[phren0logy]

Speaking as an MD, the evidence for medical marijuana is, uh, pretty thin. In fact, most people would decry the mismatch of research to marketing if it were a traditionally prescribed drug.

The barriers to meaningful research are coming down, but the research just isn't there yet. I suspect that therapeutic targets will emerge, but no amount of enthusiasm changes the fact that high-quality research hasn't happened yet. On the other hand, there are real problems associated with use, such as an increased risk of psychotic disorders, problems with concentration, etc.

I consider it part of my job to look at the evidence and remain free of bias, because most marketing is put together by those who stand to make a lot of money off of what they are selling. If I apply those same criteria I use for other drugs I prescribe to marijuana, the outlook is not so good.

Recreation marijuana, on the other hand, suffers from no such pretense. People use it to get high, and understand the risk. This, to me, seems like a much more honest system for the use most people want.

[mohawk]

Actually a lot of the data we have seen so far is quite good, here are some examples

Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review

https://jama.jamanetwork.com/article.aspx?articleid=2338266

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

http://onlinelibrary.wiley.com/doi/10.1111/epi.12631/full

[phren0logy]

The first article stalls out when I try to load it.

The from the second:

CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.

This is not good evidence.

I want to be clear: I'm hopeful about the potential, but so far the enthusiasm for marijuana is not yet supported.

[sehugg]

The first article stalls out when I try to load it.

Here you go:

Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence. Six trials that included 325 patients examined chronic pain, 6 trials that included 396 patients investigated neuropathic pain, and 12 trials that included 1600 patients focused on multiple sclerosis. Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications.

[phren0logy]

That is starting to look like real evidence. Thanks.

[kw71]

I think you're right that the research isn't up to par. But I also think there's a lot of empirical evidence to show that there are some use cases. I don't expect any scientist, chemist or doctor to recommend that I burn plant material and inhale the combustion products. But what about a hospice, end of life situation, to improve quality of life?

You mention psychotic disorders and concentration. I have PTSD and normally cannot concentrate on anything for more than a few minutes. The best my psych can do is something that makes the episodes less intense, but they still happen. I normally cannot sleep unless I am so exhausted from being awake for typically 30+ hours, and then I'm usually awoken by a terrible dream within a few hours. Guess how I cope? I smoke and my tolerance is such that I don't get high anymore, but I still receive other effects that are beneficial. I can concentrate and give attention to myself, my family, and my work. I can go to sleep and wake up at a normal time. Therefore, I think there's some demonstration here that mj can be therapeutic or helpful in at least some cases.

Fun fact: the medication I'm prescribed is new and was discovered empirically and its mechanism of action is unknown. I know I am risking cancer and two lungs full of thick tar by smoking. But for the medication, all they have is "we haven't seen it hurt anyone yet." I think maybe the community knows more about pot than this one.

Edit: Before I started smoking I was on Xanax, which I think carries a greater risk from daily use than smoking.

[simoncion]

> I know I am risking cancer and two lungs full of thick tar by smoking.

1) Why not use a vaporizer?

2) AIUI, tar isn't a byproduct of marijuana combustion. (But I may very well be misinformed about this.)

[kw71]

1. is a good idea but I don't own the equipment. I'm not "that committed" to smoking and will stop if we come across another medication that works. I would really prefer to find something else: smoking brings some restrictions such as not being able to drive for the rest of the day after I smoke (although I feel fine and in charge, safety & respect for others lives trumps all)... so I don't want to spend the money on 'durable equipment' that I hope I don't need for much longer.

2. I don't know if there's some specific definition for "smoking tar" like what's advertised for tobacco products. I consider it to be any residue, but with mj it's characteristically a gooey solid or liquid when left to accumualte on equipment. It is not water soluble but a good solvent for it is isopropanol. If you examine the ends of smoked cigarettes rolled with tobacco and mj, I think you will agree that the stains on the paper used for the mj cigarette will be heavier and may even show through the paper. Whatever this is, it goes in the user's lungs and is likely not easily removed.

[simoncion]

> (although I feel fine and in charge, safety & respect for others lives trumps all)

+1 and props for that.

> ...with mj it's characteristically a gooey solid or liquid...

Fuck me, I had forgotten about resin. Yeah, you're totally right.

Well, if -after a while- you don't find anything that works, you might consider purchasing (or causing to be purchased) a vaporiser. Hope you find something that works with fewer side effects, though! :D

[ryanmonroe]

If you are in a MMJ state it shouldn't be too hard to find a clinic with edibles or pills no?

[throwput]

Disregarding the more outlandish claims, looking only at relatively undisputed use as an analgesic and/or sleep aid: how does marijuana compare to medications I can buy, not with a prescription, but straight off the supermarket shelves? I'm thinking mainly of aspirin, acetaminophen, ibuprofen, diphenhydramine, dextromethorphan...

Clearly there's less research one way or another, but do you have reason as an MD to believe it's less preferable to regular use of those substances?

