What is the best medical marijuana?
January 25, 2010
A Twitt from a currently ailing Abel Pharmboy alerted me to this article in the Colorado Springs Gazette.
A cannabis festival in Aspen this spring will be the first in Colorado for approved growers to put their strains in a contest. The Western Slope Cannabis Crown will have about 50 medical marijuana growers enter their strains of weed. The marijuana strains will be diagnostically tested for their THC levels.
Fascinating. So the THC (one assumes Δ9-Tetrahydrocannabinol, the psychoactive one) content is the key to the “best” medical marijuana is it? Odd because there is always this huge outcry about how the synthetic capsule version of pure Δ9-THC doesn’t do the trick, right? I mean sure, higher active content means smoking less natural material so that sounds cool but c’mon. Are we really going to see significant clinical effect of having 10% higher Δ9-THC? When the evidence that the smoking itself is bad isn’t really all that good as yet? And, we’re only talking people that suffer from a major debilitating disease or condition, right?
Aaaaanyway, perhaps they have some other measures of “best”…
Growers at the Colorado contest will also be able to sell to medical marijuana patients, who will vote on a “people’s choice” strain. There will also be entries for edible forms of marijuana, such as cannabis-infused brownies.
Hmm. Well I guess perhaps for acute nausea we could be safe. I mean maybe some active chemotherapy patients will schlep their nauseated behinds up to Aspen to sample the available kind medications. Maybe. I guess.
Or maybe the study subject population random assortment of those that managed to score medical marijuana cards will just report on the kindness of the bud. Your call.
DrugMonkey 
January 25, 2010 at 6:40 pm
Let me prephase this by saying that I don’t particularly advocate the use of medical marijuana, and as a future EM doctor, it’s never going to be something in my formulary.
Still I’m pretty sure you’d be able to correct me here. The argument our profs gave for why marinol might not be as effective as marijuana was that the pharmacokinetics of a drug absorbed via the lungs wasn’t at all the same as a pill. I’m fairly certain the same argument was used for why nicotine gum isn’t as effective for some people at curing cravings as smoking. Given that argument, i’m confused why noone has talked about like, a nebulized form of synthetic THC, to avoid the whole smoking thing, and administer a consistent dose, that could be accurately tested and so on.
Is there a reason any of what I’ve just said there is terribly off base? It just seems like that is how we do things with other drugs – we don’t give people pacific yew bark, we give them taxol.
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January 25, 2010 at 6:49 pm
aww, do we have to spoil the fun so early?
Ok.
Yes, I think there is probably something to do with the smoked route but I’d argue it is not peak dose. In high doses THC is pretty aversive and I would suspect that it has to do with controlling the dose, a thing which smoking seems to be good for. IMO. Sativex, a natural products extract formulated for oral mucosal spray delivery, has high cannabidiol which might be acting to head off adverse effects of delta9-THC itself as I’ve commented briefly. Although allegedly most available street marijuana has next to no cannabidiol, maybe, perhaps other cannabinoids have a similar modulating effect on adverse responses to high dose delta9THC?
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January 25, 2010 at 8:05 pm
Medical marijuana is the “hip” version of herbalism or naturopathy, where it’s argued that the adulterated active ingredient found mixed up with all the other hundreds or thousands of contaminants in the plant is “better” or more effective than the purified pharmaceutical product.
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January 25, 2010 at 8:18 pm
This is probably one of those “tell me where I’m wrong” questions but here we go anyways.
I was under the impression that the issue with Marinol was not that hundreds of contaminants were removed in favor of the active ingredient, rather that some of the other molecules in the plant were also active ingredients.
Pour Favour, enlighten me.
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January 25, 2010 at 8:22 pm
@Drugmonkey
I’m not sure what you mean about spoiling the fun… I wasn’t really making an argument for peak dosage, I was actually asking you to educate me, all I know is that our cancer patients who use marinol don’t particularly love it and prefer zofran, and most of our attendings are afraid to use marinol anyway.
I hadn’t actually heard of sativex, that’s interesting. Now, are you saying that you’d approve of Sativex, or some sort of other mucosal/nonpill formulation, properly tested, or was that just a throwaway reference?
