3
O’Shaughnessy’s Journal of the California Cannabis Research Medical Group Autumn 2004 $3 oo Danger! Danger! Danger! Cannabinoid “Antagon ist” Will be Sold as Diet Drug By Fred Gardner Sanofi, a multinational pharma- cuetical company based in France, is planning to market a weight-loss drug called Rimonabant that works by block- ing part of the cannabinoid receptor sys- tem. Scientists employed by Sanofi re- ported at the 2004 meeting of the Inter- national Cannabinoid Research Society that Rimonabant has proven safe and effective in clinical trials involving 13,000 patients. Sanofi expects FDA approval within the year. The fact that Rimonabant blocks the “euphoric” effects of mari-  juana is a big plus in the eyes of U.S. government regulators. The marketing is already done, in a sense, because everybody knows that marijuana induces the munchies, and it seems logical that blocking the cannab- inoid receptors would reverse the effect. But the advent of Rimonabant troubles California doctors who have made a specialty of monitoring their pa- tients’ cannabis use, as well as some sci- entists who are studying the basic nature of the cannabinoid system. Jeffrey Hergenrather, MD, o f Sebastopol —one of the few clinicians to attend this year’s ICRS meeting— says, “We are only now becoming aware of the modulating ef- fects the cannabinoids have on the body and mind. The consequences of interfer- ing with the cannabinoid receptor sys- tem have not been evaluated in normal human physiology.” Some Definitions Sanofi researchers Murielle Rinaldi-Carmona , Francis Barth, and Gerard Le Fur were honored at the 2004 ICRS meeting for developing a drug that blocks cannabinoid receptors. tain compounds bind, setting off molecu- lar cascades within the cells that produce effects in the body such as reduced in- flammation, increased appetite, etc. Two kinds of cannabinoid receptors have been discovered —CB 1 , which is highly concentrated in the brain and central ner- vous system, and CB 2 , found mainly in tissues associated with the immune sys- tem. There are three different kinds of can- nabinoids, or chemical “agonists” that activate the cannabinoid receptors. They are, in order of evolutionary appearance: compounds made in the body for pur- poses of neurotransmission, compounds unique to the cannabis plant (the most famous being delta-9 THC), and com- pounds made in the lab —synthetics. Cannabinoid s made in the body are called “endocannabinoids” (the prefix chemicals are called “endorphins”). The first endocannabinoid to be identified —by Raphael Mechou- lam and William Devane in 1992— was named “anandamide” after the Sanskrit word for “bliss.” It has since been learned that endocannabinoids help regulate the cardiovascular, digestive, endo- crine, excretory, immunological, nervous, reproductive, and respira- tory systems.  Rimonabant is SR- 141716 redefined as a “therapeutic drug” Rimonabant is an “antagonist” drug that engages the CB 1 receptors so they can’t be activated. Originally called SR- 141716, it was developed by Sanofi in the early ’90s as a research tool. If a given effect is blocked by SR-141716, that effect is said to be mediated by CB 1 receptors. Rimonabant is SR-141716 redefined as a “therapeutic drug” that counteracts unwanted effects —like overeating— mediated by the cannab- inoid receptor system. In a talk at the ICRS meeting entitled “Clinical Results with Rimonabant in Obesity,” Sanofi researcher Gerard Le Fur reported that the drug had done well in phase-three clinical trials involving 13,000 patients. The trials were con- ducted at numerous sites in the U.S. Obese patients were treated with Rimonabant for 52 weeks. “Over 72% continued on page 17 Ricky Williams Protests Drug Testing By Quitting Football; Calls Marijuana “10 Times Better For Me Than Paxil” The issue is Di gnit  y By Fred Gardner In the autumn of 1995 the 49ers full- back, William Floyd, had a knee de- stroyed by tacklers. Management had been overworking him mercilessly. On the play before his injury Floyd had car- ried four defenders for about two yards. The TV replay of his leg going one way above the knee and another way below the knee ended what was left of my mild football addiction. So it was only peripherally that I fol- lowed the career of a running back named Ricky Williams, who in ’95 was a freshman at the University of Texas. He had speed, power, and dreadlocks (before they were widely fashionable). He broke conference records that had endured since the days of Doak Walker. The New Orleans Saints drafted him in 1999; Mike Ditka gave up eight players to get him. Williams’s first agent had experience in the world of rap music, not football, and the contract he negotiated with the Saints owners’ was not as lucrative as it could have been. Williams injured a shoulder in his second NFL season and missed six games, but still gained 1,000 yards. As he was recovering, he was induced by Glaxo SmithKline to be the celebrity pa- tient in a campaign to sell Paxil to the12 million Americans who allegedly suffer from “Social Anxiety Disorder.” Glaxo had to sell the concept that shy- ness is actually a medical condition — “a chemical imbalance in the brain”— that can be corrected by a pill. Williams, who is sincere and enthusiastic, gave in- terviews in which he thanked a therapist for telling him that his reluctance to be accosted by strangers at airports was an illness that could be overcome by medi- cation. Williams was traded to the Miami Dolphins in 2002. That season he led the league in yards gained rushing (1853) and number of carries (383). In 2003 his yardage dropped slightly but again he had the most carries (393). Williams won’t be playing in 2004. In late July he made two related stat e- ments: that he was retiring from football, and that he found marijuana to be “10 times better for me than Paxil” as a con- fidence builder. (Glaxo promptly purged him from the Paxil website.) Retiring isn’t an easy step. Williams’s love for football is expressed in the pages of a journal he’s been posting sporadi- cally at runrickyrun.com. He has a clear, colloquial writing style —straight ahead, like his running style. If we’re lucky, he’ll soon explain his decision to leave the game, and keep us informed of his whereabouts. Williams was facing a four-game sus- pension after testing positive for mari- “I didn’t quit football  because I failed a drug test. I  failed a drug test because I was ready to quit football.” “I didn’t quit football because I failed a drug test. I failed a drug test because I was ready to quit football,” Williams told a writer he trusts, Dan Le Batard of the Miami Herald, on July 28. “Williams said there were ‘a hundred reasons’ for his retirement and that his desire to continue smoking marijuana without inhibition was merely one of them,” Le Batard reported. “He said he was not addicted to the drug, but merely that he didn’t believe in government and NFL laws banning it. He said he had already decided to quit football even be- fore testing positive a second time for marijuana use last season and incurring a $650,000 fine. He appealed that fine, flying to New York to argue his case before an arbiter with his attorney, but received word last week that his appeal had been denied. “While the appeal was pending, Wil- liams said he continued smoking mari-  juana while on tour with rocker Lenny Kravitz in Europe and failed a third t est upon his return. He said he had been

