Respectful Insolence

Three months ago, I wrote about how the Cleveland Clinic had recently opened a clinic that dispensed herbal medicine according to traditional Chinese medicine (TCM) practice. As regular readers might expect, I was not particularly impressed or approving of this particular bit of infiltration of quackademic medicine into a major, generally well-respected academic medical center, particularly given some of the amazingly pseudoscientific treatments espoused by the naturopath who was running the clinic. I also pointed out that, although herbalism is the most plausible (or perhaps I should say the least implausible) of modalities commonly associated with “complementary and alternative medicine” (CAM) or “integrative medicine”, it still exhibits a number of problems, the biggest of which is what I like to call either the delivery problem or the bioavailability problem. In brief, herbs, when they work, are adulterated drugs. The active ingredient is usually a minor constituent, embedded in thousands of other constituents that make up herbs, and it’s almost impossible to control lot-to-lot consistency with respect to content or active ingredients given how location, weather, soil conditions, rainfall, and many other factors can affect how the plants from which the medicines are extracted grow and therefore their chemical composition. To demonstrate the concept, I pointed out that it’s much safer and more predictable to administer digoxin to a patient who needs its activity on the heart than it would be for the patient to chew on some foxglove leaves, given that the therapeutic window (the difference between the doses needed to produce therapeutic effects and the lowest dose that will cause significant toxicity) is narrow.

Which brings me to medical marijuana, a.k.a. medical cannabis.

Before I continue, let me just state my position on marijuana, which is different than it was, say, 20 years ago. Today, I believe there’s no reason why marijuana shouldn’t be legalized and treated by states the same way as tobacco products and alcoholic beverages are; they should be heavily regulated and taxed. Among physicians, this appears to be a common view, at least if you can believe a poll I saw a while back (for which I can’t find the link, alas). It’s also, these days, more and more of a mainstream view. In any case, medical marijuana has been a topic I’ve been meaning to write about for a while, now, but my “Dug the Dog” tendencies have kept popping up over squirrels topics like the Food Babe, ketogenic diets for cancer, and a variety of other topics.

Medical marijuana arrived in my state in 2008, when the voters approved a measure permitting it. After some time for the state to draft regulations, the law was implemented, and I had the strange (to me at the time) experience of receiving notices about state regulations, requirements, and documentation should I wish to prescribe medical marijuana. Indeed, more than twenty states, plus the District of Columbia, have legalized medical marijuana. They’ve done so on the basis of a political movement among patients that make pot sound like a miracle drug that can help when no other intervention can. And it’s more than that. Medical cannabis has been touted as a near-panacea for everything from pain to chemotherapy-induced nausea to HIV- and cancer-induced cachexia to even curing cancer itself. Yes, there’s a lot of hype out there, and there are a lot of claims that sometimes go viral on various social media, even though the evidence to support the claims is often, to put it mildly, less than rigorous.

Indeed, the acceptance of medical marijuana appears to be far more driven by politics than it is by science, as was pointed out in a recent New York Times article about the impending legalization of medical cannabis in New York State:

New 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.

I note that this article was written over a week before the Governor signed New York’s medical marijuana bill into law, thus legalizing it in New York. The article then goes on to give several examples, such as Alzheimer’s disease, lupus, Sjogren’s syndrome, Tourette’s syndrome, Arnold-Chiari malformation and nail-patella syndrome, and in particular rheumatoid arthritis:

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.”

As is the case with so much herbalism—and, make no mistake, medical marijuana is the new, popular herbalism of the moment—claims have far outstripped the evidence. Also, as pointed out in the NYT article, even advocates of medical marijuana admit that “the state laws legalizing it did not result from careful reviews of the medical literature.”

That’s the understatement of the year! Reading advocate websites for medical marijuana, I ask myself if there’s any disease or condition the holy weed isn’t good for? Truly, we are talking belief over science!

