Voters in six states will be weighing in on the issue of decriminalizing medical marijuana, which has come under stepped-up prosecution on the federal level in recent years. Here’s the latest science on the pros and cons of its use for a variety of health indications.

“The basic concept of using medical marijuana for the same purposes and with the same controls as other drugs prescribed by doctors, I think that’s entirely appropriate.”

Barack Obama, 2008

At a time when six states are holding referendums on marijuana,* it seems important to get a clearer understanding of what Barack Obama meant by “the same controls.” Truthout spoke with Steph Sherer, executive director of Americans for Safe Access (ASA), the nation’s largest organization of scientists, physicians and patients who advocate for the decriminalization of medical marijuana. This is just a taste of what Barack apparently meant:

During the 31/2 years of the Obama administration, the Drug Enforcement Administration (DEA), an arm of the Department of Justice (DOJ), conducted more raids on state-licensed dispensaries than the Bush administration did in eight years. The DEA hit more than 200 dispensaries, confiscated the marijuana and left a trail of wreckage in their wake. A dozen proprietors are in prison and nearly 100 more are awaiting prosecution;

The most effective method the DEA employs, is to write a menacing letter to the landlord who owns the building where the dispensary operates, threatening him with closure even though the building is up to code: This has resulted in a further 400 closures at least;

The DEA also has been obstructing scientific research into marijuana. Brad Burge, an executive officer with the Multidisciplinary Association for Psychedelic Studies (MAPS), told me how. For the past 11 years, MAPS, in collaboration with botanist/soil scientist Lyle Craker, PhD, of the University of Massachusetts, has sought to obtain a permit from the DEA to grow marijuana for research purposes: The DEA has consistently turned down their application with one excuse or another. Finally MAPS got fed up and is seeking relief in the First Circuit Court of Appeals. It’s worth a mention that MAPS is not an aging-hippie commune, but rather a major foundation that bankrolls medical and psychiatric research, here and abroad, by top scientists with an interest in hallucinogenic drugs and marijuana;

Had he wished to do so, Obama could have deftly reined in the DEA, for the term of its Bush-appointed administrator, Michelle Leonhart, was slated to expire around the time of his inauguration. Instead of replacing her, Obama appointed her to another full term in office;

The IRS has gotten into the act by harassing dispensary owners on the basis that they did not pay enough income tax, even though in almost every instance the proprietors did in fact pay the requisite amount of tax;

The Federal Deposit Insurance Corporation, though not an arm of the White House, is governed by the President and by Congress. It has squeezed Citigroup, Wells Fargo and Bank of America, along with credit card companies, to deny services to medical marijuana businesses that are legal under state law. According to ASA, no large bank in Colorado will service legal medical marijuana businesses;

The National Institute on Drug Abuse (NIDA) has begun obstructing research by denying marijuana to scientists. Thus, Sue Sisley, MD, a psychiatrist and internist at the University of Arizona, sought to conduct a trial of marijuana for treating Post-Traumatic Stress Disorder (PTSD), a condition that is severely refractory to currently-used medications. Her PTSD study was approved by the US Food and Drug Administration (FDA); all she needed was the weed, which NIDA grows from 11-year-old crops. NIDA declined her request and sent her a ten-page trashing of the very protocol the drug experts at the FDA had approved; at this writing her important study is in limbo.

To Steph Sherer, the most outrageous maneuver by the DOJ is the “Cole Memo.” This document was sent to all US Attorneys across the country, threatening governors as well as state and local officials with punishment under federal law, which bans marijuana, if they signed a medical marijuana decriminalization bill into law.

Whatever the outcome of the election for the president, 2012 is likely to be a red-letter year for marijuana activists. Five states – Arkansas, Colorado, Massachusetts, Oregon and Washington – are holding referendums that would, to some degree, legalize marijuana. The latest polls show that the referendums in Colorado, Massachusetts, and Washington State are likely to succeed. Montana’s Referendum 124, which seeks to tighten controls on marijuana, is likely to go down in flames. Arkansas’ legalization seems dicey, while Oregon’s proposition trails narrowly, but the remarkable fact about the polling data is that it cuts across the red/blue divide.

With the US public in general favors decriminalizing marijuana, and propositions to that effect on state ballots, could it be that marijuana is more dangerous than we had heretofore thought, and the Feds are protecting our health?

No. The single best source on the indications and side effects of medical marijuana was published in 2010 by Health Canada, the equivalent of our FDA (Information for Health Care Professionals: Marijuana). Since that date, new indications have come under study, but nothing gruesome has emerged to warrant Obama’s war on marijuana. As in any hot field of science, some indications will hold up, while others will turn out to be false leads. New side effects may emerge, but marijuana has been around for so many centuries that it probably holds few unwelcome surprises for us. But there was a surprise of an opposite nature from a team at Yale, which found alcohol’s “gateway” effect – its proclivity to lead to addiction to some other drug – to opiates is much greater than marijuana; if you abuse alcohol you are much more likely subsequently to abuse opiates. This is one more data point that belies the myth that “reefer madness” leads to opiate addiction.