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O’Shaughnessy’sJournal of the California Cannabis Research Medical Group • Autumn 2004

$3oo

Danger! Danger! Danger!

Cannabinoid “Antagonist”Will be Sold as Diet Drug

By Fred Gardner

Sanofi, a multinational pharma-

cuetical company based in France, is

planning to market a weight-loss drug

called Rimonabant that works by block-

ing part of the cannabinoid receptor sys-

tem.

Scientists employed by Sanofi re-

ported at the 2004 meeting of the Inter-

national Cannabinoid Research Societythat Rimonabant has proven safe and

effective in clinical trials involving

13,000 patients.

Sanofi expects FDA approval within

the year. The fact that Rimonabant

blocks the “euphoric” effects of mari-

 juana is a big plus in the eyes of U.S.

government regulators.

The marketing is already done, in a

sense, because everybody knows that

marijuana induces the munchies, and it

seems logical that blocking the cannab-

inoid receptors would reverse the effect.

But the advent of Rimonabant

troubles California doctors who have

made a specialty of monitoring their pa-

tients’ cannabis use, as well as some sci-entists who are studying the basic nature

of the cannabinoid system. Jeffrey

Hergenrather, MD, of Sebastopol —one

of the few clinicians to attend this year’s

ICRS meeting— says, “We are only now

becoming aware of the modulating ef-

fects the cannabinoids have on the body

and mind. The consequences of interfer-

ing with the cannabinoid receptor sys-

tem have not been evaluated in normal

human physiology.”

