TL neuro

July 9, 2014

Medical marijuana, skepticism and the content of that marijuana

Filed under: Cannabidiol, Cannabis — mtaffe @ 1:08 pm

Physician Peter Lipson has posted an opinion on Forbes that expresses his skepticism about the benefits of medical marijuana.

Why I’m Skeptical About Marijuana’s Medical Benefits

In this article he criticizes a CNN bit by Sanjay Gupta on medical marijuana called “Weed2: Meet Vivian“.

From Lipson:

It followed the sad case of a young girl with a horrible seizure disorder and her parents’ struggle to get her help. According to Sanjay Gupta, they finally found some help with cannabis, and the piece documents their struggle to get their daughter the medicine that they believe is helping her.

He then goes on to make an assertion that I think is really flawed:

It makes for a great story, but it gives us no help in deciding if marijuana has any legitimate medical uses. A thorough search of the medical literature finds no good studies that support the use of cannabis or any of its constituents in seizure disorders.

I think there are certainly good studies that support the use of cannabis constituents and, pertinent to the “Vivian” story a compound called cannabidiol*.

The CNN story, and much other popular media coverage of the antiepileptic effects of cannabidiol is doing a serious, perhaps intentional, disservice by referring to “marijuana” only.

There is a published case report on “Vivian” (she’s “Charlotte” in the Case) by Maa and Figi. This specifies that the strain of cannabis being used to generate the crude extract that they are dosing with contains “a high concentration cannabidiol/Δ(9)-tetrahydrocannabinol (CBD:THC)“. I didn’t find a content analysis in the Case Report but an article in the Huffington Post contains aclaim from the grower/breeder developing what is now called the “Charlotte’s Web” strain of cannabis: “This particular plant has 0.5 percent THC and 17 percent CBD — or cannabidiol“. I’ll assume that is a valid statement, although of course we have no independent verification at this time.

We can see from Morgan et al 2010 [see Figure, left, and my blogpost] and from Burgdorf et al 2011 that 0.5% THC is really low for recreational grade cannabis. The North American Industrial Hemp Council, Inc claimsIndustrial hemp has a THC content of between 0.05 and 1%. Marijuana has a THC content of 3% to 20%“. A white paper from El Sohly, who grows the marijuana supplied by NIDA for research purposes attests to about a 1.6-1.8% THC content in the “low potency” research marijuana.

These analyses also verify that 17% cannabidiol is really high for a recreational marijuana strain. CBD appears to come in around 0.5% of the vast majority of street marijuana with a range of about 2-6% in the low proportion of high CBD strains identified in Morgan et al 2010.

In short, this “marijuana” which so bothers Dr. Lipson is not really “marijuana” in terms of what people tend to assume. Most particularly, it is not “marijuana” in the sense that we infer harms associated with substantial THC content. It would be better for understanding if media reports were very clear on this because cannabidiol (CBD) has never been found to be psychoactive in the sense of producing a high or any sort of dependence profile. In fact, it seems to counter* some of the effects of THC.

This brings us to whether any marijuana constituents have evidence for utility in seizure disorders.

Here are a few papers I pulled up on PubMed which attest to the fact that CBD can block seizure in rodent models.

Hill et al 2013 : Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

Jones et al 2012: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

Jones et al 2010: Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.

Martin et al, 1987: Structure-anticonvulsant activity relationships of cannabidiol analogs. [I had to go pull this NIDA Research Monograph off the departmental bookshelf, but it indeed reports that CBD is anticonvulsant]

Finally, there is a parent survey of people like the parents of Vivian/Charlotte. Porter and Jacobson (2013) surveyed a Facebook group dedicated to parents using cannabis (allegedly CBD enriched, but this was in no way verified). Of the nineteen surveys suitable for inclusion 10 reported greater than 80% reduction in seizure frequency and 6 reported 25-60% reduction.

The paper also references a mixed bag of prior clinical trials in adult populations. The authors cite Mechoulam and Carlini (1978) and Cunha et al. (1980) as reporting some beneficial effect of CBD. Ames and Cridland (1986) found no effect.

Not overwhelming evidence, certainly. The translation from animal models to humans may be overconfident at this point. And perhaps we may find that there are other cannabinoids in “Charlotte’s Web” strains (even the remaining THC) that may be driving any anticonvulsant effect.

But there is definitely some evidence. In my view it is sufficient evidence not to dismiss the notion that CBD might have use as an anticonvulsant medication.

___
*In full disclosure, I have a grant which is funding research in the lab to determine the degree to which cannabidiol can oppose the effects of Δ9Tetrahydrocannabinol.

Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia. 2014 Jun;55(6):783-6. doi: 10.1111/epi.12610. Epub 2014 May 22.

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3 Comments »

  1. I certainly saw these studies, but all they do is point the way to potential future investigation. None justify the use of cannabis or its constituents in a clinical setting. I’m certainly open to future evidence, but we aren’t even close to canabinoids for seizure.

    Comment by PalMD — July 9, 2014 @ 2:07 pm

    • I see. It read more to me like you thought we weren’t ready to justify even clinical trials at this point.

      Comment by mtaffe — July 9, 2014 @ 6:20 pm

  2. […] Medical marijuana, skepticism and the content of that marijuana […]

    Pingback by Cannabidiol fails to attenuate THC-induced hypothermia | TL neuro — November 23, 2014 @ 11:24 am


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