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January 25, 2010 at 8:49 pm
Orac:
Is that a serious comment? Do you really imagine that a straight up prescribed meal of carbs, vitamins, lipids and proteins is, inherently, better than a decent slow meal with a huge amount of random variation, and a bit of wine?
One thing is to rail against the untested and unproven elements of herbalism, etc… But to fantasize that, in general, simple compounding is superior to complex and stochastic treatment is so very 19th century science. Kind of crackpotty, the kind of medical attitude that lead to the wonders of replacing mother’s milk with formula.
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January 25, 2010 at 9:04 pm
Why would you argue that stochastic treatment good treatment?
You are using that word, I do not think it means what you think it means.
Put another way, why would you argue that “treating” someone with a complex mix of poisons a plant has developed as defence against being eaten by animals without purifying, identifying active ingredients, and carefully titrating a dose would be superior to “simple compounding?”
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January 25, 2010 at 9:10 pm
Medical marijuana is the “hip” version of herbalism or naturopathy
Ignorant prejudiced rubbish.
Very disappointing coming from you, Orac.
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January 25, 2010 at 9:29 pm
I was under the impression that the issue with Marinol was not that hundreds of contaminants were removed in favor of the active ingredient, rather that some of the other molecules in the plant were also active ingredients.
That is but one argument, yes. See the one from frog@#6 for another one of them. It is not impossible and indeed the Sativex story makes a claim for one those “inactive” elements having a useful therapeutic effect.
our cancer patients who use marinol don’t particularly love it and prefer zofran, and most of our attendings are afraid to use marinol anyway.
Yeah, delta9 has some adverse effects…if all you are looking for is nausea control. Many of them aren’t looking to get a buzz, I would assume. Also, if you get a high dose it can be unpleasant, right? So if dose control is not good, or if the dose needed to relieve nausea is close to or above the threshold for feeling a really adverse effect- no good as a medication. It is my hypothesis that a route of administration that takes one bolus dose and shoves it on board is going to be inferior to a series of self-controlled inhalations that may permit the user to stop dosing once the critical threshold for relief has been attained.
are you saying that you’d approve of Sativex, or some sort of other mucosal/nonpill formulation, properly tested, or was that just a throwaway reference?
It IS approved in some countries and approval is being actively sought in the US. My opinion really has no bearing. We have plenty of addictive medications that are approved under the usual FDA process. I have no objections to that process on grounds of dependence liability itself.
I am fascinated by the neurochemistry though. It is a natural plant extract that depends on clonal plant material which is unusually high (for recreational cannabis anyway) in cannabidiol. Resulting in approximately equivalent cannabidiol/delta9 THC levels if I have it right. Dunno what proportions of other cannabinoid compounds are in the extract. The history of the company had, I believe, a delta9 heavy spray and a cannabidiol heavy/exclusive spray* in trials and this 1:1 sativex is what emerged. There’s some lit, but I’m not super up on it..cannabidiol is doing something if they are to be believed. what? possibly an anxiety-reducing effect.
*it isn’t entirely clear to me but it looks like maybe they grow two clonal marijuana strains developed for those purer products and mix them for sativex (?)
it’s argued that the adulterated active ingredient found mixed up with all the other hundreds or thousands of contaminants in the plant is “better” or more effective than the purified pharmaceutical product.
Right and I must emphasize points made by Abel Pharmboy, Orac and PalMD on occasion that IF there are active ingredients in a natural product, they should be able to be identified, proved in trials and used alone or in combination in a pharmaceutical product. There is no mysterious advantage about “natural” sources and/or unpurified delivery media** of active ingredients. If it passes the usual standards, it is not “alternative”, it is medicine.
**you guys know what it takes for andean folk to get an active buccal dose of cocaine out of a coca leaf, right?
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January 25, 2010 at 9:39 pm
I’ve heard it’s a good drug for people with PTSD. Hmmm. Maybe I should re-think this whole responsible-citizen thing.