Some Definitions

Cannabinoid receptors are proteins on

the surface of certain cells to which cer-

Sanofi researchers Murielle Rinaldi-Carmona,

Francis Barth, and Gerard Le Fur were honoredat the 2004 ICRS meeting for developing a drug

that blocks cannabinoid receptors.

tain compounds bind, setting off molecu-

lar cascades within the cells that produce

effects in the body such as reduced in-

flammation, increased appetite, etc. Two

kinds of cannabinoid receptors have

been discovered —CB1

, which is highly

concentrated in the brain and central ner-

vous system, and CB2, found mainly in

tissues associated with the immune sys-

tem.

There are three different kinds of can-

nabinoids, or chemical “agonists” that

activate the cannabinoid receptors. They

are, in order of evolutionary appearance:

compounds made in the body for pur-

poses of neurotransmission, compounds

unique to the cannabis plant (the most

famous being delta-9 THC), and com-

pounds made in the lab —synthetics.

Cannabinoids made in the body are

called “endocannabinoids” (the prefix

is a contraction of “endogenous,” just as

the body’s endogenous morphine-like

chemicals are called “endorphins”).

The first endocannabinoid to be

identified —by Raphael Mechou-

lam and William Devane in 1992—

was named “anandamide” after the

Sanskrit word for “bliss.”

It has since been learned that

endocannabinoids help regulate the

cardiovascular, digestive, endo-

crine, excretory, immunological,nervous, reproductive, and respira-

tory systems.

  Rimonabant is SR-

141716 redefined as a

“therapeutic drug”

Rimonabant is an “antagonist” drug

that engages the CB1

receptors so they

can’t be activated. Originally called SR-

141716, it was developed by Sanofi in

the early ’90s as a research tool. If a

given effect is blocked by SR-141716,

that effect is said to be mediated by CB1

receptors. Rimonabant is SR-141716

redefined as a “therapeutic drug” thatcounteracts unwanted effects —like

overeating— mediated by the cannab-

inoid receptor system.

In a talk at the ICRS meeting entitled

“Clinical Results with Rimonabant in

Obesity,” Sanofi researcher Gerard Le

Fur reported that the drug had done well

in phase-three clinical trials involving

13,000 patients. The trials were con-

ducted at numerous sites in the U.S.

Obese patients were treated with

Rimonabant for 52 weeks. “Over 72%

of patients at 1 year showed a weight losscontinued on page 4

continued on page 17 

Ricky Williams Protests Drug TestingBy Quitting Football; Calls Marijuana

“10 Times Better For Me Than Paxil”

The issue is Di

gnit 

 y

By Fred Gardner

In the autumn of 1995 the 49ers full-

back, William Floyd, had a knee de-

stroyed by tacklers. Management had

been overworking him mercilessly. On

the play before his injury Floyd had car-ried four defenders for about two yards.

The TV replay of his leg going one way

above the knee and another way below

the knee ended what was left of my mild

football addiction.

So it was only peripherally that I fol-

lowed the career of a running back

named Ricky Williams, who in ’95 was

a freshman at the University of Texas.

He had speed, power, and dreadlocks

(before they were widely fashionable).

He broke conference records that had

endured since the days of Doak Walker.

The New Orleans Saints drafted him in

1999; Mike Ditka gave up eight players

to get him.

Williams’s first agent had experiencein the world of rap music, not football,

and the contract he negotiated with the

Saints owners’ was not as lucrative as it

could have been.

Williams injured a shoulder in his

second NFL season and missed six

games, but still gained 1,000 yards. As

he was recovering, he was induced by

Glaxo SmithKline to be the celebrity pa-

tient in a campaign to sell Paxil to the12

million Americans who allegedly suffer

from “Social Anxiety Disorder.”

Glaxo had to sell the concept that shy-

ness is actually a medical condition —

“a chemical imbalance in the brain”—

that can be corrected by a pill. Williams,

who is sincere and enthusiastic, gave in-terviews in which he thanked a therapist

for telling him that his reluctance to be

accosted by strangers at airports was an

illness that could be overcome by medi-

cation.

