NEW, IMPROVED MEDICAL MARIJUANA DRUG READIED FOR TESTING

Washington, DC - The company that makes Marinol - the only medicinal
marijuana drug approved in the US - hopes to be in Phase I clinical trials
of a new pharmaceutical form of marijuana by the second quarter of this year.

A new form of medicinal marijuana would be good news to the patients who say
they prefer smoked marijuana to relieve their medical ailments rather than a
pill. Some came here recently to the staid National Academy of Sciences
building for a scientific workshop on medical marijuana - several in
wheelchairs with companion dogs - to state their case. Except for eight
patients grandfathered under the federal government's disbanded
compassionate use program, smoked marijuana is illegal in every state except
California.

Delta-9-tetrahydrocannabinol (THC) is the most active ingredient of the
marijuana plant and the one believed to have medicinal value for patients
with cancer, AIDS, glaucoma, and a host of other illnesses and conditions.

"We are keenly interested in a new formulation for THC," said Robert E.
Dudley, PhD, Senior Vice President of Unimed Pharmaceuticals, Inc., in
Buffalo Grove, IL, speaking here at the last of three information-gathering
workshops sponsored by the Institute of Medicine of the National Academy of
Sciences. Marinol is taken orally in gel capsules. Dr. Dudley said the
company wants to more nearly mimic inhaled marijuana, avoid the first pass
through the liver that occurs with the oral formulation, and develop a
faster-acting THC product. Drug delivery routes under consideration are
sublingual, nasal aerosol, and pulmonary aerosol formulations.

Approved Form

Marinol was approved in 1985 as an antiemetic for cancer patients undergoing
chemotherapy, and in 1992 it was approved for treatment of anorexia
associated with weight loss in AIDS patients. Today, Dr. Dudley said in an
interview, about 10 percent of Marinol sales are in oncology and about 90
percent in the HIV/AIDS treatment field. Sales data, he said, are strictly a
function of how Marinol is marketed.

Considering how much controversy swirls around providing marijuana to
patients legally, Dr. Dudley said, "I am always amazed when I meet
physicians who don't know that an approved THC product has been on the
market for 13 years." He added, "Oncologists don't know much about it; many
don't use it much. We need more awareness about Marinol among oncologists."

Dr. Dudley said he believes that the fact that Marinol is a controlled
substance has proved to be a hindrance to its acceptance by oncologists. In
1995 Unimed petitioned the US Drug Enforcement Administration to change
Marinol from a Schedule II to a Schedule III drug, he said. The company is
awaiting a US Department of Health and Human Services review of that
petition and expects final US Drug Enforcement Administration action on its
request this year. Rescheduling, said Dr. Dudley, would provide for improved
patient access to Marinol, availability of prescription refills of the drug,
increased pharmacy stocking, and a much higher comfort level among physicians.

"A lot of physicians are leery of prescribing Schedule I and II drugs," said
Dr. Dudley. "They feel they're being watched by the feds. Schedule I and II
drugs are viewed very differently from Schedule III drugs and non-scheduled
drugs." (Note by Tom Barrus, R.Ph., MBA - The DEA does not allow usual
prescribing of schedule I drugs. However, Dr. Dudley is correct about
feeling that, doctors who write prescriptions for schedule II drugs are
being watched by the feds. The DEA is watching them and counting the kinds
and numbers of pills they prescribe.)

He said the company knows Marinol is expensive (about $200 a month for the
average patient who uses it), but that there is coverage of the drug by
third-party payors. The expense of the drug - along with the fact that some
patients say smoked marijuana is more effective for them - is one reason
consumer advocacy groups such as the Marijuana Policy Project believe
patients who smoke marijuana for medicinal reasons should be allowed to do
so without risking breaking the law.

The Institute of Medicine investigators studying medicinal uses of marijuana
will produce a final report - expected to be finished by the end of this
year - on the health benefits and risks of the plant. One of the issues they
are examining is whether smoked marijuana is a "gateway drug" to other
illegal drugs.

"There is a tremendous amount of new science" on the medical benefits of
marijuana, said John A. Benson, Jr., MD, co-principal investigator of the
Institute of Medicine study and Emeritus Professor and Dean at Oregon Health
Sciences University. "My hope is that we'll go beyond asking for more
research and that we might offer some specific suggestions for research,"
said Dr. Benson.

