HEARING ON MEDICAL MARIJUANA

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House Committee on Government Reform: Subcommittee on Criminal Justice,
Drug Policy and Human Resources Holds a Hearing on Marijuana Medicine

VOLKOW: (Nora Volkow, Director National Institute of Drug Abuse, NIH)
Good afternoon, Chairman Souder and members of the subcommittee. I am
pleased to be here with my colleague, Dr. Robert Meyer from FDA and
Patricia Goode from DEA.

I would like to focus my comments today on the tremendous progress
that the National Institute on Drug Abuse has made in the past 15
years to inform us about marijuana and its health consequences. Fact
number one: Marijuana has been and continues to be the number one
illegal drug in this country.

Fact number two: Marijuana is not a benign drug. It has many adverse
health and social consequences including the often overlooked fact
that marijuana can lead to addiction.

Of the 21 million people who reported using marijuana in 2001, more
than 2 million met the diagnostic criteria for marijuana addiction.
More people are addicted to marijuana than to heroin, cocaine and all
of the other illicit drugs put together.

It is also bringing more people to our emergency rooms. There has been
164 percent increase in emergency room visits involving marijuana since 1995.

Moreover, a recent study found that early exposure to marijuana
increased the likelihood a life filled with drug and addiction problems.

Another study found that those who have engaged in a lifetime of heavy
marijuana use report an overall dissatisfaction with their mental and
physical health, as well as their life achievements.

These data provide a glimpse of the impact this drug has on our
society. Marijuana disrupts memory, attention, judgment, and other
cognitive functions. It can impair motor coordination, time perception
and balance, and is likely to contribute significantly to motor
vehicle accidents.

Basically, marijuana can affect almost every organ and system in the
body, including the lymph system, the heart and the lungs.

Because marijuana is typically rolled into a cigarette, or a joint,
and smoked, and has many carcinogenic chemicals, it can also increase
the likelihood of some cancers.

Marijuana itself is not just a single drug. It consists of dry leaves
from the hemp plant, cannabis sativa, and it contains more than 400
chemicals.

Tetrahydrocannabinol, or THC, is a primary ingredient in marijuana
that causes an intoxicating effect, or "high." While researchers were
investigating why marijuana is abused and how it affects the brains,
they discovered a new neuro-transmitter system.

They found the brain has specific sites where marijuana finds called
cannabinoid receptors. Many of these receptors are found in the brain
areas related to pleasure, motivation, memory and movement
coordination.

Recently, a second type of cannabinoid receptor was discovered. And
this cannabinoid receptor, which is outside the brain, is involved in
immune functions and in pain perception.

The discovery of these cannabinoid systems is now allowing scientists
and pharmaceutical companies to develop some very useful medications
not just for drug abuse, but for a wide variety of medical conditions,
including chronic pain, obesity, smoking and alcoholism, among others.
In addition to pursuing promising new compounds, the Department of
Health and Human Services has also responded to the recommendations
made by the NIH and the Institute of Medicine reports. Both reports
concluded that further research into the potential medical uses of
marijuana is justified.

NIH has been open to receiving research proposals on this topic, and
those that are deemed meritorious by the peer review process are
considered for funding.

One current NIH study is looking at the effects of oral THC and smoke
marijuana on appetite, weight gain, and other behavioral and
performance measures on HIV-infected patients.

To maximize research opportunities, HHS created a mechanism to provide
research-grade marijuana on a reimbursable basis, to
non-federally-funded researchers. Currently, there are 17 protocols
from a California state funded research center that have been
approved. The protocols cover a range of medical conditions including
pain, spasticity, nausea and HIV infections.

These represent a substantial increase in scientifically valid
research studies involving marijuana. This research, coupled with the
recent discovery of the cannabinoid system and the tremendous science
advances that have followed, are leading us to a wealth of new
opportunities for the development of useful non-addictive
cannabinoid-based medications, for a variety of health conditions.

To conclude, the scientific evidence is clear. Marijuana is an
addictive substance that has adverse health and behavioral
consequences.

It is also true that the cannabinoid system through which marijuana
exerts its effects offers a wide range of potential therapeutic
applications. However, cannabinoid medications are being developed
that optimize therapeutic properties and minimize adverse affects.

Thanks, and I will be happy to respond to any questions you may
have.

SOUDER: Thank you very much.

Dr. Meyer, thank you for coming to our subcommittee again, and go
ahead with your testimony.

MEYER: Good afternoon, Mr. Chairman and members of the subcommittee. I
am Dr. Robert Meyer, director of the Office of Drug Evaluation II at
FDA's Center for Drug Evaluation and Research.

