ADDICTION TREATMENT, NOVEL BUT UNPROVEN

Prometa's promoters point to anecdotal success. But critics want to
see hard numbers.

The drug treatment first raised eyebrows several months ago with its
provocative marketing campaign. Featuring deceased comedian Chris
Farley and the message "It wasn't all his fault," the billboard,
radio and Internet advertisements were a bold departure from the
often understated ads used to market addiction treatment.

But since then, it's been the therapy itself, known as Prometa, that
has caught the attention of the public and the medical community
alike, drawing both anecdotal reports of success and sharp criticism.

The philosophy of Hythiam, the small Santa Monica company that
developed the treatment, is that drug addiction is a brain-based
disorder that cannot be overcome by willpower alone. That belief
isn't unusual, but the company maintains that three specific
medications -- used in a certain sequence and dosage -- can treat
brain dysfunction and break addictions to alcohol, cocaine and methamphetamine.

Doctors using Prometa "have never seen anything this dramatic," says
Terren Peizer, Hythiam's chairman and chief executive. "This is
changing the way we approach this disease."

The drugs aren't approved for addiction treatment, and the company
makes doctors who use their method sign a disclosure agreement
promising not to divulge details. The company also charges up to
$15,000 for the two to five outpatient visits that form the core of
the treatment.

Critics point out that no randomized studies pitting Prometa against
standard treatment or a placebo have been done to show that the
method is safe, or useful, in helping addicts achieve sobriety.

"Controlled studies where participants have paid similar amounts of
money and have equally high expectations of treatment have not been
completed or published," says Dr. Lori D. Karan, a researcher in the
Drug Dependence Research Laboratory at UC San Francisco. She suggests
there is a high likelihood of a strong placebo effect.

Prometa's secrecy and lack of a track record worry doctors.

"They are using a procedure that has yet to be proven effective,
charging an inordinate amount of money and making promises they are
not able to keep," says Dr. Rick Chavez, medical director of the Pain
Institute in Redondo Beach. He says some of his patients tried the
Prometa approach and relapsed.

Hythiam officials and proponents of Prometa say critics are worrying
needlessly. Not only are no promises made, they say, more than 1,000
of people in the United States have safely undergone the treatment.
They say word-of-mouth reports show it works where most other
treatments have failed.

An Outpatient Treatment

Peizer launched Hythiam three years ago after searching worldwide for
a better way to treat drug addictions. Although he has no background
in addiction treatment, Peizer was looking for an investment
opportunity and was intrigued by the idea that addictions could be
treated with medications. Before starting Hythiam, he directed
several other science or biotechnology companies.

Prometa is based on research by a Spanish doctor who believed that
medications that control the gabaminergic system of the brain could
help break addictions. The treatment involves administration of an
intravenous medicine, flumazenil, and two oral drugs, gabapentin and
hydroxyzine, in an outpatient setting. The patient also receives
vitamins and minerals and is urged to begin traditional psychosocial
counseling and group support meetings to augment recovery.

The medications, which are approved by the Food and Drug
Administration for treating other disorders but not drug addiction,
are aimed at quieting cravings and improving mental clarity, Peizer says.

Hythiam has applied for a patent to protect its unique use of the
three medications and the specific dosing regimen. The company
licenses the protocol to addiction treatment centers or doctors for a
fee and, so far, has about 45 licensees nationwide, Peizer says.

Peizer points to data compiled by several doctors using the protocol
that show it works. Data from a drug court (a specialized court
designed to handle cases involving offenders who abuse substances) in
Pierce County, Wash., showed that 98% of methamphetamine and cocaine
addicts achieved clean urine screening tests for three months after
the Prometa treatment provided by Hythiam. That data was presented in
June at the National Assn. of Drug Court Professionals' annual conference.

Another 12-week nonrandomized study by Research Across America, a
clinical research company, on methamphetamine-dependent patients
showed that 80% of patients "experienced a significant clinical
benefit" with the medication alone (without behavioral therapy). The
benefit was defined as decreased cravings, reduction in
methamphetamine use and staying in treatment. The study, which was
also undertaken and paid for at the request of Hythiam, was presented
in June at the annual meeting of the College on Problems of Drug Dependence.

"You have different populations in different regions of the United
States all showing the same result," Peizer says.

People like the treatment, he says, because it jump-starts the
recovery process and can be accomplished on an outpatient basis.

"You don't have the added stress of being away from your friends,
family, community and workplace," he says. "You don't have the
stigma" of hospitalization.

But other addiction treatment specialists say there is scant
scientific evidence that the gamma aminobutyric, or GABA, system is
altered by addiction.

"When they talk about resetting receptors in the brain, there is no
evidence for that," says Richard Rawson, a psychologist and associate
director of UCLA's Integrated Substance Abuse Programs. "I don't know
if anyone has ever had the idea to package a bunch of medications
off-label, patent it and then go out and sell it as a unique
indication. That is a strategy many people in the field feel is of concern."

