(The problem with medical studies on Cannabis)
Cannabis, the third most popular recreational drug after alcohol and tobacco, could win new role as the aspirin of the 21st century, with growing evidence that its compounds may protect the brain against the damaging effects of ageing.
Although the drug distorts perception and affects short-term memory, it may also help prevent degenerative diseases such as Alzheimer's, Parkinson's, Huntingdon's and motor neurone diseases. Scientists at the Institute of Neurology in Queens Square, London, say the "huge potential" of cannabis compounds is emerging, as understanding of its biological and pharmacological properties improves.
Professor Alan Thompson and his colleagues wrote in Lancet Neurology: "Basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection."
The results of two trials in patients with multiple sclerosis are expected this summer and the first cannabis-based medicines are being considered for licensing. None of them will have the psychoactive properties of the raw drug when smoked or ingested.
Professor Thompson's team says: "Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear."
Cannabis was thought to affect the cells like alcohol by seeping through the cell membrane. But in 1990 the first cannabinoid receptor was found, which revolutionised the study of cannabinoid biology. The discovery revealed an endogenous system of cannabinoid receptors, similar to the opioid system, to which the drug bound when it was ingested. Just as endorphins are the body's natural equivalent of heroin, a fatty acid called anandamide ( Sanskrit for "inner bliss" ) is the natural equivalent of cannabis.
The natural system of cannabinoid receptors plays a role in maintaining the balance of chemicals in the brain which regulate the rate at which neurons fire. By altering this system, scientists believe it may be possible to slow or prevent the process of brain decay.
David Baker, lead author of the Lancet review and senior lecturer at the Institute of Neurology, said: "Alzheimer's disease is the result of very slow degeneration caused by the death of nerve cells. We probably don't see symptoms until 30 to 40 per cent of the nerve cells have died. Something regulates this decay and if we could slow it by even a small fraction we might delay by a decade the point where someone loses their memory."
But cannabis is a double-edged sword, with potentially damaging side effects. "It may be possible to develop drugs that allow selective targeting of different areas of the brain and spinal cord and there may be a way of limiting the negative effects," Dr Baker said.
A study by Dr Baker and colleagues, in which the natural system of cannabinoid receptors was removed in mice, showed that the rate of nerve loss was increased, indicating its role in preserving brain function. The study, which has been accepted for publication in a medical journal, "really clinches the argument", Dr Baker said.
He added: "Cannabis has gone from the drawing board into trials in record time, largely because of patient pressure. Hopefully it will work and be acceptably safe."
UK: Cannabis May Be 21st Century's Aspirin
URL: http://www.mapinc.org/drugnews/v03.n599.a06.html
Newshawk: Rick Day, GOP Lobby
Pubdate: Sat, 19 Apr 2003
Source: New Zealand Herald (New Zealand)
Contact:
[email protected]
Copyright: 2003 New Zealand Herald
Website: http://www.nzherald.co.nz/
Details: http://www.mapinc.org/media/300
CANNABIS MAY BE 21ST CENTURY'S ASPIRIN
Doctors Want Better Marijuana for Study
San Mateo -- Nearly two years after its launch here, doctors conducting a groundbreaking medical marijuana study want better quality weed from the federal government. The study leaders also want to allow more sick people to participate, but are stymied by stringent eligibility requirements.
"The study continues but it is going slowly for a variety of factors," said Dr. Dennis Israelski, director of medical research in San Mateo County and chief of staff at San Mateo Medical Center.
The County has waited at least six months for a response from federal agencies, officials said.
The 3-year County study seeks to discover whether marijuana "cigarettes" can be safely dispensed to HIV-AIDS and cancer patients to treat symptoms and side effects of disease treatment.
However, some believe the apparently low-grade marijuana used in the program -- grown at the University of Mississippi by the federal government -- has discouraged participants who can treat themselves with the drug through other channels.
And stringent physical requirements on often terminally ill patients have also slowed membership in the study.
The first HIV-AIDS participant, Phillip Alden, who dropped out of the study when he came down with bronchitis, said he would re-join if the marijuana were of better quality.
"I certainly hope they get better quality pot," Alden said. "If they wanted me to re-enter the study, I would. I would love to see the study succeed."
Alden also said he objected to the cigarette papers that the marijuana was rolled in, believing they contained toxins.
San Mateo County Supervisor Mike Nevin, a former San Francisco police inspector, had waged a campaign since 1997 to bring about the County's medical marijuana study. It was launched in April 2001 at the County's medical center.
"This is not a cannabis club we're talking about. It's a very tight, closed, secure program," Nevin said.
