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Thread: Hardrock69's Reefhead Madness Thread

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    http://www.cbc.ca/news/canada/britis...alization.html

    Marc Emery's U.S. prosecutor urges pot legalization
    John McKay once prosecuted B.C.'s 'Prince of Pot' Marc Emery

    CBC News
    Posted: Apr 18, 2012 12:12 PM PT
    Last Updated: Apr 18, 2012 3:11 PM PT

    The former U.S. district attorney who prosecuted B.C. marijuana activist Marc Emery in a cross-border sting is calling for the legalization and taxation of pot in Canada and the U.S.

    John McKay, a former U.S. attorney for the western district of Washington State, was joined by Emery's wife Jodie and former B.C. Attorney General Geoff Plant at a lecture in Vancouver on Wednesday.

    McKay said he did not regret prosecuting Emery because he broke U.S. law, but he believes the war on pot has been a complete and total failure. He said the laws keeping pot illegal no longer serve any purpose, but allow gangs and cartels to generate billions in profits.

    "I want to say this just as clearly and as forthrightly as I can, marijuana prohibition, criminal prohibition of marijuana is a complete failure," McKay said.

    McKay said marijuana, like alcohol, should be produced and sold to adults by the government, and that would generate at least half a billion dollars in revenue annually in Washington State alone.

    More importantly, he said, ending prohibition would end the violent reign of gangs and drug cartels who are profiting from the situation. He said any prohibition in society requires broad support from the population, and that isn't the case with marijuana.

    The appearance was organized by Stop the Violence BC, a coalition of high-profile academic, legal, law enforcement and health experts, which is working to reduce crime and public health problems stemming from the prohibition on marijuana.

    The group includes several former B.C. attorneys general, several former Vancouver mayors, a former B.C. premier and a former RCMP superintendent for the province.

    McKay, a Republican, was a U.S. Attorney from 2001 to 2007, when he resigned or was fired along with eight other U.S attorneys by President Bush.

    He is now a professor in the faculty of law at Seattle University and an avid supporter of the Washington State ballot initiative for the November election to implement a regulated, taxed market for marijuana.

    Marc Emery remains in prison in the U.S., serving a five-year sentence for conspiracy to manufacture marijuana through his mail-order cannabis seed business.




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    Can one of you guys just rename this thread? Call it something like Hardrock69's Reefer Madness Thread or something? This is going to be an ongoing thing, as there are new developments brewing all the time.


    Like THIS:

    http://www.washingtonpost.com/nation...y2T_story.html


    Connecticut Senate passes medical marijuana bill after lengthy debate

    Published: May 5

    HARTFORD, Conn. — A bill legalizing marijuana for medical purposes has passed the Connecticut Senate. The state joins 16 others and the District of Columbia in enacting such legislation.

    State senators voted 21-to-13 in favor of the measure early Saturday, after nearly 10 hours of debate dominated by bill opponent Republican Sen. Toni Boucher.


    Democratic Gov. Dannel P. Malloy, who has said he supports the measure, is expected to sign the legislation into law.

    The bill moves away from the largely criticized precedent set in California, proposing a complex regulated system of cultivation, dispensing and licensing.

    The Connecticut bill outlines specific diseases that would be treated under the drug. It requires a recommendation from an individual’s physician and establishes a system of licensing for patients, caregivers and growers.

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    Ok...latest update from US News and World Report:

    http://www.usnews.com/news/articles/...ical-marijuana

    Americans Support Ending Federal Crackdown on Medical Marijuana
    Three-fourths of likely voters favor state-level medical marijuana laws,

    By Seth Cline
    May 17, 2012

    A chart showing the results of a poll asking if Americans want the federal government to stop raids targeting medical marijuana.



    Americans think President Obama should leave states that have legalized medical marijuana alone, a new poll finds.

    In survey of 1000 likely voters, Mason-Dixon Polling and Research found three-fourths of those polled believe President Obama should respect laws in states where growing and selling marijuana is legal for medical purposes. Fifteen percent of respondents favored enforcing federal law, under which medical marijuana use is illegal.

    Sixteen states and the District of Columbia have legalized medical marijuana, most recently Connecticut. This has not kept individuals and dispensaries from being prosecuted under federal law by the Department of Justice and U.S. Attorney's Offices around the country.

    The poll found that respondents identifying themselves as Republican and over 65 years old were more likely to support using federal resources "to arrest and prosecute individuals who are acting in compliance with state medical marijuana laws." More than 80 percent of the youngest respondents, voters under 34, favored "respecting state medical marijuana laws," though this age group made up a smaller percentage of respondents.





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    Connecticut becomes the 17th state in the US to Legalize Medical Marijunana:

    http://www.care2.com/causes/medical-...#ixzz1wkrwHANF

    Medical Marijuana Is Now Legal In Connecticut

    by Beth Buczynski
    June 2, 2012
    10:08 am

    On Friday, Connecticut became the 17th state in America to legalize the use of marijuana for medical purposes. Governor Dannel Malloy signed the groundbreaking legislation that will allow licensed physicians to certify and prescribe medical marijuana for adult patients will qualifying medical conditions.

    “For years, we’ve heard from so many patients with chronic diseases who undergo treatments like chemotherapy or radiation and are denied the palliative benefits that medical marijuana would provide,” Governor Malloy said. ”With careful regulation and safeguards, this law will allow a doctor and a patient to decide what is in that patient’s best interest,” he said.

    Despite coming out strongly in favor of state’s rights to legalize and monitor medical marijuana when he was on the campaign trail, the Obama Administration has since waffled in his support of the plant’s medical use. In a Rolling Stone interview early this year, the President was quoted as saying “he can’t nullify congressional law.” Fortunately, states have forged ahead in their quest to provide ill citizens with a natural medication that can greatly improve their quality of life.

    “By giving patients safe, legal access to medical marijuana, Connecticut joins over a third of the United States in recognizing the plant’s economic and medical value,” said Brad Burge, Director of Communications for the Multidisciplinary Association for Psychedelic Studies (MAPS), a non-profit pharmaceutical development company. “The new law also reminds us how far state and federal attitudes toward medical marijuana have diverged. The Obama administration continues to fight medical marijuana, and the states just don’t agree.”

    Under the bill, patients and their caregivers must register with the Department of Consumer Protection. In addition, a doctor must certify there is a medical need for marijuana to be dispensed, including such debilitating conditions as cancer, glaucoma, HIV, AIDS, Parkinson’s disease, multiple sclerosis or epilepsy. This is the same or very similar to the way medical marijuana is prescribed in other states.

    What sets the Connecticut law apart, however, is that patients will only be able to obtain medical marijuana from pharmacists who are certified to dispense it. The Connecticut law also only allows for the licensing of at least three but not more than 10 marijuana producers statewide. Officials hope this model will reduce instances of abuse and black market dealing that have occurred in states that allow patients or appointed caretakers to grow their own.

    Despite these restrictions, Burge says it’s a step in the right direction for patients and more states are likely to follow suit. “The federal government, through a decades-long blockade on medical marijuana research, has succeeded in preventing marijuana from becoming a federally-regulated prescription medicine. In the meantime, getting patients access to the medicine they need will depend on the continued success of state-based medical marijuana policy reform.”

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    http://health.yahoo.net/news/s/nm/ma...ma-in-colorado

    Marijuana initiative could make or break Obama in Colorado
    By Samuel P. Jacobs, Reuters
    Jun. 02, 2012 2:06PM PDT

    DENVER (Reuters) - Throughout his presidency, Barack Obama hasn't exactly been a friend to marijuana users.

    Sure, he has acknowledged smoking pot as a young man, but he has disappointed marijuana advocates by opposing its legalization, regulation and taxation like alcohol.

    And the Justice Department's occasional crackdown under his administration on medical marijuana dispensaries, which 17 states and the District of Columbia allow, has angered others.

    So now, with Obama facing a stiff challenge from Republican Mitt Romney in the November 6 election, it's ironic that his chances of winning the key state of Colorado could hinge on marijuana legalization, supported by a growing number of Americans.

    At issue is whether Obama will get a boost from young voters expected to be among the most enthusiastic backers of a Colorado ballot initiative that would legalize possession of up to an ounce of pot for recreational use - and give the state the most liberal marijuana law in the nation.

    The initiative is a reflection of Colorado's unique blend of laid-back liberalism and anti-regulation conservatism that helped make the state the birthplace of the Libertarian Party.

    It's a state where people of different political stripes see marijuana laws as an example of government needlessly sticking its nose where it doesn't belong.

    It's also a proving ground for advocates who see legalization as a way to ease crowding in prisons, generate much-needed tax revenues, create jobs and weaken Mexican cartels that thrive on Americans' appetite for illegal drugs.

    The Rocky Mountain State already allows the use of marijuana for medical purposes such as severe pain relief, and some communities have embraced it enthusiastically.

    The prevalence of medical marijuana dispensaries in Denver has moved pot into the mainstream in Colorado's capital city.

    In Denver County, home to about 600,000 people, one in every 41 residents is a registered medical marijuana patient, leading to chuckles about the "Mile High City." Denver is roughly a mile above sea level.

    The number of places licensed to sell medical marijuana products has reached 400 here, according to the Denver Post. That means there are more dispensaries in the capital than there are Starbucks coffee shops (375) statewide.

    A similar bill is on the ballot in Washington, another state that already allows use of medical marijuana. If approved, the initiatives would put the states squarely in the crosshairs of federal law, which classifies cannabis as an illegal narcotic.

    PATH TO THE WHITE HOUSE

    It's unclear precisely how the U.S. Justice Department - whether led by Obama or Romney - would respond if Colorado, Washington or other states legalize marijuana for recreational use. Both politicians oppose legalizing the drug.

    But in a close presidential election in which Colorado could be a tipping point - and with polls showing Obama has up to a 30-point edge over Romney among voters age 30 and under - the state's marijuana initiative could be a factor if it inspires waves of young voters to cast ballots on November 6.

    "This is an issue that is really meaningful to young people, people of color, disenfranchised communities," groups that typically lag in registering and showing up to vote, said Brian Vicente, 35, executive director of Sensible Colorado, a group seeking less restrictive marijuana laws.

    "Democrats and Obama need these groups to win," Vicente said. "The path to the White House leads through Colorado. We feel we can motivate these groups."

    Last winter, Public Policy Polling found that 49 percent of Coloradans favored legalization, while 41 percent opposed it.