Williams was traded to the Miami

Dolphins in 2002. That season he led the

league in yards gained rushing (1853)

and number of carries (383). In 2003 his

yardage dropped slightly but again he

had the most carries (393).

Williams won’t be playing in 2004.

In late July he made two related stat e-

ments: that he was retiring from football,

and that he found marijuana to be “10

times better for me than Paxil” as a con-

fidence builder. (Glaxo promptly purged

him from the Paxil website.)

Retiring isn’t an easy step. Williams’s

love for football is expressed in the pages

of a journal he’s been posting sporadi-

cally at runrickyrun.com. He has a clear,

colloquial writing style —straight ahead,

like his running style. If we’re lucky,

he’ll soon explain his decision to leave

the game, and keep us informed of his

whereabouts.

Williams was facing a four-game sus-

pension after testing positive for mari-

 juana on two occasions, and he knew he

had tested positive a third time.

“I didn’t quit football 

because I failed a drug test. I 

 failed a drug test because I was

ready to quit football.”

“I didn’t quit football because I failed

a drug test. I failed a drug test because I

was ready to quit football,” Williams told

a writer he trusts, Dan Le Batard of the

Miami Herald, on July 28.

“Williams said there were ‘a hundred

reasons’ for his retirement and that his

desire to continue smoking marijuana

without inhibition was merely one of 

them,” Le Batard reported. “He said he

was not addicted to the drug, but merely

that he didn’t believe in government and

NFL laws banning it. He said he had

already decided to quit football even be-

fore testing positive a second time for

marijuana use last season and incurring

a $650,000 fine. He appealed that fine,

flying to New York to argue his case

before an arbiter with his attorney, but

received word last week that his appeal

had been denied.

“While the appeal was pending, Wil-

liams said he continued smoking mari-

 juana while on tour with rocker Lenny

Kravitz in Europe and failed a third test

upon his return. He said he had been

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O’Shaughnessy’s • Autumn 2004 —17—

from page 1

using a masking agent to cleanse his sys-

tem while being randomly tested for two

seasons, but said he didn’t even bother

before the last such test after returning

from Europe.”

“Williams failed his first drug test

soon after arriving in Miami in 2002.

He spent much of his two seasons with

the Dolphins in the league’s drug pro-

gram, seeing a therapist weekly and sub-

 jected to eight to 10 random urine tests

a month at his home.

“Williams said he continued smok-

ing throughout his time as a Dolphin,

stopping only for a month here and

there, but passed random tests by drink-

ing 32 ounces of a masking agent called

Extra Clean and chasing it quickly with

32 ounces of water...

“Williams, who suffers from social-

anxiety disorder and was a spokesper-

son for the anti-depressant Paxil, said

marijuana helped him once he had tostop using Paxil because it didn’t agree

with his diet.

“‘Marijuana is 10 times better for me

than Paxil,’ he said.

“Williams said he doesn’t see any-

thing wrong with marijuana because it

is ‘just a plant’ and his hero, Bob Marley,

admitted to smoking it daily. Williams

has Marley tattoos all over his body,

named his first child Marley and is

friends with Marley’s children.”

Financial Pressure Will be Applied

The Associated Press reports that the

Dolphins “will attempt to recoup about

$4.7 million in bonus money that Will-

iams has collected due to reaching rush-

ing incentives in his new contract... Mi-ami still believes there is a chance that

Williams will reconsider and decide to

play football, once he realizes he will

have a financial fight on his hands and

once real contact begins.”

The Dolphins had been

using Williams as a “battering

ram,” Steinberg said.

Williams’s current agent, Leigh

Steinberg (the model for Jerry Maguire),

who also thinks his client might change

his mind, made some sensible com-

ments on his behalf. The Dolphins had

been using Williams as a “batteringram,” Steinberg said. “In so many of his

carries he was running straight into the

line. It took a heavy physical toll. Maybe

it took an emotional toll... Running a

football into the waiting arms of 300-

pound defensive tackles whose goal is

to fling one to the turf time after time

requires an extraordinary degree of pas-

sion, and commitment, and he found it

lacking.”

