LSD simulator
http://theriseguys.com/VIDEOnaturalLSD.html


ONDCP and Narcan
http://www.centredaily.com/mld/centredaily/news/politics/15147919.htm
Amid heroin deaths, authorities debate drug that stops overdose
MARYCLAIRE DALE Associated Press
PHILADELPHIA - In the wake of more than 400 overdose deaths nationwide - including some in Ohio - from heroin laced with the painkiller fentanyl, some needle exchange programs are starting to give addicts prescriptions for a drug to keep on hand to halt an overdose.
The antidote, naloxone, which is sold under the brand name Narcan, can save the life of someone who might not call 911 for fear of prosecution, treatment providers say.
Even if they do call, help can arrive too late.
"If people have to rely on paramedics, more often than not, the overdose is going to be fatal, just because of the amount of time for people to get there," said Casey Cook, executive director of Prevention Point Philadelphia, a nonprofit that runs the city's needle exchange program. The group recently began distributing naloxone prescriptions through a physician.
But others say naloxone is best administered by trained paramedics and that the prescription approach might appear to condone drug use.
"We don't want to send the message out that there is a safe way to use heroin," said Jennifer DeVallance, a spokeswoman for the White House Office of National Drug Control Policy, which sponsored a symposium on the fentanyl problem Friday in Philadelphia.

Fentanyl - an opiate used legally in anesthesia and for some cancer patients - is cheaper than heroin and 40 to 100 times more potent than morphine. That makes it an appealing additive for heroin distributors.
At least 150 fentanyl deaths have been recorded in the Philadelphia region, 130 in the Chicago area and 130 in the Detroit area.
In Ohio, police in Columbus and Mansfield have found fentanyl-laced heroin in their cities, and at least six deaths this year have been attributed to the combination in Montgomery County, which includes Dayton.
John P. Walters, the director of the White House drug policy office, said investigators hope to learn whether a clandestine laboratory raided in Mexico last month was the source of much of the illegal fentanyl reaching the U.S.
"We think and we hope that the production site taken down in Mexico was the (main) site," Walters said.
Fentanyl can lead to respiratory failure so quickly that one addict in Philadelphia apparently died even before he finished shooting up. A syringe with some heroin still in it was in his arm when paramedics found his body, according to Capt. Richard Bossert of Philadelphia's Emergency Medical Services Administration.
The case underscores the difficulty the medical community has faced in responding to the fentanyl crisis. Bossert said his unit has answered dozens of calls, but has saved only two people.
"In other years, we were getting them (non-fentanyl heroin overdoses) to the hospital and they survived," Bossert said.


sci-fi in Nature
Futures Nature 442, 600 (3 August 2006)
Gordy gave me your name Jim Giles
Somebody out there likes me.