Unfortunately, even famous doctors like Sanjay Gupta are getting in on the act with a report, “Cannabis Madness,” full of a lot of anecdotes and rhetoric about “policy against patients.” Again, I believe that marijuana should be legalized, regulated, and taxed, just like alcohol and tobacco. If marijuana is going to be approved for use as medicine rather than for recreational use, however, the standards of evidence it must meet should be no different than any other drug, and for the vast majority of indications for which it’s touted medical cannabis doesn’t even come close to meeting that standard.

The evidence

There are definitely chemicals with potential medicinal use in the marijuana. No one, even the most die-hard drug warrior, denies that. These compounds are called cannabinoids, which is a term that describes a family of complex molecules that bind to cannabinoid receptors, which are proteins on the surface of cells. There are two types of cannabinoid receptors, type 1 (CB1) and type 2 (CB2). These receptors are seven transmembrane G-protein coupled receptors (so named for the seven protein domains that span the membrane), a class of receptor I’m pretty familiar with, because one of the receptors I study is of the same class, which looks like this:

Cb1 cb2 structure.png
Cb1 cb2 structure” by Esculapio at it.wikipediaOwn work (Original caption: “Immagine creata da –Esculapio”). Licensed under CC BY-SA 3.0 via Wikimedia Commons.

The details of how this happens aren’t essential for this particular post, but when these receptors are stimulated by the binding of cannabinoid molecules, including endocannabinoids (produced by mammals), plant cannabinoids (such as (−)-trans-Δ9-tetrahydrocannabinol, more commonly referred to by its abbreviation THC) produced by (for example) the cannabis plant, and synthetic cannabinoids (such as HU-210), downstream chemical signaling pathways are initiated from the receptor to the inside of the cell, thus producing the effects on the cell and organism. There is mounting evidence that there are more than two types of cannabinoid receptors. In any case, CB1 receptors are found widely in the central nervous system, where they modulate a variety of responses, and are also found in other parts of the body, for instance, the pituitary gland, thyroid gland, lungs, and kidney, as well as fat cells, muscle cells, liver cells, and in the digestive tract. CB2 receptors, on the other hand, are expressed primarily in the immune system, the gastrointestinal tract, and, to a much lesser extent than CB1 receptors, in the brain and have been implicated in modulation of immune responses. In particular, stimulating CB2 receptors cannabinoids could be potentially useful as anti-inflammatory drugs. Over the last couple of decades, endocannabinoids and cannabinoid receptors have been implicated a large variety of functions, including memory, pain, energy metabolism, and more. It is thus plausible that manipulation of cannabinoid signaling could have therapeutic effects in a variety of areas.

Unfortunately, one of the problems with medical marijuana, as noted in the NYT article is that enthusiasm for weed as a cure-all has far outstripped existing medical evidence. This disconnect between the existing evidence base ranges from thin to nonexistent, depending on the condition. One of the most frequent claims I see is that cannabis can be used to treat cancer. I’m not going to address that claim specifically in this post, except very briefly, because I think it’s a large enough topic to warrant its own post. Suffice to say that interesting preclinical studies have been exaggerated beyond all evidence, but nonetheless certain cannabinoids could have potential in the treatment of certain cancers. I might also review the evidence base for cannabinoids and autism, given how I’ve been seeing discussions of its use starting to pop up lately on the usual sites. In other words, stay tuned for parts two and three spread out over the next several weeks, whenever no squirrels distract Dug the Dog.

In all fairness, in this country, at least, studying the medicinal properties of marijuana and its constituents is not easy, given that it is currently an illegal drug, as was discussed in the NYT article. It’s not for lack of interest, but mainly because the law (and therefore the Drug Enforcement Agency) classifies it as a schedule 1 drug with “no currently accepted medical use.” Scientists who want to do research on marijuana and its constituents—particularly clinical trials—must register with the DEA and submit an investigational new drug (IND) application to the Food and Drug Administration for human trials. Moreover, the National Institute on Drug Abuse is the only supplier of legal, research-grade marijuana. On the other hand, while doing research on marijuana is difficult in this country, researchers in other countries that have long had much more lax laws and regulations should have an easier time of it.

