Cannabis Is A Blunt Tool

[budman]

Cannabis Is A Blunt Tool

The New Scientist
28 Jul 2006

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. David 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. Michael Walker 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 Roger 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)

[palmspringsbum]

Physicians unlikely to embrace marijuana as medicine

by Keith Humphreys, OpEd, San Francisco Chronicle
December 2nd, 2007


It wasn't just women with breast cancer who were excited last month when scientists at California Pacific Medical Center Research Institute showed that a compound found in marijuana may be able to block the growth of aggressive tumors. This finding also cheered activists who hope that mainstream medicine will soon embrace marijuana as a treatment. For a range of reasons, that's extremely unlikely.

Effective medicines can of course be derived from plants. Digoxin from foxglove, atropine from belladonna and quinine from cinchona are only a few examples. The marijuana plant likewise contains potentially therapeutic compounds known as cannabinoids, one of which, cannabidiol, was examined in the breast cancer study. Other research has examined tetrahydrocannabinol (THC) - the cannabinoid in marijuana that is primarily responsible for the plant's psychoactive effects (e.g., feeling "high," hallucinations, changes in mood). THC has been shown to benefit at least some patients with a range of problems, including chemotherapy-induced nausea and the tremors and muscles spasms associated with multiple sclerosis.

Nonetheless, only a minority of physicians harbor great enthusiasm for prescribing marijuana cigarettes. Indeed, a survey of almost a thousand physicians by Brown University researchers showed that doctors are significantly less supportive of medical marijuana than is the general public.

Older members of the field remember vividly the era when most physicians smoked tobacco cigarettes and cheerfully rated Camel their favorite brand. The tobacco industry built on this foundation with deceptive advertisements linking doctors with smoking in the public mind (currently on exhibit at the UC San Francisco library on 530 Parnassus Ave.), which damaged medicine's credibility.

These bitter historical experiences, supplemented by decades of subsequent research evidence that smoke inhalation of all forms (even wood smoke) can cause acute and long-term respiratory damage, make many physicians wary of recommending a smoked medicine. A smoked plant has the further disadvantage from a medical perspective of not being pure (e.g., what if the plant had been sprayed with pesticide?) or of a standardized dose. This exposes the patient to risk of side effects, and the physician to risk of malpractice.

As the California Pacific research team noted, for example, obtaining the correct dose of cannabidiol through smoking marijuana would be virtually impossible. It would also of course cause THC's psychoactive effects (cannabidiol is not psychoactive), which some patients find aversive. Will all the therapeutic components of marijuana one day be available in pure, standardized forms that can be safely administered without combustion?

Liquid THC, known as dronabinol, has been available by prescription for years and has some evidence of effectiveness, but its slow absorption after ingestion makes it unappealing to some patients.

Several companies are working to make a dronabinol mist that could be taken in a standardized dose with an inhaler, such as is done with medicines for asthma. An alternative approach, being tested at UCSF, is to heat marijuana in a vaporizer so that THC can be inhaled without the carcinogens found in marijuana cigarettes.

If these technological breakthroughs are achieved, some physicians will become more comfortable with prescribing THC. But others will have the opposite reaction because purified, inhalable (and therefore fast-acting) THC could carry more addictive risk than marijuana itself.

Addiction medicine specialists are aware of this possibility, which may be why the Brown University survey showed that they were less sanguine about medical marijuana than doctors in any other specialty.

In general, as plant-based compounds that can produce dependence are processed and purified (e.g., from coca leaf to cocaine or opium poppy to morphine) or are administered through a more rapid, efficient route (e.g., from ingesting to smoking), their power to produce addiction increases.

In other words, the very dosing technology that could makes THC more pure and potent as a medicine may also make it more likely to produce dangerous dependence. Unless further research reveals a way to cut that Gordian knot, THC will probably remain a bit player in mainstream medicine practice.

Keith Humphreys is a professor of psychiatry at Stanford Medical School.

[palmspringsbum]

I thought about not archiving this article because it seemed extremely slanted and 'negative'. For instance, the most recent government study regarding medical cannabis is not the survey taken by the U.S. Government in 1999, but the Canadian Government's Report in 2002. So, keep in mind as you read this that they IGNORE data that doesn't contribute to their 'point'.