Marijuana has been tried for many indications, among them pain, anorexia nervosa, multiple sclerosis, Parkinson’s disease and bladder dysfunction. Three indications that are acceptably well-studied, solid and frequent – for which there exists an adequate body of data to draw inferences, bearing in mind that subsequent clinical trials could knock this preliminary work right out of the water – are described below.

Preliminary Considerations

I use the word “marijuana” where some authors prefer “cannabis”: In plain English, a joint of dried leaves. When I use the term “THC,” I mean a capsule containing a measured amount of only one chemical, delta-9-tetrahydrocannabinol. The chemicals comprising the pharmacologically interesting components of the leaf are called cannabinoids, and with the exception of THC are identified as CBC, CBD, CBG and so forth.

There are two major ways of delivering cannabinoids. Naturalistic experiments seek to replicate the real-life use of marijuana as closely as possible, in which case the subjects or patients puff on a joint. The advantage of this method is that the subject gets the full dose of cannabinoids across the lung alveoli and into the bloodstream. The disadvantage is that the investigator does not know for sure which cannabinoid or combination is responsible for the pharmacological effect, although he can be reasonably sure that it is predominantly THC. Standardized cigarettes are available with a fixed amount of THC, but smokers can circumvent this to a certain extent by the depth and frequency of inhalations. THC capsules solve this problem, but raise another: The full amount of THC is not absorbed from the gut. Both complications can be gotten around by measuring plasma levels.

A matter of concern is that the smoked marijuana leaf contains many of the same carcinogens as ordinary cigarettes. Of course, this is not an issue in research studies, but until the matter of carcinogenicity is settled, users of marijuana would do better to ingest it in tea or brownies.

Nausea and Vomiting

The most widely known indication for marijuana is the control of nausea and vomiting in cancer patients undergoing chemotherapy and/or radiation.

Anti-cancer drugs work by killing off rapidly-dividing cells, which include, but are not confined to, cancer cells; the cells of the gastrointestinal tract “turn over” very rapidly, making them unwanted targets of chemotherapeutic agents. Radiation also rakes the gut raw, causing nausea and vomiting. Drugs that suppress nausea and vomiting are called anti-emetics, and there are a number of such drugs on the market, of which Compazine may be the most familiar, though not the most effective. Over the years, however, mounting anecdotal accounts attest to the effectiveness of smoking of marijuana for suppressing nausea and vomiting. This indication for marijuana is so well known that we need not belabor the point, though today marijuana is usually administered in capsules containing THC – the principal active ingredient, in a dose range of 5 mg to 20 mg daily in divided doses.

Less familiar are the uses of marijuana to ameliorate the wasting syndrome and loss of appetite in AIDS and cancer patients. Anorexia – loss of appetite – is one of the more difficult-to-manage complications of cancer, because many cancer patients simply do not want to eat. Some patients do benefit, in doses of 2.5 mg to 5 mg of THC three times a day, but a comparative trial of THC versus megestrol acetate [Mantovani G et al: Oncologist 2010;15:200-211] found the latter drug to be superior in both appetite stimulation and weight gain. The picture is somewhat brighter for anorexia and weight loss in AIDS patients: Oral THC (Marinol) is approved for AIDS-related weight loss in Canada, and several studies, including one large one [1], have found it effective in anorexia.

Anorexia nervosa is an eating disorder which has been little studied for marijuana’s efficacy either in the smoked or THC form. The available evidence is disappointing; one would expect that a drug which causes the “munchies” would benefit patients with anorexia nervosa, but such is not the case. Possibly anorexia from cancer and AIDS on the one hand, and anorexia nervosa on the other, are driven by different neuropsychological mechanisms. Anorexia nervosa is marked by a misperception of body image; the patient thinks she is too fat even when she is wasting away. AIDS and cancer patients do not evince such a misperception.

Cancer Pain

In Canada, Sativex (a compound of cannabinoids), is approved as an adjunct to opiate analgesics for adults with moderate to severe, advanced cancer pain in clinical situations where even the highest tolerated dose of opiates is inadequate. Is THC alone adequate for cancer pain?

One placebo-controlled study found that 15mg and 20mg, but not 5mg and10mg, of THC delivered significant relief from moderate to severe pain from advanced cancer. However, the patients could not tolerate the higher dose owing to over-sedation and confusion. One wonders, however, if the attending physicians might not welcome over-sedation if it were they who were dying of cancer.