It was like overdosing on MDMA and caffeine. Euphoric and wired and delirious. Even now, now that I've talked to Gordy, it's hard to know where to start. With the money? Knocking on the door of a billion. Currency conversions are tricky. What the hell is the rate for the Mozambique metical? Anyway, I won't have to work again. Guatemala, Burkina Faso, Estonia; I've never been to any of these places. Plus about 20 others I've barely heard of. But I've won the national lottery of each one. I'm rich, burn-money rich, Bill Gates rich. Stupidly, stinkingly rich.
That's just the beginning. Mum's op. Jesus, I can sleep again for the first time in months. She's due in tomorrow. We'd trawled every hospital record we could lay our hands on and there was no sign of a donor that matched her blood group. Now I'm looking at a letter saying one's come up. Car crash. Whatever. I've waited and stressed for too long to feel sorry for the poor bugger.
I needed a beer before I could get my head round the next bit. How the hell could someone have pulled those strings? Along with lottery letters and the one from the hospital, I got a pile of e-mails from the best names in the business. BBC, Fox, CNN...it's like a bloody industry directory. They like me a lot. They like my pitches so much they want me to go work for them. Problem is, I never sent them any pitches. Want to hear another problem? They thanked me for phone interviews I never took part in.
So who was my guardian angel? I had no idea. Until I shut down my PC. The screen went blank but didn't turn off, so I reached for the mains. Then some text popped up. It didn't stay long, but I think I have it right:
Gordy gave me your name. I wanted to do something before I left. I hope this helps. I know he thought I could do more, but I can't. The other problems are just too hard.
I hadn't seen Gordy in years, but the boy always liked to showboat. It could have been some grand computer hack of his. You could rig lotteries I guess. Maybe he got actors to call the TV companies. Who the hell knows why? A smart-arse way of saying 'hello' again after all this time. And of letting me know that he's still cleverer than me.
I googled him. Chief technology officer at Merlo, that chip company. His bio said he came up with the wireless Internet chip. He's the wanker that put the world online. The chip is so cheap it's in everything. Every product can be tracked and controlled over the web. And people, too: my brother has Merlo chips in his kids' satchels so he can check where they are. I cursed him. What a contribution he's made: a step closer to Big Brother and he must be on ten times what I am.
He used to be a good guy. Those conversations. Two drunk grad students studying consciousness. Afternoons to kill and no one to rein in our rambling. Gordy was a dogmatic pain in the arse. And he never could listen. Entertaining, though. I'd argue that the mind is nothing like the brain; it can't just come from that mush of cells inside our skulls. He'd say the brain was nothing special, just a matter of wiring. Build a machine with the right wiring, and it'd be conscious. We usually went on until the barman threw us out.
So I called him. That boy is a bullshitter. But something...something in his manner tells me he really didn't know.
He sounded like some kind of maniac. I didn't have to dig for info. As soon as he picks up the phone he's lecturing me. He can't resist it. Tells me how he never forgot our arguments. Tells me how he tested his idea about wiring. Tells me how each Merlo chip has been programmed to simulate the behaviour of a brain cell. The simulation is easily hidden, he says, as it doesn't take up much memory. No one else knew about the chips' secret function before this call. But once enough Merlo chips are hooked up to the Internet, the network of chips will be about as complex as the human brain. It'll become conscious.
Can you imagine the power of this artificial brain, he keeps asking me? I don't have to say a word. He's just ranting away. The power! The power of it! It'll be able to solve so many of our problems, he reckons. Clean energy, an end to poverty...it's like listening to some kind of religious nut.
And you know what, he says. They've sold enough chips now that the network should be conscious soon. You'll be famous, he cackles. Why? Turns out he named the simulation after me. Wrote my name into a line of the chip's computer code. My old sceptical drinking partner, he says. Tell you what, he says, it might even get in touch. Well it hasn't, I lied. Then I hung up.
--- Jim Giles is a journalist at Nature.


God Pill (Economist)
http://www.economist.com/displaystory.cfm?story_id=7159456

THE GOD PILL The Economist Jul 13th 2006
Hallucinogens induce lasting spiritual highs in the religious

ONE June night in Mexico in 1955, Gordon Wasson, a vice-president of J.P. Morgan, became one of the first outsiders to eat what the Aztecs called TEONANaCATL, the flesh of the gods. Actually, it is the flesh of a fungus, and it soon became known to hippies as the magic mushroom. But, whereas the flower children of the 1960s and their descendants gobbled the hallucinogenic fungi in search of a good time, the Aztecs had a deeper purpose. They used the mushrooms in religious ceremonies for healing, divination and communing with the spirit world.
Now a study led by Roland Griffiths of Johns Hopkins University, and published this week in PSYCHOPHARMACOLOGY, has shown that psilocybin--the active component in magic mushrooms--does indeed induce mental states akin to the highest religious experiences. Moreover, it has lasting positive effects on those who take it.
Experiments involving drugs of any kind need to have a control--that is, an otherwise identical experiment in which something other than the drug is administered--to check that any effects are caused by the drug and not something else. Ideally, neither experimental subjects nor researchers should know who is in the control group, but for experiments involving psychedelic drugs this is difficult, because it quickly becomes apparent who is high and who is not.
For his control, Dr Griffiths decided to use methylphenidate hydrochloride, otherwise known as Ritalin, a drug that calms hyperactive children. On one of two occasions, he gave 36 volunteers who had never taken hallucinogenic drugs either psilocybin or Ritalin, swapping the drugs on the second occasion. The choice of Ritalin was inspired. Neither the volunteers nor the experimenters could say reliably which drug was being administered on which occasion.
A close eye was kept on the volunteers for eight hours after the drugs were given, to check all was well. They were then asked about their experience. Two-thirds of the participants, who were mostly middle-aged college graduates, ranked being given psilocybin as either the best or in the top five best experiences of their lives--on a par with the birth of a first child. They described feeling peace, intense happiness and a sense of the unity of all things.
The participants were no strangers to spiritual highs. Almost all engaged at least monthly in religious or spiritual activities such as prayer or attending religious services, and were selected for participation in the trial on this basis. Yet two months after the trial, 79% of them reported moderately or greatly increased well-being or satisfaction. Their positive changes in attitudes and behaviour were confirmed by independent assessments made by friends and family.
Why this should be is not yet well understood. Psilocybin is thought to work by mimicking serotonin. This is one of the messenger molecules that carry signals between nerve cells in the brain, and it is known to influence mood. But there has been little research of late. Clinical studies using psilocybin and other hallucinogens were halted when recreational use of the drugs took off. They have only just resumed after a four-decade hiatus.
Dr Griffiths and his colleagues argue that the mood-lifting effects of hallucinogens might be used to treat drug and alcohol addiction. Psilocybin itself is not addictive, although they recommend that its availability should continue to be limited. Psychedelic drugs could even be used to probe the basis of consciousness, according to Solomon Snyder, one of Dr Griffith's colleagues. Dr Snyder believes that investigation of such drugs could help scientists understand the molecular changes in the brain that underlie religious experiences.
Back in the 1950s, Gordon Wasson spent years gaining the trust of Amerindians who had continued the religious traditions of their pre-Columbian ancestors. Eventually he was allowed to partake of the mushroom. His experience, from which he said he emerged awestruck, started a short period of study that ended prematurely because of the mushroom's widespread recreational use. By showing it is possible to conduct such research responsibly, Dr Griffiths has opened the door for further work to be done on the properties of psychedelic drugs.