    As much as some Democrats feel they have the wind at their backs, they are fighting history in Colorado. Obama won the state in 2008, but he was the first Democratic presidential contender to do so in 16 years.

    And even though a majority of the delegates at the Colorado Democratic Party's convention last month said they supported legalization, some party officials are skeptical the politically diverse movement will help Obama much this fall.

    They note that Colorado voters rejected such a legalization measure in 2006, and that Californians blocked a similar initiative two years ago.

    "If they get 40 percent" of voters supporting legalization, "they should throw themselves a party," said Matt Inzeo, spokesman for Colorado's Democratic Party.

    Others see more potential in the legalization debate's impact on the presidential race.

    Tom Jensen of Public Policy Polling said that if the state-by-state race for the 270 electoral votes needed to win the presidency comes down to Colorado's 9 electoral votes, marijuana "could be a difference maker."

    BROADENING SUPPORT

    During a recent visit to Colorado, Romney seemed irritated when a local television reporter quizzed him on his views about gay marriage, immigration reform and marijuana legalization.

    "Aren't there issues of significance you'd like to talk about?" an exasperated Romney asked.

    In Colorado, however, marijuana is significant. And its acceptance hasn't been limited to more liberal areas.

    Colorado Springs, home to the U.S. Air Force Academy and the evangelical Christian group Focus on the Family, is one of the most conservative cities in the United States. But the city of 400,000 about 70 miles south of Denver has nearly as many marijuana dispensaries as churches, according to city records.

    Supporters of Colorado's initiative point to a broadening coalition of those who support legalization, including local civil rights and union leaders.

    Those opposing marijuana legalization often cite the drug's impact on youths.

    Roger Sherman, a strategist for the campaign against Amendment 64, said "there's a tremendous amount of enthusiasm and a high level of concern" among those who oppose legalization. His group cites increased drug use among children and increasing cases of impaired driving.

    Nationwide polling on marijuana legalization, although sparse, suggests that support now equals support for marriage equality, which just found a new backer in Obama.

    In October, 50 percent of Americans said "yes" when asked by Gallup, "Do you think the use of marijuana should be made legal, or not?" When Gallup asked that in 1969, 12 percent said yes.

    Last week, a Rasmussen Reports survey said 56 percent of likely U.S. voters favored legalizing and regulating marijuana.

    QUESTIONING OBAMA

    Supporters of legalization also argue that regulating marijuana - and capturing tax revenue from its sale - could help governments, cities and towns face increasingly tight budgets.

    In 2011, taxes for medical marijuana generated $5 million for Colorado. Denver-based political strategist Rick Ridder said that depending upon the cost of an ounce, legalization would likely generate $20 million to $80 million in annual tax revenue for Colorado and local communities.

    As designed, Amendment 64 would designate its first $40 million in tax revenue for rebuilding public schools. As part of a bond issue, that amount could turn into a treasure chest for public education funding in Colorado.

    Legalization advocates see Obama's crackdown on some medical marijuana outlets as hypocritical, noting that in his memoir "Dreams from My Father" he acknowledged smoking pot as a youth.

    "It's really insulting with this president. He actually smoked pot in high school and college. The only difference is he didn't get caught. If he had gotten caught, he would not be president," said Wanda James, 48, whose business, Simply Pure, supplies 300 Colorado dispensaries with edible marijuana.

    She tells community leaders that legalization is not just about pot smokers having a good time, legally. She sees it as a way to ease prison crowding, help cash-strapped governments, provide jobs and weaken drug cartels.

    Legalization, of course, would mean a larger market for James' indica sesame brittle bars and sativa peppermint cups.

    To James, legalizing marijuana boils down to what could be a good slogan for this year's elections: "Jobs, jobs, jobs."



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    If Obama came out in favor a legalization now the remaining conservatard heads that DIDN'T explode when he endorsed marriage equality certainly would...
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    There would be no going back.

    Funny how such an issue at just the right moment could ensure that the Retardlicfucks would be shown once and for all as the regressive, superstitious fools that they truly are......the world is moving forward without them, no matter how much they scream and cry and throw tantrums......

    And it is interesting how this issue DOES exist at this particular moment in history in THIS election year with THESE candidates.

    Mittens - The man who has no plans for anything, only looks presidential, but like all other Conservafucks wants to live in the 1950s forever.......and that is the only platform he has to run on....
    At least he is a Moron, which has got to bother most conservative Christians to no end....

    Obama - An intellectual who has a plan for everything. Valid or not, at least he can analyze every issue and create a program to deal with it. And he wants to move FORWARD into the future.

    I have no desire to live in the 1950s. The 1960s were no piece of cake either.

  8. Thanked Hardrock69 for this KICKASS post:

    jhale667 (06-04-2012)


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    Seems this year there is going to be a lot to post in this thread.

    Looks like possession of less than 25 grams of pot in New York is already legal unless it is burning or in "Public view". All cops have to do is ask someone to empty their pockets, and if they have pot, doing so will put it in "public view" and cause the person to be arrested. Governero Cuomo wants to stop the practice.

    http://www.huffingtonpost.com/2012/0...n_1567521.html

    Cuomo Targets Stop-And-Frisk, Seeks To Lower Number Of Low-Level Marijuana Arrests

    Posted: 06/04/2012 9:40 am Updated: 06/04/2012 1:28 pm

    Entering the debate over NYPD stop-and-frisks, Governor Andrew Cuomo is proposing legislation that would decriminalize possession of small amounts of marijuana in public view.

    The Governor plans to meet with state lawmakers Monday, The New York Times reports, in an attempt to amend a state law that was the basis for the arrest of over 50,000 people in New York City last year, most of whom were black or Latino.

    Under the current law, possession of 25 grams or less of marijuana shouldn't result in arrest unless it's "burning or in public view." The NYPD, however, will often ask the hundreds of thousands they stop on the streets to empty their pockets, and when the marijuana comes out of the pocket, it becomes "in public view," and they can make an arrest.

    There are more arrests for low-level marijuana offenses than any other crime in New York City. According to the Associated Press, marijuana arrests in New York account for one out of every seven cases in the city's criminal courts. In 2010, the city spent $75 million to put pot-smokers behind bars.

    In September, Police Commissioner Ray Kelly issued a memo, telling city cops, "A crime will not be charged to an individual who is requested or compelled to engage in the behavior that results in the public display of marijuana." The Times reports, however, that the effect of Kelly's order on the number of marijuana arrests has been minimal.

    "This proposal will bring long overdue consistency and fairness to New York State's Penal Law and save thousands of New Yorkers, particularly minority youth, from the unnecessary and life-altering trauma of a criminal arrest, and, in some cases, prosecution," a Cuomo official told The Times.

    Mayor Bloomberg disagrees with Cuomo's position on marijuana arrests. The Mayor's argued before that the arrests deter other, more serious crimes.

    UPDATE: Mayor Michael Bloomberg has come out in support of Governor Cuomo's plan. Bloomberg said Cuomo's plan "strikes the right balance," by allowing cops to still arrest those who are smoking in public. “We look forward to working with legislative leaders to help pass a bill before the end of session,” the mayor said in a statement. Ray Kelly will attend Cuomo's press conference Monday in a show of support of the bill.


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    Ok....latest attempt to make it possible for farmers to grow industrial hemp:

    http://www.huffingtonpost.com/2012/0...05.html?ref=tw

    Ron Wyden Introduces Industrial Hemp Amendment To Farm Bill

    Posted: 06/07/2012 1:46 pm Updated: 06/07/2012 1:57 pm


    Senator Ron Wyden (D-Oregon) on Thursday introduced an amendment to the farm bill that would allow farmers to grow industrial hemp.

    The amendment, S.3240, would exclude industrial hemp from the definition of "marihuana," thereby allowing hemp farming to be regulated by state permitting programs, bypassing the federal government's long-standing prohibition of marijuana. A sister bill, H.R. 1831, was introduced in the House earlier this session by Rep. Ron Paul (R-Texas).

    "The federal prohibition on growing industrial hemp has forced companies to needlessly import raw materials from other countries," said Wyden in a statement on Thursday. "My amendment to the Farm Bill will change federal policy to allow U.S. farmers to produce hemp for these safe and legitimate products right here, helping both producers and suppliers to grow and improve Oregon's economy in the process."

    Seventeen states have passed pro-hemp legislation, while eight have removed barriers to its production. Still, farmers in these states are at risk of being raided by federal agents and losing their crops.

    Vote Hemp, a national nonprofit dedicated to promoting the crop, is encouraging people to write and call their senators in support of the amendment and has received hundreds of supporter emails, according to National Outreach Coordinator Tom Murphy.

    The organization's president, Eric Steenstra, said he thinks current hemp prohibitions stem largely from the failure of federal policy to distinguish between oilseed and fiber varieties of cannabis.

    "Senator Wyden's effort is unprecedented and totally commendable, but in my view the existing prohibition of hemp farming stems less from current law, but rather the misinterpretation of existing law by the Obama administration," he said.


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    Rhode Island is poised to become the 15th state to decriminlize small amounts of marijunana:

    http://www.foxnews.com/us/2012/06/10...omentum-in-us/


    Efforts to relax pot rules gaining momentum in US

    Published June 10, 2012

    Associated Press

    PROVIDENCE, R.I. – Catharine Leach is married and has two boys, age 2 and 8. She has a good job with a federal contractor and smokes pot most every day.

    While she worries that her public support for marijuana decriminalization and legalization could cost her a job or bring the police to her door, the 30-year-old Warwick resident said she was tired of feeling like a criminal for using a drug that she said is far less harmful than the glass or wine or can of beer enjoyed by so many others after a long day's work. Like others around the nation working to relax penalties for possession of pot, she decided to stop hiding and speak out.

    "I'm done being afraid," she said. "People in this country are finally coming around and seeing that putting someone in jail for this doesn't make sense. It's just a changing of the time."

    Once consigned to the political fringe, marijuana policy is appearing on legislative agendas around the country thanks to an energized base of supporters and an increasingly open-minded public. Lawmakers from Rhode Island to Colorado are mulling medical marijuana programs, pot dispensaries, decriminalization and even legalization. Seventeen states and the District of Columbia now authorize medical marijuana and 14, including neighboring Connecticut and Massachusetts, have rolled back criminal penalties for possession of small amounts of pot.