When the County got initial state and federal approvals in 2001 -- including approvals from federal law enforcement agencies under the Clinton administration -- it was considered groundbreaking.
County officials hoped the study would not only provide relief to patients, but would begin to bridge the gap between Proposition 215, the successful 1996 state ballot measure that allowed medical marijuana, and existing laws that criminalize the drug.
"They need to supply us with something more meaningful for our trials," Nevin said. "We're losing patients."
Nevin frequently refers to personal testimony of the late Joni Commons -- the County's deputy director of health services -- as his inspiration for the medical marijuana study. Commons struggled with breast cancer and said she found relief from treatment only through the use of marijuana, according to those who knew her.
Israelski -- medical director of the study -- also sees a need for a non-smokable form of marijuana for pain relief from chronic disease.
"The County is well-positioned to lead in this effort because of the enlightened leadership here and the environment of dynamic change at San Mateo Medical Center," Israelski said.
Source: San Mateo County Times, The (CA)
Author: Jean Whitney, Staff Writer
Published: January 24, 2003
Copyright: 2003 MediaNews Group, Inc.
Contact:
[email protected]
Website: http://www.sanmateocountytimes.com/
Activists Complain About Government Pot Quality
Activists who support the legalized use of marijuana for medical purposes say U.S. government-run farms are growing low-quality pot, thereby undermining research into its medicinal benefits.
"It's unconscionable that they would be giving this marijuana to patients," National Organization for the Reform of Marijuana Laws coordinator Dale Gieringer told the San Jose Mercury News. "It's stale, low-potency ditch weed."
The newspaper noted that several observers were critical of the marijuana grown on farms in Mississippi run by the National Institute on Drug Abuse.
They said the pot was full of sticks, stems and seeds, with stale leaves caused by repeated freezing and thawing during storage.
Journal of Cannabis Therapeutics editor Ethan Russo said patients participating in any other medical study would not be given such a stale product.
Officials overseeing a marijuana study in San Mateo County, Calif., say fewer than 10 subjects are participating, even though they had budgeted to accommodate up to 60.
Mike Nevin, the program's supervisor, said he does not want the perception to ruin the research.
"We've put too much effort into this, and we don't want to be playing games here," he said. "It needs to be a certain grade of substance, and unless it's stronger, they'll set us up for defeat."
Stanford University clinical professor Dennis Israelski said problems with the marijuana have gotten out via the Internet and from HIV support groups.
"We've been hurt by word on the streets," Israelski said. "But the word on the street might not reflect reality."
Steve Gust, a special assistant with the drug abuse institute, downplayed the quality issue, saying there's nothing wrong with the government-grown grass that is pre-rolled, frozen and sent from the Mississippi farms to sanctioned researchers across the U.S.
Gust said re-humidification of the plant "makes it kind of harsh," adding that "certain procedures are needed to make it smoke right."
Gust also said he thinks NORML and other marijuana legalization activists are looking for excuses should studies show that marijuana has little medicinal value.
"They can say the marijuana isn't of sufficient quality," he said.
Source: United Press International
Author: Gregory Tejeda, United Press International
Published May 15, 2002
Copyright: 2002 United Press International
Website: http://www.upi.com/
Contact: http://www.upi.com/about/contact.cfm
Critics Aren't High On Federal Weed
With all the marijuana the government has seized throughout the years, one thing appears abundantly clear: The feds still don't know the first thing about pot. At least that seems to be the case in Mississippi where the government's controversial weed farm has been besieged with complaints.
"Ditch weed" is what some critics call the pot being grown on government farms and shipped to San Mateo County, Calif., for the first-ever publicly funded analysis of HIV patients smoking joints in their homes.
Characterizing the federal product as a bunch of sticks, seeds and stems with stale leaves, observers ranging from patients to a cop turned county supervisor are not high on the socialized product.
Of course those pushing for the reform of marijuana laws are quite upset as well. Some charge that the government sabotaged the study to show pot can have adverse effects on patients who are seeking help in battling AIDS and other life-threatening illnesses. When complaints started to filter out in San Mateo about the poor quality of the federal weed, Dale Gieringer, California coordinator for the National Organization for the Reform of Marijuana Laws (NORML), blasted the government. "It's unconscionable that they would be giving this marijuana to patients," he says. "It's stale, low-potency ditch weed." A 1999 NORML survey showed that among 48 samples, the government's pot scored the lowest on levels of THC ? the active ingredient in marijuana.
