http://www.sciencebasedmedicine.org/med ... more-31706New York moved last week to join 22 states in legalizing medical marijuana for patients with a diverse array of debilitating ailments, encompassing epilepsy and cancer, Crohn’s disease and Parkinson’s. Yet there is no rigorous scientific evidence that marijuana effectively treats the symptoms of many of the illnesses for which states have authorized its use.
Instead, experts say, lawmakers and the authors of public referendums have acted largely on the basis of animal studies and heart-wrenching anecdotes. The results have sometimes confounded doctors and researchers.
The lists of conditions qualifying patients for marijuana treatment vary considerably from state to state. Like most others, New York’s includes cancer, H.I.V./AIDS and multiple sclerosis. Studies have shown that marijuana can relieve nausea, improve appetite and ease painful spasms in those patients.
But New York’s list also includes Parkinson’s disease, Lou Gehrig’s disease and epilepsy, conditions for which there are no high-quality trials indicating marijuana is useful. In Illinois, more than three dozen conditions qualify for treatment with marijuana, including Alzheimer’s disease, lupus, Sjogren’s syndrome, Tourette’s syndrome, Arnold-Chiari malformation and nail-patella syndrome.
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Amanda Hoffman of Basking Ridge, N.J., who has ulcerative colitis, makes cannabis caramels. Credit Matt Rainey for The New York Times
“I just don’t think the evidence is there for these long lists,” said Dr. Molly Cooke, a professor of medicine at the University of California, San Francisco, who helped research a position paper on cannabis for the American College of Physicians. “It’s been so hard to study marijuana. Policy makers are responding to thin data.”
Even some advocates of medical marijuana acknowledge that the state laws legalizing it did not result from careful reviews of the medical literature.
“I wish it were that rational,” said Mitch Earleywine, chairman of the executive board of directors for Norml, a national marijuana advocacy group. Dr. Earleywine said state lawmakers more often ask themselves, “What disease does the person in a wheelchair in my office have?”
Research into marijuana’s effects is thin not because of a lack of scientific interest, but chiefly because the federal government has long classified it as a Schedule 1 drug with “no currently accepted medical use.” Scientists who want to conduct studies must register with the Drug Enforcement Administration, submit an investigational new drug application to the Food and Drug Administration for human trials, and win approval from the Department of Health and Human Services or one of the National Institutes of Health. The National Institute on Drug Abuse is the only supplier of legal, research-grade marijuana.
The legal and administrative hoops make it hard for investigators to start the randomized, placebo-controlled trials that are the gold standard of medical research and the basis for determining which drugs are effective, at what doses, and in which patients.
“It’s one thing to say we need to have more research, and it’s another thing to obstruct the research,” said Dr. Steven A. Jenison, former medical director of New Mexico’s medical cannabis program.
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The dearth of data has not prevented legislators and voters across the nation from endorsing marijuana for more than 40 conditions. Patients with rheumatoid arthritis, for instance, qualify for marijuana treatment in at least three states.
Yet there are no published trials of smoked marijuana in rheumatoid arthritis patients, said Dr. Mary-Ann Fitzcharles, a rheumatologist at McGill University who reviewed the evidence of the drug’s efficacy in treating rheumatic diseases. “When we look at herbal cannabis, we have zero evidence for efficacy,” she said. “Unfortunately this is being driven by regulatory authorities, not by sound clinical judgment.”
New York considered including the chronic inflammatory disease on its list, a development that astonished Dr. Mary K. Crow, an arthritis expert at the Hospital for Special Surgery, in Manhattan. People with rheumatoid arthritis have higher rates of certain respiratory problems, she noted.
“Inhaling into your lungs is not a great idea with rheumatoid arthritis, given the substantial number of patients who have lung disease,” Dr. Crow said. (The final version of New York’s law prohibits smoking marijuana and did not end up including rheumatoid arthritis.)
In Arizona and Rhode Island, among other states, people with Alzheimer’s disease may receive medical marijuana to help quell nighttime agitation. But Dr. Gary Small, director of the division of geriatric psychiatry at the University of California, Los Angeles, said he does not recommend cannabis to Alzheimer’s patients: Agitation and increased confusion are possible side effects.
Still, he said he would not discourage a caregiver from providing it if it calmed a family member with dementia.