    Rhode Island is poised to become the 15th state to decriminalize marijuana possession. The state's General Assembly passed legislation last week that would eliminate the threat of big fines or even jail time for the possession of an ounce or less of pot. Instead, adults caught with small amounts of marijuana would face a $150 civil fine. Police would confiscate the marijuana, but the incident would not appear on a person's criminal record.

    Minors caught with pot would also have to complete a drug awareness program and community service.

    Gov. Lincoln Chafee has said he is inclined to sign the legislation.

    One of the bill's sponsors, state Rep. John Edwards of Tiverton, has introduced similar proposals in past years but the idea always sputtered in committee. Each year, though, he got more co-sponsors, and the bill passed the House this year 50-24. The state Senate passed it 28-6.

    Some supporters of decriminalization say they'd like to go even further.

    "America's 50-year war on drugs has been an abysmal failure," said Rep. John Savage, a retired school principal from East Providence. "Marijuana in this country should be legalized. It should be sold and taxed."

    Opponents warned of dire consequences to the new policy.

    "What kind of message are we sending to our youth? We are more worried about soda — for health reasons — than we are about marijuana," said one opponent, Rhode Island state Rep. John Carnevale a Democrat from Providence.

    A survey by Rasmussen last month found that 56 percent of respondents favored legalizing and regulating marijuana. A national Gallup poll last year showed support for legalizing pot had reached 50 percent, up from 46 percent in 2010 and 25 percent in the mid-'90s.

    Medical marijuana helped bring marijuana policy into the mainstream back in 1996, when California became the first state to authorize the use of cannabis for medicinal use. Other states followed suit.

    "It's now politically viable to talk about these things," said Robert Capecchi, legislative analyst with the Marijuana Policy Project, a Washington, D.C.-based group that supports the reduction or elimination of penalties for medical and recreational pot use. "The public understands that there are substances that are far more harmful — alcohol, tobacco — that we regulate. People are realizing just how much money is being wasted on prohibition."

    Colorado and Washington state will hold fall referendums on legalizing marijuana. A ballot question on legalization failed in California in 2010.

    This month, Connecticut's governor signed legislation to allow medical marijuana there. Last week, New York Gov. Andrew Cuomo proposed cutting the penalty for public possession of small amounts of pot.

    Liberal state policies on marijuana have run into conflict with federal prohibition. Federal authorities have shut down more than 40 dispensaries this year in Colorado, even though they complied with state and local law. In Rhode Island, Gov. Lincoln Chafee blocked three dispensaries from opening last year after the state's top federal prosecutor warned they could be prosecuted. Chafee and lawmakers then rewrote the dispensary law to restrict the amount of marijuana dispensaries may have on hand.

    Robert DuPont, who served as the nation's drug czar under presidents Richard Nixon and Gerald Ford, said Americans should be wary of a slippery slope to legalization. While marijuana may not cause the life-threatening problems associated with heroin, cocaine or methamphetamine, it's far from harmless.

    "It is a major drug of abuse," he said. "People ask me what the most dangerous drug is, and I say marijuana. Other drugs have serious consequences that are easy to recognize. Marijuana saps people's motivation, their direction. It's a drug that makes people stupid and lazy. That's in a way more dangerous."


    Ha...Robert Dupont is a fucking moron. And I am GLAD they drag him out to get his side of the story, as his opinion is so removed from reality, it only serves to show intelligent people that he has no valid argument.

    Marijuana is the most dangerous drug? Dangerous how? A majority of all other illegal drugs cause people to DIE!

    So how is it that drugs that cause you to die are NOT more dangerous than a drug that CANNOT cause you to die?

    Fucking idiot.

    Standard asslicker of the Retardlican party with the standard intelligence level. An IQ that is the same as his shoe size.
    Last edited by Hardrock69; 06-11-2012 at 05:35 AM.

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    http://www.huffingtonpost.com/2012/0...n_1602508.html

    Chicago Mayor Supports Reducing Pot Penalty

    DON BABWIN 06/15/12 06:31 PM ET

    CHICAGO — With the murder rate in Chicago climbing at an alarming rate, police may soon get some help keeping a lid on violent crime from an unlikely source: marijuana.

    Mayor Rahm Emanuel and Police Superintendent Gary McCarthy both support an ordinance that would allow police officers to ticket anyone caught with a small amount of marijuana instead of going through the time-consuming arrest process that takes them off the street for hours at a time.

    Police arrested more than 18,000 people last year for misdemeanor possession of 10 grams or less of marijuana, which "tied up more than 45,000 police hours," McCarthy said in a statement. "The new ordinance nearly cuts that time in half... freeing up cops to address more serious crime."

    More significantly, the alderman who drafted the ordinance – which turns small amounts of pot into a ticketable, not jailable offense_ said it not only addresses concerns about fairness but also provides increased safety for city's most dangerous neighborhoods.

    Alderman Danny Solis said most of those arrested are black and Hispanic and come from predominantly minority neighborhoods – the ones in the thick of the violence.

    "The irony is that the worst crime is happening in our city is happening in the same neighborhoods where the possession (arrests) are happening," said Alderman Danny Solis. "The police officer is now going to be more in the neighborhoods that need him or her than in the district doing paperwork."

    States across the country are starting to relax their laws on marijuana possession. This month alone, governors in Rhode Island and New York moved toward decriminalization of small amounts of the drug.

    In Rhode Island, Gov. Lincoln Chafee signed a bill that imposes a $150 civil fine on adults caught with an ounce or less of marijuana. And New York Gov. Andrew Cuomo has proposed a bill that would change possession of small amounts of marijuana from a criminal misdemeanor to a violation with a fine up to $100.

    Current marijuana laws disproportionately affect minority communities. Cuomo acknowledged, for example, that 82 percent of those arrested in New York City were either black or Hispanic. And when Solis first introduced the ordinance in November, he and others also pointed to statistics that suggest that the arrests themselves are a colossal waste of time.

    Of the 8,625 misdemeanor marijuana cases between 2006 and 2010, about 87 percent were dismissed, according to statistics from the Cook County Clerk of the Circuit Court.

    But it's a marked jump in Chicago's homicide rate that may have given Solis' proposal more steam. Murders are up by about 50 percent so far this year compared to the same period last year.

    "I'm a realist," said Solis. "That has to have been an influence."

    Emanuel had made it clear in November that he was open to the idea of the ordinance, even saying a member of the police department's gang unit had made the same suggestion. He then directed McCarthy to study it, with McCarthy also signaling that he would consider it because it would free up officers.

    "The mayor was serious about this, but he wanted to make sure we had all the research and analysis done," Solis said. "So I told him I won't call it to a committee until your staff and the police do that work."

    With that work done, Solis said he expects the full City Council to vote and pass the ordinance later this month, with it becoming the law sometime this summer.

    Under the ordinance, anyone in possession of 15 grams of marijuana – roughly the equivalent of 15 marijuana cigarettes – faces a fine between $100 and $500.


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    Rahm Emanuel is actually on the logical side of an issue?

    Shit, there really IS a first time for everything!
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    AWESOME NEWS....is it news? Well CHECK THIS SHIT OUT!

    URUGUAY IS APPARENTLY GOING TO LEGALIZE THE SALE AND POSSESSION OF POT!!!!

    http://www.theweedblog.com/uruguay-g...ell-marijuana/

    A Government Finally Embraces Reality

    The local media in Uruguay, citing unnamed lawmakers, is reporting a plan to legalize and sell marijuana to registered users to combat crime, and cut off the flow of money to dangerous cartels. Hmm, seems like I’ve heard this idea before. Oh yeah, it’s what we have all been saying for years. It’s what several latin American countries have been wanting to do, but can’t because of staunch opposition from Obama. Well, it looks like the U.S. is no longer calling the shots in the western hemisphere.

    The president of Uruguay has not yet confirmed the report, but did tell the The Associated Press in an email to expect a announcement soon addressing “the marijuana issue.” The program would be based on the notion that getting people off drugs is about rehabilitation, not punishment. In order to buy marijuana users must first register with the government. Any user who goes past the monthly limit of government joints will be required to undergo drug rehabilitation, but will not face prosecution. All income from the program will be used to treat hardcore addicts. Wow! Is that reason I smell in the air?

    We need to send Obama to Uruguay asap for leadership training. Apparently, the idea is to reduce crime by reducing the flow of money to dangerous drug dealers, as well as by giving cannabis users an alternative source of ganja so they are not drawn into using more dangerous drugs.

    “This measure should be accompanied by efforts to get young people off drugs,” said ruling party Sen. Monica Xavier.

    Well, you heard it here folks: the tide is turning fast against the U.S. Drug War. Nations will no longer be bullied by Obama into accepting drug violence within their borders. The time is now to rise up against prohibition and demand legalization. Our brothers and sisters in Latin America have our backs. Let’s do this!

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    ALL OUT CHICAGO BITCHES CAN REJOICE!!! Well...sort of....

    http://www.theweedblog.com/chicago-c...ijuana-policy/

    Chicago City Council Committee Approves New Chicago Marijuana Policy

    Chicago City Council Committee Approves Rahm Emanuel’s Marijuana Policy

    The Chicago City Council committee on Thursday voted 12 to 1 to approve a new Chicago marijuana policy. Mayor Rahm Emanuel last week indicated his support of the proposed policy that would allow Chicago Police to issue tickets instead of making arrests for possession of 15 grams of marijuana or less.

    Emanuel has said the change frees up police for more serious crime and saves the department about $1 million annually. The mayor’s office finds that there were 45,000-plus police hours used for 18,298 arrests last year for possession of less than 10 grams of marijuana. Each case needed four officers to arrest and transport offenders.

    Police Superintendent Garry McCarthy told the committee, “We are not talking about decriminalization, we are talking about holding people accountable.”

    Under the new policy, McCarthy said officers would have the option of issuing a ticket to someone, rather than placing them under arrest. Arrests would be mandated for anyone caught smoking marijuana in public or possessing marijuana in or near a school or in or near a park

    Under the plan, anyone caught with marijuana under the age of 17 or without proper identification would still be arrested. Tickets would range from $250 to $500.

    The plan goes to the full City Council next week.



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    My sister and her husband lived in Peru during the days of the Shining Path terrorist group. That part of Latin America was dangerous in the early 1980's. They just recently came back from there and things are much better. In fact, a lot of US citizens are moving down to Equador and Panama to retire. John Hopkins just built a new hospital in Panama due to the demand from retired US citizens moving there. Mexicans are moving back to Mexico because parts of the economy are on the uprise.