Controlled studies compared THC with opiates. In one study, the opiate was 60 mg to 120 mg of codeine against 10 mg and 20 mg of THC. Aside from over-sedation – difficulty walking and blurred vision – 20 mg THC caused severe anxiety. Though the higher dose of THC was comparable to codeine for analgesia, it was not deemed useful owing to its side effects.

THC clearly has a place in the management of cancer pain, but on the basis of limited data, opiates are probably superior analgesics. It is probably useful as an adjunctive agent. Marijuana has been found to augment the analgesic effects of morphine and oxycodone without altering opiate plasma levels; the implication is that opiates might be given in lower doses, with fewer side effects, but the same degree of analgesia. This hypothesis remains to be tested. In the meantime, patients in pain should not be deprived of therapeutically adequate doses of opiates; pain is not a moral issue.

Non-Cancer Pain

Two types of common non-cancer pain for which the evidence is either adequate, compelling or promising are described below. Other types of pain, i.e., post-operative, had to be left out because of inadequate or inconclusive studies.

Arthritis

Rheumatologists (specialists in joint diseases) recognize three types of arthritis:

Osteoarthritis, a degenerative disease caused by the breakdown of the “padding” cartilage between bones. It is the most common form of arthritis; the rubbing of bone against bone causes pain and inflammation. Marijuana has both analgesic and anti-inflammatory effects, so it is not surprising that it is reported to be effective for symptomatic relief of osteoarthritis

Rheumatoid Arthritis (RA), less common than osteoarthritis, is an autoimmune disease (the organism produces antibodies that attack its own tissues). A good controlled trial using Sativex, led the authors of Health Canada to conclude that “the results indicated a therapeutic potential for cannabinoids in RA and further research was suggested.”

Juvenile Arthritis. Few physicians would be likely to advocate the use of marijuana in children at the present time because scientists do not know the effects of the drug on development, However, older teens could probably use the drug safely.

Multiple Sclerosis

Multiple sclerosis (MS) is one of the most heartening indications for marijuana. The disease, which is irreversible, is marked by the patchy degeneration of the myelin sheath that surrounds nerve fibers. Myelin serves the purpose of an insulator that ensures the orderly dispersion of electrical signals in the brain. When the sheath begins to deteriorate, the electrical activity is no longer confined to discrete pathways; it goes wild and the patient starts to experience neurological and psychiatric symptoms, among them painful spasticity, muscle weakness, visual disturbances and depression. As the disease progresses, the patient becomes increasingly disabled and may end up in a wheelchair. People with MS have about the same life expectancy as the general population, but the quality of life can be ghastly. In other cases, however, the disease is mild and sufferers can hope to lead a reasonably normal life

Fortunately, the pharmaceutical industry has developed powerful new drugs to treat the symptoms and arrest the progression of MS. Corticosteroids are effective for treating acute flare-ups of the illness. Interferons slow the course of the disease. Copaxone injections block the immune system’s assault on the myelin sheath, thereby preventing further degeneration. Other effective, specific drugs have hit the market in the past few years. And older drugs are available for treating specific symptoms such as bladder incontinence and depression.

Yet two recent Canadian surveys [2] found that, depending on the province, a third to nearly a half of MS sufferers had either experimented with marijuana or used it regularly for relief of pain and spasms. MS may be an instance where the patients are ahead of the scientists: Two large clinical trials [3] sought to assess the efficacy of smoked marijuana for pain and spasms. Outcome was measured by patient reports and by a rating scale called the Ashworth Scale. In both studies, the patients reported significant relief that could not be measured on the neurologists’ Ashworth Scale; it is now believed that the Scale may be defective and that the patients just might be correct. While the scientists dither over this one, MS continues to be one of the major uses for marijuana. It would not be surprising if marijuana turned out to exert anti-inflammatory properties in MS sufferers, as it does in patients with arthritis.

Other Conditions

Candidate Obama was correct: Marijuana is no different from any other drug, only older, centuries older. But thanks to the hysteria embodied in movies like “Reefer Madness,” little serious research was conducted until after World War II. As far as the pharmacological community was concerned, marijuana was a “new” drug (history repeats itself) and like any new drug with a broad spectrum of action (analgesic, anti-inflammatory, anti-emetic), marijuana was tried against a plethora of indications. These include neuropathic pain (that is, pain caused by damage to the nerve, as in AIDS neuropathy, as distinguished from pressure on the body’s pain receptors, as caused by malignant tumors), and glaucoma, for both of which the available evidence is pretty solid.There are theoretical reasons, namely the presence of receptors for marijuana alkaloids in muscle tissue, why marijuana might be effective in movement disorders like Parkinson’s disease. Preliminary studies of various movement disorders are encouraging but small in scale. THC dilates the bronchial tubes and decreases bronchospasm, so it has been tried with some success in asthma, but this indication would not seem to be a matter of great urgency because there are a number of excellent anti-asthma drugs on the market. There are also a number of drugs for treating migraine and cluster headaches, both of which are often excruciating and refractory to conventional treatments. Curiously, most of the same drugs are used for migraine and cluster headaches, and a few case reports or small trials suggest that marijuana is also effective for both; this would seem to be an area that merits a faster pace of research.