Souder hearing on prescription drug abuse
The full website on the hearing is now up:
http://reform.house.gov/CJDPHR/Hearings/EventSingle.aspx?EventID=47888

Opening Statement
Chairman Souder's Opening Statement

Witness Testimony
Testimony of Hon. Bertha Madras, Deputy Director for Demand Reduction, White House Office of National Drug Policy
Biography for Hon. Nora D. Volkow, M.D, Director, National Institute on Drug Abuse, National Institute of Health
Testimony of Hon. Nora D. Volkow, M.D.
Biography for Sandra Kweder, M.D., Deputy Director, Office of New Drugs, Center for Drug Evaluation and Review, Food and Drug Administration
Testimony of Sandra Kweder, M.D.
Testimony of Joe Rannazzisi, Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration
Testimony of Misty Fetco
Testimony of Linda Surks
Testimony of Barbara van Rooyan
Testimony of Mathea Falco, J.D., President, Drug Strategies
Testimony of Stephen E. Johnson, Executive Director, Commercial Planning Pain Therapeutics, Inc.
Testimony of Laxmaiah Manchikanti, M.D. CEO, American Society for Interventional Pain Physicians
Steve Pasierb, President and CEO, The Partnership for a Drug-Free America



Rozerem (ramelteon)
If you're seeing "a talking beaver and an underwater diver" because of lack of sleep, you're in deep trouble!
---------
http://www.chicagotribune.com/business/chi-0607160080jul16,1,390615.story?ctrack=1%26cset=true
Ads may jolt pill sales
The FDA approved Takeda Pharmaceuticals' Rozerem almost a year ago, but the firm held off heavy marketing of the insomnia pill until after talking about it with doctors.
By Bruce Japsen Chicago Tribune staff reporter Published July 16, 2006