    If you get outside of the major European and north American countries the world economy is better. The reason is the banking structure in Europe is tied with the banking structure in North America. The old Euro/American power house no longer runs the world the way it used to. Brazil, China, Russia, India, and South Africa will be the rising stars on the world stage.

    The IMF and World Bank no longer rape these countries like they used to. They have more money now and apparently it's being used more intelligently.
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    In short, due to the skyrocketing homicide rate, the cops can't waste their resources on some reefer smokers. Yeah, Chi town sounds like it's in competition with Detroit these days.

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    Congressman Jared Polis Owns DEA Administrator Michele Leonhart In Hearing - posted June 21, 2012

    Congressman Jared Polis questions DEA Administrator Michele Leonhart during a hearing on the agency’s priorities. He repeatedly pressed the administrator on the relative health impacts of marijuana versus other drugs.

    This woman is a TOOL. She obviously is lacking in intellect, should be more aware of the effects of ALL drugs, which ones are more severe and have more harmful effects on humans.


    However, she has demonstrated beyond all reasonable doubt that she is an idiot. She sits there with a deer-in-the-headlights stare, as if she is incapable of comprehending the questions asked of her in her official capacity as Chief Administrator of the DEA, and when Congressman Polis dumbs down the questions to their most basic form to assist her in comprehending what is being asked in PLAIN FUCKING ENGLISH, she STILL is unable to coherently form even the most basic answer to his questions, which should be easily understandable to the most average human with average intelligence.

    And she is the Chief Administrator of the DEA?

    She needs to be fired.




    I know she could not have gotten the job without being smart. I also know she could not answer his questions truthfully, as that would go against the policies of the DEA, and she could lose her job.

    So that leaves her open to criticism that she is an idiot...she gets asked the questions....and is suddenly realizing she needs to figure out how to answer his questions without saying anything that could cause her to be fired....and then fails to come up with a reasonable answer.

    This sort of stupidity just pisses me off. She knows that reefer is WAY less dangerous than even ASPIRIN, but for her to admit it would undermine the mission of the DEA, which is to prosecute all illegal drug cases.
    Last edited by Hardrock69; 06-22-2012 at 04:41 AM.

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    On the international scene, the Columbian Constitutional Court has ruled that people cannot be jailed for possessing small amounts of pot or coke for personal use.

    http://www.washingtonpost.com/world/...BCW_story.html

    Colombia court: No jail time for possession of cocaine, marijuana for personal use

    By Associated Press,

    BOGOTA, Colombia — Colombia’s Constitutional Court has ruled that people cannot be jailed for possessing cocaine and marijuana for personal use.

    The decision ratifies a previous Supreme Court ruling that said people cannot be jailed for possession of a so-called personal dose. A 2009 law placed the dose at up to 20 grams of marijuana and one gram of cocaine.

    Thursday’s ruling came in a challenge to a 2011 citizen’s security law that specified persons found with up to 1 kilogram (2.2 pounds) of marijuana or 100 grams (3.5 ounces) of cocaine should be punished with at least 64 months in prison.

    While striking down that provision, the court did not mention a quantity acceptable for personal use.

    Chief prosecutor Eduardo Montealegre said Friday that the decision does not amount to drug legalization.


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    Study shows beyond a shadow of a doubt, the GATEWAY drug is ALCOHOL:


    http://www.rawstory.com/rs/2012/07/0...not-marijuana/

    Study: The ‘gateway drug’ is alcohol, not marijuana

    By Stephen C. Webster
    Thursday, July 5, 2012 13:52 EDT



    A study in the August edition of The Journal of School Health finds that the generations old theory of a “gateway drug” effect is in fact accurate, but shifts the blame for escalating substance abuse away from marijuana and onto the most pervasive and socially accepted drug in American life: alcohol.

    Using a nationally representative sample from the University of Michigan’s annual Monitoring the Future survey, the study blasts holes in drug war orthodoxy wide enough to drive a truck through, definitively proving that marijuana use is not the primary indicator of whether a person will move on to more dangerous substances.

    “By delaying the onset of alcohol initiation, rates of both licit substance abuse like tobacco and illicit substance use like marijuana and other drugs will be positively affected, and they’ll hopefully go down,” study co-author Adam E. Barry, an assistant professor at the University of Florida’s Department of Health Education & Behavior, told Raw Story in an exclusive interview.

    While Barry’s study shows evidence that substance abuse behaviors can be predicted with a high degree of accuracy by examining a subject’s drug history, he believes that the persistent and misguided notion of marijuana as the primary gateway to more harmful substances went awry because its creators — who called it the “Stepping Stone Hypothesis” in the “Reefer Madness” era of the 1930s – fundamentally misread the data and failed to conduct an adequate follow-up.

    “Some of these earlier iterations needed to be fleshed out,” Barry said. “That’s why we wanted to study this. The latest form of the gateway theory is that it begins with [marijuana] and moves on finally to what laypeople often call ‘harder drugs.’ As you can see from the findings of our study, it confirmed this gateway hypothesis, but it follows progression from licit substances, specifically alcohol, and moves on to illicit substances.”

    “So, basically, if we know what someone says with regards to their alcohol use, then we should be able to predict what they respond to with other [drugs],” he explained. “Another way to say it is, if we know someone has done [the least prevalent drug] heroin, then we can assume they have tried all the others.”

    And while that standardized progression certainly doesn’t fit every single drug user, the study took that into account too. “There were a low enough number of errors that you are able to accurately predict [future substance abuse behavior]… with about 92 percent accuracy,” Barry said.

    By comparing substance abuse rates between drinkers and non-drinkers, they ultimately found that seniors in high school who had consumed alcohol at least once in their lives “were 13 times more likely to use cigarettes, 16 times more likely to use marijuana and other narcotics, and 13 times more likely to use cocaine.”

    Barry also noted that the rates of tobacco and marijuana use among all 12th grade high school students were virtually the same, confirming a report the Centers for Disease Control published in June, and an analysis Raw Story published in May.

    The study should give pause to anyone involved in youth drug awareness programs, as its findings suggest that making science-based alcohol education a top priority could actually turn the tide of the drug war — but only if lawmakers and leading educators decide to use that same science as a foundation for public policy and school curriculum.

    “I think [these results] have to do with level of access children have to alcohol, and that alcohol is viewed as less harmful than some of these other substances,” Barry added.

    That social misconception, largely driven by the sheer popularity of alcohol and the profits it generates for private industry, is diametrically opposed to the most current science available on drug harms. A study published in 2010 in the medical journal Lancet ranked alcohol as the most harmful drug of all, above heroin, crack, meth, cocaine and tobacco. Even more striking: The Lancet study found that harms to others near the user were more than double those of the second most harmful drug, heroin.

    “This is a time of budget tightening,” Barry concluded. “Many social services are being cut. If you take [our findings] and apply them to a school health setting, we believe that you are going to get the best bang for your buck by focusing on alcohol.”

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    Once again, PROOF that marijuana DOES have medical uses. This brought to you by a GOVERNMENT-SPONSORED STUDY, no less!

    http://www.rawstory.com/rs/2012/07/0...-of-marijuana/

    Government-sponsored study destroys DEA’s classification of marijuana

    By Stephen C. Webster
    Tuesday, July 3, 2012 9:46 EDT

    A government-sponsored study published recently in The Open Neurology Journal concludes that marijuana provides much-needed relief to some chronic pain sufferers and that more clinical trials are desperately needed, utterly destroying the U.S. Drug Enforcement Agency’s (DEA) classification of the drug as having no medical uses.

    While numerous prior studies have shown marijuana’s usefulness for a host of medical conditions, none have ever gone directly at the DEA’s placement of marijuana atop the schedule of controlled substances. This study, sponsored by the State of California and conducted at the University of California Center for Medicinal Cannabis Research, does precisely that, driving a stake into the heart of America’s continued war on marijuana users by calling the Schedule I placement simply “not accurate” and “not tenable.”

    Reacting to the study, Paul Armentano, director of the National Organization for the Reform of Marijuana Laws (NORML), told Raw Story that the study clearly proves U.S. drug policy “is neither based upon nor guided by science.”

    “In fact, it is hostile to science,” he said. “And despite the Obama Administration’s well publicized 2009 memo stating, ‘Science and the scientific process must inform and guide decisions of my Administration,’ there is little to no evidence indicating that the federal government’s ‘See no evil; hear no evil’ approach to cannabis policy is not changing any time soon.”

    Schedule I is supposedly reserved for the most inebriating substances that the DEA believes have no medical value, including LSD, ecstasy, peyote and heroin.* As the DEA describes it: “Drugs listed in schedule I have no currently accepted medical use in treatment in the United States and, therefore, may not be prescribed, administered, or dispensed for medical use. In contrast, drugs listed in schedules II-V have some accepted medical use and may be prescribed, administered, or dispensed for medical use.”

    And that’s the problem, the study’s authors portend.

    “The classification of marijuana as a Schedule I drug as well as the continuing controversy as to whether or not cannabis is of medical value are obstacles to medical progress in this area,” they wrote. “Based on evidence currently available the Schedule I classification is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking. It is true cannabis has some abuse potential, but its profile more closely resembles drugs in Schedule III (where codeine and dronabinol are listed). The continuing conflict between scientific evidence and political ideology will hopefully be reconciled in a judicious manner.”

    They add that their evidence showed marijuana reliably reduced chronic neuropathic pain and muscle spasticity due to multiple sclerosis versus trials where a placebo was used. They also specifically tested marijuana’s effects when smoked, calling the delivery method “rapid and efficient” but noting that vaporization is a better choice because it produces less carbon monoxide.

    The study adds that, like all medicines, there are negative side effects associated with marijuana, such as dizziness, fatigue, lightheadedness, muscle weakness and pain and heart palpitations — all of which can pose a risk in some chronic pain patients with co-occurring conditions like cardiovascular disease or substance abuse disorders. However, they call these side effects “dose-related” and “of mild to moderate severity,” adding that they “appear to decline over time, and are reported less frequently in experienced than in naïve users.” Researchers also noted that “fatal overdose with cannabis alone has not been reported.”

    Authors additionally found that marijuana does cause withdrawal symptoms within 12 hours of use, noting the symptoms are mild in experienced users and typically abate within 72 hours. They added that ingesting marijuana “can acutely impair skills required to drive motor vehicles,” but noted that the data on marijuana and traffic accidents is “inconclusive.”

