Recent Research on Medical Marijuana

Emerging Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2008

Despite continued political debates regarding the legality of medicinal marijuana, clinical investigations of the therapeutic use of cannabinoids are now more prevalent than at any time in history. A search of the National Library of Medicine’s PubMed website quantifies this fact. A keyword search using the terms “cannabinoids, 1996” reveals just 258 scientific journal articles published on the subject for that year. Perform this same search for the year 2007, and one will find over 3,400 published scientific studies.

While much of the renewed interest in cannabinoid therapeutics is a result of the discovery of the endocannabinoid regulatory system, some of this increased attention is also due to the growing body of testimonials from medicinal cannabis patients and their physicians. Nevertheless, despite this influx of anecdotal reports, much of the modern investigation of medicinal cannabis remains limited to preclinical (animal) studies of individual cannabinoids (e.g. THC or cannabidiol) and/or synthetic cannabinoid agonists (e.g., dronabinol or WIN 55,212-2) rather than clinical trial investigations involving whole plant material. Predictably, because of the US government’s strong public policy stance against any use of cannabis, the bulk of this modern cannabinoid research is taking place outside the United States.

As clinical research into the therapeutic value of cannabinoids has proliferated exponentially, so too has investigators’ understanding of cannabis’ remarkable capability to combat disease. Whereas researchers in the 1970s, 80s, and 90s primarily assessed cannabis’ ability to temporarily alleviate various disease symptoms — such as the nausea associated with cancer chemotherapy — scientists today are exploring the potential role of cannabinoids to alter disease progression. Of particular interest, scientists are investigating cannabinoids’ capacity to moderate autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, as well as their role in the treatment of neurological disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (a.k.a. Lou Gehrig’s disease.)

Investigators are also studying the anti-cancer activities of cannabis, as a growing body of preclinical and clinical data concludes that cannabinoids can reduce the spread of specific cancer cells via apoptosis (programmed cell death) and by the inhibition of angiogenesis (the formation of new blood vessels). Arguably, these latter trends represent far broader and more significant applications for cannabinoid therapeutics than researchers could have imagined some thirty or even twenty years ago.

HOW TO USE THIS REPORT

As states continue to approve legislation enabling the physician-supervised use of medicinal marijuana, more patients with varying disease types are exploring the use of therapeutic cannabis. Many of these patients and their physicians are now discussing this issue for the first time, and are seeking guidance on whether the therapeutic use of cannabis may or may not be appropriate. This report seeks to provide this guidance by summarizing the most recently published scientific research (2000-2008) on the therapeutic use of cannabis and cannabinoids for 17 separate clinical indications:

* Alzheimer’s disease
* Amyotrophic lateral sclerosis
* Diabetes mellitus
* Dystonia
* Fibromyalgia
* Gastrointestinal disorders
* Gliomas
* Hepatitis C
* Human Immunodeficiency Virus
* Hypertension
* Incontinence
* Multiple sclerosis
* Osteoporosis
* Pruritis
* Rheumatoid arthritis
* Sleep apnea
* Tourette’s syndrome

In some of these cases, modern science is now affirming longtime anecdotal reports of medicinal cannabis users (e.g., the use of cannabis to alleviate GI disorders). In other cases, this research is highlighting entirely new potential clinical utilities for cannabinoids (e.g., the use of cannabinoids to modify the progression of diabetes.)

The diseases profiled in this report were chosen because patients frequently inquire about the therapeutic use of cannabis to treat these disorders. In addition, many of the indications included in this report may be moderated by cannabis therapy. In several cases, preclinical data indicates that cannabinoids may halt the progression of these diseases in a more efficacious manner than available pharmaceuticals. In virtually all cases, this report is the most thorough and comprehensive review of the recent scientific literature regarding the therapeutic use of cannabis and cannabinoids.

For patients and their physicians, let this report serve as a primer for those who are considering using or recommending medicinal cannabis. For others, let this report serve as an introduction to the broad range of emerging clinical applications for cannabis and its various compounds.