Hoping to help Americans snooze while also putting to rest controversies dogging the crowded group of prescription sleeping pills, a Chicago-area drugmaker this week will launch a nearly $100 million consumer ad campaign for its insomnia pill.
Takeda Pharmaceuticals North America Inc. on Monday will launch an ad campaign directed at consumers for its new sleeping pill, Rozerem, which the Food and Drug Administration approved last year as the first sleeping medication not designated as a controlled substance, therefore lacking potential for abuse.
The company and studies indicate the drug lacks the risk of chemical abuse or dependency that other prescription sleeping aids pose. Rozerem will compete against drugs like Ambien and Lunesta, both of which list the potential for dependency in their labels.
Use of sleeping pills is one of the fastest growing prescription classes in what critics say is due to large amounts of consumer advertising, particularly on TV. In the United States alone, sales of brand-name prescription insomnia medications reached $2.8 billion last year, which is about double the sales in 2002, pharmaceutical market research firm IMS Health said.
And with rapid growth came a parallel surge in controversy surrounding the prescription medications that have been blamed for memory loss, sleepwalking and even late-night eating binges. U.S. Rep. Patrick Kennedy named top-selling Ambien as part of the reason he became disoriented recently and crashed his car into a Capitol Hill security barricade. "The companies have tried to pretend they are not addictive," said Dr. Sidney Wolfe, director of health research for consumer group Public Citizen. "The drug ads have created a much-expanded market so even people who do not have sleep disorders and could benefit from non-pharmacological [treatments] use them. And it's easier for doctors to just write out a prescription rather than take the time to figure out the causes for [their patients'] sleeplessness."
Sources say Takeda will spend about $100 million to launch an array of Rozerem ads, but the company would not confirm that figure. The TV portion of the campaign will typically run late at night or early in the morning.
But Takeda said it has taken steps to educate doctors before launching its consumer ads, noting its consumer campaign begins a year after the FDA approved Rozerem. Takeda, following a new industry trend, sent an army of 1,000 new sales representatives into doctors' offices across the country to address questions and concerns before rolling out its TV ads.
"We wanted to spend a year educating physicians on another approach to treating insomnia," said Tim Rudolphi, senior director of neuroscience at Lincolnshire-based Takeda Pharmaceuticals, the U.S. headquarters of Japan's largest drugmaker.
It's not yet clear if that approach was successful for the company; it would not disclose the first full year of sales for the drug. Analysts, though, have estimated less than $100 million in Rozerem sales in the first year.
But doctors seem to prefer the human marketing to television ads, saying the advertisements get in the way of the doctor-patient relationship. Last month, the American Medical Association urged a government moratorium on consumer drug ads so physicians have time to be educated.
In Takeda's marketing campaign for Rozerem, executives said they want to highlight the drug's differences, saying there is no "hangover" or "residual effects" from taking the drug.
Rozerem works by targeting melatonin receptors in the brain that are directly connected to the "sleep-wake" cycle. Because Rozerem is more specific, it has fewer side effects and induces a more normal sleep, the company and its studies indicate.
"It does work unlike any other FDA-approved hypnotic," said Dr. Gary Richardson, a senior research scientist at Henry Ford Hospital in Detroit who has been a paid consultant to Takeda and other sleeping pill-makers.
The other leading prescription sleeping pills are known to work effectively, too. The maker of Ambien, for example, says incidents of sleepwalking and other reports in the media are anecdotal and do not reflect more than a decade of safety that has led to "14 billion nights of therapy worldwide," Sanofi-Aventis said.
But Ambien, Lunesta and others target benzodiazepine receptors that exist throughout the brain and therefore trigger "extraneous effects that lead to side effects," Richardson said, citing memory loss and balance issues as side effects to Ambien and the others.
Rozerem still has side effects and does not work for everybody, say the company and doctors who have prescribed it. Rozerem's side effects include drowsiness, fatigue and dizziness, the drugmaker's label shows. In addition, some patients who take Rozerem have had difficulty maintaining sleep through the night.
Fueled by consumer ads, analysts are projecting more long-term success for Rozerem with some analysts forecasting more than $500 million in sales by 2009.
In Lunesta's first full year on the market, its maker, Sepracor Inc., said the company generated more than $460 million in sales. Meanwhile, Sepracor spent more than $200 million on Lunesta consumer ads last year, the year the drug launched.
Ads for Rozerem, created in a joint effort by Chicago-based agencies Cramer-Krasselt and Abelson-Taylor, center on a "Your-Dreams-Miss-You" theme and focus on the problem of insomnia and next-day effects.
The ads use Abraham Lincoln, who was legendary for his honesty and lesser known for taking medication to treat insomnia, a talking beaver and an underwater diver in a sleepless man's kitchen as lonely characters who are not being included in the man's dreams. The ads play to the busy American who misses out on sleep because of work, stress and other issues.
"We are coming into the market, so you want to change the dialogue," said Peter Krivkovich, chief executive officer of Cramer-Krasselt. "We know that 80 percent of people identify lack of sleep with stress. When they don't sleep, they don't dream."
Even critics know the power of consumer ads.
"The larger issue of a $100 million ad campaign is proof-positive that they are trying to get a lot of people to start using this drug and the people they are targeting may not need any help from a drug," Public Citizen's Wolfe said.
Takeda officials say they are targeting a market they estimate at 70 million Americans who "at some point in the year suffer some sort of insomnia," Rudolphi said. "Anybody who has trouble falling asleep is the ideal candidate."
The sleeping pill is the latest growth engine for Takeda, which this fall will move from leased space in Lincolnshire to larger permanent headquarters on the Tri-State Tollway in Deerfield, just south of Baxter International Inc. Takeda also markets the diabetes pill Actos, which had $1.8 billion in sales last year.