I'm pleased to be here today with my colleagues NIDA and DEA. FDA
appreciates the opportunity to discuss the need for a science-based
approach to evaluating the merits of marijuana for medical purposes.

Marijuana, botanical marijuana, is not an approved drug. Let me first
speak about the drug approval process. FDA's primary mission for over
90 years has been to promote and protect the public health under the
authority of the federal Food Drug and Cosmetic Act and the Public
Health Service Act.

The FD& C Act requires that new drugs be shown to be safe and
effective before being marketed in this country. A new drug may not be
distributed in interstate commerce until a sponsor, usually a drug
manufacturer, has submitted and FDA has approved a new drug
application or a biologics license application for that product.

For approval, an NDA or BLA must contain substantial scientific
evidence that demonstrates the safety and effectiveness of the drug
for its intended use.

The first step a sponsor usually must take to obtain approval for a
new drug is to test to drug in animals for toxicity. The sponsor
submits these data along with proposed studies, the qualifications of
its investigators and assurances of informed consent and protection of
the rights and safety of the human subjects to the FDA in the form of
an investigational new drug application, or an IND.

FDA reviews the IND for assurance that the proposed studies, generally
refereed to as clinical trials, do not place human subjects at
unreasonable risk of harm.

FDA also verifies that there are adequate assurances of informed
consent and human subject protection.

At that point, the first of three phases of studies in humans can
begin. Phase one studies primarily focus on the safety of the drug in
humans. Phase two studies are clinical studies involving a limited
number of studies to explore the effectiveness of the drug for a
particular indication over a range of doses and to determine
short-term, common side effects.

The next step is to conduct phase three studies involving up to
several thousand subjects. These studies firmly establish efficacy for
a particular indication. It also provides further safety data.

Once the phase three trials are completed, the sponsor may submit the
results of all the relevant testing to the FDA in the form of an NDA.

FDA's reviewers review the application to determine if the sponsor's
data, in fact, showed the drug is both safe and effective. The drug's
manufacturing processes are also evaluated to make sure the drug can
be produced consistently with high quality.

Results of controlled clinical trials, which form the core of an NDA
or BLA, are the basis for evidence-based medicine. These trials allow
physicians and patients to use therapies with a clear understanding of
their benefits and risks and, in some cases, form the basis for strong
public health recommendations.

Let me now turn to the topic of marijuana. I want to repeat: Botanical
marijuana is not approved for any indication in the United States.

Pursuant to the Food, Drug and Cosmetic Act, FDA is responsible for
the approval and marketing of drugs for medical use, including
controlled substances.

DEA is the lead federal agency responsible for regulating controlled
substances and enforcing the Controlled Substances Act, or the CSA.
The CSA separates controlled substances into five schedules depending
upon their approved medical use and abuse potential. Schedule one
controls substances such as marijuana or those deemed not to have any
legitimate medical use, as well as a high potential for abuse.

The primary responsibility for enforcing the CSA, again, resides with
the DEA. MEYER: The criminal penalties related to Schedule One
controlled substances are far greater under the CSA than those
available under the Food, Drug and Cosmetic Act for the distribution
of an unapproved drug.

The FDA regulates marijuana when it is being investigated for use in
the diagnosis, cure, mitigation, treatment or prevention of disease in
man or animals.

Much of that research is focused currently on smoked marijuana.
However, due to the inherent toxicity of the smoking, it is likely
that any future approvals would not be of a smoked botanical
marijuana. Indeed, the Institute of Medicine has recommended that
clinical trials be conducted with the goal of developing safe delivery
systems.

To date, FDA has approved two drugs, Marinol and Kesimet, for
therapeutic use in the U. S., both of which contain active ingredients
related to those present in botanical marijuana.

As approved drugs, these products have been through FDA's rigorous
approval process, and have been determined to be safe and effective.

In conclusion, when a drug treatment goes through the FDA drug
approval process, solid clinical data are obtained, and scientifically
based assessment of the risk and benefits of the investigational drug
is made.

Upon FDA approval for marketing, patients who need the medication
could have confidence that the approved medication will be both safe
and effective. Without this rigorous scientific evaluation, benefits
and safety remain uncertain.

However, FDA will continue to be receptive to sound scientifically
based research into medical uses of botanical marijuana and its
derivative cannabinoids.

I'd like to thank the subcommittee again for this opportunity to
testify on this important issue, and I'd be happy to take any
questions the members of the subcommittee may have. Thank you.