Paul Armentano
Deputy Director
NORML | NORML Foundation
Washington, DC
January 24, 2008

* The author would like to acknowledge Drs. Dale Gieringer, Gregory Carter, Steven Karch, and Mitch Earleywine, as well as NORML interns John Lucy, Christopher Rasmussen, and Rita Bowles, for providing research assistance for this report. The NORML Foundation would also like to acknowledge Dale Gieringer, Paul Kuhn, and Richard Wolfe for their financial contributions toward the publication of this report.

** Important and timely publications such as this are only made possible when concerned citizens become involved with NORML. For more information on joining NORML or making a donation, please visit: http://www.norml.org/join. Tax deductible donations in support of NORML’s public education campaigns should be made payable to the NORML Foundation.

Members Of Congress Demand An End To Federal Pot Possession Arrests

Members of Congress convened a Capitol Hill press conference in July to demand lawmakers enact legislation to eliminate the government’s authority to arrest and prosecute adults who possess marijuana.  Lawmakers called on colleagues to endorse HR 5843, which sought to remove federal penalties for the possession and non-profit transfer of marijuana by adults.  The legislation was the first proposal introduced in Congress in 30 years to eliminate criminal marijuana penalties.  Read the full story at: http://www.norml.org/index.cfm?Group_ID=7670.

FURTHER EVIDENCE OF THE COLLAPSE OF THE WEST

Times, UK – After years of being relegated to the office party and hen nights, disco has shimmied her way back up to the top of the cool kids’ party playlist. Blanketed in glitzy memories of Studio 54, disco provides the perfect antidote to the all-pervading grimness of the life ahead. “When times are good, you could argue that people get turned on by darker, edgier music, such as drum’n’bass or electro,” says Jim Stanton, who started the iconic Horse Meat Disco in Vauxhall, south London. “As soon as life gets harder, people look for something more uplifting, which is where disco comes in – it’s an escape. The first big-haired disco moments happened in America during the 1970s, when there was a depression caused by an oil crisis.”. . .

Thelonious-

812monk-774918

INTERNET SIGHTINGS: MEMORIES OF MONK

Circulating on the web are some great quotes from Thelonious Monk, as collated by fellow musician Steve Lacy. Some excerpts:

– Just because you’re not a drummer, doesn’t mean that you don’t have to keep time.

– Pat your foot and sing the melody in your head when you play.

– Stop playing all that bullshit, those weird notes, play the melody!

– Make the drummer sound good.

– You’ve got to dig it to dig it, you dig?

– Don’t play the piano part, I am playing that. Don’t listen to me, I am supposed to be accompanying you!

– The inside of the tune [the bridge] is the part that makes the outside sound good.

– Don’t play everything (or everytime); let some things go by. Some music just imagined.

– What you don’t play can be more important than what you do play.

– A note can be small as a pin or as big as the world, it depends on your imagination.

– Stay in shape. Sometimes a musician waits for a gig & when it comes, he’s out of shape & can’t make it.

– (What should we wear tonight?) Sharp as possible!

– Whatever you think can’t be done, somebody will come along & do it. A genius is the one most like himself.

– They tried to get me to hate white people, but someone would always come along & spoil it.

Your editor never heard Monk, but recalls one evening in the late 1950s a friend returned from a Boston club to report seeing Thelonious sit at the piano for innumerable choruses, just smoking and listening to the bass player and playing no more than one or two notes. Someone at a front table shouted out, “Hey, Thelonius, play something.” Monk let his cigarette drop to the floor and then kicked it onto the complainer’s table. He then got up and slowly stalked the outside aisle of the club before leaving and reportedly ended up in a mental institution that night.

Proteins change as pot plants clean up soil

[April 1, 2007]

When cannabis hits the headlines it is often in response to the latest cannabis farm that has been unearthed, be it in a remote field in the country or in someone’s roof in the city. Bad press all round for a plant known for its psychoactive properties and misuse, even though it is finding support from individuals and doctors for alleviating the symptoms of many illnesses. But what many people fail to appreciate is that there are other, safer, varieties of Cannabis sativa that bring different qualities to society.