The groundbreaking study, which surprisingly has been supported quietly by the Bush administration, monitors its participants via self-reports, home visits, medication logs and return of leftover marijuana cigarettes. To be accepted into the study, a participant must be HIV-positive and suffering from neuropathy, a condition that afflicts AIDS, diabetes and other patients with severe tingling and pain in their hands and feet. Participants must have used pot before, have no record of other drug abuse, enjoy a stable home life and keep the government joints in a locked box.
"We have no interest, at present, in introducing people to marijuana use," claimed Dennis Israelski, chief of infectious disease and AIDS medicine at San Mateo County Health Center, when announcing the pilot program, which operates with about 600 marijuana cigarettes from the Mississippi pot farm kept in a hospital freezer. The study has a budget of $500,000 and is expected to last perhaps a year. About 30 joints per week are supplied to each patient. At first the patient smokes only in a special room in the health center but then is allowed to take the stash home.
But attracting qualified participants has been a serious problem ever since San Mateo County received the go-ahead about a year ago from the U.S. Food and Drug Administration (FDA). In fact, after several months of screening patients, the county had only one patient who fit all the stringent criteria. That was free-lance journalist and AIDS activist Phillip Alden. Each week he would receive his federally grown marijuana cigarettes to smoke in his home.
But Alden tells Insight he couldn't finish the study. "I was unable to complete the last week because I developed an upper respiratory infection similar to bronchitis," he says. The illness more than likely came from the substandard product, critics say. "The smoke was old, it contained seeds which taste awful when they burn and it was harsh on my throat," Alden says.
Since Alden left the program, fewer than a dozen patients have participated ? far short of the 60 patients San Mateo County had hoped to use as human guinea pigs for the clinical trial.
Some say the county's inability to attract suitable patients might be linked to word on the street that the free pot being provided is unsmokable. The National Institute on Drug Abuse (NIDA), which grows the Mississippi farm weed, insists the problem is not with socialism but with dehumidifying. Steve Gust, special assistant to the director of NIDA, admitted to the San Jose Mercury News that the federal stash is "harsh." But he dismissed the NORML complaints as simply coming from biased activists looking for someone to blame if the results from the study show marijuana has little medicinal value for HIV/AIDS treatment.
But Alden's public disclosure about the low-grade federal pot may have hurt efforts to attract HIV patients. In response, researchers recently asked for FDA permission to expand the base of potential patients to include those suffering from nausea and eating disorders. More recently, on May 14, the U.S. Supreme Court ruled against a claimed constitutional right to marijuana for medicinal purposes, which initially created alarm that such studies might cease.
The ruling sent chills up the back of people such as Alden who worry about what he calls "rampant federalism" spreading across the nation. "It started before 9/11 and has only gotten worse," he says. "How a state chooses to care for its ill residents should not be subjugated by people outside the state." So far, however, the Supreme Court ruling has not affected the study, which Alden hopes will continue despite the poor product.
Expanding the study to include others will be another hurdle to overcome for a program that has taken almost three years to put together, says San Mateo County Board of Supervisors President Mike Nevin, a former San Francisco cop who used to bust those who engaged in illegal trafficking of marijuana. San Mateo began clinical trials last July after an exhausting and burdensome regulatory process and now will have to wait for another regulatory approval to expand the participant base.
As a former cop, Nevin admits he initially had reservations about the study, but tells Insight he became convinced after a close friend, Joni Commons, who was deputy director of the county's health services, confided to him that smoking pot was the only thing that relieved her otherwise constant nausea from chemotherapy treatment for breast cancer. Commons eventually died, but Nevin says he was inspired to try to help others. "We need scientific proof. The federal government never had the courage to do the study, so San Mateo is doing it now," he says.
Nevin initially approached the San Mateo County Health Center about using pot confiscated by police, but that was turned down and the federally approved clinical cannabis study was born. But the recent problems from the inferior quality has certainly "hurt our efforts," Nevin admits. "Right now all we are trying to do is get a scientific finding to determine if marijuana should be pharmaceutically prescribed by a doctor."
If it does work, Nevin thinks people may get the wrong impression that San Mateo will be handing out joints to all comers. Instead, he says, cannabinoids might be placed in an inhalable substance similar to pharmaceutical inhalants used by those who suffer from asthma.
Currently, the only prescribable cannabinoids are THC (dronabinol, Marinol) and the dronabinol derivative nabilone. THC has been successful in destroying brain cancer in rats. Marinol was approved in the United States as a nausea drug in 1985 and as an appetite stimulant for AIDS patients in 1992. More recently, several large pharmaceutical companies, including Pfizer, GlaxoSmithKline and Novartis, have expressed interest in the medical use of cannabinoids and their derivatives. Previously the companies had turned away from marketing pot as a medicine because of political and cost problems.
