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ing different combinations of cannab- in the brain tumor model where the ma-
inoids –and other components of the jority of the drug’s effect is inducing cell
plant– as anti-cancer agents. death. With breast cancer it looks like
McAllister: We’re about to publish there are two primary pathways.
the results of the work we’ve done in O’S: If and when high-CBD strains
vitro, combining THC and CBD against become available to cannabis users in
glioblastoma multiforme, an aggressive California and people start using it for
form of brain cancer. We found a syner- various reasons –with or without input
gistic increase in the ability of the com- from their doctors– is there a downside,
pounds to induce apoptosis –pro- a danger to that?
grammed cell death. That finding is go- McAllister: Yes. I’ve actually seen
ing to be presented at the ICRS [Inter- this in my in vivo experiments. There’s
national Cannabinoid Research Society] AGGRESSIVE BREAST CANCER CELLS lose ability to invade through an definitely a specific dose-response oc-
meeting. I was quite surprised at how extracellular matrix. Cells at left are untreated controls; at right are cells treated with curring with CBD. If you’re too low or
well the combination worked. Now CBD. Invasive ability is an indication of the cells’ metastatic potential in the body. too high you won’t see an effect. You
we’re trying to get the funding to do the Photomicrographs by Sean McAllister need to be within specific therapeutic
experiment in vivo. window. If the treatment is not formu-
I proposed to look at many different lines that have been passaged for a long and humans but we need more detailed lated and you don’t really know what
combinations. I started with THC and time. The problem with cell lines can be in vivo data before we can proceed. dose you’re getting, you might not see
CBD because they’re the most abundant. that when you passage them for years O’S: Who provides your CBD? any effect.
We found that in two out of three ag- and treat them with semi-artificial high- McAllister: NIH. They synthesize it. O’S: If somebody’s using high-CBD
gressive brain-cancer cell lines that we serum and all the things that you do in O’S: You know that a high CBD cannabis for, say, spasm, they could ti-
looked at, when you added CBD at a cultures their genetic profile can change strain has been located in California. trate and figure out an effective dose -
lower concentration than THC, we saw so that they’re not the same as the origi- McAllister: I have a DEA license two puffs, or three, or four...
a synergism in terms of its ability to in- nal primary tumor. here and I’m working towards getting McAllister: They probably could.
duce cell death. But now we have techniques where standardized plant extracts from Arno One problem would be the placebo ef-
O’S: What was the most effective ra- you can actually take the tumor out of Hazenkamp in the Netherlands to test. fect. You wouldn’t really know if the
tio of THC to CBD? the patient and keep it under conditions It’s always been my goal to work with effect was due to the drug or the placebo
McAllister: About fourfold less CBD where years down the road it would have extracts. But it’s not easy to find a place effect on that person.
than THC. This occurred in more than the same genetic profile as the original to give you extracts with quality control. O’S: I’ve heard it suggested that the
one cell line. And we have discovered a tumor. Which gives you a real model to To do an experiment in a sound, scien- placebo effect itself might involve the
molecular mechanism that may explain test the efficacy of whatever treatment tific manner you have to know exactly endocannabinoid system.
why if you add THC and CBD together, you’re testing. where the material’s coming from, and McAllister: Why not? When it came
they might synergize. The in vivo work we’ve done so far its make-up. to reduction of pain, the placebo effect
O’S: Could you explain the mecha- looks promising in regard to CBD being There’s so much to learn about how involved the endorphin system-this sys-
nism? able to inhibit metastasis. And now we’re these components interact. It was just a tem was discovered through research on
McAllister: There is a family of sig- going to combine it with THC. It makes few years ago that they found CB-2 ago- opiates/opium. So why couldn’t the pla-
naling proteins called mitogen activated sense to attack cancer with multiple nists in terpenes. And there’s probably cebo effect for spasticity involve the
kinases (MAPK). These proteins control types of treatments that target different even more structures in the extracts that endocannabninoid system? It makes
cell growth and survival. Depending on pathways. That’s a classical approach might modulate the activity, depending sense. And there’s nothing wrong with
how they function, they can either stimu- with cancer treatments. on whatever physiological effects you’re the placebo effect. But for cancer it’s
lates cell growth or, if you stimulate them O’S: At the forum you said you had looking for. going to be important to have the cor-
for too long in cancer cells, you can begun using a mouse model. O’S: How do the cannabinoids exert rect dosing schedule.