Marijuana and medical science

The Willits News
By Linda Williams/TWN Staff Writer
Article Launched: 12/14/2007 11:00:00 PM PST


The rhetoric surrounding marijuana, or cannabis sativa, as medicine ranges from calling it everything from "the killer weed" to "the miracle drug." Each side in the debate pulls snippets from scientific studies to confirm or rebut their point of view. One need only review information provided by groups like the National Organization for Reform of Marijuana Laws or the White House policy room to see this effect.

The most comprehensive look at the issue to date is Marijuana and Medicine: Assessing the Science Base, conducted by the U.S. Institute of Medicine and published in 1999. With minimal research being conducted in the U.S. on marijuana as medicine, in 2000, the California Legislature created the University of California's Center for Medicinal Cannabis Research in San Diego. The center was tasked to assess the use of cannabis as an alternative for treating specific medical conditions.

Research is now being conducted in institutions around the world, trying to unlock the potential medical benefits of compounds called cannabinoids found in cannabis sativa. A summary of research published in 2007 is at the end of the article.

One of the spurs to this increased interest was the discovery in the 1990s of special receptors in different areas of the brain, which respond to cannabinoids. This led to the identification of a substances created naturally by the body that resemble THC the main active ingredient in marijuana.

Most people smoke marijuana to get "high." This high provides a "sense of well-being or euphoria and increased talkativeness and laughter alternating with periods of introspective dreaminess followed by lethargy and sleepiness. A characteristic feature of a marijuana 'high' is a distortion in the sense of time associated with deficits in short-term memory and learning. A marijuana smoker typically has a sense of enhanced physical and emotional sensitivity, including a feeling of greater interpersonal closeness. The most obvious behavioral abnormality displayed by someone under the influence of marijuana is difficulty in carrying on an intelligible conversation, perhaps because of an inability to remember what was just said even a few words earlier," according to the 1999 IOM study.

"Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke. In addition, plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect. For those reasons, there is little future in smoked marijuana as a medically approved medication," concluded the IOM study.

The study further concluded that for some patients, such as the terminally ill, if marijuana would possibly benefit the patient, the long-term risk was "not of great concern."

For other patients, the study advised that physicians could consider marijuana for a narrow range of short term health issues such as AIDs wasting diseases, severe nausea and vomiting associated with cancer and its treatment and relief of neuropathic pain. While the study concluded marijuana had the potential in some patients to relieve the symptoms, the study also suggested stringent guidelines for physicians recommending marijuana to their patients.

The prescription guidelines were established to relieve symptoms considered debilitating such as intractable pain or vomiting. The key points were for marijuana to be tried after all approved medications had failed to provide relief; the prescription be for less than six months; a follow up program be implemented to assess effectiveness; and the recommendation be supported by an oversight review board within the hospital or clinic.

For chronic debilitating conditions such as pain or AIDS wasting, the IOM study recognized that the issues of long-term medical use of marijuana was more complex. Patients who had exhausted the other available medical options could not be reasonably expected to wait until some time in the unknown future for someone to isolate and synthesize the precise cannabinoid drug cocktail that provided the best benefit or to develop a "nonsmoked rapid-onset cannabinoid drug delivery system."

Since the IOM study, a number of vaporizers, which claim to provide the user with the benefit of marijuana without the hazard of the smoke, have been developed. A recent pilot study tested one such device on 18 healthy volunteers and concluded it had the potential to provide the benefit of marijuana without the toxic smoke.

The psychoactive effects of marijuana make it difficult for users to function in society while on a marijuana high. Those desiring to operate a vehicle or machinery, conduct a conversation, get to work on time, stay awake or learn new things may find it difficult to conduct routine business while high on marijuana. These side effects were found particularly hard for patients not already familiar with marijuana use.

Other physiological effects from marijuana use such as increased heart rate and its effects on blood pressure make it a concern for older patients already suffering from heart disease, potentially leading to heart attacks or other cardiovascular event.

<span class=postbigbold>Medical treatments</span>

A review of the literature shows that very few rigorous studies have been conducted on the use of marijuana to treat disease. While cannabinoid receptor locations in the brain offer some insight into which diseases may be helped by drugs developed from marijuana, most studies have involved few participants and were not conducted following traditionally recognized methods for evaluating treatments. Despite this, some synthetic derivatives from marijuana are now available and are being prescribed to patients for specific ailments.

A large part of the medical research community has recommended increased research into how marijuana compounds can be harnessed to reduce suffering while minimizing any negative effects.

Despite recognizing the substantial potential for future benefit, the IOM study believed that only a small group of patients would actually benefit from using marijuana. The study observed that for most symptoms marijuana was being considered to treat there were other more effective treatment options, which most patients responded to.