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January 25, 2010 at 9:43 pm
Some clever people have manipulated the legal system and found a way to enjoy a benign alternative to alcohol without the government putting them in jail, stealing all their stuff, and looking the other way while they’re RAPED and BEATEN.
Other methods of keeping the jack booted thugs at bay have failed. Medical marijuana cards are one of the VERY few victories for personal freedom in recent times. Smug doctors fighting medical marijuana are helping the totalitarians to destroy people’s lives and they should be ashamed of themselves.
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January 25, 2010 at 11:25 pm
inverse_agonist –
Actually, several of these self-same doctors have implied, if not outright stated support for outright legalization for recreational use. Asshats who are willing to consider medical marijuana some sort of victory, give lie to the very notion and ought to be ashamed of themselves.
And for the record, before you go off on assumptions about my attitude – I have been to jail for cannabis, I support the legalization of cannabis and other illicit drugs and yes, I have in fact gotten my ass beat by the cops, for engaging in peaceful protest, sparking a joint in front of the MI state capital building. That would not, however, be the only time I have been assaulted by cops for smoking pot.
I have also remodeled part of a warehouse to create a more efficient growing space for a cooperative in Portland and had the right to medical cannabis in OR.
But the fact of the matter is, that while cannabis does seem to make some people with certain conditions feel better – able to develop an appetite and keep food down, it is not some bloody damned magical cure all. It is flat damned ridiculous that I was able to qualify for a card. I have no problem with someone on HIV drugs smoking or ingesting pot – I have lived with someone who was HIV positive and volunteered my time to help people with HIV. Cancer – same thing. Glaucoma – have at it and I can even put up with you calling it medicine if you need to.
But my bad back and trashed knees? Seriously? If I am not mistaken, I probably qualify for the card here in MI. In spite of the fact that since I have been working out, the pain is easily managed with the occasional tylenol – not that it makes me pain free, just makes it tolerable. More really, than the weed ever did.
Cannabis makes many people feel better. So does crack – that doesn’t make it medicine.
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January 25, 2010 at 11:29 pm
i really don’t get how this kind of event serves in the least to advance even the idea of marijuana as medicine. srsly, a “medicine” tasting fair? a people’s choice voting event on which “medicine” they like best? come on. consider if that went on with opiates or something.
i do find the pharmacokinetics discussion fascinating, and i think DM has it very well covered. THC is considerably degraded in low pH of the stomach, undergoes a lot of first-pass metabolism (with several active metabolites) and then proceeds to equilibrate with fatty tissues on its way up to the brain. so not only do you lose the immediacy/metering of the effect by not taking it in through the lungs (which is something to speak of in and of itself) but you lose a substantial amount of the drug to normal absorption and distribution processes, the specific amount of which will vary by individual as well. this leads to a depot effect, in which a lower blood concentration is present for an extended time as drug leaches out of fatty tissues, but that concentration relative to that needed for a therapeutic effect is likely irrelevant.
on first exposure, such as someone who is dealing with nausea trying oral THC for the first time, using a dose that is too high can be quite aversive. it’s associated with anxiety/panic. which is why the dose metering is nothing to sneeze at.
there is something to be said for the multi-cannabinoid molecule argument, but the variability of any given cannabinoid compound in differing strains of cannabis makes me wonder about how real it is when so many strains with these variabilities are all purported useful for condition x. CBD is a topic of interest, most certainly.
and the mention of use in PTSD… it’s of interest, but i haven’t personally seen much in terms of real evidence. and i have looked. there’s preclinical evidence of a role in fear extinction in rodents, but that’s a very large bridge to make. given the chance of an increase in anxiety, and some of the cannabinoid signaling-stress signaling interactions, i would consider that very carefully.
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January 26, 2010 at 11:52 am
I completely agree with Orac, DM and others on the issue of marihuana as medicine. However, it is interesting that two weeks ago a paper was published in Molecular Cancer Therapeutics about the potential of certain cannabinoids in the treatment of glioblastoma.
Cannabidiol enhances the inhibitory effects of Delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival.
Marcu JP, Christian RT, Lau D, Zielinski AJ, Horowitz MP, Lee J, Pakdel A, Allison J, Limbad C, Moore DH, Yount GL, Desprez PY, McAllister SD.