SOUDER: Thank you very much. Ms. Good?

GOOD: (Patricia Good, Chief, Liaison and Policy, Diversion Control
Program, Drug Enforcement Administration) Chairman Souder, Congressman
Cummings, and distinguished members of the panel.

I appreciate your invitation to testify today regarding the process
that would need to be gone through for someone to obtain a DEA
registration under the Controlled Substances Act, known as the CSA, to
grow marijuana for scientific research.

While I cannot discuss any specific pending applications, or discuss
hypothetical situations, I'm pleased to explain the general process.

In the United States, anyone who wishes to cultivate marijuana to
supply scientific requirements would have to obtain a bulk
manufacturer registration from the Drug Enforcement
Administration.

The statutory basis for considering applicants is contained in title
21, U. S. Code, section 823-A.

And these considerations are applied to anyone who wishes to apply to
manufacture a substance in schedules one or two of the Controlled
Substances Act.

The attorney general, and subsequently the DEA, is empowered to
register those whose applications are consistent with the public
interest and are in compliance with various U. S. treaty
obligations.

The statute sets out six factors that DEA shall consider when
determining whether or not to grant an application and considering
whether it's in the public interest.

First is DEA's ability to maintain effective controls against
diversion of the substance in question to make sure it does not get
into other than legitimate medical scientific research or industrial
channels. This is done by limiting the number of bulk manufacturers to
that number necessary to produce an adequate and uninterrupted supply
of marijuana or any other substance under adequately competitive
conditions for legitimate medical, scientific and research purposes.

We must also consider the applicants compliance with state and local
law, the applicants ability to promote technical advances in the art
of manufacturing controlled substances and in the development of new
substances.

DEA must also consider any conviction record that the applicant may
have under state or federal law relating to the manufacture,
distribution or dispensing of controlled substances.

We must also consider the applicants past experience in the
manufacture of controlled substances and the existence of effective
controls by that applicant to prevent diversion.

And finally, DEA must consider any other factor which is relevant to
and consistent with the public interests. In order to determine
whether a proposed applicant will be consistent with U. S. treaty
obligations as the law requires, we must consider the requirements of
the Single Convention on Narcotic Drugs of 1961 and the Convention on
Psychotropic Substances of 1971.

Among the basic principles of these treaties is that the cultivation
of marijuana should be limited to the number of producers who can
provide an adequate supply to meet the country's legitimate medical,
scientific and research needs. Congress expressly incorporated this
principle into the CSA.

The DEA regulations provide more detailed information on the process
of obtaining registration to bulk manufacture of marijuana. This is
contained in chapter 21 of the Code of Federal Regulations, Section
1301.33.

Briefly, an applicant wishing to cultivate marijuana for scientific
studies or to bulk manufacture any class of a schedule one drug for
that matter is required to submit a DEA form 225, an application for
registration along with the appropriate fee.

Upon receipt of that application, assuming it's completed in its
entirety, DEA publishes a notice of application in the federal
register. This notice identifies the applicant as well as the
controlled substances they're wishing to apply to handle, and a copy
of that notice is provided to every other bulk manufacturer who
handles that same class of drug.

By regulation, all those other manufacturers have sixty days to file
written comments or objections to the proposed registration of this
new applicant by filing a notice with the DEA administrator.

At the same time, DEA conducts an investigation of the applicant to
determine the information necessary to satisfy the six public interest
factors I described previously.

DEA takes into consideration any comments or objections filed on
behalf of the other registered manufacturers in that same class of
drug, as well as information gathered during the investigation, in
making its decision on whether or not the applicant in question would
be consistent with the public interest.

In general, if no comments or objections are filed, and the results of
the investigation conclude that the registration is consistent with
the public interest, and that all U. S. obligations under
international treaty have not been contravened, then the applicant
will be approved and a notice of registration will be published in the
federal register.

If DEA seeks to deny a registration, it must serve the applicant with
an order to show cause, which provides that applicant with an
opportunity for a hearing in accordance with the Administrative
Procedures Act.

Any applicant whose application is denied is then entitled to seek
review of that decision to the U. S. Court of Appeals.

In conclusion, DEA will carefully consider any application for
registration of the bulk manufacturer of marijuana consistent with the
relevant statutory criteria.

Mr. Chairman, thank you for your opportunity to testify today. And
I'll be happy to answer any questions.

SOUDER: Thank you very much. Dr. Meyer, I wanted to ask you a few
questions. If the pharmaceutical companies wish to bring a new or even
an existing medical product to market and chose to bypass the FDA
approval process by using ballot initiatives or state legislative
approval, would FDA take any action? If so, what would it be?

