Medical Cannabis Is A Blunt Tool

[Guest guest]

Medical Cannabis Is A Blunt Tool

http://www.medicalnewstoday.com/medicalnews.php?newsid=48127

IF anecdotes and ancient medicine are to be trusted, cannabis is a

wonder drug. Yet results of clinical trials have been mixed and its

use in modern medicine remains limited. Now it seems the reasons may

be practical as much as political and cultural: there are fundamental

problems with how our bodies respond to the stuff.

Some compounds in cannabis, including THC and cannabidiol, interfere

with a natural signalling system throughout our brains, nerves and

immune system. This system, which produces its own cannabis-like

compounds called endocannabinoids, plays a role in many medical

conditions including pain, epilepsy, multiple sclerosis, Parkinson's

disease, depression and schizophrenia.

Because the system is so widespread, smoking or ingesting cannabis is

bound to have varied effects, including its influence on the mind.

Now it seems that even with purified cannabis extracts, changing the

amount, time or place of a dose could produce completely opposite

effects on the body, according to evidence presented at the

Federation of European Neuroscience Societies (FENS) meeting in

Vienna earlier this month. This could explain why the medical

benefits have proved so difficult to harness.

In one study, Vincenzo Di Marzo of the National Research Council in

Pozzuoli, Italy, boosted levels of an endocannabinoid called

andandamide in rats engineered to develop an Alzheimer's-like

disease. This appeared to protect the rats from memory loss and nerve

degeneration. But if the rise was prolonged, cannabinoids became

ineffective or even damaging.

Beat Lutz of the University of Mainz in Germany found a similar

paradox in models of epilepsy in mice. Anandamide is synthesised

during epileptic fits, providing a natural calming effect. " If we

apply cannabinoids we should protect from seizures, " says Lutz. " But

no, we actually get worsening of seizures in mice. "

He believes he has found the reason. The main class of cannabinoid

receptor, called CB1 receptors, occurs in two distinct populations of

neurons, those that excite neighbouring neurons and those that

inhibit them - so cannabinoids can have opposite effects depending on

which neurons they hit. Baker, a multiple sclerosis expert at

University College London has found the same problem in MS. Mice that

have been engineered to have a condition like MS and no CB1 receptors

suffer much worse nerve damage than those with normal CB1 receptors,

suggesting that cannabinoids are involved in protecting against the

nerve damage seen in MS. But other experiments in mice have shown

that cannabinoid signalling also prompts release of stress hormones

called glucocorticoids that can kill neurons.

The greatest anecdotal evidence for the medical benefits of cannabis

comes from its painkilling properties, and animal models have

produced promising results. Yet even here new evidence suggests that

an endocannabinoid called NADA binds not only to cannabinoid

receptors but to a completely different class of receptor as well,

where it mimicks the effect of a pain-producing chemical called

capsaicin, says J. of Indiana University in

Bloomington, who also presented his research at FENS. This may

explain why human trials of cannabis for the treatment of pain have

produced mixed results.

" The problem with cannabis is that there's no way of targeting the

drug to any particular place, " says Baker.

The answer will be to manipulate the system from within, he says. New

ways of amplifying natural cannabinoid release include reuptake

inhibitors that prolong this release just as Prozac does for

serotonin. Such methods look promising for a range of conditions from

pain and cancer to nerve degeneration and MS.

Other methods now being tried in the lab include the manipulation of

enzymes that make and deliver endocannabinoids, as well as compounds

that stimulate and block them. Drugs that bind to CB1 receptors and

alter their efficiency are also being discovered, says Pertwee,

director of pharmacology at GW Pharmaceuticals, based in Porton Down

Science Park, Wiltshire, UK. His company developed Sativex, the first

pharmaceutical cannabis extract to gain clinical approval.

Ironically, the first offshoot of endocannabinoid research to gain

clinical approval, last month, has the opposite effect to cannabis:

Acomplia (rimonabant), an appetite suppressant, works by blocking CB1

receptors (New Scientist, 8 July, p 5).