Monday, 20 February 2017

#OffLabel & #ClinicSpeak: nabilone instead of street cannabis

Off label Nabilone is a treatment option for MS-related spasticity #OffLabel #ClinicSpeak #MSBlog

I grew up in apartheid South Africa and recall the sweet smell of 'dagga' (SA street lingo for cannabis), that wafted from the workers, or gardeners, quarters at my primary school. The workers, who were all black at that time, generally used cannabis in large amounts to survive the drudgery of their apartheid existence. They were all migrant workers with families who tragically lived far away. They barely survived on a minimum wage, doing menial unskilled labour. Their bloodshot eyes, clouded awareness and sweet bodily aroma made me aware  at a very young age, that the torpor due to their excessive cannabis use could not be good for either their physical or mental health. Apartheid has many wrongs to answer for; the mental and physical health of the majority comes close to the top of the list.  

It would be decades later as a MS researcher that I would discover, from the MouseDoctors, that cannabis could have real benefits for pwMS. Our research led to the development of THC as a symptomatic treatment for pwMS and should also have led to the development of THC as an add-on neuroprotective drug for people with more advanced MS. Unfortunately, the phase 2 neuroprotective trial we were involved in was done at a time when we did not have the insights we now have about the EDSS (not fit for purpose), asynchronous progressive MS, nor that MS is a length-dependent axonopathy. I am confident that if we had the opportunity to do a trial of THC as an add-on neuroprotective agent in more advanced MS we would design the trial very differently and have more than a fighting chance of getting a positive result. 



Although we do have a licensed cannabinoid for the treatment of MS-related spasticity we can't prescribe it under the NHS. Sativex, which contains the active ingredients of cannabis (THC and CBD), cannot be prescribed as it has not been 'NICEd'. Sativex has not bee shown to be cost-effective. This is very frustrating as so many of our patients would benefit from this drug. This very unfortunate situation forces many pwMS in the UK to buy street cannabis. As a neurologist I can't sanction this; cannabis is illegal in the UK and I would be putting myself at risk if I prescribed, or even recommended, street cannabis. I am aware that in other parts of the world, where cannabis has been legalised for medicinal use, neurologists can prescribe cannabis. 

How to get around this problem in the UK? I have recently started prescribing nabilone, a licensed small molecule drug that works on the CB1 receptor. CB1 is the cannabinoid receptor responsible for THC's anti-spastic effects. Nabilone is licensed in the UK for the control of nausea and vomiting, caused by chemotherapeutic agents and used in the treatment of cancer. I have recently had two patients who were using excessive street cannabis to control their spasticity and nocturnal leg spasms. Nabilone at a dose of 2 mg twice of day has allowed both these patients to stop smoking street cannabis and both have noted improved control of their spasticity. On the plus side both these patients have stopped smoking cannabis, which in itself has health benefits in that they are not exposing their lungs to smoke. 

Please be aware that the use of off-label nabilone is not ideal and in a perfect world we would have unfettered access to Sativex. What is galling is that Sativex was developed, and made, in the UK by a small start-up Pharma company. If the NHS does not support its own, UK-based, Pharma industry what hope is there for Pharma UK? This is in distinct contrast to France and Germany, where the politicians go out of their way to make sure their national healthcare systems support their own, home-grown, Pharma Companies. Is this nepotism? Is this the reason Trumpster's want to the UK to shutdown NICE?  

Please note that some patients are prescribed Sativex in the UK under the IFR (individual funding request) system, via patient access schemes paid for by individual NHS Trust's and not NHS England, or via the private prescription route. 

CoI: multiple

30 comments:

  1. Some pwMS are buying CBD oil which they say combined with physiotherapy is helping their MS symptoms.

    In the Mirror newspaper 2nd Jan 2017, there was an article that CBD part of Cannabis is to be classed as medicine in the UK.
    'Cannabis ingredient to be classed as medicine in UK as it helps calm patients down'.

    The Medicines & Healthcare products Regulatory Agency (MHRA) said cannabis-based ingredient cannabidiol is an effective medicine in calming people down. (Mirror 2nd Jan 2017).

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    1. The question is which symptoms. CBD does not work in the same way as THC

      I think you will find that the CBD oil often contains THC, certainly the Sativex CBD contains THC.

      It has been reported to affect epilepsy, our work (Pryce et al. 2015) gives a clue why that could be so.