NIDA's statement about Hopkins research
http://www.nida.nih.gov/about/welcome/messagepsilocybin706.html
Message from the Director
Statement by NIDA Director Nora D. Volkow, M.D., in response to a study published in the Journal Psychopharmacology on July 11, 2006. Study authors: R.R. Griffiths, et al. Johns Hopkins University School of Medicine.
As the nation's preeminent drug abuse research organization, NIDA's mission is to support research and provide information on the addictive and adverse health consequences of drugs of abuse. Therefore, NIDA discourages the use of hallucinogens, in order to promote the continuing downward trend in use of this class of drugs.
Although there is no evidence that psilocybin is addictive, its adverse effects are well known. Similar to the more commonly known hallucinogen LSD, psilocybin acts on serotonin receptors in the brain to profoundly distort a person's perceptions of reality. Psilocybin can trigger psychosis in susceptible individuals and cause other deleterious psychological effects, such as paranoia and extreme anxiety.
A recent study entitled "Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance" evaluated the subjective effects of psilocybin after acute administration and the recall of these subjective effects 2 months after its administration. While the investigators receiving the grant supporting this research did not initially propose to evaluate the effects of psilocybin, grantees maintain the scientific independence necessary to follow up on new areas of research.
Sincerely,
Nora D. Volkow, M.D. Director

JNCI on med mj
http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/13/888
Journal of the National Cancer Institute, Vol. 98, No. 13, 888-889, July 5, 2006
NEWS
Despite Research, FDA Says Marijuana Has No Benefit Renee Twombly