Another issue is how to do a proper placebo control. Given that many of the conditions for which medical marijuana is touted are conditions with a large subjective symptomatic component, such as pain, nausea, fatigue, or lack of appetite, clinical studies of medical marijuana are going to require really good placebo controls. Given that at least one of the active components causes a high, it’s arguably even more difficult than in the case of, for instance, acupuncture, to design studies with adequate controls. That’s why most of the more rigorous studies have used specific purified cannabinoids. For example, in this study, a titanium pipe loaded with doses of THC varying potencies is used rather than plant, while this study of cannabis for neuropathic pain used high-dose cannabis, low-dose cannabis, and placebo cigarettes.

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 supporting medical cannabis use, from my interpretation, ranges from nonexistent (most indications) to suggestive (e.g., anti-inflammatory), to fairly good in one case (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—and, make no mistake, medical marijuana is 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.

Medical cannabis: Politics versus science

There’s no doubt that what is driving the legalization of medical marijuana in so many states has far more to do with politics than with science. Right now, for all but a handful of conditions, the evidence is slim to nonexistent that cannabis has any use as a medicine, and those conditions, such as CINV and chronic pain, can often be treated more reliably with purified or synthesized active components. Moreover, for one condition for which there is reasonably good evidence for the efficacy of cannabis and/or cannabinoids, namely chronic pain, politicians are reluctant to approve medical marijuana, as described in the recent NYT article:

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.

So, for one indication for which there is reasonably good evidence for the use of cannabis, legislators in Illinois were reluctant to approve its use, while approving its use for a lot of indications for which there is no evidence to support them. Clearly, this is a policy area that cries out for better science, given how legislators are being swayed by anecdotes that do not demonstrate that cannabis is effective and stories of “persecution” for growing medical marijuana, rather than by well-designed randomized clinical trials. Add to that the conflict with currently existing federal law, which outlaws cannabis as a schedule I drug, and the political situation is a mess, making doing research to find out for what indications cannabinoids have efficacy much more difficult. Antidrug zealots hugely exaggerate the danger of pot smoking, while pro-medical marijuana zealots claim that “cannabis cures cancer.” (It doesn’t, as I will discuss in the next installment.)

Moreover, THC can have biphasic activity:

THC has what doctors and researchers know as biphasic activity. “At low doses it has certain effects, and at high doses it has opposite effects,” Dr. ElSohly explains. “Somebody using to get high at the right dose will be calm, happy, getting the munchies, and all of that,” Dr. ElSohly says. Someone using at the right dose could see medicinal benefits, too. But take in too much THC, and you can become irritable, even psychotic. “There are more emergency room admissions today than ever because of marijuana use,” Dr. ElSohly says. “That’s simply because of the psychoactive side effects of the high THC content that the public uses.”

This makes standardization and getting the dose right more important for medical cannabis than for most other drugs, which is why I’m not enamored of smoking pot as a THC/CBD delivery system. At the risk of being too personal and “anecdotal,” I couldn’t smoke pot if I wanted to, for recreational or medicinal uses, whatever my feelings about its legalization. I can’t smoke cigarettes, either, and have never tried either pot or cigarettes. The reason is simple. Inhaling just secondhand smoke sends me into fits of coughing—and has since I was a child. Inhaling smoke directly into my lungs has been and still is more or less unthinkable. And I’d bet I’m not alone, either.

My personal sensitivities aside (which are obviously not shared by most people), I see two critical unaddressed questions with respect to cannabis. The first issue is standardization. I’m sorry, herbalists and pot smokers, but smoking a dried plant just isn’t it, particularly given the relatively low doses of active compound needed for optimal effects. That means pharmaceutical-grade material. If cannabis is a therapeutic drug, it should be treated like every other therapeutic drug and be subject to clinical trials. The second issue is comparative effectiveness research. It’s not enough just to say cannabis (or whatever cannabinoid drug or derivative you might wish to use) is “efficacious” against this disease or this condition. We need to know how efficacious it is compared to the existing standard of care. In most cases, even for indications for which there is evidence of efficacy, the existing evidence base suggests that cannabis is less effective than existing treatments, with the possible exception of its use as an antiemetic. Yet none of this sways the zealots, just as similar evidence with respect to other herbs doesn’t sway believers in herbalism. Meanwhile, medical cannabis is rapidly becoming big business.