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    2. CBD is really 'in' there's a lot of it around. So, having heard all the wonder stories I wanted to see if it would help with my horrible central pain and did a little micro trial at home (n=1,p=0.5) haha ;-)
      Method
      Month 1 C sativa (hemp) oil daily (high CBD, no THC).
      Month 2 C sativa var Indica oil daily (less CBD, some THC)
      Month 3 C sativa var Indica paste (as month 2 but higher dose)
      Results
      Despite desparately wanting it to work cannabis did absolutely nothing :-(
      Conclusion
      Social media is full of anecdotal CBD miracles and lots of MSers are taking it. I so wanted it to work for me! All I can say is never underestimate the power of placebo ;-)

      In UK, I understand legit CBD suppliers have to provide MHRA with regular analysis results demonstrating max 0.05% THC content.
      Sativex contains (target) 2.7mg THC and 2.5mg CBD per spray. GW pharma have gone for the synergy of whole bud extract approach. Personally I think it's better to know your receptor, isolate the active compound and deliver an exact dose. Digitalis extract anyone?

      Ps sorry I am so late with comment, ProfG probably has a name for people like me ;-)

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    3. We spent quite abit of time with CBD as a symtomatic treatment for spasticity and got nowhere. We did find a neuroprotective effect but put it with THC and the effect with THC reduced.

      There is so much rubbish said about CBD, historically the pot in the US had very little CBD but the claims by people with MS on both side of the pond were similar, telling us, THC is the doing the business.

      Once you find a mechanism for ask if it work, in North America the claims are for epilepsy not neuropathic pain.

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  2. As a result of the popular pressure to regulate and release medicines based on Cannabis in Brazil, Anvisa (which is the National Health Surveillance Agency) has regulated and released the controlled use of Sativex and analogues, including CBD.

    Unfortunately it seems that the "hierarchical high" in the whole world seems to only listen to the popular will when it is literally pressing ...

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  3. In the US you can also use Dronabinol another CB1 agonist:

    https://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf

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    1. Dronabinol is a trade name for THC it is also known as Marinol. It is not licenced in the UK.

      CBD is not a CB1 agonist and if you believe the the pharmaclogists it is a weak antagonist. This is maybe why it is reported to reduce the physhoactive effects of THC. Therefore it blocks the therapeutic effect of THC. You can't have it both ways...its called biology

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  4. We have knowledge of what amounts to state sponsorship over and above any sensible grant award.

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  5. Hmm, neuroprotective properties of cannabis... the street experiment tells me otherwise - are regular long-term cannabis users (not pwMS) experiencing any "neuroprotective" benefits? I have not noticed any so far -actually all observations point to the contrary ( I work in healthcare).

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    1. You can't argue with the science/biology of the neuroprotective properties of the endocannabinoid system and cannabinoids, which is well documented and replicated. If you base your experience on stoners you are liable to confuse the issue.

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    2. MD2, do you have any previous posts outlining those effects and the related studies? And if not, could you put one together?

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    3. We have published on the neuroprotective potential in a number of publications. Importantly if you do not have a cannabinoid system your are liable to neurodegenerative. We first reported this in Pryce et al. 2003

      We have an excellent review of this in MSARDS. Maybe I will get this uploaded on QMUL website if it is not open access.

      The problem is the cupid trial killed this line of research.

      Cannabinoids affect synaptogenesis

      Delete
  6. Don Giovannoni, I'm so busy at the moment but have a lot to say.

    I will post a long comment soon.

    ReplyDelete
    Replies
    1. We await your no-doubt brilliant contribution with bated breath.

      Delete
    2. MD2...your reply should surely have been

      fo shizzle

      Delete
  7. Prof G, If you could prescribe street cannabis, i.e. if it was legal, would you?

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    1. Re: "Prof G, If you could prescribe street cannabis, i.e. if it was legal, would you?"

      No. The whole purpose behind licensed pharmaceuticals is quality and consistency. With Sativex you get a high-quality product, with street cannabis you don't. Street cannabis varies in quality and highly variable in relation to TCH content. Then there all the other impurities you have to deal with. I also try and discourage my patients from smoking, cannabis included.

      The Pharma industry is there for your safety. I would prefer to prescribe a licensed product and preferably an on label product. Getting a license and getting a label requires massive investment and innovation. We either reward this investment and innovation or expect, as Pharma has done in the recent past, to dis-invest from the UK.