[agumonkey]

The papers on THC triggering the immune system in lungs (quicker cell death, etc) aren't strong enough ? That was the main reason I wanted to try vaporized THC (bringing back air intake/capacity, asthma).

[TelmoMenezes]

So research is too thin to assume any therapeutic use, but strong enough to claim real problems such as an increased risk of psychotic disorders and problems with concentration?

[phren0logy]

Yes. Each individual paper covers a very narrow topic. For example, here's a recent paper - White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study

This paper tells me nothing about headache relief, or nausea related to chemotherapy.

[delluminatus]

It sounds like you are reasonably well informed in this field, whereas I can barely parse the abstract for the linked paper. I was hoping you could give me an educated opinion about negative effects of cannabis use in non-adolescents. It seems like papers are mostly finding negative effects for adolescents only.

Also, the particular paper you mention seems to be studying adolescents with "Cannabis Use Disorder (CUD)". Is this just a roundabout way of saying they are a pot smoker, or is there a difference between cannabis use and "cannabis use disorder"?

For example, consider a non-adolescent who uses cannabis sporadically but does not have a "disorder" (i.e. no addictive tendencies). Do you have an opinion about cannabis use for that individual?

[phren0logy]

To answer your first question, Cannabis Use Disorder specifically refers to a pattern of use that leads to health problems, disability, and failure to meet important responsibilities at work/school/home. So it's not defined by use but rather by consequences of use.

Second, there are a number of large cohort studies looking at this question. Here's a recent one: http://www.ncbi.nlm.nih.gov/pubmed/26006253 Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study.

It followed a group of 1200+ kids in New Zealand for all kinds of stuff, but in this particular paper they looked at cannabis use.

Their conclusion: In general, the findings of the CHDS suggest that individuals who use cannabis regularly, or who begin using cannabis at earlier ages, are at increased risk of a range of adverse outcomes, including: lower levels of educational attainment; welfare dependence and unemployment; using other, more dangerous illicit drugs; and psychotic symptomatology. It should also be noted, however, that there is a substantial proportion of regular adult users who do not experience harmful consequences as a result of cannabis use.

In conclusion, it seems that some adults can use occasionally, or even regularly, without a problem on one of the outcomes they looked at. Those with a personal or family history of addiction or a psychiatric disorder are probably at higher risk for a problem.

But, it comes back the same problem mentioned before: Every study can only answer the narrow questions they have considered, How does cannabis impact the risk for vascular disease, or dementia? Perhaps it helps, perhaps it hurts.This study does not answer that question.

[delluminatus]

Thank you for the reply. I am beginning to understand what you mean about how there is not enough research to make general statements about side effects or medical efficacy, because there are just so many potential factors that could have an influence on how cannabis affects an individual.

I can see why one would hesitate to make recommendations, especially as a doctor, when it's simply uncertain if a user would get medical benefits, or whether they would have negative side-effects. As unlikely as side effects may be on average, for people with specific conditions a negative effect might be predictable if that condition and its interaction with cannabis was isolated in a study.

[kw71]

Is it possible that the subjects who went to cannabis already had problems, are self-medicating, and would have achieved the adverse outcomes anyway?

[phren0logy]

This was partially controlled for in their analysis, but it's a cohort study meaning that people weren't randomized into groups. So certainly there could be some of that happening, but the analysis minimizes (but doesn't totally eliminate) how much that influences the outcome.

Behavioral science is hard, and messy.

[schwabacher]

It's different research, and yes.

[bryans]

I'm finding it very difficult to understand your insistence that all of the currently published research[0] into the benefits of marijuana use is somehow "low quality", or invalid, or an advertisement, while simultaneously claiming that all of the research into the detriments are completely valid. That's pretty silly, and quite the opposite of "remaining free of bias."

If you had stopped at saying we should be wary of touting marijuana as this utopian drug with no downsides, I would completely agree with you. In fact, I don't need research to know that marijuana use can be detrimental to health, as I am susceptible to a very extreme form of cannabinoid hyperemesis syndrome[1], and have come uncomfortably close to being the first person to die directly from its use. This has led me to actively investigate the subject for years. Experiencing first-hand results which are identical to both positive and negative research, I can't help but question the "non-bias" in your approach to the topic.

Just because people exploit medical marijuana programs for the purpose of recreation, doesn't mean there aren't legitimate therapeutic benefits. The reason why those programs are being so heavily exploited, is that marijuana has long been subject to prohibition in many countries, despite wide acceptance (even among your peers) that it is no more harmful than other legal drugs. Prohibition, of course, has not stopped anyone from growing and smoking it, which is exactly why these medical programs get exploited: they can be. Why go through the hassle of growing and harvesting and curing, or risking fines and jail time, when you can make a trip to a doctor's office and lie about muscle pain?

