Reacting to a surprise laboratory finding that cannabidiol (CBD), one of the many active agents in cannabis, can inhibit metastasis in breast cancer, Keith Humphreys of Stanford Medical School had a thoughtful op-ed revisiting the “medical marijuana” issue in the Sunday SF Chronicle. His basic point: medicines may be developed from cannabis, but American physicians simply aren’t going to have their patients smoke their medicine.
That seems right. But that doesn’t mean that the combination of active chemicals in whole cannabis (as opposed to isolated molecules in pill form) can’t be made into a pharmaceutical product.
Full text of the Humphreys piece, with my commentary, at the jump.
Physicians unlikely to embrace marijuana as medicine
Keith Humphreys
San Francisco Chronicle, Sunday, December 2, 2007
It wasn’t just women with breast cancer who were excited last month when scientists at California Pacific Medical Center Research Institute showed that a compound found in marijuana may be able to block the growth of aggressive tumors. This finding also cheered activists who hope that mainstream medicine will soon embrace marijuana as a treatment. For a range of reasons, that’s extremely unlikely.
Effective medicines can of course be derived from plants. Digoxin from foxglove, atropine from belladonna and quinine from cinchona are only a few examples. The marijuana plant likewise contains potentially therapeutic compounds known as cannabinoids, one of which,
cannabidiol, was examined in the breast cancer study. Other research has examined tetrahydrocannabinol (THC) - the cannabinoid in marijuana that is primarily responsible for the plant’s psychoactive effects (e.g., feeling “high,” hallucinations, changes in mood). THC has been
shown to benefit at least some patients with a range of problems, including chemotherapy-induced nausea and the tremors and muscles spasms associated with multiple sclerosis.
Nonetheless, only a minority of physicians harbor great enthusiasm for prescribing marijuana cigarettes. Indeed, a survey of almost a thousand physicians by Brown University researchers showed that doctors are significantly less supportive of medical marijuana than is the general public.
Older members of the field remember vividly the era when most physicians smoked tobacco cigarettes and cheerfully rated Camel their favorite brand. The tobacco industry built on this foundation with deceptive advertisements linking doctors with smoking in the public mind (currently on exhibit at the UC San Francisco library on 530 Parnassus Ave.), which damaged medicine’s credibility.
These bitter historical experiences, supplemented by decades of subsequent research evidence that smoke inhalation of all forms (even wood smoke) can cause acute and long-term respiratory damage, make many physicians wary of recommending a smoked medicine. A smoked plant
has the further disadvantage from a medical perspective of not being pure (e.g., what if the plant had been sprayed with pesticide?) or of a standardized dose. This exposes the patient to risk of side effects, and the physician to risk of malpractice.
As the California Pacific research team noted, for example, obtaining the correct dose of cannabidiol through smoking marijuana would be virtually impossible. It would also of course cause THC’s psychoactive effects (cannabidiol is not psychoactive), which some patients find
aversive. Will all the therapeutic components of marijuana one day be available in pure, standardized forms that can be safely administered without combustion?
Liquid THC, known as dronabinol, has been available by prescription for years and has some evidence of effectiveness, but its slow absorption after ingestion makes it unappealing to some patients. Several companies are working to make a dronabinol mist that could be taken in a standardized dose with an inhaler, such as is done with medicines for asthma. An alternative approach, being tested at UCSF, is to heat marijuana in a vaporizer so that THC can be inhaled without the carcinogens found in marijuana cigarettes.
If these technological breakthroughs are achieved, some physicians will become more comfortable with prescribing THC. But others will have the opposite reaction because purified, inhalable (and therefore fast-acting) THC could carry more addictive risk than marijuana itself.
Addiction medicine specialists are aware of this possibility, which may be why the Brown University survey showed that they were less sanguine about medical marijuana than doctors in any other specialty. In general, as plant-based compounds that can produce dependence are
processed and purified (e.g., from coca leaf to cocaine or opium poppy to morphine) or are administered through a more rapid, efficient route (e.g., from ingesting to smoking), their power to produce addiction increases.
In other words, the very dosing technology that could makes THC more pure and potent as a medicine may also make it more likely to produce dangerous dependence. Unless further research reveals a way to cut that Gordian knot, THC will probably remain a bit player in mainstream.
Some comments:
1. “Cannabidiol isn’t psychoactive.” True, pure CBD isn’t an intoxicant, though there’s some evidence for it as an anxiolytic. But the presence of CBD in smoked cannabis helps moderate the anxiogenic effects of pure THC; indeed, the THC/CBD ratio may be more important than the THC content (“potency”) in determining the frequency of panic attacks. (That may help explain rising ED visit rates for cannabis despite fairly flat prevalence; the current generation of high-potency cannabis on the illicit market tends to have high THC/CBD ratios.)
2. Marinol has had a hard time with patient acceptance partly because of oral administration (which means delayed an uncertain timing of effects and impossibility of titration) but partly because of the increased risk of feeling “too stoned” from pure THC as opposed to the mix of active agents in cannabis smoke.
3. GW Pharma’s Sativex doesn’t deliver just THC. It delivers the full range of active chemicals in the plant material. In addition, GW claims to be able to “tune” the THC/CBD ratio from 1:4 to 4:1 by using different strains of cannabis. Of course that makes hash of GW’s claims that their products don’t get patients stoned.
4. The same is true of vaporization. Again, the issue is producing a known and consistent profile of active agents, which in turn means learning how to grow, test, and blend different kinds of cannabis.
So I see no reason, other than carryover fears from the recreational use of cannabis, to doubt that either the nasal spray or vaporization could be made into “medicine” acceptable to MDs. If morphine is a medicine, there’s no reason why vaporized or nebulized cannabis extract can’t be a medicine.