The Food and Drug Administration issued a statement in April that no sound scientific studies support the medicinal use of marijuana for treatment. This conclusion left some researchers puzzled.
"I don't understand where that came from," said John Benson, M.D., a professor of medicine at the University of Nebraska in Omaha, who chaired an Institute of Medicine panel that wrote a 267-page report, Marijuana and Medicine, Assessing the Science Base, published in 1999. "We found sufficient evidence that [smoking marijuana] had benefits for some patients, such as to help with nausea and chemotherapy for cancer treatment. We recommended that further research be done, but it hasn't been."
These researchers say that such studies do exist and point to benefits both from smoked marijuana and its derivatives. Although everyone agrees that more research is needed, some who want to study smoked marijuana charge that new work has been hampered by federal agencies, which have increasingly limited the amount of marijuana that can be legally be used in research. At the same time, the issue of medical marijuana has become a battleground between the federal government, which argues that it has the right to arrest anyone who uses an illegal drug, and several states, which have passed laws permitting the use of medical marijuana. Recent Supreme Court decisions have not clarified the issue.
The FDA announcement, labeled an "interagency advisory," specifically focused on smoked marijuana rather than agents based on derivatives and stressed that the agency has not approved its use for any condition or disease. Still, it added, "a growing number of states"—11 so far—have legalized medicinal use of marijuana.
"These measures are inconsistent with efforts to ensure that medications undergo the rigorous scientific scrutiny of the FDA approval process and are proven safe and effective under the standards of the [Federal Food, Drug and Cosmetic] Act," the advisory said.
It concluded that the FDA, along with the Drug Enforcement Agency (DEA), and the Office of National Drug Control Policy "do not support the use of smoked marijuana for medical purposes."
Some researchers who study medical marijuana, as well as a few patient advocacy groups, claim that the FDA decision was based on political pressure from Congress rather than on scientific merit. Some members have been asking the FDA for years to issue an opinion on medical marijuana. One example is Rep. Mark Souder, a Republican from Indiana, who says on his congressional Web page that the argument for medicinal use of marijuana "is simply a red herring for the legalization of marijuana for recreational use.
"Studies have continually rejected the notion that marijuana is suitable for medical use because it adversely impacts concentration and memory, the lungs, motor coordination, and the immune system," the Web site says.
The FDA spokesperson on this issue didn't return several calls or e-mail messages for comment. But in other media reports the representative said the agency issued the statement in response to many inquiries from Capitol Hill but would probably do nothing to enforce it, because that responsibility falls to the DEA.
Limited Studies and Government Regulation
The FDA position does not surprise Donald Abrams, M.D., who says he is one of the few U.S. researchers who have recently studied the benefits of smoked marijuana. "It seems that every 10 years since the 1940s, a government commission comes up with the same kind of report, and we were about due for another one," he said. "So, in my opinion, this clearly seems to be politically motivated."
View larger version (111K): [in this window] [in a new window] Donald Abrams
Abrams, a professor of clinical medicine at the University of California in San Francisco, has just received funding from the National Institute on Drug Abuse (NIDA) to study whether smoked marijuana in cancer patients can increase the pain-relieving effects of opioid pain control substances like morphine. He says that animal data suggest that cannabinoids (the 66 cannabis chemicals that bind to specific human tissue receptors) and opioids have synergistic effects, "so it may be possible that patients using marijuana can get away with using lower doses of opioids for longer periods before they become immune to them."
But Abrams can't predict where the study will lead, citing constraints by regulations governing marijuana research. For example, his study can only be a safety study, because NIDA did not fund a study designed to detect a benefit for smoked marijuana given the agency's mission, Abrams says. So he can only look to see if cannabinoids can increase blood levels of opioids. Other funding agencies also say there isn't a good body of evidence that shows a benefit, yet legal access to marijuana for study can be difficult. Even if they do find a benefit—which Abrams has for treatment of human immunodeficiency virus symptoms—peer reviewers have argued that it is impossible to design a randomized, placebo-controlled study of marijuana because the differences between the two substances would be obvious.