“All NFL players get hurt,” says vet-

eran AP football reporter Dave

Goldberg. “The beating you take is hor-

 Ricky WilliamsFrom Ricky Williams’ Journal• “My shoulder was extremely sore af-

ter this week’s game, and it’s always go-

ing to be [written Sept. 11, 2002] . The

trainers told me that it’s basically going

to flare up every time I get hit on it di-

rectly because I’ve got so much junk inmy shoulders from the wear and tear of football. I’ve gotten what seems like hun-

dreds of X-rays, and it’s amazing to see

how much stuff is in my joints. I’ve sepa-

rated both my shoulders before, and I’m

going to keep getting hit there becauseof how hard I run. It’s kind of unavoid-

able. I can get my shoulder scoped after

the season, but I’m not doing anything

right now except working really hard to

strengthen and protect it. I can’t let any-

thing take me off the field. It’s too im-portant for me to be in there for me and

for the team.

I’m going to have to start doing a lot

more shoulder work. It feels fine right

now because of all the treatment I’ve got-

ten on it, but feeling fine is usually tem-porary in football. I played all last year

with it banged-up pretty good, so it’s not

that big a deal. I’ll treat it and take care

of it, but you better learn t o play with

pain in this game. You always play a littlehurt. The difference between good play-

ers and better players is usually who

plays the best when hurting. It’s amaz-

ing to me to think about the numbers I

could have put up by now if I hadn’t cho-sen to play with so many injuries. I’ve

always had big numbers when I’ve been

healthy, but that’s part of playing in the

NFL. You rarely feel 100 percent, so most

people are trying to do whatever they do

when they don’t feel 100 percent (espe-

cially late in the season). You know howit is when you are young? You always

feel bullet-proof, invincible, and can play

forever. But all I had to do was look at

some of my X-rays to know my days arenumbered.”

• “The marketing lady from the NFL

called and asked if I wanted to do it [a

VISA commercial for which another par-

ticipant would be paid three times asmuch]... Me, thinking I was in the top

echelon of players in the NFL... the mar-

keting lady explained that I wasn’t there

yet. We got into an argument about the

top 3 selling jerseys in the NFL. I startedto realize that I don’t ever want to be there

if that means acting the way she wantsme to, or anyone else wants me to. If I

get there the way I want, being myself,

then I can be proud of it, but I’m not go-

ing to be proud of it if I get there behav-ing the way someone else thinks I

should.”

• “Whenever I do a commercial, the

director always tries to get me to acttough and talk tough. If you haven’t heard

me talk, I have a soft voice. I shouldn’t

have to act tough, I play football. I AM

tough.”

• “Everyone wants to hear what I haveto say. Even when I don’t have anything

to say.”

• “Today I had another interview. I

don’t really understand how many dif-ferent people it takes to write the same

story.”

• “Believe it or not, making a football

team has a lot more to do with who the

coaches like than who the best player is.”

• “Friday night, Coach Wannstedt

brought in a sports psychologist to talk

to us as a team. The psychologist told us

rendous.” Goldberg calls Williams “a

throwback to the ’60s, a free spirit, very

bright. When he was at Texas he decided

he wanted to get to know Doak Walker,

the old SMU halfback, and they became

friends. It was an interesting pairing...

Ricky is really atypical. The profes-sional football environment is —let’s

not call it fascist, but it’s the military

mindset, and the players buy into it.”

Goldberg recalls an NFL executive he

admired, George Young, deciding to

shock everybody at an owners’ meeting

by announcing that he was a Democrat.

When he heard about Williams’s retire-

ment, Goldberg says, he recalled a com-

ment by Young, who was the Giants’

general manager: “Never draft a guy

who’s too smart.”

Attorney David Cornwell has been

helping Steinberg represent Williams. A

former assistant general counsel for the

NFL, he sometimes sounds as if he was

speaking for management: “My recol-lection is we began testing for marijuana

sometime in the ’87-89 contract. The

players association said it was not ap-

propriate. We believed that not only was

it appropriate under the law, it was nec-

essary.”

