California Cannabis Research Medical Group


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Winter/Spring 2005
Journal of the California Cannabis Research Medical Group

Approval as a Botanical Drug

By an FDA Consultant
I’ve never heard anyone at a drug company or FDA talk about medical marijuana, but there’s a lot of useful experience with other botanicals.
The first step in qualifying a product for medicinal purposes, here or in any other developed country, is to have a well-defined product, and this is where most botanicals have difficulty. Even a botanical with a strong claim for homogeneity (e.g., one made in huge, well-mixed batches, with some sort of convincing standards to control batch-to-batch variation) would be suspect; it must contain many chemical species, and it’s unlikely that all are useful or even benign.
Why not hold out for a better-defined preparation? Opium and digitalis leaf were both important, but regulators and clinicians feel that they are on firmer ground with morphine, codeine, digoxin, or digitoxin. It might have turned out that morphine works only in the presence of codeine, and so on, but I don’t know of any example where anything like that is the case.
There is no legal basis for FDA recognition of the differential cost of one medication over another, so moderate difficulty in separating the components of a botanical does not elicit any bankable official sympathy.
On the other hand, many so-called ‘pure’ substances are in fact racemic mixtures, and there is only tepid interest in specificity at the enantiomer level. Even returning to botanicals, the heterogeneity issue would be tractable if there were solid proof of safety and efficacy, and if separation of the active components appeared to be extraordinarily difficult. Suppose that a sponsor presented data to that effect to FDA.
That’s the point at which the FDA would start to hear from outsiders in the Administration and in drug companies. The Administration would be able to weigh in first because an application before FDA is not publicly discussed until an (optional) Advisory-Committee meeting, late in the course of review. Before then, the Administration could quietly arrange that the application be rejected. I would have regarded this possibility as far-fetched until this year, but all things are possible with Bush.
The drug companies might chime in at an Advisory-Committee meeting, but it’s hard to imagine a scenario in which things got that far. If it were agreed that some easy-to-produce version of medical marijuana could be considered by FDA, then its sponsor would face two problems, one much more serious than the other.
The easy problem would be opposition from drug companies with competing products, but aspirin has always held its own against the brand-name NSAIDs, and even within the aspirin business, Bayer has made no serious attempt to drive the cheaper brands from the field.
The more serious problem is that if marijuana were approved, then the original sponsor would have no effective way of making any money from it. This is the reason why newer uses of aspirin are rarely studied.
You ask if there are any significant differences between the FDA and the UK’s Medicines and Healthcare products Regulatory Agency. The main difference is that the FDA is much bigger, so FDA is the only drug-regulating agency in the world able to look at raw data instead of working from the summaries provided by academic experts. Also, there are at least a few deep thinkers at FDA, but in my experience I came across only one at any other drug-regulating agency, and she was from the German agency, not the UK.
Some other agencies (notably that of Australia) have arms that look at cost-effectiveness, unlike FDA. Some (notably that of Germany) have arms that look at various folk medicines (homeopathy, etc.) by different standards.

Another Indication for Sativex

GW Pharmaceuticals reported a favorable result in a phase 3 trial of Sativex involving 177 patients with severe cancer pain who were not getting adequate relief from opiates. Sativex is a cannabis-plant extract containing approximately equal concentrations of THC and CBD (cannabidiol). Patients in the study continued taking morphine and added either Sativex, a placebo, or another plant extract high in THC (all sprayed into the mouth). Some 40% of the patients taking Sativex reported pain reduction of 30% or more —significantly more relief than the placebo or the high-THC extract provided.
The oft-repeated myth that Marinol (synthetic THC) contains the active ingredient of marijuana is dispelled by this and other studies showing that CBD plays a beneficial role.
GW’s application to market Sativex has been denied, to date, by the Medicines and Healthcare products Regulatory Agency (MHRA, the UK equivalent of the FDA). GW submitted data from clinical trials showing that Sativex reduced spasticity in multiple sclerosis, but in Dec. ’04 the Committee on Safety of Medicines (CSM), an advisory body to the MHRA, questioned the “clinical relevance” of the reduced spasticity (its meaning to the patients, a fuzzy concept) and required a confirmatory study.
GW is carrying out the extra study and also appealing the rejection of Sativex to the Medicines Commission, the senior advisory body to the MHRA. Several of the doctors who conducted the trials have expressed dismay. Derick Wade, Professor in Neurological Rehabilitation, University of Oxford, an authority on MS, said, “I have treated more than 60 patients in clinical trials with Sativex. We have seen improvements in spasticity, and in other symptoms, usually sustained for many months. For patients, relief of spasticity is, like relief of pain, a substantial benefit in its own right. Many of those involved in the studies had already tried all other available treatments and so I believe Sativex is a valuable treatment option for people with MS whose spasticity is not yet adequately controlled.”
Is GW Getting the Runaround?
Is GW Pharmaceutical getting the kind of runaround from British regulatory authorities that Americans interested in developing cannabis-based medicines get from NIDA, the DEA and HHS?

The British government would treat him fairly, Guy assured us. He had no doubt about it.

GW founder Geoffrey Guy remarked our astonishment back in ’98 when he said he’d been granted a license by the Home Office to grow cannabis, develop extracts with different cannabinoid ratios, and test them in clinical trials. The British government would treat him fairly, he assured us. He had no doubt about it. There were hoops that had to be jumped through —levels of purity and consistency to be achieved, etc.— but he was a successful pharmaceutical entrepreneur and it was all do-able.
With every passing day that GW fails to get approval to market Sativex, our old cynicism is restored. The British government isn’t more enlightened than our own, just more sophisticated.
Big Pharma swallowed the UK regulators whole in 1989 when Margaret Thacher cut MHRA off from Department of Health funding and the drug companies undertook to pay for the approval and regulation of their products.
Recently it was revealed that an influential psychiatrist named Stuart Montgomery, a member of the Committee on Safety of Medicines, had advised Pfizer how to rewrite its application for Zoloft (called “Lustral” in the UK) and held off becoming a paid consultant until after the approval had gone through so he wouldn’t be disqualified from voting. That level of coziness between the pharmaceutical companies and the CSM is very ominous. The more influence Pfizer et al have over the British regulators, the longer the runaround GW —and thousands of MS patients— can expect.



O'Shaughnessy's is the journal of the CCRMG/SCC. Our primary goals are the same as the stated goals of any reputable scientific publication: to bring out findings that are accurate, duplicable, and useful to the community at large. But in order to do this, we have to pursue parallel goals such as removing the impediments to clinical research created by Prohibition, and educating our colleagues, co-workers and patients as we educate ourselves about the medical uses of cannabis.
The Society of Cannabis Clinicians (SCC) was formed in the Autumn of 2004 by the member physicians of CCRMG to aid in the promulgation of voluntary standards for clinicians engaged in the recommendation and approval of cannabis under California law (HSC §11362.5).

As the collaborative effort continues to move closer to issueing guidelines, this site serves as a public venue for airing and discussing these guidelines.

Visit the SCC Site for more information.