    Ultimately, they concluded that more clinical trials are needed to determine which individual components of the marijuana plant are causing the medicinal effects, and whether the plant can be used to treat a host of other ailments.

    SEE ALSO: Study: The ‘gateway drug’ is alcohol, not marijuana

    “Medical marijuana is mostly used for chronic pain, and has enabled countless patients to either reduce or eliminate their pharmaceutical drug regimen,” Kris Hermes, a spokesman for Americans for Safe Access (ASA), one of the nation’s leading medical marijuana advocacy groups, told Raw Story. “However, it can also be used for: arthritis, nausea or as an appetite stimulant for people living with HIV/AIDS or cancer, gastrointestinal disorders, and movement disorders (not just for people with multiple sclerosis). That is only a sampling of health conditions for which cannabis has been found helpful in alleviating symptoms. Other health conditions include: [post-traumatic stress disorder], [attention deficit disorder], [attention deficit hyperactivity disorder] and other mental health conditions, glaucoma, and migraines.”

    In hopes of forcing recognition of marijuana’s medical value, ASA sued the federal government last year after a long-running appeal for the reclassification of marijuana was shot down nearly a decade after it was filed. That case should go before the U.S. Court of Appeals District of Columbia Circuit later this year.

    “The federal government’s strategy has been delay, delay, delay,” ASA chief counsel Joe Elford said in an advisory. “It is far past time for the government to answer our rescheduling petition, but unfortunately we’ve been forced to go to court in order to get resolution.”

    “Reform advocates can and should use this study to show their congressional representatives that our country’s leading medical marijuana researchers agree that it should be reclassified,” Hermes added. “…This certainly should also have a bearing on the D.C. Circuit’s deliberations in the appeal of the rescheduling petition denial.”

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    Ok, now we have a spokesman from Law Enforcement Against Prohibition speaking out, and boy does he have a lot to say about the DEA!

    http://www.huffingtonpost.com/jamie-...b_1660526.html

    The Fallacy of the DEA: Why the Agency Needs to Concede to Legal Marijuana

    Jamie Haase, a speaker for Law Enforcement Against Prohibition, is a former Immigration and Customs Enforcement agent.

    There's no denying the pressure that the Drug Enforcement Administration must be feeling lately. The popularity behind the marijuana legalization movement is at an all-time high, and prohibitionists are jumping ship at record rates to support cannabis reform. The drug agency has never been without opposition in its near 40 year history, but it's hard remembering a time when there's ever been this much heat on the narc outfit. The DEA is obviously still alive and well at present, but government bureaucracies are in no way immune from having to evolve with the times for lasting survival.

    Looking back, 1973 was an epic year in the United States. The Supreme Court ruled on Roe v. Wade in January, the Watergate hearings began in May, the legendary thoroughbred Secretariat won the Triple Crown in June, and then a month later in July, the world was introduced to the biggest narcotics police conglomerate ever known to man: The United States Drug Enforcement Administration.

    I say conglomerate because the DEA wasn't created from thin air. Instead, several existing agencies gelled together to form the inaugural drug enforcement monopoly. The main forerunners to the Justice Department's newest play-toy were the Bureau of Narcotics and Dangerous Drugs (BNDD), the Office for Drug Abuse Law Enforcement (ODALE), the Office for National Narcotic Intelligence, and many of the enforcement components from the U.S. Customs Service. These agencies ceased to exist entirely once the DEA came onto the scene, excluding Customs of course, which only relinquished some of its arsenal to the new kid on the block.

    Coincidentally, the U.S. Customs Service was the first federal law enforcement agency I worked for, though it was several years later and towards the end of the organization's historic span when I was employed. I bring this up because the fate of U.S. Customs, as it was under the Treasury Department, is a perfect example of the government evolution I alluded to earlier. Ultimately, neither the Customs Service nor the Immigration and Naturalization Service (INS) could stand the test of time as standalone entities post-9/11, thus the merging of their authorities under the newly formed Department of Homeland Security (DHS) in 2003.

    Going back to the DEA's similar rocky formation, President Richard Nixon's purpose for establishing the agency was to have a single and streamlined unit at the federal level to combat the nation's growing problem of drug consumption. Leading up to that point, the feds had no real teeth to combat the illicit narcotics industry. Actually, it's not that the feds didn't have the teeth, it's more that they weren't chewing and operating in sync with one another (as is still the case today with the constant red-tape and rivaling between certain agencies).

    The concept of having a centralized narcotics bureau might have been admirable in the early seventies. However, we're now witnessing the long-term flaws associated with creating such a robust agency with the sole purpose of drug enforcement, especially considering one of the DEA's biggest targets is marijuana (which is obviously a commodity becoming more and more acceptable every day).

    The growing tolerance towards cannabis poses a huge risk for the DEA, or at least the agency seems concerned with pot going mainstream. If this weren't the case, they wouldn't be so relentless in their fight against the medical marijuana industry. Polls consistently show that the use of cannabis via doctor recommendation is welcomed by almost eighty percent of the population. Yet, the DEA refuses to throw in the towel when it comes to this costly and unpopular crusade, even if it means trampling all over the rights of state and local governments in the process. Common sense should tell the DEA to give up on marijuana entirely at this point, including policing against recreational usage, which a majority of Americans now believe should be legally on par with alcohol consumption.

    Many long-term factors were neglected when the DEA was formed in 1973. For example, what if public perception changed over time and people later determined that drug abuse and addiction should be treated as health issues rather than law enforcement ones? Or what if society came to agree that prohibition's caustic side effects weren't worth fronting a fruitless multi-billion dollar drug war each year? Or what if citizens deemed that one illicit substance in particular, the one realistically funding more of the DEA's annual enforcement budget than any other, was a plant that could generate a taxable fortune for a country in need of financial aid more than ever?

    Unfortunately for the Drug Enforcement Administration, the organization is single minded for the most part, meaning there's no backup plan should Americans one day decide to do away with prohibition altogether. As a result, the agency has a vested interest in maintaining the Controlled Substances Act as it now stands. This is why the agency fights tooth and nail over losing its grip on any banned substance, let alone the most popular and abundant one.

    Other agencies (i.e. FBI, ICE, ATF, etc.) have wider scopes, broader authorities, and more mission flexibility. If the threat from terrorism ended tomorrow, the FBI would certainly survive due to the agency's array of enforceable statutes. Likewise with ICE's investigative division, Homeland Security Investigations (HSI), as this DHS component actually has the broadest statutory authority of all federal investigative agencies.

    One factor often overlooked regarding the futility of drug policing is the fact that the relationship between drug suppliers and drug users is essentially victimless. It's not as if Chapo Guzman and company are down in Mexico with their guns drawn to the heads of Americans, forcing their products into the mouths and noses of Yankee gringos. Rather, it is Americans seeking out the services of the cartels, and ironically and unfairly for Mexico, drug traffickers south of the border have American guns drawn amongst themselves as they compete over U.S. business.

    The horrific bloodshed below the Rio Grande is reason enough to legalize marijuana entirely and immediately at this point, and for Americans who still don't get it, our shared boundary with Mexico is 1,969 miles long and unsecured. It's obvious the violence can't remain isolated to only Mexico if it's allowed to foster long enough. Indeed, the Department of Justice reports that Mexican cartels have already set up shop in more than 1,000 U.S. cities.

    The southwest border will never be fully secured as long as much of the trade between South and Central America crosses America's southern border. However, there's no denying we'd be much safer if it weren't for the constant criminalization of our neighbors to the south. Illicit marijuana revenues make up around sixty percent of cartel profits per the Office of National Drug Control Policy (ONDCP), and it's the earning potential from this substance alone that tempts and lures most recruits into the narco game. Maintaining marijuana's illegality is only producing, enriching, and weaponizing more and more psychopath killers in Mexico, while simultaneously wasting valuable and scarce resources here in the United States.

    Just recently, the DEA's administrator, Michele Leonhart, only reaffirmed her agency's stubborn position on marijuana. She was questioned in front of the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security, and it's intriguing to me that a congressman from Tennessee, Steve Cohen, was the one who grilled Leonhart the most on the DEA's outdated stance towards cannabis. Not because Tennessee ranks second to only California when it comes to the domestic production of marijuana, but mostly because I imagine the DEA feels confident hedging its bet on "indefinite marijuana prohibition" with southern conservative mindsets. However, as a speaker for Law Enforcement Against Prohibition (LEAP), who is tasked with giving presentations in some of the bible belt's deepest parts imaginable, I feel confident stating that I don't think the south will be the DEA's saving grace when it comes to deterring pot legalization.

    Obviously the Drug Enforcement Administration is at a crossroads right now, and in no way am I implying the organization should be eliminated or disbanded. However, when it comes to marijuana the ballgame is over, and resources need to be drastically and quickly shifted. The agency needs to bow down gracefully to cannabis's legitimacy at this point, instead of continuing to prolong the inevitable. The government was set up to be run by the people for the people, and it's time for the DEA to recognize this. It might've been in 1971 when President Richard Nixon declared drug abuse to be public enemy number one, but it's nearly half a century later today, and prohibition itself has now become a much bigger nuisance to society (especially concerning marijuana).

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    This is my favorite park:


  26. Thanked Hardrock69 for this KICKASS post:

    jhale667 (08-11-2012)


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    Washington: Legalizing Marijuana Could Bring in $2B Over 5 years
    August 11, 2012 4:02 AM

    SEATTLE(AP) — The state’s latest financial analysis says legalizing and taxing marijuana could bring Washington as much as nearly $2 billion over the next five years — or as little as nothing.

    The Office of Financial Management released its fiscal impact statement for Initiative 502 on Friday, and the results track closely with its earlier analysis, released in March.

    I-502, which will be on the November ballot, would legalize pot under state law and allow its sale at state-licensed stores, with tax proceeds dedicated to education, health care and substance abuse prevention. Oregon and Colorado voters will also decide on marijuana legalization measures this fall.

    Marijuana would remain illegal under federal law, however, and it isn’t clear how the federal government would respond if any of the states voted to legalize it. The Justice Department could prosecute employees of state-licensed pot shops, sue in federal court to block the laws from taking effect, or simply seize the tax revenue from the states as proceeds of transactions that are illegal under federal law.

    Because the federal response remains unclear, Washington’s analysts said they could not determine the ultimate effect of I-502 on the state’s finances. However, they said, assuming a fully functioning marijuana market develops — and that it entirely replaces the existing illicit market — state revenue from pot sales could be more than $1.9 billion over the next five years. The state typically spends $30 billion per two-year budget cycle.