Mol Cancer Ther. 2010 Jan;9(1):180-9. Epub 2010 Jan 6.
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January 26, 2010 at 12:40 pm
shorter Rivlin: phospho ERK proves Orac RONG*!
Seriously, I know the complexity is a PITA to deal with, but applying two compounds in combination *frequently* makes *enormous* differences. Though I may be slightly biased by spending way too much time looking at phospho ERK, interferon gamma, and IL-12.
*Note: I realize this depends on a willful misunderstanding of Orac’s likely actual position. But it’s funnier that way.
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January 26, 2010 at 12:47 pm
becca,
Orac is correct when he points to hundreds, maybe thousands of cannabinoids and other compounds in marihuana’s smoke, which is a big difference from combining THC with cannabidiol.
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January 26, 2010 at 1:37 pm
I knew Rivlin was an old fuck, but I didn’t know he was a hundred and fucking fifty!
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January 26, 2010 at 2:08 pm
From the Webster New Collegiate Dictionary:
marijuana also marihuana
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January 27, 2010 at 4:31 pm
DuWayne,
The fact that medical marijuana cards are handed out with a wink and a nudge to anybody who, like, twisted their knee that one time is a GOOD thing. It’s de facto legalized the drug in places like Los Angeles. It’s a political victory. Making the cards hard to get misses the point entirely. They should go to anybody who wants them. Marijuana could be as medically useful as homeopathy and the principle would remain the same.
Anybody should be able to walk to the store, buy some marijuana, and decide for themselves if it’s helping them or not (or whether the trade-offs are worth it). That’s not going to happen immediately, for political reasons, so we should look to the anti-abortion movement as an inspiration.
It hasn’t been politically possible to get Roe v. Wade overturned. That doesn’t mean the anti-abortion movement hasn’t succeeded in causing de facto bans on abortion in many places. They’ve done it indirectly, with a lot of nonsense about pharmacists’ right to refuse customers, waiting periods and parental notification laws, etc. On paper you can get an abortion, but in practice you can’t in certain parts of the country.
Medical marijuana is the same way. On paper marijuana is illegal, but in practice you can go anywhere in Los Angeles and buy some over the counter without police interference. Mission accomplished. Of course this runs the risk of political backlash, but in practice what we see is open discussion of just dropping the pretense and starting to tax it.
This might seem intellectually dishonest, but it’s not any more so than developing things like THC pills and Sativex spray because they’re “medically necessary.” They’re only “necessary” in the sense that nobody can generate millions of dollars in revenues by patenting the idea “put the cannabis in the vaporizer and inhale.”
What bothers people about the idea of people smoking marijuana for relief is not the fact that the smoking is medically dangerous (compared to common practices like off-label prescription of antipsychotics? Really?). It’s the idea that people don’t need a doctor to hold their hand every time they make a minor decision about their own health (“consult your doctor before beginning any exercise program”).
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January 28, 2010 at 2:20 pm
Of course this runs the risk of political backlash, but in practice what we see is open discussion of just dropping the pretense and starting to tax it.
Open discussion where? Have I somehow missed the discussion in the CA legislature? Or on the pop media in CA? Did I miss the ballot measure supporting it, that actually has legs? Short of that, there is open discussion about this in a lot of places that is completely meaningless for lack of real support.
This might seem intellectually dishonest, but it’s not any more so than developing things like THC pills and Sativex spray because they’re “medically necessary.” They’re only “necessary” in the sense that nobody can generate millions of dollars in revenues by patenting the idea “put the cannabis in the vaporizer and inhale.”
I am not entirely sure I disagree with you on this. That doesn’t mean that either is the right way to go about it. For the sake of ease of use, there are a lot of people who would like pills or spray – but that is a different story altogether. (one of the highest demand items from the coop I worked with was hash tablets that could be ingested or stuffed in a vaporizer or pipe – the highest demand was food grade, the suppositories were also rather popular)
I agree with you – a person should be able to walk into a store and just buy what they want. That includes alternative preparations. That does not mean playing these games of “medical cannabis,” wink, wink, nudge, nudge are right. I would argue that it is more of a roadblock to general legalization, which is why it is so heavily abused.