That’s because cannabis is the new herbalism. With relatively few exceptions, it’s about belief first, and then trying to get the science to to support its magical properties.

Comments

  1. #1 c0nc0rdance
    July 10, 2014

    Orac, what a breath of fresh air! Well written, accurate, and accurately representing the state of research. You continue to impress me writing on an area that I usually cringe about.

    I’m a bit frustrated by other medical sources and skeptics who deal with cannabis from a pro-legalization perspective.

    Here’s my position:
    1. Medical uses should have no bearing on whether a drug can be used for recreation. Codeine makes a great cough syrup, but I don’t think that means it should be legal to sell at the local gas station or 7-11. Likewise, hydrocodone is an indispensable drug for pain management, but legalizing its use for recreation makes no sense. If cannabis has medical applications, let it be treated the way we treat prescription drugs. We shouldn’t mix and match and encourage self-medication.

    2. Tobacco and alcohol are not legal because they are safe. Let’s keep reminding ourselves that, combined, these two legal drugs are involved in causing more preventable deaths than any other single factor. They are only legal because we lack the political will to make them illegal.

    To me, this is no different than saying we should release any serial murderer who killed fewer people than Jack the Ripper, because that guy never served any jail time, so why should anyone else? Let each drug stand or fall on the merits and harms shown by research.

    I’ll stop there. This is a sore issue for me. I’m a little frustrated with a lack of clear, rational thought on the issues around physicians encouraging the legalization of a recreational party drug. I appreciate this well-written article.

  2. #2 Narad
    July 10, 2014

    The article then goes on to give several examples, such as Alzheimer’s disease, lupus, Sjogren’s syndrome….

    Yes, I can see why a substance well known for producing cottonmouth would be a natural therapeutic choice here.

  3. #3 Narad
    July 10, 2014

    On the antiemetic front, I don’t know how long it would typically be prescribed for, but longer term use carries some risk of the peculiar cannabinoid hyperemesis syndrome.

  4. #4 Marie
    July 10, 2014

    You never smoked marijuana? Well your GPA was probably a lot better than mine.
    The irony for me was that when I was prescribed Marinol for weight gain I hated it. Threw all the pills out. When you are taking a lot of meds as I was at the time, the last thing you want is another med with central nervous system side effects. IMHO. Plus I never really was one for getting the munchies – but I sure loved music & art! Sometimes I kind of miss it when I go to concerts now. sigh.

  5. #5 AngryScience
    July 11, 2014

    And because it’s my job to basically pick from the bottom of the barrel in science blogging…

    …Well, there’s this guy.

    http://phoenixtears.ca/

    Specifically, his “how it works and what it does” page, where he writes, I shit you not:

    “Many people who have taken the oil have stated that they thought it to be the fountain of youth. From my own experiences with the oil I believe this to be true.”

    I’m as much a fan of the odd johnny as the next fella, but seriously, backing up attempts to legalize a drug with dishonest science is just fucking dumb.

  6. #6 T.
    July 11, 2014

    @c0nc0rdance
    I seem to recall that alcohol had indeed been made illegal in the US, circa 1930?
    Did it work SO AMAZINGLY well?

    Prohibitioning aside, I am in agreement with 100% of what Orac said. Interesting possibilities indeed, but blown out of proportion.

  7. #7 JJ
    Outside the US
    July 11, 2014

    I’ve been a long time lurker, finally commenting!

    This was a great post. My nephew has Dravet, and my mother was talking a few years ago about taking him to CO for cannabis oil. I think I talked her out of it based upon dosage/quality arguments learned here from our esteemed host (or perhaps that’s a bit egocentric-his mother may have simply nixed the idea). Been following epidiolox (sp?) for about a year now-they’ve opened up a trial in the midwest and that may be a possibility for my nephew if his neurologist agrees.