    I-502 would create a system of state-licensed growers, processors and stores, and impose a 25 percent tax at each stage. People 21 and older could buy up to an ounce of dried marijuana, one pound of marijuana-infused product in solid form, such as brownies, or 72 ounces of marijuana-infused liquids.

    The analysis anticipates 100 state-licensed growers supplying 328 marijuana stores that would sell more than 187,000 pounds to at least 363,000 customers. Those numbers are based on federal drug-use surveys.

    Consumers would pay $12 per gram — the price currently charged by many medical marijuana dispensaries — plus the 25 percent marijuana tax, 10 percent state sales tax, and any local sales tax, the analysts assumed.

    The document noted that Washington would likely lose some federal money to fight drugs, such as a marijuana eradication grant from the Drug Enforcement Administration.

    However, the analysis did not take into account any possible savings from no longer arresting, prosecuting and jailing people for having small amounts of marijuana, and Alison Holcomb, campaign manager for I-502, said she found that disappointing.

    About 10,000 people in Washington are charged with misdemeanor marijuana possession each year.

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    You should try that with tacos...
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    Tacos can't get you as high as reefers....

    One interesting thing. They noted the Feds may cut their subsidies for drug eradication.

    If that happens, nothing will happen.

    All the State of Washington has to do, is reallocate the state budget for marijuana eradication to the budget for fighting heroin, crack, meth, etc.

    They noted there was no mention in the study of how much money would be saved by not having to prosecute pot offenders. Well, they would not have to arrest, process, etc. anyone for pot. That would free up tremendous amounts of time in the judicial system. Free up tremendous resources in Law Enforcement, as they could focus on other crimes. The former State pot-fighting funds would make up for the Federal shortfall, and the tax revenue would definitely make up for any shortfall.

    I predict if it passes, and they are able to set up a system of growers, distributors, etc. and start getting tax revenue, within 5 years there are going to be a bunch of cash-starved (or just greedy) states who will see similar measures being introduced to legalize pot.

    We already have 3 states in ONE election now trying to legalize it.
    So we are on the way.....
    Last edited by Hardrock69; 08-12-2012 at 05:35 AM.

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    The Feds are trying hard to shut down clinics in califoreignia and killerado...

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    Well now.

    Looks like Arkansas has successfully gotten enough signatures to put Medical Marijuana on the ballot for November.

    http://www.kait8.com/story/19344729/...TFm5A.facebook

    Medical marijuana measure OK'd for Arkansas ballot

    Posted: Aug 22, 2012 3:56 PM CDT
    Updated: Aug 22, 2012 3:56 PM CDT

    LITTLE ROCK, Ark. (AP) - A proposal to legalize medical marijuana has been approved for the November ballot in Arkansas.

    The secretary of state's office on Wednesday said that Arkansans for Compassionate Care had turned in enough signatures to qualify the proposed initiated act for the November ballot. The proposal needed at least 62,507 signatures from registered voters to qualify.

    The group fell short in the number of signatures needed last month, but it was given additional time to circulate petitions.

    The proposal would allow Arkansans with qualifying conditions to purchase marijuana from non-profit dispensaries with a doctor's recommendation. Qualifying conditions include cancer, glaucoma, HIV, AIDS and Alzheimer's disease.

    The proposal acknowledges that marijuana is illegal under federal law.

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    This ad is now playing regularly on TV up here....


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    I never thought I would see the day when an ad like that was on TV.....anywhere....

    Amazing...

    Meantime, back in the Shire....

  36. #112
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    Even if Frodo didn't get high in those movies, he hits the bong all the time on his TV show "Wilfred". So does his dog......


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    Springfield, MO Decriminalizes Pot

    http://nationalcannabiscoalition.com...ize-marijuana/

    I am sure Homer Simpson is happy now.

    Breaking News: Springfield, Missouri, City Council Votes to Decriminalize Marijuana
    by Anthony Johnson • August 27, 2012 • Blog

    A Springfield, Missouri, ordinance, heavily funded by the National Cannabis Coalition, came before the Springfield City Council tonight, August 27, and have voted to pass the ordinance, instead of having the voters have their say in November. On one hand, the vote is certainly a major victory for the hardworking Show-Me Cannabis activists in Missouri. On the other hand, our work is not done, as members of the city council have vowed to “gut” the measure when they will have the opportunity to alter the measure after 30 days. Springfield Cannabis Regulation, an off-shoot of Show-Me Cannabis, did a great job on the ground, putting this measure before the city council and leading a great lobbying effort that led to its passage.

    We will help Springfield activists effectively lobby their city council, so that the measure will remain one that protects personal cannabis users from arrest and criminal penalties while allowing law enforcement resources to be better utilized fighting serious and violent crime. If the city council turns the measure into one that doesn’t meet these, goals, activists will continue to fight for an ordinance that effectively decriminalizes personal amounts of cannabis.

    For now, celebrate this win Missouri cannabis activists as you have achieved a major victory in forcing a conservative city council in voting for a cannabis decriminalization measure. As usual, the work of a cannabis activists won’t be completely done, but go ahead and celebrate, as you certainly deserve it.

  38. #114
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    Marijuana And Cancer: Scientists Find Cannabis Compound Stops Cancer

    http://www.sfgate.com/health/article...562.php#page-1

    Marijuana, already shown to reduce pain and nausea in cancer patients, may be promising as a cancer-fighting agent against some of the most aggressive forms of the disease.

    A growing body of early research shows a compound found in marijuana - one that does not produce the plant's psychotropic high - seems to have the ability to "turn off" the activity of a gene responsible for metastasis in breast and other types of cancers.

    Two scientists at San Francisco's California Pacific Medical Center Research Institute first released data five years ago that showed how this compound - called cannabidiol - reduced the aggressiveness of human breast cancer cells in the lab.

    Last year, they published a small study that showed it had a similar effect on mice. Now, the researchers are on the cusp of releasing data, also on animals, that expands upon these results, and hope to move forward as soon as possible with human clinical trials.

    "The preclinical trial data is very strong, and there's no toxicity. There's really a lot of research to move ahead with and to get people excited," said Sean McAllister, who along with scientist Pierre Desprez, has been studying the active molecules in marijuana - called cannabinoids - as potent inhibitors of metastatic disease for the past decade.

    Like many scientific endeavors, connections made between disparate elements - in this case, a plant considered a controlled substance and abnormal cells dividing out of control - involved a high degree of serendipity. The two researchers were seemingly focused on unrelated areas, but found their discoveries pointing in the same direction.

    Desprez, who moved to the Bay Area from France for postdoctoral research in the 1990s, was looking at human mammary gland cells and, in particular, the role of a protein called ID-1.

    The ID-1 protein is important in embryonic development, after which it essentially turns off and stays off. But when Desprez manipulated cells in the lab to artificially maintain a high level of ID-1 to see if he could stop the secretion of milk, he discovered that these cells began to look and act like cancer cells.

    "These cells started to behave really crazy," Desprez said. "They started to migrate, invade other tissues, to behave like metastatic cells."

    Based on that discovery, he took a look at metastatic cancer cells - not just standard cancer cells, but those responsible for aggressively spreading the disease throughout the body. He found the vast majority tended to express high levels of ID-1, leading him to conclude that ID-1 must play an important role in causing the disease to spread.
    Anticancer potential

    Meanwhile, McAllister was focused on studying anabolic steroids in drug abuse. McAllister, who also made his way to CPMC from Virginia in the 1990s, became fascinated with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.

    Marijuana's better known cannabinoid - delta-9 tetrahydrocannabinol, or THC - had already shown some anticancer properties in tumors, but the non-psychotropic cannabidiol had largely gone unstudied. McAllister initial research showed CBD had anticancer potential as well.

    About eight years ago McAllister heard his colleague, Desprez, give an internal seminar about his work on ID-1, the manipulated protein cells that masquerade as cancer cells, and metastases. That produced an idea: How effective would cannabidiol be on targeting metastatic cancer cells?

    The pair teamed up - Desprez with his apparently cancer-causing ID-1 and McAllister with his cancer-fighting CBD - deciding to concentrate their research on metastatic cells of a particularly aggressive form of breast cancer called "triple negative." It is so named because this type of breast cancer lacks the three hormone receptors that some of the most successful therapies target. About 15 percent of breast cancers fall into this category, and these cells happen to have high levels of ID-1.
    Consistent results

    When McAllister and Desprez exposed the cells to cannabidiol in a petri dish, the cells not only stopped acting "crazy" but they also started to revert to a normal state. Both scientists were shocked.

    "We thought we did the experiment the wrong way," McAllister said. But they got the same results each time they did it.

    "I told Sean, 'Maybe your drug is working through my gene,' " Desprez said.

    What they found is that the cannabinoid turns off the overexpression of ID-1, which makes the cells lose their ability to travel to distant tissues. In other words, it keeps the cells more local and blocks their ability to metastasize. Cancer kills through its ability to metastasize.

    The researchers stressed cannabidiol works only on cancer cells that have these high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. But they've found such high levels in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.

    McAllister and Desprez, who hope to publish results of their research before the end of the year, have received various grants through the National Institutes of Health, the U.S. Department of Defense, the California Breast Cancer Research Program and Susan G. Komen for the Cure.
    Pot smoking of no help

    Still, no one is suggesting that patients with metastatic cancer smoke or ingest marijuana to absorb this potentially cancer-fighting compound.

    While cannabidiol, or CBD, is the second-most abundant cannabinoid within marijuana, it has largely been bred out of the plant in favor of a higher percentage of THC, the active chemical that causes the psychotropic high widely associated with the plant.
    A long way to go

    Martin Lee, director of Project CBD, a Sonoma County group that works to raise awareness of the scientific promise of the compound, described the cannabidiol research as potent both as a medicine and a myth buster.

    "It debunks the idea that medicinal marijuana is really about people wanting to get stoned," said Lee, author of "Smoke Signals," a book published last month about the medical and social history of marijuana. "Why do they want it when it doesn't even get them high?"

    Lee said the role of marijuana in cancer research is not limited to CBD and that further research needs to be done on how it interacts with THC for possibly greater effect. "While CBD is quite amazing as a molecule, it's really a way of drawing attention to the whole plant," he said.

    The researchers know there's a long road ahead as they move from animal studies into human clinical trials and ultimately turning it into a pill or an infused drug that people can take. But they are already developing human trial models and hope to test the drug, probably in combination with current chemotherapies.