For example, if a company tried to pass a state referendum allowing
oxycontin to be recommended by a doctor for any condition whatsoever,
what action would FDA take?

MEYER: Actually, Mr. Chairman, I'm having a little trouble hearing
you, but I believe I did hear the question. I don't think I can
speculate on what the FDA action would be. I'm more of a scientific,
medical expert than I am a legal expert. So I'd hate to speculate on
that.

SOUDER: Well, let me ask you this question then: Would you think it's
fairly safe to say that the FDA would not approve of pharmaceutical
companies avoiding the federal FDA guidelines through state
referendums to introduce new drugs?

MEYER: I think that you could certainly point to instances where the
FDA has acted in such circumstances.

SOUDER: Would that not call into some degree the whole question of
having an FDA and the scientific process that you described so
thoroughly? In other words, what would be the point of having you and
others do all this research if it can just be done by referendum?

MEYER: Right. Again, I don't want to talk about speculation here, but
I think FDA is certainly strongly feels that our FD& C Act and our
actions under that are protective of the public health and the right
way to develop drugs.

SOUDER: One of our concerns is that this whole so-called medicinal
marijuana movement has implied that marijuana is medicinal. And, as
Dr. Volkow has pointed out, there's 200 ingredients inside marijuana
and we're debating in --just like heroin and cocaine and other
narcotics that are dangerous have sub-ingredients that can be used and
harnessed in certain ways to help with certain conditions, but that
FDA has been virtually absent in the debate over the medical value of
marijuana use.

And when FDA was established --and its funded by Congress --it's to
make sure that such confusion, in fact, doesn't exist. Will the FDA
now consider issuing warning letters to all states, localities and
sellers of marijuana explaining that botanical marijuana has not been
approved by the FDA for medical use and cannot be advertised as such,
as you would do in other things.

In fact, as just announced in the Washington Post, you're
investigating walnuts. And the question is: Why hasn't this been more
aggressively handled by FDA and will it consider imposing penalties as
appropriate on those that continue to illegally promote this dangerous
drug as medicine?

We're not even talking about, at this point, the clinics. We're
talking about those who advertise it as medicine without FDA
approvals; if nothing else, false advertising.

MEYER: Let me answer that in two ways, Mr. Chairman. First, within the
last couple of years, the FDA has given a consultation to the DEA on
the status of marijuana as far as where it should be scheduled. And we
agreed that it should remain in schedule one under the Controlled
Substance Act, and should, therefore, be controlled and that should be
enforced as a schedule one product meaning it has no known medical use
and has substantial possibility for abuse.

The second things is I believe part of your question was directed to
the FDA in a written form recently.

And I believe that the preparation for answering that is under way,
and I'll defer to that written answer for that.

SOUDER: OK, and I understand that when we bring a researcher in,
you're not necessarily making the political policy level decision, but
it's been a frustrating process, because as we read the FDA cracking
down on other things --and by the way, we had, I feel compelled to
make this comment. We had one of our most appalling hearings in
Florida on oxycontin just recently, with the sweeping number of deaths
there in Florida.

And we have a similar number problem in Indiana. Number one, just
exploded through a bunch of bank robberies, a bunch of kids, and the
abuse of a legal drug. And as I understood Ms. Good's comment, one of
the first criteria is: Can this be controlled and managed?

And what we learned at that hearing is the number one cause of
narcotics deaths in the United States are from legal, approved drugs
that were supposed to be in this category of things that we were
managing. And it's going to be pretty hard to convince a lot of us
that, in fact, there can be a management process for controlled drugs.

I wanted to, I'll actually go a second round here. Let me yield to Ms.
Sanchez.

SANCHEZ: Thank you, Chairman. At this time, I actually have no
questions for the first panel.

SOUDER: OK. I wanted to move to Dr. Volkow. What do you think --you
know you went through the research, you isolated pretty clearly what
we're trying to find out in subcomponents of marijuana where we might
find some things to help some people.

This, however, has been seized upon by some to try to falsely imply
that marijuana itself is safe. What do you think are the best ways we
can try to balance this very difficult thing that we're having with
oxycontin, with heroin, with other types of derivatives, the opiates,
that we find some medical things that can be treated through very
controlled usage that then give the impression that the narcotic
itself is somehow safe?

How can we more aggressively show through the federal government
health divisions that marijuana is actually very dangerous? You've
outlined a whole series of things not only including gateway, but
impacts on individuals and addition and other things.

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