Chavez, who resigned last year from the chemical dependency treatment
staff at Little Company of Mary-San Pedro Hospital, says one or more
of the drugs in the Prometa protocol may be helpful in the withdrawal
and recovery process -- but only in a limited way.

"I believe there is a place for the chemical treatment of alcohol
addiction," he says. "But that is not the way they are using this.
They are using it as a one-shot deal. I don't think it will work
beyond two to four weeks."

No 'Magic' Drug Cure Yet

Many neuroscientists are studying the biological basis for addiction
in hopes of finding medications that might augment recovery, but no
drugs have been found that can cure addiction.

For alcoholism, the FDA has approved three medications as adjuncts to
psychosocial treatment. Disulfiram is a decades-old medication that
produces a sensitivity to alcohol and an unpleasant reaction when the
patient under treatment drinks even small amounts of alcohol.
Naltrexone and acamprosate are used to decrease the cravings for alcohol.

"None of these is a magic bullet," Karan says.

The FDA has not approved any medications specifically for the
treatment of cocaine or methamphetamine addiction.

In contrast with Prometa's emphasis on medications to treat
addiction, standard treatment for substance abuse typically involves
education, family therapy, behavioral and psychosocial counseling and
support groups. This type of therapy can occur in hospitals,
residential programs, outpatient classes or free self-help groups.
Costs range widely, but insurance typically covers such care.

Some physicians who use Prometa say it works in patients for whom
standard approaches have failed.

The use of a new, untested remedy is justified when it's safe and
when there is little else to help addicts, says Dr. Matthew
Torrington, medical director of the Prometa Center, an outpatient
clinic in Santa Monica founded to provide the treatment.

"I don't expect anyone to believe me until there is [randomized,
controlled] data," Torrington says. "But for people who are suffering
today, this really helps. What else is there?"

Prometa costs between $12,000 and $15,000 for self-paying patients,
although Peizer says the company offers discounts to insurers,
Medicaid recipients and the criminal justice system. No insurers have
covered the treatment as yet.

Stephen Beebe, 44, was treated with Prometa in June for
methamphetamine addiction. "After the first infusion, I felt like
somebody had cracked open my head and shined a flashlight into my
brain," he says. "I had mental clarity right away. I knew I was going
to make it." He said he experienced no desire for meth and has been
free of the drug while undergoing counseling and attending support meetings.

Another man, who asked that his name not be used because he fears his
history of addiction may jeopardize his employment, said he spent
$8,000 on the treatment several years ago. The San Pedro
longshoreman, 55, was addicted to cocaine and heroin when the
treatment was recommended. He relapsed one month later even though he
was participating in after-care counseling and group support meetings.

"They said it would help me stay clean and sober," he says. "I paid
$8,000 to be a guinea pig. But when you're desperate and they tell
you this stuff, you'll do it. I got no benefit from it."

Studies Now Underway

Some of the questions surrounding Prometa may be resolved by more
rigorous studies. Two randomized, controlled clinical trials funded
by Hythiam are underway at UCLA and the Medical University of South
Carolina. Results from the studies are expected in a year or two.

The trials are being conducted by highly regarded scientists and,
says Rawson, "that is absolutely to [Hythiam's] credit. But they
should wait for the results before they do all the marketing. Between
now and 2008, there is a lot of marketing going on. What if the
results show it's no better than placebo?"

[Sidebar]

The Prometa Regimen

Prometa can be used to treat alcohol, cocaine and methamphetamine
addictions, says Hythiam, the company that licenses the treatment regimen.

For alcohol dependence, patients receive the prescription drug
flumazenil intravenously over two to three visits on consecutive days
followed by oral administration of the prescription drugs gabapentin
and hydroxyzine.

For cocaine and methamphetamine dependence, patients receive
intravenous flumazenil doses on three consecutive days followed by a
second treatment about three weeks later. They also receive
gabapentin and hydroxyzine.

Flumazenil, gabapentin and hydroxyzine are not approved by the FDA
for the treatment of addiction.

The accepted use for Flumazenil is to help reverse the effects of
benzodiazepine drugs, such as drowsiness, after surgery or a drug
overdose. Gabapentin is used to help control some types of epileptic
seizures. Hydroxyzine is used to relieve itching caused by allergies
and to control nausea. It is also used for anxiety and to treat
symptoms of alcohol withdrawal.

Hythiam does not reveal the dosages and precise sequencing of the
medications that are used and even requires its licensees to sign
nondisclosure forms protecting the information. Patients are also
prescribed vitamins, minerals and amino acids and are encouraged to
attend after-care counseling and group support meetings.

- -- Shari Roan