    "They've been doing studies on mice and showing the effect in tumors. All that is wonderful, but what you don't know is whether it will make people go pea green or colorblind," said Dr. William Goodson, a breast cancer specialist at California Pacific Medical Center who is familiar with the researchers' work.
    Patient intrigued

    Nonetheless, Goodson said he is intrigued by the potential to inhibit the factor that makes triple-negative breast and other cancers particularly aggressive. "For people who don't have other options, I think that's an exciting possibility," he said.

    Patients with triple-negative breast cancer are eager, too, about the potential of another treatment and hope the research will translate into a drug in the pipeline - sooner rather than later.

    Susan Rancourt of San Carlos was just diagnosed with triple-negative breast cancer in July and is in the middle of chemotherapy.

    "I don't have doomsday outlook. I feel like I am going to make it through this. But the trick is the next five years," said Rancourt, 59, who is being treated at Stanford. "If this research is advanced to the point of something (a drug) in the next five years, that will make a difference to me."
    Sense of immediacy

    As for the fact it is derived from marijuana, Rancourt said that's the least of her concerns. "I don't care if it comes from acorns," she said. "It's not the source, it's the result."

    Desprez also has a timeline. The researcher learned his 41-year-old sister was recently diagnosed with aggressive breast cancer that has already spread to her lymph nodes. While her cancer is receptive to hormone therapies, he's worried about the potential of recurrence of metastatic disease - one that lacks the hormone receptors and is even more unforgiving.

    "I want to be ready for that," he said. "There is a deadline."


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    i was able to sample some "lucid dreams" yesterday, that shit cures everything...
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    Well....isn't this interesting. A PATENT held by the United States Government!

    http://www.google.com/patents?id=0pc...page&q&f=false

    [QUOTE]Cannabinoids as antioxidants and neuroprotectants

    Patent number: 6630507
    Filing date: Feb 2, 2001
    Issue date: Oct 7, 2003
    Application number: 09/674,028

    Abstract

    Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH.sub.3, and COCH.sub.3. ##STR1##
    Inventors: Hampson; Aidan J. (Irvine, CA), Axelrod; Julius (Rockville, MD), Grimaldi; Maurizio (Bethesda, MD)
    Assignee: The United States of America as represented by the Department of Health and Human Services (Washington, DC)
    Appl. No.: 09/674,028
    Filed: February 2, 2001
    PCT Filed: April 21, 1999
    PCT No.: PCT/US99/08769
    PCT Pub. No.: WO99/53917
    PCT Pub. Date: October 28, 1999

    Current U.S. Class: 514/454
    Current International Class: A61K 31/35 (20060101); A61K 031/35 ()
    Field of Search: 514/454
    References Cited [Referenced By]
    U.S. Patent Documents

    2304669 December 1942 Adams
    4876276 October 1989 Mechoulam et al.
    5227537 July 1993 Stoss et al.
    5284867 February 1994 Kloog et al.
    5434295 July 1995 Mechoulam et al.
    5462946 October 1995 Mitchell et al.
    5512270 April 1996 Ghio et al.
    5521215 May 1996 Mechoulam et al.
    5538993 July 1996 Mechoulam et al.
    5635530 June 1997 Mechoulam et al.
    5696109 December 1997 Malfroy-Camine et al.
    6410588 June 2002 Feldmann et al.
    Foreign Patent Documents

    427518 May., 1991 EP
    576357 Dec., 1993 EP
    656354 Jun., 1995 EP
    658546 Jun., 1995 EP
    WO9305031 Mar., 1993 WO
    WO9412667 Jun., 1994 WO
    WO9612485 May., 1996 WO
    WO9618600 Jun., 1996 WO
    WO9719063 May., 1997 WO
    99/53917 Oct., 1999 WO

    Other References

    Windholz et al., The Merck Index, Tenth Edition (1983) p. 241, abstract No. 1723.* .
    Mechoulam et al., "A Total Synthesis of d1-.DELTA..sup.1 -Tetrahydrocannabinol, the Active Constituent of Hashish.sup.1," Journal of the American Chemical Society, 87:14:3273-3275 (1965). .
    Mechoulam et al., "Chemical Basis of Hashish Activity," Science, 18:611-612 (1970). .
    Ottersen et al., "The Crystal and Molecular Structure of Cannabidiol," Acta Chem. Scand. B 31, 9:807-812 (1977). .
    Cunha et al., "Chronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients.sup.1," Pharmacology, 21:175-185 (1980). .
    Consroe et al., "Acute and Chronic Antiepileptic Drug Effects in Audiogenic Seizure-Susceptible Rats," Experimental Neurology, Academic Press Inc., 70:626-637 (1980). .
    Turkanis et al., "Electrophysiologic Properties of the Cannabinoids," J. Clin. Pharmacol., 21:449S-463S (1981). .
    Carlini et al., "Hypnotic and Antielpileptic Effects of Cannabidiol," J. Clin. Pharmacol., 21:417S-427S (1981). .
    Karler et al., "The Cannabinoids as Potential Antiepileptics," J. Clin. Pharmacol., 21:437S-448S (1981). .
    Consroe et al., "Antiepileptic Potential of Cannabidiol Analgos," J. Clin. Pharmacol., 21:428S-436S (1981). .
    Colasanti et al., "Ocular Hypotension, Ocular Toxicity,a nd Neurotoxicity in Response to Marihuana Extract and Cannabidiol," Gen Pharm., Pergamon Press Ltd., 15(6):479-484 (1984). .
    Colasanti et al., "Intraocular Pressure, Ocular Toxicity and Neurotoxicity after Administration of Cannabinol or Cannabigerol," Exp. Eye Res., Academic Press Inc., 39:251-259 (1984). .
    Volfe et al., "Cannabinoids Block Release of Serotonin from Platelets Induced by Plasma frm Migraine Patients," Int. J. Clin. Pharm. Res., Bioscience Ediprint Inc., 4:243-246 (1985). .
    Agurell et al., "Pharmacokinetics and Metabolism of .DELTA..sup.1 -Tetrahydrocannabinol and Other Cannabinoids with Emphasis on Man*," Pharmacological Reviews, 38(1):21-43 (1986). .
    Karler et al., "Different Cannabinoids Exhibit Different Pharmacological and Toxicological Properties,"NIDA Res. Monogr., 79:96-107 (1987). .
    Samara et al., "Pharmacokinetics of Cannabidiol in Dogs," Drug Metabolism and Disposition, 16(3):469-472 (1988). .
    Choi, "Glutamate Neurotoxicity and Diseases of the Nervous System," Neuron, Cell Press, 1:623-634 (1988). .
    Eshhar et al., "Neuroprotective and Antioxidant Activities of HU-211, A Novel NMDA Receptor Antagonist," European Journal of Pharmacology, 283:19-29 (1995). .
    Skaper et al., "The ALIAmide Palmitoylethanolamide and Cannabinoids, but not Anandamide, are Protective in a Delayed Postglutamate Paradigm of Excitotoxic Death in Cerebellar Granule Neurons," Neurobiology, Proc. Natl. Acad. Sci. USA, 93:3984-3989 (1996). .
    Alonso et al., "Simple Synthesis of 5-Substituted Resorcinols: A Revisited Family of Interesting Bioactive Molecules," J. Org. Chem., American Chemical Society, 62(2):417-421 (1997). .
    Combes et al. "A Simple Synthesis of the Natural 2,5-Dialkylresorcinol Free Radical Scavenger Antioxidant: Resorstation," Synthetic Communications, Marcel Dekker, Inc., 27(21):3769-3778 (1997). .
    Shohami et al., "Oxidative Stress in Closed-Head Injury: Brain Antioxidant Capacity as an Indicator of Functional Outcome," Journal of Cerebral Blood Flow and Metabolism, Lippincott-Raven Publishers, 17(10):1007-1019 (1997). .
    Zurier et al., "Dimethylheptyl-THC-11 OIC Acid," Arthritis & Rheumatism, 41(1):163-170 (1998). .
    Hampson et al., "Dual Effects of Anandamide on NMDA Receptor-Mediated Responses and Neurotransmission," Journal of Neurochemistry, Lippincott-Raven Publishers, 70(2):671-676 (1998). .
    Hampson et al., "Cannabidiol and (-).DELTA..sup.9 -tetrahydrocannabiono are Neuroprotective Antioxidants," Medical Sciences, Proc. Natl. Acad. Sci. USA, 8268-8273 (1998)..

    Primary Examiner: Weddington; Kevin E.
    Attorney, Agent or Firm: Klarquist Sparkman, LLP
    Parent Case Text


    This application is a 371 of PCT/US99/08769 filed Apr. 21, 1999, which claims benefit of No. 60/082,589 filed Apr. 21, 1998, which claims benefit of No. 60/095,993 filed Aug. 10, 1998.
    Claims


    We claim:

    1. A method of treating diseases caused by oxidative stress, comprising administering a therapeutically effective amount of a cannabinoid that has substantially no binding to the NMDA receptor to a subject who has a disease caused by oxidative stress.

    2. The method of claim 1, wherein the cannabinoid is nonpsychoactive.

    3. The method of claim 2, wherein the cannabinoid has a volume of distribution of 10 L/kg or more.

    4. The method of claim 1, wherein the cannabinoid is not an antagonist at the NMDA receptor.

    5. The method of claim 1, wherein the cannabinoid is: ##STR22##

    where R is H, substituted or unsubstituted alkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino.

    6. The method of claim 5, wherein R is H, substituted or unsubstituted alkyl, carboxyl or alkoxy.

    7. The method of claim 2, wherein the cannabinoid is: ##STR23##

    where A is cyclohexyl, substituted or unsubstituted aryl, or ##STR24## but not a pinene; R.sub.1 is H, substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl; R.sub.2 is H, lower substituted or unsubstituted alkyl, or alkoxy; R.sub.3 is of H, lower substituted or unsubstituted alkyl, or substituted or unsubstituted carboxyl; R.sub.4 is H, hydroxyl, or lower substituted or unsubstituted alkyl; and R.sub.5 is H, hydroxyl, or lower substituted or unsubstituted alkyl.

    8. The method of claim 7, wherein R.sub.1 is lower alkyl, COOH or COCH.sub.3 ; R.sub.2 is unsubstituted C.sub.1 -C.sub.5 alkyl, hydroxyl, methoxy or ethoxy; R.sub.3 is H, unsubstituted C.sub.1 -C.sub.3 alkyl, or COCH.sub.3 ; R.sub.4 is hydroxyl, pentyl, heptyl, or diemthylheptyl; and R.sub.5 is hydroxyl or methyl.