The pot-smoking species is C. sativa subsp. indica, characterised by relatively large amounts of tetrahydrocannabinol (THC), the psychoactive component. However, another cultivar, C. sativa subsp. sativa, produces only trace amounts of THC and grows long and tall, with little branching. This form is cultivated for its fibres and is more often known as industrial hemp. It is easy to grow, typically taking 4 months to rise to heights of 3-10 feet, its fast growth negating the need for herbicides.

It has been estimated that hemp is used in more than 25,000 products, including paper, fibreboard, textiles, biodegradable composites, plastics, rope, sails and furniture. Compared with wood chippings, hemp produces at least double the amount of fibre and does not require bleaching or other toxic chemicals.

But Cannabis sativa has one further property that can get careless industrialists and farmers off the hook. It can help to clean up soil that has been contaminated with toxic heavy metals such as cadmium, nickel and copper. Plants grown in soil that has been fouled by industrial effluent, metal-enriched fertilisers or herbicides can absorb metals into their root systems. So, ideally, crops could be grown on contaminated soil, then the fibres harvested for industrial use.

Little is known about how the Cannabis plant reacts when it takes up excess copper, especially within the proteome. How does it manage this, while still maintaining growth and its normal protein functions? This question has now been addressed by scientists from the University of Piemonte Orientale in Alessandria who have studied the proteome of Cannabis sativa var. Felina 34 grown under copper stress.

Seedlings were planted in a quartz sand-loam-gravel mix that was dosed with 150 ppm copper sulphate. This level is well above the mean world soil copper concentration of 20 ppm, while remaining below that at which serious plant toxicity is observed. After 6 weeks, the copper-treated plants were smaller than control plants, with shorter leaf areas, root lengths and root volumes.

The copper content, determined by ICPMS, doubled in the shoots, but increased 8-fold in the roots compared with controls. This distribution confirmed that copper intake was preferentially localised in the root system in agreement with published work which declared the copper gradient in hemp to be roots > stems > leaves > seeds.

Proteins in the roots were extracted by standard methods and separated by 2D gel electrophoresis. The protein spots that had statistically significant intensity differences from the control gel were selected for in-gel digestion with trypsin for tandem mass spectrometry analysis. Seven proteins were down-regulated, five were up-regulated and two disappeared altogether.

Subsequent identification was not straightforward, since the C. sativa genome has not yet been sequenced. So the researchers, led by senior reporter Maria Cavaletto, used de novo sequencing from the MS/MS spectra then aligned the proteins to database sequences of related organisms. This cross-species protocol was able to identify some of the protein with altered abundances.

Since no new proteins were observed under copper stress, the team concluded that the plant does not evolve a copper-specific mechanism to incorporate the excess metal ions. They proposed a copper-coping mechanism in which the first protein to interact with the copper ions, present as copper(II), was aldo/keto reductase. It acts as a scavenger, reducing copper(II) to copper(I), a process which makes it available for interactions with other proteins such as phytochelatins that bind copper(I). This reductase is an auxin-induced protein, confirming the involvement of auxin as a plant growth regulator handling the excess metal.

Other implicated proteins include the stress proteins formate dehydrogenase, a protein that increases in response to other stresses such as dark, cold and drought, as well as enolase and elicitor-inducible protein. Other implicated proteins are those which confer greater copper resistance and provide an efficient reducing system (thioredoxin peroxidase, peroxidase and cyclophilin) and those which regulate root growth (actin, ribosomal proteins and glycine-rich protein.

This preliminary work will mark a useful basis for future phytoremediation studies, perhaps being used to develop plants for biomonitoring or for the remediation of heavily metal-polluted soil.

Related links:

* Department of Environmental and Life Sciences, University of Piemonte Orientale

http://www.disav.unipmn.it/


* Proteomics 2007, 7, 1121: “Proteomic characterization of copper stress response in Cannabis sativa roots”

http://www3.interscience.wiley.com/user/accessdenied?ID=114182347&Act=2138&Code=4717&Page=/cgi-bin/fulltext/114182347/PDFSTART


http://www.spectroscopynow.com/coi/cda/detail.cda;jsessionid=B9527441DE1FE87DF66C0D19CA250C2E?id=16011&type=Feature&chId=10&page=1