Parents of children with intractable epilepsy have lobbied hard in several states, including New York, for inclusion in medical marijuana legislation. They want access to an oil called Charlotte’s Web that is rich in CBD, a nonpsychoactive ingredient of marijuana that they say reduces the number of seizures.
This month, Gov. Rick Scott of Florida, a conservative Republican, signed a law allowing epilepsy patients access to the oil, calling it “the best treatment available.”
Scientists have begun randomized, placebo-controlled research to determine whether CBD effectively treats severe forms of childhood epilepsy. But at the moment, high-quality research showing that marijuana is a safe or effective treatment for epilepsy does not exist, experts say.
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A green sludge made with marijuana is used for the caramels. Credit Matt Rainey for The New York Times
“As far as data out there, there are great animal models and very provoking anecdotes,” said Dr. Orrin Devinsky, director of the Comprehensive Epilepsy Center at NYU Langone Medical Center. “The human data is not there right now.”
Psoriasis was included in the New York legislation after representatives of Gaia Plant-Based Medicine, a Colorado company operating dispensaries, met with State Senator Diane J. Savino and suggested that cannabis lotions helped people with those red, raised skin plaques. It was dropped from the measure after questions were raised about the lack of supporting evidence — as were other conditions, like diabetes and lupus.
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Medical marijuana advocates contend that suffering people should not have to wait for scientific research to catch up to patients’ needs. And why limit marijuana use to only certain conditions, they ask, when doctors routinely prescribe drugs off-label for anything they feel like?
Amanda Hoffman, 35, an information technology specialist in Basking Ridge, N.J., struggles with ulcerative colitis, an inflammatory bowel disease. She has tried steroids and Remicade, an intravenous infusion, but no drug has given her as much relief from frequent daily diarrhea and abdominal pain as her homemade cannabis caramels.
On a recent Sunday, Ms. Hoffman used a green buttery sludge made with marijuana she bought for $500 an ounce from Garden State Dispensary to make a new batch. She is grateful that the state legalized marijuana for patients like her, whatever the scientific evidence.
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RECENT COMMENTS
JB 11 days ago
It is clear to me that Big Pharm is behind all of the negative publicity from the New England Journal of Medicine to the New York Times. As...
LuckyDog 12 days ago
Truthfully, there is NO reason for marijuana to be used medically because there are better drugs available in all cases. Sadly, in some...
Nigel 12 days ago
Because doctors, as well as politicians, should be the ones who decide what adults can put into their bodies?The reason people use marijuana...
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“Cannabis to a lot of people is a punch line, but it can also be a lifesaver,” she said.
Even if strong medical research regarding marijuana did exist, it is not clear that state lawmakers would be swayed.
“It would be possible to take case studies or anecdotal information from patients or research done from a university, put it in front of a legislator and say, ‘We need to include this disease,’ ” said State Representative Lou Lang, sponsor of the medical marijuana law in Illinois.
“But the legislative mind, be it in D.C. or in Springfield, Illinois, doesn’t always go to public policy,” Mr. Lang said. “The default position is politics.”
Often state legislators have been motivated not just by constituents in distress, but also by the desire to restrict access to limited patient populations so that legal marijuana does not become widely available as a recreational drug in their states.
For example, while there is research suggesting that marijuana alleviates certain kinds of chronic pain, Mr. Lang noted, legislators in Illinois were reluctant to legalize its use in such a broad patient population. The state’s list of qualifying conditions is lengthy partly because lawmakers tried instead to specify a number of diagnoses that result in pain, some quite rare.
“I’ll bet there are hundreds of conditions that cause pain, and now 30 are listed,” Karen O’Keefe, director of state policies at the Marijuana Policy Project, said of Illinois’s legislation.
Medical experts, rarely included in these statehouse discussions, have often been caught off guard by the sudden passage of laws permitting patients to ask them for marijuana.
Since at least 2009, for instance, the American Glaucoma Society has said publicly that marijuana is an impractical way to treat glaucoma. While it does lower intraocular eye pressure, it works only for up to four hours, so patients would need to take it even in the middle of the night to achieve consistent reductions in pressure. Once-a-day eye drops work more predictably.
Yet glaucoma qualifies for treatment with medical marijuana in more than a dozen states, and is included in pending legislation in Ohio and Pennsylvania. At one point, it appeared in New York’s legislation, too.
