Cannabinoids may modulate the spread of cancer cells

Matrix metalloproteinases (MMPs) are a family of enzymes that are involved in many physiological processes, helping to balance inflammatory signals; regulate cell growth, division, death, and cleanup; and model new tissues and blood vessels. They seem to play a central role in tumor metastasis and survival in many cases.
New research out of Germany looks at the role of anandamide and THC in reducing the invasiveness of cervical cancer cells, and seems to indicate that invasion is reduced through the cannabinoids' inhibitory effect on MMPs. The results look promising, even though they are still in vitro, and give us another insight into the immune- and inflammation-regulating power of Cannabis in the human physiology.

Cannabis and psychosis

The current issue of the Lancet published a meta-analysis of multiple trials concerning the use of cannabis and its association with mental illness. There were 35 longitudinal studies selected for the analysis. All of them followed patients starting before any mental illness, and included cannabis use as a variable along with many other factors, such as personality, background, use of other drugs. 7 out of 35 trials concerned "psychosis" (ranging from 'mild symptoms' to 'schizophrenia') and were the only ones that showed any connection with cannabis use. Conditions of mental illness such as depression, mood disturbances, or others did not have any connection.
The study's authors rightly point out that there can be no way to say for certain that there is a direct causal link between smoking pot and experiencing at least one major psychotic episode (and the definitions are a bit of a problem for me here as well), but that caution, especially in folks with a personal or family history, is warranted. In the end, I would have to agree -- but this is true of any medicine, really...
There is a brief (6-minute) interview with the study's author here.

Cannabinoids and skin allergies

Fresh research published in Science seems to hint at a topical anti-allergic effect for cannabinoids. The trial was done in mice using an artificial allergen, and the research proceeded in two steps: first, the scientists found that mice genetically engineered to lack cannabinoid receptors were much more sensitive to environmental allergens like nickel. I suspect the mice were modified as part of Dr. Karsak's ongoing obsession with understanding the role that mammalian cannabinoids (which occur naturally in our bodies, as well as in mice -- one example is anandamide) play in a variety of processes, from atherosclerosis, to generalized inflammation, to mood.
Anyway, Karsak and the rest of the research team decided to take things a step further, and see if cannabinoids from Cannabis itself could reduce skin sensitivity in normal mice. So they cooked up some kind of marijuana salve and applied it to mice that had been exposed to a synthetic allergen (2,4-dinitrofluorobenzene). The results: a 50% reduction in inflammation and swelling. While the mechanism of action is still unclear, preliminary evidence seems to point to cannabinoids' role in modulating the expression of genes that code for pro-inflammatory compounds like histamine. I'd be curious to hear more about this: it could help explain how effective marijuana has been in curbing GI and upper respiratory inflammation (colitis, asthma, e.g.) in previous studies, some of which were in humans.
One final note of wisdom from Roman Rukwied, a pain and inflammation researcher: "We are far before the day when we could say 'oh, I have a nickel allergy. I will smoke marijuana and I won't have it anymore'," he says. "That is definitely not the case." Fair enough.

Cannabis decreases neuropathy

Dr. Abrams (and others), who has a history of working on treatments to improve the quality of live for HIV patients, has co-authored a small but statistically significant trial on the effects of smoked cannabis on the neuropathy associated with HIV. The nerve pain in question is characterized by hypersensitivity to even the smallest stimuli, like the brushing of clothing on the skin, and has some similarities to the intense burning and pain associated with shingles, the herpes zoster infection.
Here is a quick summary of some of this placebo-controlled study's findings:

• Over the course of the study, smoked cannabis reduced daily pain by 34%, versus 17% with placebo.
• 52% of the cannabis group reported at least a 30% reduction in pain, compared with 24% in the placebo group.
• The first cannabis cigarette reduced chronic pain by 72%.
• No serious adverse events were reported.

And, bottom line: "Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain". This is a significant result: not only is chronic neuropathy very difficult to deal with, both as a patient and as a clinician, but conventional drugs like neurontin (not to mention the narcotics) leave a lot to be desired.
This trial provides yet another safe and effective clinical use for this much-maligned botanical medicine.

Cannabinoids mellow out a spastic colon

Our bodies are riddled with receptors for the class of molecules, known as cannabinoids, that are found in large concentrations in marijuana. While it may be that our own endogenous anandamide-like substances are the reason for the presence of these receptors, it seems that in the plant world marijuana is the only source of cannabinoids we have available. Co-evolution, anyone?
Regardless, a preliminary investigation by Michael Camilleri, M.D. (Mayo Clinic), who has spent the last decade researching drugs, neurotransmitters, receptors and pharmacological pathways involved in irritable bowel syndrome and other spasmodic conditions of the lower bowel, shows promise for using cannabinoid receptors in the gut to help modulate these distressing conditions. Doctor Camilleri's plan: feed folks with sensitive digestive systems over a pint of chocolate milkshake after giving them a pill of Marinol, a synthetic THC (tetra-hydro-cannabinol). Without getting into what a pint of chocolate milkshake would do to me (or anyone really) if taken on an empty stomach, and whether that represents cruel and unusual punishment for someone with colitis or irritable bowel, it seems that the synthetic cannabinoid is one of the most effective remedies the good doctor has ever seen for the cramping and pain people experience after pounding said milkshake. The next step: back to the lab, to find a synthetic cannabinoid that "does not have psychoactive properties".
If you ask me, that seems like a time-consuming, expensive proposition. Over and over, folks who have used cannabinoids as medicine (for glaucoma, wasting syndrome, chemo-induced nausea, and bowel trouble) complain that the pharmaceuticals are not as effective as a crude, inhalable folk-preparation of the marijuana plant (a.k.a. "the joint"). One puff may not be psychoactive, but it still seems to be quite medicinal if you trust the reports of those who have tried. But the feds might not appreciate that (nor the pharmaceutical companies, for that matter). And we all know the best way to fund research is to come up with a good, actionable, patentable pharmaceutical, not some devil-weed - regardless how cheap, accessible, or useful it may be.

Cannabinoids and Alzheimer's

A preliminary study seems to imply that the use of cannabinoids (one of the many biochemically active agents in marijuana) can protect the brain from inflammatory degeneration and its complications, such as Alzheimer's disease. The current study relies on an animal model and requires the consumption of cannabinoids during youth - but in that particular situation, the results are a dramatic reduction in the changes in brain tissue that lead to the formation of amyloid plaque, thought to be a chief culprit in Alzheimer's.
Gary Wenk, Ph.D, conducted the research at the University of Ohio:

... as the animals age, Dr. Wenk said, they develop inflammation in parts of the brain analogous to the parts damaged by inflammation in people with Alzheimer's.

Recent research in other fields suggested that cannabinoids -- the active ingredients in marijuana -- can cross the blood-brain barrier, even at low doses, and can reduce inflammation, Dr. Wenk said.

So, in young rats, Dr. Wenk and colleagues created brain inflammation by infusing nanogram quantities of lipopolysaccharide and then treated them with a synthetic cannabinoid called WIN-55212-2.

"We saw an 80% to 90% drop in the inflammation in the brain," he said, "and also the impairment in memory that inflammation produces could be reversed."

http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb2/4321