    As much fun as this blog is, I rather miss some of our more “entertaining” visitors. I know Greg asked to be banned (still gives me the grins), but whatever happened to Augie, or Jen, or Sid? I know getting spanked isn’t fun, but their apparent decisions to leave us left a deficit in my daily dose of giggles.

  8. #8 brewandferment
    July 11, 2014

    Trying to ban stuff that can be grown (tobacco, pot, grain for alcohol) and then easily produced with household ingredients/equipment (alcohol, there might be more but I don’t know the facts there) is an enormous game of whack-a-mole that the moles definitely will win.

    I’ve heard that synthetic pot is more dangerous than plant pot. Don’t know if it’s the usual anti-drug scaremongers, or if the unintended consequences have actually become a bigger problem than weed let well enough alone.

    Disclosure: never been a user and I only say that to make clear I have no agenda other than wanting to see the end of the likes of the DEA and military involvement in stuff that is not in its charter. Way too much resources involved in chasing pot for no benefit and likely much harm.

  9. #9 Paul
    July 11, 2014

    I believe there’s a place in the world for healthful, non-medicine products. For example, my wife will drink a cup of coffee when she’s having asthma rather than jumping right to the emergency inhaler. Could that instead be an FDA regulated pure caffeine powder? Sure. But coffee works.

    So certainly claims of Cancer and Glaucoma cures need to be treated as medicine and carefully studied with specifically extracted compounds. But if a cancer patient finds a pot brownie helps their nausea or appetite? Great! Even if it were just placebo, that’s still a good thing.

    I think that’s where this confusion of marijuana and medicine comes in. It’s not that it needs to be a medicinal appetite stimulant, it’s that if a very sick person finds help in it, why not just let them consume it? Not as medicine, but as something fairly benign that helps them feel better. But since marijuana is illegal it needs to be couched in the terminology of medication to get a legal exemption for the individual. Which as you point out confuses the issue of what a medicine is.

    I’ll reiterate some other commenters, this was a remarkably clear-headed piece on this topic.

  10. #10 Eric Lund
    July 11, 2014

    I’ve heard that synthetic pot is more dangerous than plant pot.

    I’m willing to believe that synthetic pot is more potent than plant pot. It’s easier to adjust the THC content of synthetic pot to what you want, and I would think[1] that for most users higher is better. Whether that’s more dangerous depends on your perspective. A user who is used to plant pot could be overwhelmed by a similar dose of the more potent synthetic pot. But with synthetic pot, at least for medicinal purposes, you know how much you need, unlike with plant pot where the potency can vary from negligible (ditch weed) to quite strong. The latter comes up with other herbal medicines: in synthetic form you know how much you are getting, whereas with grown product you are never sure.

    [1]Not that I have any personal experience on this topic….

  11. #11 Narad
    July 11, 2014

    I’m willing to believe that synthetic pot is more potent than plant pot. It’s easier to adjust the THC content of synthetic pot to what you want….

    I think B&F may have been referring to compounds such as JWH-018, which are full agonists of the cannabinoid receptors.

  12. #12 Van
    United States
    July 11, 2014

    I mostly agree with this but I think one of the reasons patients prefer to smoke is that it’s actually easier to control the dose then with a pill, such as Marinol. I think most people who use it for medicinal purposes probably just take a puff or two at a time, wait to gauge their reaction and then smoke a little more if needed. I had a friend with abdominal cancer who after surgery and chemotherapy decided to quit treatment. He said narcotic pain medicine made his pain worse because it constipated him. Pot and hot baths in his jacuzzi were the only things that helped. And anyone who smokes a whole joint of todays’ marijuana is hard core. I haven’t smoked in years, but once they came up with the powerful strains, i found one or two tokes was all I could handle. As far as nausea meds, at least some of them have potential extrapyramidal side effects. I believe they black boxed Reglan for this. And I think compazine and phenergan also have that potential. Don’t know about Zofran, though.