Your correspondent opined that drug

testing is an assault on a person’s dig-

nity and that by refusing to put himself 

through it, Williams was doing what

millions of Americans wish they could

afford to do. Cornwell responded, “I

think, there is a place for it, if for no

other reason than the stature that pro-

fessional athletes enjoy.”

Cornwell expressed concern that the

NFL program “tends to devolve into aprocess where they focus more on catch-

ing the guy than treating him —if, in

fact, there is a substance abuse problem

or some other underlying issue. When

it comes to education and treatment,

there’s a substantial breakdown.”

Cornwell acknowledged that NFL

team owners use the drug-testing policy

to reduce players’ earning power. “There

have been players that I represented who

have had multiple violations of league-

sponsored substance abuse policy and

were facing some level of suspension.

That certainly had a chilling effect on

their marketability —finding teams to

sign them, and then once a team is will-

ing to sign them, the structure of the con-tract. Because the next violation could

result in either another suspension, a

ban, or something in between. As a re-

sult, teams are reluctant to put in up-

front money or guaranteed money into

a deal if they might lose the guy.”

that the biggest mistake athletes make is

that we think. Off the field, we don’t think

as much as we should. On the field, we

think too much. That make sense? Any-

way, the psychologist told us that we all

have genies that are 7 feet tall, run the40 in 3.5 and vertical j ump 60 inches.

All we have to do is tell our genie what

to do and he’ll do it. In other words, say

positive things and visualize them and

let your genie (your subconscious) playbecause it can do better things that we

can do within the limits of our own bod-

ies. As he talked, I was wondering how

many of the guys on the team thought he

was full of it...[After the game] ...I guess it wasn’t

me that who scored that touchdown,

though, it must have been the genie. Ev-

eryone knows my hands are small, so I

tried to spike the ball but I had a hard

time getting a grip on it and it kind of squirted to the side and I didn’t get the

bounce I was aiming for. I’m pathetic. I

guess my genie still has small hands.”

• “I was an education major in col-lege. I wanted to be a teacher because of 

the important role teachers played in my

life. Growing up with a single mom who

is out trying to provide leaves a lot of 

opportunity for trouble. Without the help,

guidance and confidence I received frommy teachers [in the San Diego public

schools], I would not be where I am right

now. While living in New Orleans, I be-

came aware of the disparity between pub-

lic and private schooling. A lot of chil-dren who can’t afford a private educa-

tion don’t have a fair shake. I was under

the assumption that, as Americans, wewere all supposed to have equal access

to an education. I guess I was wrong.”

• “It’s kinda weird how people just

give us stuff. Just last night some guy

came over and paid for my dinner for no

reason. It wasn’t cheap, either. He just

came over and asked if he could buy it. Iwasn’t going to argue. I got the loaded

Ranger Rover I was telling you about just

for agreeing to do two appearances. I get

it for a year. And I got a $20,000 check

 just for two hours of work on an EA

sports commercial...”

• [After meeting the great running

back Jim Brown]  “He told me the otherday, ‘You are no mystery to me. I knew

you from the time we met.’ We talked alot about athletes using the voice that

sports gives them. Jim is really down on

some athletes for not using theirs, and so

am I. Jim says we are just like slaves who

don’t use the voice because we’re too in-

terested in making money for ourselvesand taking care of ourselves chasing that

all mighty dollar. Instead of a better ex-

istence for everyone...

• “I wish athletes today could have thesame impact on social reform as they did

when he was playing. When the likes of 

Ali, Malcolm X and Jim Brown all sat in

the same room and discussed their viewson America. Nowadays, it seems all some

of us are interested in is how muchmoney we can make. I love playing foot-

ball, and I love making money, but I am

starting to realize that those aren’t the

only reasons God has given me so much

talent. Jim and I talked until about fivein the morning. We talked about every-

thing from how the Browns lost yester-

day to prison riots. It was rewarding for

me to be able to chat with one of the only

people I truly admire in this world.”

Doak Walker

“In a country where they pre-

scribe Prozac to a teenager for

shyness, all marijuana use is

medical.” —Dennis Peron