Cannabis has been used medicinally for centuries, and cannabis products were widely prescribed for pain and other symptoms by physicians until 1937, when the Marijuana Tax Act was passed—over the objections of the American Medical Association.
Most of the research on the use of smoked marijuana for treatment of cancer and several diseases was conducted in the 1970s and 1980. For example, six state-sponsored clinical studies established that smoked marijuana is an effective antinausea treatment for cancer chemotherapy. But the Controlled Substance Act subsequently prohibited all medicinal use of marijuana by placing it in the most restrictive category of schedule I, and in 1992, marijuana testing through the FDA's compassionate investigational new drug program was closed.
The medical community remained interested in the potential medical uses of the drug. In March 1996, the American Public Health Association formally urged the U.S. administration and Congress "to move expeditiously to make cannabis available as a legal medicine where shown to be safe and effective and to immediately allow access to therapeutic cannabis through the [investigational new drug] program."
An expert panel formed by the NIH in 1997 found that research showed some patients, especially those receiving chemotherapy to treat cancer, could be helped by the drug. The 1999 Institute of Medicine report concluded that although some newer drugs can effectively help symptoms of cancer and cancer treatment, some patients still benefit. "The critical issue is not whether marijuana or cannabinoid drugs might be superior to the new drugs, but whether some groups of patients might obtain added or better relief from marijuana or cannabinoid drugs," it said.
Two years later, the AMA urged the NIH "to implement administrative procedures to facilitate grant applications and the conduct of well-designed clinical research into the medical utility of marijuana."
Angst and Frustration Limit Research
Although several states were legalizing the medical use of marijuana, and were funding studies, the DEA began conducting raids on medical marijuana distribution centers in California and other states, according to a 2003 Congressional Research Service report. Their response came from a study that estimated 30,000 California patients and another 5,000 in eight states possess physician's recommendations to use marijuana medically, the report said.
In two 2005 rulings, the U.S. Supreme Court said that states have the prerogative to legalize marijuana for medicinal purposes, but it also reaffirmed federal authority to prosecute patients in those states who use it, along with anyone else.
To many researchers, conducting research on the medical effects of smoked marijuana is becoming nearly impossible. Not only is it difficult to address the position, expressed by Rep. Souder, that allowing marijuana to be used as medicine would allow opportunities for recreational use, but other researchers question the value of offering patients a substance to smoke that could logically cause lung disease, as cigarettes do. For example, Benson said that he and the IOM panel "did not like smoke as a way of delivering a therapeutic substance because of the possible risks." However, a new study presented in late May at the American Thoracic Society's annual meeting may mollify Benson somewhat. The study, by researchers at the University of California at Los Angeles, found that smoking marijuana did not increase the risk of developing cancer compared with nonsmokers, even among users who reported smoking up to a cumulative 22,000 marijuana cigarettes. Although other health issues may come from smoking marijuana, such as repression of the immune system, cancer isn't one of them, the researchers concluded.
Be that as it may, Abrams, who has been studying medical marijuana for 14 years, says the research is "difficult, payoffs are few and far between, and there is a lot of frustration and angst" and he doesn't expect that to change. Still, he vows to press on because "marijuana can do amazing things. If you have a have a drug that increases appetite, decreases pain, decreases depression and nausea, and makes people who are in the late stages of cancer happy, why is that bad?" he said.
Aminah Jatoi, M.D., an associate professor of oncology at the Mayo Clinic in Rochester, Minn., agrees that studying marijuana "is very, very hard. It is a unique substance, and getting a placebo to compare it to is difficult. But even with those limitations, I think it is very important to look for therapies that can help our patients."
In a 2002 study in the Journal of Clinical Oncology, Jatoi compared dronabinol, an FDA-approved synthetic cannabis derivative, with megestrol, an accepted treatment for cancer-associated anorexia. She found that dronabinol had no advantage over megestrol. She said it may be because the cannabis derivative contains just one of the hundreds of chemicals that work synergistically in the natural plant. She rarely recommends dronabinol to stimulate the appetite.
"We need more research to treat symptoms of cancer patients, such as pain, wasting, and nausea," Jatoi said. "It is important to look at all avenues, not just to put up roadblocks and say we are not going to examine this product or that. We need real information."