In the meantime, Nevin says the quality of the pot has to get better or the trial is going to be deemed a failure. But even if the San Mateo study becomes a total bust, other jurisdictions have taken note. In fact, medicinal-marijuana research slowly is taking hold in other parts of the country. The Center for Medicinal Cannabis Research in La Jolla, Calif., plans to oversee studies at more than a dozen university sites. The clinical trials at the center will cost the University of California-San Diego and the University of California-San Francisco about $841,000 and more in other state funds.
The studies will investigate whether smoking marijuana can alleviate neuropathy. One study will focus on patients in hospitals, while the other will serve outpatients. Yet another study will look at how pot affects the ability of patients with HIV-related neuropathy or multiple sclerosis to drive a car, and another will look at whether pot eases the uncontrollable muscle spasms and pain associated with multiple sclerosis.
Initial reports indicate that the Southern California patients in the La Jolla studies also are complaining about the federal government's Mississippi farm weed. But these complaints are a little different. "Too potent," say at least two subjects, who claim they want relief rather than to get stoned. At least these complaints do not seem to be driving away patients. La Jolla currently has a waiting list of 500 eager participants hoping to get their take-home tokes.
Timothy W. Maier is a writer for Insight.
Source: Insight Magazine (US)
Author: Timothy W. Maier
Published: June 24, 2002
Copyright: 2002 News World Communications, Inc.
Contact:
[email protected]
Website: http://www.insightmag.com/
San Mateo Pot-Study Sign-Up Low
The pot is unsmokable, they say, full of sticks, stems and seeds. The leaves have gone stale after at least a year of storage, freezing and then thawing.
Marijuana supplied to researchers from the government farm in Mississippi isn't quality product, according to a range of observers, from Redwood Shores HIV patient Phillip Alden to a cop-turned-county supervisor. Alden said he knows from experience -- he's smoked it. And the result?
An upper respiratory infection and an early departure from a landmark research study, the first publicly funded analysis of HIV patients smoking cannabis in their homes.
In 10 months, fewer than 10 subjects have been accepted into San Mateo County's marijuana study, which took years to get funded and approved. The county's medical chief of staff, Dr. Dennis Israelski, had planned for 60.
Some say it must be the pot.
``I couldn't smoke the stuff any more,'' said Alden, a freelance writer who relies on marijuana to ease HIV-related wasting disease. ``I was disgusted with the federal government.''
Dale Gieringer, California coordinator for the National Organization for the Reform of Marijuana Laws, agrees. ``It's unconscionable that they would be giving this marijuana to patients,'' he said. ``It's stale, low-potency ditch weed.''
The National Institute on Drug Abuse, which grows the marijuana plants that are pre-rolled, frozen and sent to officially sanctioned researchers across the country, denies its research product is substandard.
``The marijuana we provide does not contain sticks and seeds. The problem is re-humidifying -- it makes it kind of harsh,'' said Steve Gust, special assistant to the director of NIDA. ``Certain procedures are needed to make it smoke right.''
Gust said researchers aren't complaining about quality. He thinks groups like NORML are looking for something to blame if the results of the studies show it has little medicinal value. ``Then they can say the marijuana isn't of sufficient quality,'' Gust said.
Damaging rumors
Cannabis trials in San Mateo County began in July, but few patients so far meet the strict standards to enroll. There is no hard evidence that the quality of the cannabis used in the study is hindering recruiting.
But stories -- and rumors in some cases -- have slowed progress, said Israelski, an associate clinical professor at Stanford University. When Alden was forced to drop out of the study late last year because of an inflamed throat, for example, published reports of his experience swirled quickly through Internet circles and HIV support groups.
``We've been hurt by word on the streets,'' Israelski said. ``But the word on the street might not reflect reality.''
To counteract the slow start, the county is trying to broaden its study.
In a letter sent to regulatory agencies this month, researchers ask to expand the HIV patient pool to include people suffering from nausea, weight loss and wasting disease.
Supervisor Mike Nevin is frustrated that the county is once again asking for approvals from the myriad agencies that must OK any changes to the research plan. He spent three years fighting for funding and regulatory approval.
Nevin envisioned his county's research program after a colleague, Joni Commons, died of breast cancer in 1998. Commons won him over, convincing the former San Francisco police inspector that marijuana brought her critical pain relief.
``We've put too much effort into this, and we don't want to be playing games here,'' Nevin said. ``It needs to be a certain grade of substance, and unless it's stronger, they'll set us up for defeat.''
Study in La Jolla
Medicinal marijuana research is moving steadily forward in other parts of the country, with multiple sclerosis, cancer and AIDS patients. The newly inaugurated Center for Medicinal Cannabis Research in La Jolla will soon oversee studies at 15 university sites.