In an interview, Dr. Benson added, "In general, patients like the plant.
They say, why bother [to do more research]? Or they say, 'Let us use the
plant while you do your research.' But that's not up to Drs. Benson and
Watson." Dr. Benson's co-principal investigator on the Institute of
Medicine's marijuana study is Stanley J. Watson, Jr., MD, PhD, Co-Director
and Senior Research Scientist at the University of Michigan's Mental Health
Research Institute.

Difficult Drug to Study

The use of medical marijuana is so political and controversial that it has
been hard to subject it to rigorous scientific scrutiny. In August, the
National Institutes of Health released the report of a panel that met the
previous February to review the scientific data on the potential therapeutic
benefits of marijuana and the need for, and feasibility of, more research.
The NIH panel concluded that the risks linked to marijuana, especially
smoked marijuana, must be considered not only in terms of immediate adverse
effects on the lung, but also in terms of long-lasting effects in patients
with chronic diseases who might use it for long periods of time.

The NIH panel felt that frequent and prolonged marijuana use might reduce
immune function (especially in patients with compromised immune systems);
they were also concerned about the dangerous combustion byproducts of smoked
marijuana on patients with chronic diseases. Thus they favored the
development of a smoke-free inhaled delivery system that could deliver purer
forms of THC or related cannabinoid compounds.

NIH Director Harold Varmus, MD, said the NIH is open to receiving research
grant applications for studies of the medical efficacy of marijuana, and
will put applications through "our normal scientific review."

The National Institute on Drug Abuse maintains a contract with the
University of Mississippi to grow marijuana for research purposes, according
to Institute sources. The Institute also has a contract with Research
Triangle Institute to package the product into cigarettes distributed for
NIH-approved research to scientists who have an Investigational New Drug
clearance from the Food and Drug Administration. A small portion of these
cigarettes - which are made according to standardized specifications from
marijuana of known origin and quality - go to eight patients legally
supplied with marijuana under the government's compassionate use program,
which has been discontinued.

At the Institute of Medicine workshop, speakers said marijuana's status as a
controlled substance discourages scientists from attempting to study its
therapeutic benefits. There is a "tremendous bureaucratic tangle to get a
protocol approved," said J. Richard Crout, MD, a former FDA official who now
runs Crout Consulting. He said that in addition to the constraints of the
Drug Enforcement Administration, state agencies may also become involved in
controlling marijuana trial protocols.

Nevertheless, other speakers said studies of cannabinoids are underway.
David Pate, a senior technical officer with HortaPharm, BV, in Amsterdam,
said his company is manufacturing a generic THC drug and that he is studying
another cannabinoid-like drug that goes to the same receptor as THC.

Smokeless Cannabinoids

Phyllis I. Gardner, MD, a dean at Stanford University and a consultant to
Alza Corporation in Palo Alto, CA, said if she had a choice, she would
choose inhalation as her first choice of delivery because it seems to
provide the most therapeutic benefit. She said Alza tried to make a
cannabinoid transdermal patch in the 1970s, but "it didn't work." She cited
transmucosal delivery as a promising route, noting that in general Americans
accept nasal delivery but do not accept rectal suppositories as readily as
Europeans do.

Reid M. Rubsamen, MD, Vice President for Medical Affairs of Aradigm
Corporation in Hayward, CA, said he is working on a respiratory-tract drug
delivery system for analgesics in which the patient holds a device with a
light that tells him how to breathe; a liquid-formulated drug flows through
the device in fine-particle, low-velocity aerosolized form. With this
system, he noted, more of a given drug goes into the alveoli.

Mahmoud A. ElSohly, PhD, President of ElSohly Laboratories, Inc., in Oxford,
MS, said he is studying delta-9-THC-hemisuccinate in suppository form as an
alternative to oral and smoked THC. He is testing this formulation on
patients with spasticity, and said he was "very encouraged" from preliminary
results.

The Institute of Medicine carefully warned observers at the Washington
workshop about the dangers of drawing inferences too hastily about what may
be in the final report on medical use of marijuana. It stated that
"observers who draw conclusions from the workshop about the Institute of
Medicine study, will be doing so prematurely. The goal of this meeting is
not to draw conclusions, but to listen to the evidence."

Checked-by: Melodi Cornett