Marijuana – The Truth – Part 3

In the book that I co-wrote with my good friend, Donal O’Mathuna, Ph.D., Alternative Medicine: The options, the claims, the evidence, how to choose wisely, we wrote an evidence-based article on marijuana. Here’s our fourth excerpt of that information:

In earlier excerpts, we discussed “What It Is,” and “The Claims People Make about Marijuana.” Today we’ll review the “Study Findings.” Next week,  we’ll discuss, “Cautions,” and in the final week, our final excerpt will review “Our Recommendations.”

Study Findings

After California voters legalized medical marijuana, the White House Office of National Drug Control Policy asked the Institute of Medicine (IOM) to review the scientific evidence concerning marijuana.

The IOM is the same organization that issues the Recommended Dietary Allowances for vitamins and nutrients. It is a private, nonprofit organization that advises the federal government on medical issues, especially those involving controversy over scientific evidence.

In March 1999, the IOM released a report, Marijuana and Medicine: Assessing the Science Base, that has become the focus of much of this controversy. The report concluded, “Until a non-smoked, rapid onset cannabinoid drug delivery system becomes available, we acknowledge that there is no clear alternative for people suffering from chronic conditions that might be relieved by smoking marijuana, such as pain or AIDS wasting. One possible approach is to treat patients as ‘n-of-1’ clinical trials.”

The n-of-1 design means that each individual patient acts as his or her own control and is carefully monitored while given different test substances. The patients and researchers can be “blinded” to which substance the patient is taking at any particular time. This design allows greater individualization of care but makes it very difficult to generalize the results across groups of patients. It also makes it impossible to know how much the individualized care contributed to any changes observed.

The first of such n-of-1 trials with a sublingual spray was published in 2004. These sprays contain a liquid extract of marijuana and deliver a precisely measured amount of cannabinoid under the tongue. The thirty-four patients had chronic pain that had not been helped by many other conventional treatments.

Some patients found the sprays ineffective or the study too burdensome. Others found the sprays helpful. Eight patients had pain due to failed spinal surgery, and all reported benefits. Common side effects were dry mouth, dizziness, and euphoria or dysphoria (a term for generalized “bad” feelings).

The benefit of the pain relief was viewed as much greater than any negative effects. Being able to use the spray in public, compared to smoking marijuana, was viewed as a major advantage.

Much progress has been made in recent years in understanding how the compounds in marijuana might help patients. Researchers discovered that  THC interacts with very specific proteins in the brain called “receptors.” Many different types of receptors are found throughout the body carrying out a wide range of activities. Researchers have discovered that THC works in the brain on what is now called a “cannabinoid receptor.” We naturally make at least one compound that interacts with this receptor, called “anandamide” (the name comes from ananda, which means “bliss” in Sanskrit).

This research is showing that the human brain has a cannabinoid system that is naturally involved in controlling pain, movement, and memory. This system is overactive in obesity, which may open up a way to treat obesity if a receptor blocker is discovered.

However, cannabinoids stimulate this system.

There is great excitement about research in this new area. Traditional use of marijuana is based on real interactions between cannabinoids and this system in people’s brains. This research may lead to new treatments in various areas, but much remains unknown.

The fact that our brains have a cannabinoid system means that marijuana may influence us in many ways that we currently are unaware of or don’t understand.

The second area of research has been with pure cannabinoid drugs, such as THC or Marinol. Marinol is FDA-approved for two indications. Anorexic AIDS patients who took Marinol in randomized controlled trials recovered their appetite significantly better compared to those taking placebo. They also experienced less nausea and improved mood and regained some of their lost weight. Marinol was not as effective as another pharmaceutical drug used to stimulate the appetite (megestrol acetate, or Megase). One small study found Marinol of no benefit in anorexia nervosa.

Other studies with chemotherapy patients have shown significant benefit in reducing nausea and vomiting. However, when researchers compared THC to another antiemetic drug  (metoclopramide, or Reglan), three times as many patients receiving metoclopramide reported effective relief. So, while Marinol works, it is not as effective as other available drugs. In addition, the researchers noticed that different people responded very differently to the same dose of Marinol. A lot of people also reported unpleasant feelings while taking Marinol. Recreational users of marijuana report these same unpleasant effects.

This drug therefore has to be closely monitored until individualized doses are determined.

The use of THC for pain relief has very little controlled research. The IOM reviewers could find only one study conducted since 1981 using THC, and none with marijuana. The studies conducted prior to then were poorly designed. The results of studies with acute pain were contradictory, and in some cases those taking THC reported feeling increased pain.

Studies of THC for chronic pain were more encouraging, though still limited. Three small double-blind studies reported significantly more pain relief for cancer patients. A 2001 review still found no studies of smoking marijuana for pain relief, but examined nine randomized controlled trials of THC and other pure cannabinoids. The review concluded that these drugs were about as effective as codeine in relieving cancer pain or postoperative pain, but with significantly more adverse effects. The cannabinoids were much less effective than conventional analgesics.

A report released in December 2005 by the Royal College of Physicians in Britain could add only two studies using oral sprays of pure cannabinoids: the n-of-1 trial described earlier and one randomized controlled study. The latter study tested two cannabinoid sprays against a placebo spray. A standard for measuring effectiveness of pain treatments is a 2-point improvement over placebo on an 11-point scale. Although both sprays were significantly better than placebo, the improvement was only 0.6 point.

This same report found some evidence that THC may be helpful for patients with multiple sclerosis.

Mounting laboratory and animal studies show that cannabinoid receptors are involved in multiple sclerosis, though much remains unclear. A few small randomized controlled studies have shown some benefit from purified products such as Marinol. The largest study to date was funded by the Medical Research Council (MRC), Britain’s governmental funding agency. Published in 2003, it found significant improvements in muscle spasticity with Marinol compared to placebo, but not with an oral cannabis extract. Patients took the capsules for fifteen weeks, and the findings led the MRC to fund a three-year study of THC for multiple sclerosis that started in 2005.

Note that the studies cited so far have used purified cannabinoid drugs. Controlled studies of smoking marijuana have not been conducted widely, yet this is the use that receives most attention. One study with cancer patients found smoking marijuana similar in effectiveness to THC capsules for controlling nausea and vomiting. Other studies comparing marijuana to antiemetic drugs have found marijuana effective in about one-quarter of the patients and much less effective than pharmaceutical drugs. During the 1970s, when interest in medical marijuana increased, acute nausea and vomiting occurred in almost 100 percent of chemotherapy patients. Since then, and especially in the 1990s, much more effective drugs have been developed that control these side effects in 70 to 80 percent of chemotherapy patients.

However, some patients remain unresponsive to these newer drugs.

Medical marijuana use is probably more popularly reported to counteract the wasting syndrome experienced by AIDS patients. However, this area has received very little controlled research, with most of the claims being based on anecdotal reports. The only controlled evidence is that for Marinol.

Overall, there is little evidence to support the claim that smoking marijuana is medically useful.

However, a small proportion of patients do not respond well to pharmaceutical agents. The euphoric effect of marijuana also might help some people feel better. These factors will be taken into consideration in our conclusion.

Here’s the entire series:

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