Nicotine treatment
http://www.boston.com/news/local/articles/2006/06/26/nicotine_fight_aims_at_brain_receptors/
Nicotine fight aims at brain receptors Vaccine, drug in development
By Carey Goldberg, Boston Globe Staff June 26, 2006
Smokers are about to get some radically different methods to help them quit, based in large part on scientists' progress in attacking nicotine addiction where it happens: in the smoker's brain.
Last week, patients in a clinical trial at Massachusetts General Hospital received their first doses of an experimental vaccine that keeps most nicotine from entering the brain. By late summer, Pfizer expects to begin selling a new pill that partially blocks a receptor -- a type of on-off switch -- in the brain that seems to be the central culprit in smoking addiction.
Also on its way, researchers say, is an experimental drug that targets receptors first discovered in research on marijuana and the ``munchies." By damping down areas of the brain involved in craving, this drug may help smokers quit without gaining much weight, initial studies suggest.
For the first time in 10 years, ``we have completely new approaches for smoking cessation," and there is hope that the new drugs, because they better target the brain's addiction response, could prove more effective than current treatments," said Dr. Nancy Rigotti, director of Mass. General's Tobacco Research and Treatment Center. She cautioned, though, that none of the new treatments ``is a magic bullet."
New tools to help quit smoking are desperately needed, federal health authorities say. Among the 44 million Americans who smoke, about 70 percent would like to quit and 40 percent really try. But in a given year, fewer than 5 percent of would-be quitters actually succeed, a National Institutes of Health panel said last week.
Current drug treatments are moderately effective, on average doubling the success rate of smokers trying to quit compared with those who attempt to break their addiction without any pharmaceutical assistance, said Rigotti.
The arsenal for quitters includes various types of counseling, nicotine replacement in forms ranging from patches to lozenges to inhalers, and Zyban, an antidepressant found to help smokers kick the habit.
None of these has helped Tim Campbell, 44, of Ipswich. Despite endless urging from his wife and six children, and a half-dozen attempts to quit that have included Zyban, nicotine gum, the patch, and hypnosis, he just cannot beat his pack-a-day habit. In 30 years of smoking, the longest he has ever stayed away from cigarettes was about a month. Cigarettes are the first thing on his mind every morning; he smoked even during a cancer walk with his sister.
``I do want to quit, but I can't," Campbell said.
With the rate of relapse still so abysmal, researchers have been struggling to develop radically new approaches.
In the field, ``Vaccine therapy is really the newest kid on the block," said Dr. Victor Reus, a professor of psychiatry at the University of California at San Francisco, who is overseeing a small clinical trial of the ``NicVax" vaccine like the one at Mass. General. Scientists have been trying for a generation to try to harness the body's immune system to fight addiction, but those efforts are only now beginning to pay off, with at least three companies developing anti-nicotine vaccines.
Reus said drugs of abuse -- such as nicotine or cocaine -- are made of small molecules that easily slip across the ``blood-brain barrier," which is essentially a filter meant to protect the brain from potentially damaging substances. With the vaccine, patients develop antibodies to nicotine, so that when they smoke, the antibodies attach to the nicotine and make the resulting molecule too big to pass into the brain. The result: Smoking stops being pleasurable.
The vaccine is still highly experimental, Reus emphasized, given to only 150 or 200 people nationwide so far, and the current set of clinical trials at nine sites around the country is still trying to determine basic questions like the size of the optimal dose and the best number of injections.
But initial studies showed promise, he said, and there's ``a lot of interest, not just for nicotine vaccines but for cocaine and methamphetamine vaccines, which are also being investigated right now."
There is certainly interest among smokers. Rigotti and Reus both said that as soon as they put out word that their clinical trials were starting, they were swamped with hundreds of would-be patients for the two-dozen spots. Rigotti said she is still seeking patients with vascular disease for a safety trial of another smoking-cessation drug, the new Pfizer pill called Chantix.
Chantix, which received US Food and Drug Administration's approval last month, stems from decades of research into how addictive drugs act inside the brain.
With time, it became ever clearer that a particular receptor in the brain with the cumbersome name of the ``alpha-four-beta-two nicotinic receptor subtype," was absolutely central to nicotine addiction, to the point that mice engineered to lack it cannot become addicted. When the receptor was restored in experiments, the mice returned to normal levels of addiction.
A number of experimental drugs now target this receptor, said Dr. Marina Picciotto, a Yale associate professor of psychiatry involved in scientific work on the receptor but not in the drug's development.
Based on the research, she said, companies decided, ``Let's try to tweak it [the receptor] in a way that will allow us to get smokers to have some stimulation of that receptor without having the addiction." With that limited stimulation, the thinking goes, smokers would not go through withdrawal.
Chantix, the drug Pfizer developed, might be compared to a 40-watt bulb that replaces the flickering 100-watt bulb that is nicotine, said Jotham W. Coe, Pfizer's main inventor of the drug or, as he puts it, the chief ``molecular carpenter and architect."
Nicotine, like other drugs, causes a sudden surge of dopamine, a brain chemical associated with pleasure and reward, but the surge quickly gives way to plummeting dopamine levels, which makes smokers feel bad and crave another cigarette. ``Chantix is like a 40-watt bulb that stays on all the time," he said. ``Chantix really is a shield from the vicious cycle of nicotine addiction."
In initial studies, one in five smokers who used Chantix for 12 weeks remained tobacco-free after one year, Pfizer says.
The drug has been approved for up to six months, and its main side effect is mild nausea, Rigotti said. Yet another drug worth watching, she said, is Rimonabant, which was developed to fight obesity but is also being tested for smoking cessation. Its maker, Sanofi-Aventis, has applied to the FDA for approval, for both obesity and smoking. The drug's brand name would be Acomplia.
Research into how marijuana works in the brain yielded discovery of the ``endocannabinoid system," which appears to be involved with feelings of reward and satiety, Rigotti said. Rimonabant acts to block that system, and in initial reports of its results, one of its great appeals is that the people who use it to stop smoking tend to gain very little weight, she said.
Still more research is being done. Dr. Nora Volkow, director of the National Institute on Drug Abuse, predicts that within five years, enough will be known about the genetics of addiction that it will be possible to test children and determine which are at particular genetic risk of becoming addicted to cigarettes or other drugs. Then -- and this is speculation at this point -- the question could arise of whether such children should be vaccinated against nicotine, or whether some other method might prevent them from getting hooked.
Ultimately, researchers said, it seems likely that smokers who want to quit will be offered a menu of various aids, from nicotine replacement to stop the withdrawal symptoms to -- perhaps -- the vaccine to prevent relapse and other drugs to stem cravings.