  13. #13 Politicalguineapig
    July 11, 2014

    T: You’re a bit off. the ban started in 1920, went through 1932 when it was finally repealed.

  14. #14 KayMarie
    July 11, 2014

    Some of the stuff sold as “synthetic pot” may not be the active ingredients in pot just derived synthetically. Some of the so-called “bath salts” are sold as synthetic pot.

    How much they are really like the compounds in pot I don’t know (as last I heard on the news they are whichever designer drugs hasn’t been banned yet and as one gets banned a new compound gets put in the products). I assume they call the whatever they cooked up synthetic pot because people don’t think of pot as dangerous so it makes them more likely to buy it than whatever chemical they put in it this month.

  15. #15 Narad
    July 11, 2014

    Some of the stuff sold as “synthetic pot” may not be the active ingredients in pot just derived synthetically. Some of the so-called “bath salts” are sold as synthetic pot.

    I really doubt that MDPV and friends are smokable.

  16. #16 Incitatus
    July 11, 2014

    One thing smoking ones pain drugs would do would be to normalise it, to make it social. Everyone i know on opiates, and these are prescribed ones, is under constant censure and judgement from others, often their family, for taking them. Even when the pills are all that allows them to function.
    Turning pain relief into a fag break would help.

    note for merkins…fag in English means cigarette. If fag break sounds odd to you think how the reference to a johnny sounded to me upthread. As a johnny is a prophylactic…

  17. #17 Narad
    July 11, 2014

    As a johnny is a prophylactic…

    Well, those are “jimmies” here, but I think that’s mostly Black slang (as is “squares” for cigarettes, which seems to be falling out of use, although I still say it, sometimes to the surprise of the hearers; “that’s jail talk, man”).

  18. #18 Mephistopheles O'Brien
    July 11, 2014

    I thought that jimmies were sprinkles. Live and learn.

  19. #19 Antaeus Feldspar
    July 12, 2014

    MO’B, I didn’t know you were a fellow Massachusettsian!

  20. #20 Mephistopheles O'Brien
    July 12, 2014

    @Antaeus Feldspar – I lived in Mass for 4 years ago some time back. I learned the difference between a frappe and a milkshake and what a tonic is.

  21. #21 blinkyeb
    Baltimore
    July 12, 2014

    Google patent US 6630507 Heard of this?

  22. #22 Delurked Lurker
    A mote of dust suspended in a sunbeam
    July 12, 2014

    Boy its hard to stay away from this place :)

    I have personal experience and yes what I am going to do is provide an anecdote so keep that in mind.

    I have cancer and have had chemotherapy for it. I did take cannabis to try and put a lid on my nausea. While it helped a bit it had no where near the effect that the anti emetics that were given to me did. Compared to Aprepitant it was pretty useless.

    As for analgesia it works but for me it is no better than paracetamol. Codeine has a much greater effect. I know this as I also have Rheumatoid Arthritis. It is also claimed that cannabis is an effective anti inflammatory agent. Well compared to Celecoxib it really is ineffectual. As for modifying RA’s effect on the joints compared to methotrexate it is useless.

    I am a member of a cancer support forum. We regularly get people on board who claim that cannabis is protective against cancer. I really find that hard to believe as I personally know stoners who ended up with cancer. What I really want to see is a large scale study that investigates the incidence of cancer in people who regularly use Cannabis for recreational purposes. I could then point to the study and shut them up. Mind you it is a support forum so any argument is short lived. it would be nice though to have some evidence to educate the clueless.

    Someone commented on political will to make things illegal. Well we tried that in the 1920′s with alcohol and it was an unmitigated failure. Making things illegal does nothing but empower criminal organizations and turn decent citizens into criminals. We have had a war on drugs now for decades and nothing has happened except tens of thousands have died in drug related violence and the use of illegal drugs has skyrocketed. I applaud those countries and those states in the US who have made it legal for recreational purposes. Make them legal, tax them, then use the money in public health campaigns. It has worked for tobacco and it will work for cannabis, or any other illegal drug for that matter. In the US and Australia we have managed to get smoking rates down from over half of all men down to around 15%. We never had to resort to banning it and to do so I think would be counter productive.

