word that federal prosecutors are following up with a giant crackdown on all California dispensaries. Associated Press reports that U.S. attorneys sent letters this week to at least 16 pot dispensaries, “warning the stores they must shut down in 45 days or face criminal charges and confiscation of their property even if they are operating legally under the state’s 15-year-old medical-marijuana law.”

Sources say that cease-and-desist letters from U.S. Attorney Melinda Haag in California had been received by some dispensaries, stating the “violations of the federal law referenced…. is a federal crime,” and further stipulating that the penalties could include property forfeitures and 40 years of prison time, reports Chris Roberts at SF Weekly.

And the Associated Press obtained copies of letters sent to San Diego dispensaries, in which federal prosecutors claim that marijuana shops are illegal and subject to criminal prosecution and civil enforcement actions. “Real and personal property involved in such operations are subject to seizure by and forfeiture to the United States… regardless of the purported purpose of the dispensary.”

The action follows warning letters that were sent to dispensary owners and state officials by federal prosecutors in June, which strongly hinted that state employees might be liable for prosecution as well. A California attorney told SF Weekly that the feds were now embarking on a more effective “passive-aggressive” approach to shutting down the medical marijuana industry. “They’ve systematically changed their approach,” said the attorney. “Probably after talking to a PR professional.”

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