      Delete
    2. Interestingly some of the impurity is bacteria. If you are immunosuppressed due to DMT inhaling bacteria may not be the best thing.

      However with legalisation on cannabis unlike the cartel approach to MS drugs where the prices increase, in the states there is price competition making the cost go down.

      However if you look at the strengths of some of the so called medicinal cannabis then they are Taylor made to get one high. I think the levels in some are ridiculous.

      whilst I realise this is part of the efficacy for many and if you are not getting high you are taking suboptimal amounts. However,many people do not want to get high.

      We all know of the stoner personality that removes ambition..

      We have stopped going to some cannabinoid meetings as the scientists were being replaced by growers...Too many of them appear to sampling their wares. They claim it can do everything.

      You have the medical cannabis lobby and the recreational cannabis lobby. I don't think people should be prosecuted for medicinal use. However the recreational and medical use has become blurred.

      Sativex is having problems in the USA because they are being treated as a pharmaceutical needing to supply proof of efficacy. The legalise cannabis approach has got approval without showing real proof.

      Delete
  8. Are you somehow blaming apartheid for condoning excessive cannabis use amongst the South African black population?

    ReplyDelete
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    1. Re: "Are you somehow blaming apartheid for condoning excessive cannabis use amongst the South African black population?"

      Not really, all races used cannabis is apartheid South. It was illegal. However, in the mining industry the owners turned a blind-eye to cannabis use and also supplied massively subsidised alcohol to the miners. A sedated disenfranchised workforce were more malleable.

      The mine owners also scarily provided subsidised prostitutes for the workforce (I studied this with a colleague when I was running an epidemiology unit). The mix of migrant labour without their families, cheap drugs and sex was the powder keg that would lead to the HIV epidemic. Yes, apartheid, and its legacy, are one of the main drivers of the HIV epidemic.

      Delete
  9. This is your daily work to spout on .

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    1. Re: "This is your daily work to spout on."

      No it is extracurricular and not part of my day job. I do it out of hours.

      Delete
  10. I would mention that smoking is not the only way to use cannabis. There are a wide variety of vaporizers available that can operate at temperatures well below combustion and spare patients the vast majority of negative effects from smoking (fewer toxins, less tar, lower temperatures into airways). Now this isn't to say vaporizing is "risk free" as I'm sure it causes some minimal amount of damage, but there are also numerous benefits from better sleep, muscle relaxation, improved mood, etc. Not to mention is costs almost nothing compared to pricey prescription drug copies that don't even contain all the compounds.

    It seems to me the cost/benefit tradeoff of vaping is similar or better to many MS medications like alemtuzumab and natalizumab, so I'd suggest you at least reconsider your strong dislike of "street marijuana".

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    1. Re: "... cost/benefit tradeoff.."

      To make an assessment of cost/benefit you need data. You can't compare natalizumab/alemtuzumab with street cannabis.

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    2. I have seen a volcano in action (at a cannabinoid meeting in Canada, used legally by someone with a medical dispensation to use cannabis)...

      ...it was claimed to be smokeless...what a load of rubbish.

      The aspirin of the twenty-first century? I suspect a THC (THC/CBD) vape would do the trick, no need to use the plant?

      However in terms of heat the heat turns the THC acids into THC so I am told

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  11. It is the other effects of street cannabis that worry me. I have seen its effects upon my son and a friends his. It was not good, I believe these are psychotic reactions. Back in the day (circa 1970) you just got stoned on Moroccan now there is the possibility of going off the rails aas well.

    To my mind the side effects are sufficcient to stop me using street cannabis. Luckily I do not suffer spasticity so the problem has not arisen yet but ...

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    1. Back in the day morrocan was about 5percent THC now it can be up to 50percent. This gives a problem of pyschosis in some individuals. Even some of the CBD strains are high percentage THC.
      This makes it difficult to titrate and is Taylor made for the high.

      Delete
  12. For those people using street cannabis for MS, do you know the background of how it was produced? - the Guardian has an article today. Huge cannabis farm (in Wiltshire,UK) 'was staffed by trafficked Vietnamese teenagers'. Three teenagers were found working in slave-like conditions at former nuclear bunker in Wiltshire, police say.

    ReplyDelete

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