Marijuana has also long been subject to many, many smear campaigns[2] from people with zero understanding of the drug. Which ought to tell you that there are likely just as many people pushing for negative research results as there are positive. But that doesn't mean all of the negative research is "low quality", or invalid, or an advertisement, just as it doesn't define the positive research. It just means there are a lot of ignorant and greedy people in the world, which I think we can both agree on.

[0] https://www.reddit.com/r/science/search?q=marijuana&restrict...

[1] https://en.wikipedia.org/wiki/Cannabinoid_hyperemesis_syndro...

[2] https://en.wikipedia.org/wiki/Reefer_Madness

[phren0logy]

I didn't say that all positive evidence is low quality, and I definitely didn't say that all negative evidence is high quality.

My logic works like this:

1. Cannabis has a number of plausibly pharmacologically active chemicals.

2. The effects these pharmacologically active chemicals have may help some things, and make other things worse. Both are almost certainly true, depending on which things we are talking about.

3. Many of the sources of information on this topic are biased, either by the anti-drug movement, which cannot abide any positive findings, and the pro-drug movement driven both by the counter-culture and more recently commercial interests.

4. In the face of both of these biases, US federal regulations has made study of therapeutic use next to impossible. Studies of those using voluntarily in the community, however, is still possible.

5. Of the studies that have been done, most focus on the negative impacts. Not all of these studies are good, but many of them are. In fact, a good number of them are excellent. I'm not saying it's a fair fight, but that is the state of the science in 2015.

6. Perhaps, in time, as the playing field is leveled and good randomized controlled trials with strong blinding can be conducted, high-quality evidence for cannabis as a legitimate therapy can happen. That has not yet happened.

7. Despite the absence of evidence, many people are making lots of money off of cannabis, and have a strong incentive to promote this message regardless of the evidence (or lack thereof).

8. As the benefits are mostly unknown, and the risks are quite well known (based on lots of poor research but also quite a bit of high quality research), I cannot recommend medical marijuana at this time.

9. This is a moving target. I will need to continue to follow research trends, and my recommendations will change based on available data.

I hope that is more explicit.

Also, I know it's ad hominem, but I would be remiss not to point out that linking to reddit and wikipedia is not nearly as strong as pointing to well-conducted primary literature sources. Also, take a look at the reddit link you posted. The ratio of negative outcomes of use to positive is very high.

[bryans]

I appreciate that you have clarified your reasoning, and I certainly don't intend to insult, but I really feel there is some amount of cognitive dissonance going on here. For example, from your original comment and new comment:

> but no amount of enthusiasm changes the fact that high-quality research hasn't happened yet.

> I didn't say that all positive evidence is low quality

You are now conceding that there is high-quality research, but have since made more claims which are completely dismissive of that evidence. So, while I wouldn't argue with most of the points you just made, I still feel that your basis for dismissing positive research is flawed, at best.

The purpose of linking to Reddit was to provide an encompassing list of the published papers. It isn't a list of comments from random people on the internet, it's a list of scientific journals and websites which you, yourself, would recognize as being respectable sources. Likewise, the purpose of linking to Wikipedia entries was to give an overview or example. You are more than welcome to scroll to the bottom of the page and look at the actual sources for that information. It is unreasonable to insist that someone provide hundreds of sources at the bottom of a comment, when they are already consolidated elsewhere.

As to your point about negative results being more likely or common than positive ones, I don't see how that has anything to do with the topic at hand, which is that you seem to be convinced that positive claims are either flawed or tainted to the point of being illegitimate. Even if 99 out of 100 research efforts resulted in negative outcomes, that is not a reason to dismiss the one. Just as it is not a reason to dismiss positive research based on some (or even a majority) of it being supported or influenced by third parties.

[phren0logy]

You are right to point this out as contradictory, and I'm happy to clarify. It's more a product of trying to reply quickly.

Often in medical research, we see early high-quality studies purporting an effect. As a recent example, fish oil for hyperlipidemia. Positive studies (meaning ones that show an effect beyond placebo) are more likely to get picked up for publication, and ones that show new/interesting findings even more so. But the general trend, for nearly everything, is that continued research shows less effectiveness than the original studies. All too commonly, the effect with more and better studies becomes nearly indistinguishable from placebo. The media is very fond of pointing out this apparent "fip-flopping" as evidence that scientists are idiots.

That's where we are now with marijuana research. A handful of high-quality studies is a compelling start for more research, but not a basis for a robust conclusion, especially in the face of the large body of evidence for harm. Fish oil does not have that degree of harm, for example, so the early studies of effectiveness could meet a threshold of risk/benefit much more easily.

Hope that helps.

The reddit link does indeed have a bunch of peer-reviewed studies, but they are of highly variable quality. Not all articles, regardless of journal, are great. The negative outweighing the positive was related to my observation of the bias of cannabis research, and as you rightly point out that does not preclude a well-conducted body of research on a specific indication (for example, pain) from demonstrating an effect beyond placebo.

[bryans]

I think we are on the same page now.