    So in passing if anyone can point to a large study showing cancer incidence in heavy cannabis users I would be most appreciative.

    Cheers

  23. #23 Drew Bright
    Ponce Inlet Florida
    July 13, 2014

    I challenge you to a public debate, you paid-for, antiscientific shill! Continue to help the Prohibitches withhold God’s healing plant and reap the karmic consequences…Repeal – Amnesty – Reparations! We will settle for nothing less. Respect existence or expect resistance ;)

  24. #24 AdamG
    July 13, 2014

    Did you even bother to read the article, not-so-Bright?

  25. #25 Julian Frost
    Gauteng East Rand
    July 13, 2014

    AdamG, did you not notice the winking emoticon at the end of Drew Bright’s comment? Drew is Poeing.

  26. #26 Antaeus Feldspar
    July 13, 2014

    Google patent US 6630507 Heard of this?

    Yup. But if your point was “there must be something to it, or they’d never have gotten a patent granted” then you’re quite mistaken. Patents have been granted for many things that don’t do what they’re claimed to – for perpetual motion machines, or for infinite data compression methods (which, believe it or not, are actually more impossible than perpetual motion.)

  27. #27 Mephistopheles O'Brien
    July 13, 2014

    infinite data compression methods

    I’m still convinced that a really good compression method using deduplication and zero suppression should be able to take any data and compress it to a single bit.

  28. #28 Narad
    July 13, 2014

    Google patent US 6630507 Heard of this?

    G—gle patented cannabis? Oh, wait…. Your point is that CB1/CB2 affinity is wholly unnecessary?

  29. #29 blinkyeb
    July 13, 2014

    Who owns controls that patent?

  30. #30 Mephistopheles O'Brien
    July 13, 2014

    @blinkyeb – are you here to make some point or to play 20 questions? If you’d like to make a point, please state it. Thanks.

  31. #31 Narad
    July 13, 2014

    Who owns controls that patent?

    You didn’t understand that whole receptor business, did you? Do you surmise that the best acute treatment for stroke is trying to figure out how to get a joint into the patient ASAP?

  32. #32 rs
    July 14, 2014

    MOB “I’m still convinced that a really good compression method using deduplication and zero suppression should be able to take any data and compress it to a single bit.”

    Yes, but it only works reliably for political speech and marketing copy.

  33. #33 Bill Price
    July 14, 2014

    I’m still convinced that a really good compression method using deduplication and zero suppression should be able to take any data and compress it to a single bit.

    There are any number of techniques that would suffice for compression to a single bit. None of them, however, have corresponding de-compression techniques.

  34. #34 Mephistopheles O'Brien
    July 14, 2014

    rs – I’ve heard of a two-bit politician, so it’s within reach.

    Bill Price – that’s where it all falls down, of course, unless one has a quantum computer.

  35. #35 Bill Price
    July 15, 2014

    that’s where it all falls down, of course, unless one has a quantum computer.
    In other words, Deepitypak can do it, but not us regular folk?

  36. #36 herr doktor bimler
    July 15, 2014

    I’m still convinced that a really good compression method using deduplication and zero suppression should be able to take any data and compress it to a single bit.

    You’re giving me flashbacks to Barnsley’s “fractal compression” algorithms from the 1980s.

  37. #37 AdamG
    July 15, 2014

    AdamG, did you not notice the winking emoticon at the end of Drew Bright’s comment? Drew is Poeing.

    Oh I googled around before commenting, and sadly Mr. Bright is not a Poe.

  38. #38 jackvsworld
    July 17, 2014

    If you were wrong about marijuana 20 years ago, maybe it’s also possible that you’re wrong now about some of the things you describe as “woo.”

  39. #39 jackvsworld
    July 17, 2014

    >”Inhaling just secondhand smoke sends me into fits of coughing—and has since I was a child. Inhaling smoke directly into my lungs has been and still is more or less unthinkable. And I’d bet I’m not alone, either.”