Most researchers interviewed, unlike marijuana advocates, did not complain about the quality of the NIDA product. According to strict protocols, they can't unroll the carefully measured, frozen joints they receive, although several said they can hear seeds popping when some of their patients smoke, or they see the seeds fall out the untwisted end of the joint. They've heard that the sticky buds gum up the government's rolling machine.
But that hasn't stopped more than 500 people from joining waiting lists for clinical trials at the La Jolla center, where, in contrast, two recently enrolled subjects complained that the pot was too potent.
High after few puffs
``They've reported getting high shortly after the first few puffs,'' said Dr. Andrew Mattison, the center's co-director. ``These are people with a chronic, debilitating illness who do not want to get high. They want to get pain relief.''
Researchers concede that the less a patient has to smoke, the better. More potent cannabis delivers a more concentrated effect, with fewer smoking-related hazards.
According to a 1999 NORML survey, the government's cannabis scored lowest on levels of THC, marijuana's essential ingredient, compared with 48 samples.
Dr. Ethan Russo, a Montana neurologist and editor of the Journal of Cannabis Therapeutics, said NIDA's marijuana is ``medically inexplicable and inexcusable.'' He said American patients in any other drug study would not be given a stale product, and cannabis subjects deserve equal treatment.
Complete Title: San Mateo Pot-Study Sign-Up Low; Cannabis Quality Disputed
Source: San Jose Mercury News (CA)
Author: Karen de Sá, Mercury News
Published: Monday, May 13, 2002
Copyright: 2002 San Jose Mercury News
Contact:
[email protected]
Website: http://www.sjmercury.com/
One long held claim is the production of gynecomastia in males associated
with cannabis use. A case study or 3 cannabis smokers with this
malady was reported by Harmon and Aliapoulios (1972). A more thorough
investigation a few years later failed to show any differences in
cannabis use in affected males between users and controls (Cates and
Pope 1977).
Similarly, Kolodny et al. (1974) reported decreased testosterone levels
in chronic marijuana smokers, while no differences in testosterone
or luteinizing hormone (LH) levels were identified in a 3-week trial of
smokers vs. non-smokers (Mendelson et al. 1978).
LH levels in menopausal women showed no significant changes after
cannabis usage (Mendelson et al. 1985), but the next year, a similar
group noted a 30% suppression of LH in women by smoking a single
cannabis cigarette during the luteal phase (Mendelson et al. 1986).
Subsequently, a more in-depth study of both sexes was undertaken to
assess multiple hormone effects comparing subjects with different levels
of cannabis usage vs. controls (Block, Farinpour, and Schlechte
1991). No significant effects were noted on testosterone, LH, FSH,
prolactin or cortisol in young women and men.
Jamaican chronic use studies were confined to examinations of thyroxine
and steroid excretion with no significant findings observed due
to cannabis use (Rubin and Comitas 1975).
In the 94-Day Cannabis Study, acute drops in testosterone and LH
levels were noted after smoking a cannabis cigarette (Cohen 1976).
Subsequent drops in testosterone levels were noted after the 5th week of
daily usage. LH levels fell after the 4th week and FSH after the 8th week
to unspecified degrees.
In Costa Rica, no differences were noted in male testosterone levels
between abstainers and cannabis smokers stratified according to amount
of use (Carter 1980). Similarly, fertility was unimpaired, with both
groups having identical numbers of progeny. The author stated (p. 172),
“These findings cast serious doubt on cause-and-effect relationship between
marihuana smoking and plasma testosterone level in long-term
use.”
Zimmer and Morgan (1997) summarized their observations by stating
(p. 92), “There is no scientific evidence that marijuana delays adolescent
sexual development, has a feminizing effect on males, or a
masculinizing effect on females.”
The latter statement would seem to be borne out by our findings.
While one male subject had a minor degree of gynecomastia associated
with obesity, none of the Patients A-D displayed any abnormal values in
any endocrine measure (Table 5).
Gynecomastia and cannabis smoking. A nonassociation among US Army soldiers.
Cates W Jr, Pope JN.
Eleven patients diagnosed with idiopathic gynecomastia requiring mammoplasty were compared with matched controls to determine if there was an association between cannabis use and gynecomastia. Patients with gynecomastia were not significantly different from controls regarding their history of cannabis use. For those who admitted using cannabis, patients had a higher frequency but a shorter median duration of use than controls; differences were not statistically significant. Our epidemiologic evidence does not support the previously reported relationship between chronic cannabis use and gynecomastia.
PMID: 920892 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/...2&dopt=Abstract