Dr. Paul N. Orloff, the legislative chairman for the New York State Ophthalmological Society, reached out to Richard N. Gottfried, a Manhattan Democrat and sponsor of the Assembly bill, and succeeded in getting glaucoma removed.
“It’s very illogical to prescribe a medication where it’s not standardized,” Dr. Orloff said, adding, “None of my 60-year-old patients are interested in being stoned to treat their glaucoma.”
(Edited a much longer blog post from SBM blog)Be that as it may, let’s look at the evidence base for conditions for which medical marijuana might provide a benefit. Remember, again: I’m leaving out cancer and autism for another day. Leaving these aside, here are the potential medical uses for marijuana for which evidence exists that ranges from reasonably good to suggestive.
Chronic pain. It’s been known for a long time that cannabinoids modulate pain responses; so it’s plausible that either smoked marijuana or cannabinoids isolated from marijuana (or synthetic cannabinoids) could be useful for chronic pain. Fortunately, this is one of the more widely-studied uses for medical cannabis. For example, a recent review of uses of cannabinoids for the treatment of non-cancer pain concluded that there was evidence that cannabinoids are safe and modestly effective in neuropathic pain, citing preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. As is the case with most reviews, more study was recommended. This particular review included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone (a synthetic cannabinoid), dronabinol (a synthetic delta-9-THC), and a novel THC analogue. Most studies have only been short term, and adverse events have tended not to be serious. The current general recommendation is that cannaboids should probably not be used as first line agents “for conditions for which there are more supported and better-tolerated agents,” and adverse effects are not well studied.
Appetite stimulation. I’ve never smoked marijuana, but those who have, have told me about the “munchies,” something that anyone who’s ever seen a comedy in which characters smoke post has likely seen used as fodder for jokes. Given its ability to stimulate appetite, it is therefore plausible that medical cannabis might be useful for appetite stimulation in patients with cachexia due to cancer or HIV/AIDS. (Cachexia is the “wasting” that can occur in advanced cases of malignancy and AIDS, among other diseases.) Unfortunately, a recent Cochrane review noted variable outcomes and concluded that the “efficacy and safety of cannabis and cannabinoids in this setting is lacking” and noting no good evidence of long-term effects on AIDS-related mortality and morbidity. Regarding cancer cachexia, Peter Lipson noted several years ago a study that failed to find any benefit from cannabis extract for cancer-related cachexia, speculating that maybe the mechanisms that cause appetite suppression in cancer are different than the mechanisms by which cannabinoids modulate appetite.
Currently, there are few controlled trials cited at the NCI website, which, taken together, find that oral THC has variable effects on appetite stimulation and weight loss in patients with advanced malignancies and human immunodeficiency virus (HIV) infection. A PubMed review by yours truly also found the evidence rather sparse. For instance, this randomized trial testing cannabis extract (CE), THC, and placebo (PL) reported that “no differences in patients’ appetite or quality of life were found either between CE, THC, and PL or between CE and THC at the dosages investigated.” Another randomized trial comparing megestrol acetate (Megase) and dronabinol found that “megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone” and that “combination therapy did not appear to confer additional benefit.” A more recent small randomized trial tested THC versus placebo and found that “THC may be useful in the palliation of chemosensory alterations and to improve food enjoyment for cancer patients.” To be honest, I was shocked at how sparse the literature is covering this particular indication. Indeed, as the NCI notes, there are no randomized controlled trials of smoked cannabis for this indication in cancer patients.
Nausea/antiemetic. Despite many advances in anti-emetics (anti-nausea and vomiting) agents, cancer-induced nausea and vomiting (CINV) is still among the most troubling symptoms cancer patients face. There are two FDA-approved cannabis products for this indication, dronabinol and the synthetic cannabinoid nabilone. The NCI cites several clinical trials and meta-analyses finding that these two drugs are efficacious against CINV, and the National Comprehensive Cancer Network guidelines recommend these drugs as treatment for breakthrough nausea and vomiting due to chemotherapy. One systematic review from 2001 found that cannabinoids were slightly more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride, but were not more effective in patients already using large doses of antiemetic drugs. A more recent systematic review and meta-analysis found that cannabinoids were superior to conventional drugs but that “adverse effects were more intense and occurred more often among patients who used cannabinoids.” In children with cancer undergoing chemotherapy, a Cochrane systematic review concluded that “cannabinoids are probably effective but produce frequent side effects” and that the review “suggests that 5-HT(3) [seratonin] antagonists with dexamethasone added are effective in patients who are to receive highly emetogenic chemotherapy although the risk-benefit profile of additional steroid remains uncertain.”