cause the cells to undergo programmed McAllister: We use a mouse model their anti-cancer ef-
cell death, which is a desirable property of aggressive breast cancer. We treat the fects?
in a cancer drug. We found that when mice every day with a very reasonable McAllister: In the
you add either compound at lower con- concentration –5 milligrams per kilo- breast cancer model,
centrations alone you produce either no gram [of body weight]. We inject it –sys- CBD appears to target
effect or marginal effects on certain temic administration. These mice get a two major pathways,
MAPK. But when you combine them, primary tumor in the breast and just like resulting in modula-
you get a pretty dramatic change that the common human progression, after a tion of MAPK and an
leads to increased cell death and reduc- certain amount of time it metastasizes increase in production
tions in proliferation. to the lung. We find that if it we treat it of reactive oxygen
This ties in a little to Guzman’s work. with the drug, you get significantly less species. Both changes
[A 1998 paper by Manuel Guzman and metastasis to the lung. lead to damaging ef-
colleagues documented the anti-cancer O’S: Are you still on track to have fects in cancer cells.
effects of THC and inspired McAllister clinical trials in less than two years? That’s different than
to test other cannabinoids for similar ef- McAllister: STI pharmaceuticals is
fects.] He showed that modulation of talking to clinics in the UK that do these
MAPK was essential for THC’s ability kind of trials. They’re looking at the data. PhRMA Denial Campaign Continues, But...
to increase cell death. So we’re carrying
on with that story and looking at the dif-
Yes. We’re definitely getting closer.
O’S: Who has the IND [license to
Hormone Replacement Therapy
ferent components and seeing which can
help. Which fits in with the theory that
conduct the trial] in the UK?
McAllister: STI pharmaceuticals.
Link to Breast Cancer Confirmed
the endogenous cannabinoids have an That’s where we’re thinking the trial will In July 2002 the Women’s Health gestin in Postmenopausal Women,”
“entourage effect.” One compound is be. Initiative reported that women taking by Chlebowski et al). The conclusion:
not the whole story. O’S: Women in California will be Wyeth’s blockbuster HRT drug “The increased risk of breast cancer
We really want to follow up in vivo disappointed. Prempro —a combination of estrogen associated with estrogen-plus-proges-
now. We have access to actual primary McAllister: We’re going to try and and progestin— had a heightened in- tin therapy declined markedly soon
brain tumors from patients –not just cell do a parallel trial here as well. I don’t cidence of breast cancer. Wyeth and after discontinuation of the therapy
think it will be a problem. their allies in the medical establish- and was unrelated to a change in the
O’S: What will that trial look like? ment challenged the WHI data, claim- use of mammography.”
McAllister: I need to collect data for ing that a drop in the rate at which Chlebowski estimates that HRT
about another six months to a year and women were getting mammograms led caused breast cancer in 200,000
talk with physicians in order to propose to fewer breast cancers being detected. women between 1992 and 2002.
a trial design. I have questions with re- But millions of women stopped tak- “About 22 percent of women who get
gard to dosing. In the model we’ve been ing Prempro, and when the data for breast cancer die from it,” according
using, the mice have a functional im- 2003 was analyzed, the U.S. breast to medical writer Virginia Hopkins, “
mune system. Vincenzo Di Marzo’s cancer rate, which had been rising for so by extrapolation we can infer that
group did a study using a human cell line decades, was shown to have dropped some 44,000 women died during that
with a compromised immune system. 7%, from 210,000 new cases to fewer decade due to taking synthetic HRT,”
I’ve read reports of CBD modulating the than 190,000. This excellent news was HRT also increases the risk of
immune system, which raised some con- reported by researchers at the M.D. breast cancer, stroke, heart disease and
cerns. I want to try a couple of different Anderson Cancer Center, and again gallbladder disease and dementia...
dosing schedules. Do we want to give Wyeth et al tried to downplay it. The HRT link to breast cancer prob-
these patients a systemic dose every Now the numbers through 2005 ably explains why Marin County has
three days? Every four days? Would oral have been analyzed in The New En- had an elevated breast cancer rate: it’s
administration be effective? It is diffi- gland Journal of Medicine (“Breast a function of more and “better” health
cult to truly extrapolate between mice Cancer after Use of Estrogen plus Pro- care available to the affluent.