What bothers people about the idea of people smoking marijuana for relief is not the fact that the smoking is medically dangerous (compared to common practices like off-label prescription of antipsychotics? Really?). It’s the idea that people don’t need a doctor to hold their hand every time they make a minor decision about their own health (“consult your doctor before beginning any exercise program”).
So it is all a conspiracy by big pharma and MDs? Seriously? I am not going to say there aren’t conspiracies involved with our laws regarding cannabis and hemp – there have been and there are. But you’re way off base as to the foundation of those conspiracies.
MD’s who are not very keen on medical cannabis are not keen on it for a lot of very good reasons. Several were listed in this comment thread. Are you honestly going to sit here and impugn the integrity of the doctors on this thread out of hand? Before you do that, you might consider actually paying attention to what they are saying about this and other plants with possible medicinal properties. Agree with them or not, they are not lying – they are expressing a consistent position and one that is far more nuanced than you seem to believe.
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January 29, 2010 at 12:02 am
[i]The fact that medical marijuana cards are handed out with a wink and a nudge to anybody who, like, twisted their knee that one time is a GOOD thing. It’s de facto legalized the drug in places like Los Angeles. It’s a political victory. Making the cards hard to get misses the point entirely. They should go to anybody who wants them. [/i]
Except this misses another point entirely.
My job is to care for the patient, not to overthrow the system.
When I am asked to sign my name to a medicinal marijuana order (I’m not in CA), I am clinically endorsing it. I’m fussy. I think MM isn’t appropriate for my patients with certain conditions.
I am supposed to make effective treatment decisions. If I don’t think MM is the appropriate substance for your condition, I’m not going to authorize it. Not as a moral stance, not even because OMG I Might Get Sued – but because it’s the wrong thing to do and it’s stupid practice.
I have a few patients for whom I have authorized MM orders. MS spasticity, and a clear pattern of that worsening when not ingesting cannabis and then improving when restarting. HIV wasting. You get the idea.
As for DuWayne’s ankle? Yeah, Tylenol works well for me too, DuWayne. Lots of other options.
That’s an individual discussion between each person and his or her doc.
But my job is not to be part of anyone’s political victory. It’s to take care of my patients using evidence-based methods that I believe are appropriate and safe, and to stay up to date on the evidence. Sativex is definitely an attractive alternative – not because Marijuana Is Evil, but because of the metering/standardization – and also because I see a fair number of people towards end of life, when getting them to ingest anything is hard enough.
I think that in my area, at least, some of the resistance to MM is coming from providers who resent the political overtones (note: but have no objection to legalization), and also the use of scarce office visit time for MM requests.
Silliness: If amoxicillin were a C-II for some reason, but readily available on the street, and there were a big “Legalize Amoxicillin” movement, and the state gave me the option for a ‘medical amox’ order… I’d get darned tired of people coming in most days saying “Yeah… I get… a lot of ear infections? or strep? or what kind of infections was it… oh, yeah, ear! So, see, I need an amoxicillin card!” and then waving their written list of symptoms at me.
(I wish I could say I was making that exchange up, but only the diagnosis/substance details have been changed.)
No doubt many people would have a legitimate need for amoxicillin. I know that resistance in my community is through the roof anyway, and most people are familiar with the concept of resistance and even know how to use it appropriately.
But if I examine you and I see no need for amoxicillin, I just… don’t want to write what is, basically, a rx for amoxicillin. Don’t ask me to. I won’t. Cheer up, I also won’t give you homeopathic treatment. I’m just interacting with reality.
If you wanna buy street amoxicillin, well, OK, I can’t stop you, it’s quite available. Don’t ask me to medically ‘bless’ your use.
Goodness, I get all ranty without my coffee when I’m on call. Off to the lounge with me.
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February 15, 2010 at 7:21 am
Yes I agree with Some clever people have manipulated the legal system and found a way to enjoy a begin alternative to alcohol without the government putting them in jail, stealing all their stuff, and looking the other way while they’re RAPED and BEATEN.
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