Inflammatory bowel disease (IBD). Last fall, the first clinical trial of cannabis in IBD was reported by a group of Israeli researchers. It was a small trial (21 patients), in which subjects were assigned randomly to groups given cannabis, twice daily, in the form of cigarettes containing 115 mg of Δ9-tetrahydrocannabinol (THC) or placebo containing cannabis flowers from which the THC had been extracted. A clinical response was achieved in 10 of 11 patients receiving cannabis with THC and 4 of 10 in the placebo group. Overall, this was a small study, but intriguing. No difference in complete remissions between the groups was observed, but that could easily be because of the small numbers. As with many conditions, all one can conclude is that more research is needed.
There is, of course, a laundry list of other conditions. Cannabinoids have been shown to lower intraocular pressure, making them potentially useful for treating glaucoma, although using cannabis to treat glaucoma is impractical in the vast majority of patients (see below), and there exist better treatments. After that, other conditions for which medical cannabis is frequently recommended include schizophrenia, for which a Cochrane Review concludes that there is no good evidence for or against the use of cannabis for schizophrenia. For epilepsy, data from double-blind randomized controlled clinical trials is lacking, although clinical trials are finally being done.
Overall, the evidence base, from my interpretation, ranges from nonexistent (most indications) to suggestive (anti-inflammatory), to fairly good (ant-emetic). However, most of the good clinical trials didn’t use marijuana cigarettes as most patients get them, but rather either purified cannabinoids (or synthetic analogues) or cannabis cigarettes spiked with varying amounts of THC. Indeed, all of these studies tend to suggest that purified drugs from cannabis or synthetic drugs based on compounds designed to mimic either endocannabinoids or cannabinoids from marijuana will be the future. I realize that that’s not what medical marijuana activists want to hear. I also realize that it is likely I will be lambasted as a “pharma shill” or as so conventional that I can’t think outside the box, but I’ve endured those attacks before when I’ve criticized other forms of herbalism. In any case, mine, I believe, is a reasonable interpretation of the currently existing medical literature.
Moreover, contrary to what advocates will claim, cannabis, particularly smoked cannabis, is not without adverse health effects, as was recently reviewed in the New England Journal of Medicine. Potential medical effects reported in long time users include motor vehicle collisions (not unreasonable to expect because driving while high is not a good idea), chronic bronchitis (not surprising as a result of smoke inhalation), schizophrenia (one wonders whether correlation really suggests causation here), depression, and addiction to other drugs, although the risk for cancer due to marijuana smoke appears to be much lower than with tobacco cigarettes. True, drug warriors and moralists will frequently exaggerate the risks in order to promote their agendas, but that doesn’t mean that cannabis is perfectly safe and doesn’t produce significant side effects or complications.
Then there’s the delivery problem.
Delivery, purity, highs
Let’s consider, for a moment, a generic herb that has medicinal properties. I began this post by briefly discussing the problems with herbs as medicine, but I didn’t discuss delivery. If one were to come up with a delivery method for an effective herb, one would be hard pressed to come up with a worse method than burning it and inhaling it. Consider the case of tobacco. The combustion of dried tobacco leaves produces a toxic stew of gases with carcinogenic effects. Of course, the main reason tobacco is so addictive is because it does have an active drug in it, specifically nicotine, which rapidly reaches the circulation through the alveolar sacs in the lungs. However, that nicotine is mixed with numerous combustion products that can cause cancer and contribute to the numerous other diseases to which smoking tobacco has been linked.
This brings us back to delivery. People have been using marijuana for the high and for medicinal purposes for a very long time, but cannabinoids were only first isolated from the plant in the 1940s, and the main active ingredient, (−)-trans-Δ9-tetrahydrocannabinol (THC), wasn’t discovered until the 1960s. Now, like the case with cigarette smoke and its delivery of nicotine to the bloodstream, the THC and other active cannabinoids delivered to the bloodstream through smoking marijuana are mixed in a similarly toxic stew of combustion products. While it is probably true that marijuana smoke is less carcinogenic than tobacco smoke, it has the same potential for respiratory irritation and deposits four times as much tar into the lungs as a typical cigarette, mainly because marijuana is usually smoked unfiltered. However, occasional marijuana use appears not to have a significant effect on lung function up to seven joint-years of lifetime exposure. (I chuckled when I read that term; it means one joint a day for seven years or one joint a week for 49 years). Of course, this hardly compares to a typical tobacco smoker, who smokes anywhere from a half pack to two packs a day (10-40 cigarettes), and those using medicinal marijuana can be expected to be smoking at least a couple of times a day. Medical cannabis advocates even basically admit that this is true.