The foregoing considerations do not exhaust the afflictions against which marijuana has been tested. Notably absent are psychiatric indications. Clinical trials for anxiety and depression are contradictory: Some patients get better, others get worse. Of greater concern are a number of studies that suggest a link between marijuana and psychotic ideation and suicidal thoughts or attempts. To confound matters even further there are data reporting that marijuana has antipsychotic activity.

One publication of great interest – assuming it can be supported – found that an evening dose of THC calms the restlessness and mental agitation of demented, elderly patients. [4] If supported, it would be a major breakthrough because there is as yet no safe and effective medication for this patient population. Marijuana has also been tried with promising results in Alzheimer’s dementia, but again, the studies are small and require replication before marijuana can be advocated for these indications, bearing in mind the fragility of the data in the field of psychiatry.

Side Effects

The most conspicuous side effects of marijuana are related to the central nervous system (CNS). Although the occasional recreational use of marijuana is probably harmless, heavy usage – usually smoking – is associated with disorientation, confusion, depersonalization, and paranoia. According to the Health Canada paper cited earlier, persons with schizophrenia are at much greater risk to these side effects.

Marijuana exerts a significant effect on thought processes (cognition). It disrupts memory, attention, concentration and scores on psychological tests designed to measure cognitive processes. There is no doubt about the deleterious side effects of marijuana on short-term cognition, but its long-term effects are more controversial. Further research on the long-term effects of marijuana is required, but it is difficult to see how this can be accomplished in the present climate of re-criminalization by the Obama administration; users of marijuana are unlikely to come forward for study.

Non-CNS side effects are generally dose-related; moderate recreational use is unlikely to produce worrisome deleterious effects. Clinicians are concerned about the use of marijuana by AIDS patients, because marijuana may suppress the immune system, although the data are conflicting. More convincingly, studies show that initial use of marijuana increases the heart rate, but after 8 to10 days the heart rate fell below normal. Since marijuana exerts numerous effects on the cardiovascular system, there is some concern that heavy use may predispose to angina pectoris and heart attacks.

Three studies spanning 20 years and summarized in the Health Canada paper concur that smoking of marijuana by the mother while pregnant causes cognitive deficits (attention span, visual analysis, hypothesis testing) in the adult offspring. Effects on the newborn, on the other hand, are contradictory.

Marijuana clearly has multiple effects on human sperm, such as a decrease in sperm count. [5] However, infertility has not been demonstrated yet.

A number of studies have demonstrated that the liver is a major target organ for damage from heavy marijuana usage. Daily smoking of marijuana for protracted periods of time has been linked to fatty liver and to fibrosis – the replacement of functional liver tissue by inert fibrous tissue. Oddly, studies on the effect of marijuana on the course of Hepatitis C are conflicting, a significant issue which is counterintuitive to the known damage that marijuana causes to liver tissue. [6]

Conclusion

There is good evidence for the efficacy of marijuana in cancer and non-cancer chronic pain, nausea and vomiting from chemotherapeutic drugs, radiation and multiple sclerosis, as well as promising evidence for a number of other illnesses. Like every other drug, marijuana has side effects, but they are comparatively few and confined to heavy users. Barack Obama was correct in likening marijuana to other pharmaceutical products, right in promising to end W’s marijuana witch hunt, and deceitfully wrong in escalating that witch hunt beyond Bush’s wildest dreams. It is to be hoped that the referendums legalizing marijuana for medical use pass and the federal persecution of those using, studying or providing the drug for medical purposes cease.

* The six states holding referendums concerning marijuana include:

Arkansas – Arkansas Medical Marijuana Act of 2012 – Legalizes marijuana for medical indications

Colorado – Amendment 64 – Legalizes possession and growing of small quantities of marijuana

Massachusetts – Question 3 – Legalizes marijuana for medical indications

Montana – Referendum 124 – seeks to restrict availability of marijuana

Oregon – Measure 80 – Would license production and sale of marijuana

Washington State – Initiative 502 – Decriminalizes up to 1 oz for personal use

1.

Beal JE et al: J Pain Symptom. Manage. (1995) 10:89-97

2.

Page SA et al. (2003) Canadian Journal of Neurological Science 30:201-205 and Clark A.J. et al.(2004)neurology.62:2098-2100



Zajicek J et al.: Lancet (2003) 362:1517-1526 and Wade D.T. et al. (2004):Multiple Sclerosis 10:434-441 3.



Walther S et al Psychopharmacology (Berl)2009; 185:524-528 4.



Whan L B et al:(2006) Fertility and Sterility 85:653-660 5.