For cancer patients undergoing chemotherapy, the study found the public was not aware of the major strides made in medicine to treat nausea and side effects. While cannabinoid substances were only effective in 24 percent of the cases, a combination of currently available drugs is considered nearly 100 percent effective if started before chemotherapy begins. Because pills are less effective once a patient starts vomiting, an inhaled fast acting drug, such as the THC from marijuana could provide some benefit.

For HIV patients, while marijuana may provide some relief from wasting diseases it has also been linked to suppressing the immune system. For unknown reasons the relative 12-year risk of death from marijuana smokers with HIV is nearly twice that of those not using it. Many HIV patients are effectively taking synthetic derivatives of marijuana for wasting diseases.

In a 2003, 23 percent of HIV patients in a public health study in San Mateo used marijuana. Of those users, only 17 percent met the strict definition of medical marijuana use for the relief of nausea, anorexia or pain. Some used a synthetic to treat AIDS wasting and smoked marijuana recreationally.

Marijuana is no longer believed by most to be an effective treatment for glaucoma. While it does temporarily reduce the pressure within the eye, it acts for a short period of time and reduces the blood flow to the optic nerve, potentially damaging it. Other treatments are now considered significantly more effective in managing glaucoma.

For multiple sclerosis, the studies have not shown marijuana to be particularly effective in managing the pain, spasticity or the disease. Studies have had mixed results, although the cannabinoid receptors are particularly abundant in areas of the brain controlling movement so further study is being conducted.

<span class=postbigbold>2007 research developments</span>

Some new studies show the importance of being able to deliver predictable and repeatable dosages of THC to patients and clearly established that more is not always better.

A study of 15 healthy volunteers found that medium doses of marijuana relieved some neuropathic pain in healthy volunteers while higher doses actually made the pain worse. Neuropathic pain is associated with cancer, AIDS, diabetes, etc. Low doses had no effect. Report published in October 2007

While low doses of THC seem to alleviate depression, higher doses makes the depression worse, concluded McGill University researchers in a report published in October 2007.

These studies show the value of being able to control and adjust the amount of THC delivered to a patient to get the desirable outcome.

<span class=postbigbold>Other developments</span>

Foot pain associated with HIV (neuropathic) shows some relief from smoking marijuana over a placebo according to a study in February 2007.

Smoking one joint causes the same lung damage as three to five tobacco cigarettes according to an August 2007 Danish study.

A cannabinoid called CDB in marijuana has shown early promise in laboratory tests for treating metastatic forms of breast cancer. Very small quantities of CDB are present naturally in marijuana. Published in November 2007.

THC may help the virus causing Kaposi's sarcoma both infect healthy cells and then multiply according to a study conducted by Harvard Medical School researchers and published in August 2007. Kaposi's sarcoma is a cancer affecting those with depressed immune systems such as HIV and transplant patients.

A team of Swedish researchers has identified how the brains of unborn babies are damaged by mothers smoking marijuana, published in May 2007.

Harvard researchers have shown in lab and mice studies that certain THC treated lung cancer cells grew at half the rate of untreated cells, published in April 2007.

Research done in Cardiff University in Wales, suggests that marijuana use could increase the risk of developing psychotic illness later in life by 40 percent, published in August 2007.

THC may help reduce the symptoms of allergic skin disease according to study on mice by an international group of researchers published in August 2007.

GW Pharmaceuticals in Britain has been conducting tests for eight years on Sativex, a prescription drug derived from cannabis to relieve symptoms of neuropathic dysfunction and pain. The drug is being reviewed in Canada for market approval.

EDITOR'S NOTE: Information on the medical effects of marijuana was gleaned from research published in a variety of scientific journals. The basis of much of the article came from the Institute of Medicine Marijuana and Medicine study published in 1999, which was requested by White House Office of National Drug Control Policy in 1997. While the study is much referenced by medical marijuana support groups, it is less quoted in White House drug policy. The IOM is one of four US National Academies and is a not-for-profit and non-governmental agency established as an independent think tank to advise the nation on matters concerning health and medicine. It remains the most comprehensive treatise available on the issue. The Canadian Senate authored a similar study in 2002 that mirrored much of the IOM findings. Many of these findings were also supported by several sponsored reports from the UC Center for Medical Cannabis Research and the Medical Board of California marijuana policy. An effort was made to focus this article on the science associated with marijuana's medical value and not explore other medical marijuana issues.