In any case, if one were going to decide on a drug delivery device for cannabinoids, one could hardly design a worse device than burning the leaf and inhaling the gases, where the active drug is just one of hundreds of products of combustion, all loaded with particulate matter and tar. Sure, toking one joint a day probably doesn’t do appreciable lung damage in the intermediate term, but smoking one cigarette a day probably doesn’t either. In the case of glaucoma patients, a condition for which there is some evidence of efficacy, it’s been noted that patients would have to be toking up several times a day:
Since at least 2009, for instance, the American Glaucoma Society has said publicly that marijuana is an impractical way to treat glaucoma. While it does lower intraocular eye pressure, it works only for up to four hours, so patients would need to take it even in the middle of the night to achieve consistent reductions in pressure. Once-a-day eye drops work more predictably.
Yet glaucoma qualifies for treatment with medical marijuana in more than a dozen states, and is included in pending legislation in Ohio and Pennsylvania. At one point, it appeared in New York’s legislation, too.
And:
What’s more, for some of the ailments, such as glaucoma, patients would have to toke up every three to four hours day and night to maintain therapeutic levels in the bloodstream or tissues. Routinely consuming that much weed would be incapacitating.
Clearly, even if marijuana is efficacious for some conditions, there are serious drawbacks to burning the plant and inhaling the smoke as a drug delivery system. Other problems exist, not the least of which are the psychoactive effects of THC, which cause much of the “high” that pot smoking produces. To paraphrase one of the ophthalmologists in the NYT, his 60-year-old patients with glaucoma don’t want to be stoned all the time to get the beneficial effect of medical marijuana. The high is a particular problem for children, but none of this has prevented parents with autistic children from claiming that pot can treat autism, complete with seemingly-heartwarming anecdotes. One can imagine the temptation to simply keep the child toking until he becomes mellow and more “manageable.”
Of course, medical marijuana being in essence herbalism, with the same claims for efficacy of the “whole plant” due to synergy of its ingredients and the same attitude that “natural is better,” it’s not surprising that the same problems exist that are routinely observed for any herb sold for medicinal purposes. These problems include as inconsistent potency and purity, adulteration with contaminants—or even questions of whether the plant being sold is actually what is being claimed. Indeed, a fascinating story that sounds very familiar to those of us who have been paying attention to adulterated herbs and supplements was published a month ago in The Seattle Times:
Tonani, 38, decided several years ago to try pot. And it has worked for her, she said, especially strains low in the psychedelic chemical THC and high in the non-psychoactive ingredient cannabidiol, known as CBD.
As a medical-marijuana patient, Tonani knows it can be hard to find the rare strains that don’t make you high — and it can be even harder to get the same kind of pot consistently.
Testing shows that some marijuana strains are not what they purport to be in name, chemical content and genetics. This is particularly concerning for patients seeking pot low in intoxicants and high in pain-relief or other therapeutic qualities.
One strain widely known for its high-CBD and popular among medical-marijuana patients is called Harlequin. But when Tonani and a leading Seattle pot-testing lab analyzed 22 samples of Harlequin from various growers and dispensaries, five of them were high in THC and had virtually no CBD, which means people trying to take medicine were just getting high instead.
Again, this is a very common problem with herbal medicines, and cannabis, when smoked or ingested as the plant, is an herbal medicine.
As I posted before on SB and on other forums, the effectiveness of marijuana for conditions like nausea and pain is that it isn't better than the current treatment we give.
The study of CINV in children has some........ amusing side effects, from coughing, dizziness, altered mental state and yes...... kids getting high.
Granted, I'm no expert, but Dr Gorski is a breast cancer oncology surgeon and his comments about drug dosage and the need to smoke multiple times for relief is something that strikes me as being a huge negative point for marijuana based therapy.