    Actually, unless you have allergies, asthma or some kind of respiratory condition, that’s VERY unusual. Most people can inhale smoke no problem.

  40. #40 Chris,
    July 18, 2014

    jacksvsworld, a quick question:

    Did smoking pot make you stupid, or were you stupid before you started to smoke it?

    I ask this because I spent two hours a couple of days ago waiting for old Honda that was parked in my driveway to be removed by the police. Not just blocking the driveway, but backed to being not far from the garage. In the back seat was a bong, and the police officer told me it was a stolen car.

    What kind of intelligent person steals a old small car and then backs it up a driveway, while leaving their stuff in the back? Needless to say, I am not impressed with that person’s cognitive function.

    By the way I only smoked pot for a week in college because it gave me annoying “itchies”, and I did not like that it made me stupid. I also have a real verifiable allergy to nicotine, so I don’t like being around tobacco smoke. Or wood smoke. Or any other airborne particulates.

    ‘Most people can inhale smoke no problem.”

    Really? Provide the PubMed indexed studies from qualified reputable researchers to prove otherwise. While we have had several in our family die from tobacco smoke inhalation (including a 42 year old who lost his jaw to cancer), I will only use the sixty plus years of epidemiological studies showing tobacco smoking is deadly.

    Since pot smoking has only become legal in the past couple years in a few places, I predict there will be similar results from studies in the next forty years for marijuana.

    By the way, I voted to legalize marijuana smoking in my state. I really don’t care what chemicals you inhale, I just don’t want doing it in my air space. Committing acts like stealing a car and abandoning it in someone’s driveway may or may not be the affect of smoking pot.

    It just does not reflect well on the users. So please clean up that image, unlike this city attorney. You can start by being coherent.

  41. #41 Antaeus Feldspar
    July 18, 2014

    If you were wrong about marijuana 20 years ago, maybe it’s also possible that you’re wrong now about some of the things you describe as “woo.”

    And it’s also possible that “jackvsworld” is actually a criminal wanted by the FBI for sordid acts of bestiality against endangered species.

    It’s not enough to say something is ‘possible’.

  42. #42 Narad
    July 18, 2014

    I also have a real verifiable allergy to nicotine

    A small amine isn’t able to act as an allergen. It would have to somehow function as a hapten, but with a protein that also ignored vitamin B3.

  43. #43 Chris,
    July 18, 2014

    Narad, you’ll have to take my skin tests results with the allergist MD who explained them to me. Personally I was glad in the late 1970s to have a verifiable piece of paper to bolster my annoyance at those who wanted to smoke tobacco in my presence.

    That included my dorm roommate who chose a non-smoking room thinking it would help her quit. Oh, and the folks in movie theaters, and the woman seated in the nonsmoking section of the airplane, and the woman in our office who kept telling us how we should only eat organic food while sucking on a cigarette (so glad when the company went smoke free, and surprised when some tried to hide the lit cigs under their desks).

    I just hope that we can convince the ones who wish to now legally smoke marijuana can be reminded that many of really find it annoying.

    By the way, not all things that cause reactions are proteins. Though sometimes things that cause dermatitis do that as a combined reaction to items in the body, like nickel reacting to perspiration.

  44. #44 Chris,
    July 18, 2014

    Note I was very upset that some idiot abandoned a stolen car with a bong in on my driveway that trapped me from driving somewhere before it closed. Plus waiting two hours after calling the police for it to be removed (had to resort to “911″ after spending several minutes on hellish voice mail trying the “non-emergency” parking infraction police number).

    That alone illustrates one reason why I detest the idiocy of folks like jacksvsworld. Oh, and pedantic comments that may follow. So if you’ll excuse me I will still think very little of the intellectual capability of anyone who says “people can inhale smoke no problem.”

    Because it doesn’t take a rocket scientist (fortunately I used to be one) to know that it is not healthy to intentionally inhale particles contained in any kind of smoke.