    9. The method of claim 1, wherein the cannabinoid is: ##STR25##

    where R.sub.1, R.sub.2 and R.sub.3 are independently H, CH.sub.3, or COCH.sub.3.

    10. The method of claim 9, wherein the cannabinoid is: ##STR26##

    where: a) R.sub.1 =R.sub.2 =R.sub.3 =H; b) R.sub.1 =R.sub.3 =H, R.sub.2 =CH.sub.3 ; c) R.sub.1 =R.sub.2 =CH.sub.3, R.sub.3 =H; d) R.sub.1 =R.sub.2 =COCH.sub.3, R.sub.3 =H; or e) R.sub.1 =H, R.sub.2 =R.sub.3 =COCH.sub.3.

    11. The method of claim 2, wherein the cannabinoid is: ##STR27##

    where R.sub.19 is H, lower alkyl, lower alcohol, or carboxyl; R.sub.20 is H or OH; and R.sub.21 -R.sub.25 are independently H or OH.

    12. The method of claim 11, wherein R.sub.19 is H, CH.sub.3, CH.sub.2 OH, or COOH, and R.sub.20 -R.sub.24 are independently H or OH.

    13. The method of claim 2, wherein the cannabinoid is: ##STR28##

    where R.sub.19 and R.sub.20 are H, and R.sub.26 is alkyl.

    14. The method of claim 10, wherein the cannabinoid is cannabidiol.

    15. A method of treating an ischemic or neurodegenerative disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a cannabinoid, where the cannabinoid is ##STR29##

    where R is H, substituted or unsubstituted alkyl, carboxyl, alkoxy, aryl, aryloxy, arylalkyl, halo or amino.

    16. The method of claim 15, wherein the cannabinoid is not a psychoactive cannabinoid.

    17. The method of claim 15 where the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease.

    18. A method of treating a disease with a cannabinoid that has substantially no binding to the NMDA receptor, comprising determining whether the disease is caused by oxidative stress, and if the disease is caused by oxidative stress, administering the cannabinoid in a therapeutically effective antioxidant amount.

    19. The method of claim 18, wherein the cannabinoid has a volume of distribution of at least 1.5 L/kg and substantially no activity at the cannabinoid receptor.

    20. The method of claim 19, wherein the cannabinoid has a volume of distribution of at least 10 L/kg.

    21. The method of claim 1, wherein the cannabinoid selectively inhibits an enzyme activity of 5- and 15-lipoxygenase more than an enzyme activity of 12-lipoxygenase.

    22. A method of treating a neurodegenerative or ischemic disease in the central nervous system of a subject, comprising administering to the subject a therapeutically effective amount of a compound selected from any of the compounds of claims 9 through 13.

    23. The method of claim 22 where the compound is cannabidiol.

    24. The method of claim 22, wherein the ischemic or neurodegenerative disease is an ischemic infarct, Alzheimer's disease, Parkinson's disease, and human immunodeficiency virus dementia, Down's syndrome, or heart disease.

    25. The method of claim 24 wherein the disease is an ischemic infarct.

    26. The method of claim 1, wherein the cannabinoid is not an antagonist at the AMPA receptor.
    Description


    FIELD OF THE INVENTION

    The present invention concerns pharmaceutical compounds and compositions that are useful as tissue protectants, such as neuroprotectants and cardioprotectants. The compounds and compositions may be used, for example, in the treatment of acute ischemic neurological insults or chronic neurodegenerative diseases.

    BACKGROUND OF THE INVENTION

    Permanent injury to the central nervous system (CNS) occurs in a variety of medical conditions, and has been the subject of intense scientific scrutiny in recent years. It is known that the brain has high metabolic requirements, and that it can suffer permanent neurologic damage if deprived of sufficient oxygen (hypoxia) for even a few minutes. In the absence of oxygen (anoxia), mitochondrial production of ATP cannot meet the metabolic requirements of the brain, and tissue damage occurs. This process is exacerbated by neuronal release of the neurotransmitter glutamate, which stimulates NMDA (N-methyl-D-aspartate), AMPA (.alpha.-amino-3-hydroxy-5-methyl-4-isoxazole propionate) and kainate receptors. Activation of these receptors initiates calcium influx into the neurons, and production of reactive oxygen species, which are potent toxins that damage important cellular structures such as membranes, DNA and enzymes.

    The brain has many redundant blood supplies, which means that its tissue is seldom completely deprived of oxygen, even during acute ischemic events caused by thromboembolic events or trauma. A combination of the injury of hypoxia with the added insult of glutamate toxicity is therefore believed to be ultimately responsible for cellular death. Hence if the additive insult of glutamate toxicity can be alleviated, neurological damage could also be lessened. Anti-oxidants and anti-inflammatory agents have been proposed to reduce damage, but they often have poor access to structures such as the brain (which are protected by the blood brain barrier).

    Given the importance of the NMDA, AMPA and kainate receptors in the mechanism of injury, research efforts have focused on using antagonists to these receptors to interfere with the receptor mediated calcium influx that ultimately leads to cellular death and tissue necrosis. In vitro studies using cultured neurons have demonstrated that glutamate receptor antagonists reduce neurotoxicity, but NMDA and AMPA/kainate receptor antagonists have different effects. Antagonists to NMDAr prevent neurotoxicity if present during the glutamate exposure period, but are less effective if added after glutamate is removed. In contrast, AMPA/kainate receptor antagonists are not as effective as NMDA antagonists during the glutamate exposure period, but are more effective following glutamate exposure.

    Some of the research on these antagonists has focused on cannabinoids, a subset of which have been found to be NMDA receptor antagonists. U.S. Pat. No. 5,538,993 (3S,4S-delta-6-tetrahydrocannabinol-7-oic acids), U.S. Pat. No. 5,521,215 (sterospecific (+) THC enantiomers), and U.S. Pat. No. 5,284,867 (dimethylheptyl benzopyrans) have reported that these cannabinoids are effective NMDA receptor blockers. U.S. Pat. No. 5,434,295 discloses that the 1,1 dimethylheptyl (DMH) homolog of [3R,4R]-7-hydroxy-.DELTA..sup.6 THC (known as HU-210) is a superpotent cannabinoid receptor agonist with cannabinomimetic activity two orders of magnitude greater than the natural .DELTA..sup.9 THC. The HU-210 dimethylheptyl cannabinoid, has severe side effects, including fatigue, thirst, headache, and hypotension. J. Pharmacol. Sci. 60:1433-1457 (1971). Subjects who received this synthetic cannabinoid with a dimethylheptyl group experienced marked psychomotor retardation, and were unwilling or incapable of assuming an erect position.

    In contrast to HU-210, the (-)(3R,4R) THC-DMH enantiomer (known as HU-211) displays low affinity to the cannabinoid receptors, but retains NMDA receptor antagonist neuroprotective activity. ##STR2##

    THC (tetrahydrocannabinol) is another of the cannabinoids that has been shown to be neuroprotective in cell cultures, but this protection was believed to be mediated by interaction at the cannabinoid receptor, and so would be accompanied by undesired psychotropic side effects. ##STR3##

    Although it has been unclear whether cannabimimetic activity plays a role in neuroprotection against glutamate induced neurological injury, the teaching in this field has clearly been that a cannabinoid must at least be an antagonist at the NMDA receptor to have neuroprotective effect. Hence cannabidiol (2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenedi ol or CBD), a cannabinoid devoid of psychoactive effect (Pharm. Rev. 38:21-43, 1986), has not been considered useful as a neuroprotectant. Cannabidiol has been studied as an antiepileptic (Carlini et al., J. Clin. Pharmacol. 21:417S-427S, 1981; Karler et al., J. Clin. Pharmacol. 21:437S-448S, 1981, Consroe et al., J. Clin Phannacol. 21:428S-436S, 1981), and has been found to lower intraocular pressure (Colasanti et al, Exp. Eye Res. 39:251-259, 1984 and Gen. Pharmac. 15:479-484, 1984). ##STR4##

    No signs of toxicity or serious side effects have been observed following chronic administration of cannabidiol to healthy volunteers (Cunha et al., Pharmacology 21:175-185, 1980), even in large acute doses of 700 mg/day (Consroe et al., Pharmacol. Biochem. Behav. 40:701-708, 1991) but cannabidiol is inactive at the NMDA receptor. Hence in spite of its potential use in treating glaucoma and seizures, cannabidiol has not been considered a neuroprotective agent that could be used to prevent glutamate induced damage in the central nervous system.

    SUMMARY OF THE INVENTION

    It is an object of this invention to provide a new class of antioxidant drugs, that have particular application as neuroprotectants, although they are generally useful in the treatment of many oxidation associated diseases.

    Yet another object of the invention is to provide a subset of such drugs that can be substantially free of psychoactive or psychotoxic effects, are substantially non-toxic even at very high doses, and have good tissue penetration, for example crossing the blood brain barrier.

    It has surprisingly been found that cannabidiol and other cannabinoids can function as neuroprotectants, even though they lack NMDA receptor antagonist activity. This discovery was made possible because of the inventor's recognition of a previously unanticipated antioxidant property of the cannabinoids in general (and cannabidiol in particular) that functions completely independently of antagonism at the NMDA, AMPA and kainate receptors. Hence the present invention includes methods of preventing or treating diseases caused by oxidative stress, such as neuronal hypoxia, by administering a prophylactic or therapeutically effective amount of a cannabinoid to a subject who has a disease caused by oxidative stress.

    The cannabinoid may be a cannabinoid other than THC, HU-210, or other potent cannabinoid receptor agonists. The cannabinoid may also be other than HU-211 or any other NMDA receptor antagonist that has previously been reported. A potent cannabinoid receptor agonist is one that has an EC.sub.50 at the cannabinoid receptor of 50 nM or less, but in more particular embodiments 190 nM or 250 nM or less. In disclosed embodiments the cannabinoid is not psychoactive, and is not psychotoxic even at high doses. In some particularly disclosed embodiments, the cannabinoid is selected from the group: ##STR5##

    where A is aryl, and particularly ##STR6##

    but not a pinene such as: ##STR7##

    and the R.sub.1 -R.sub.5 groups are each independently selected from the groups of hydrogen, lower substituted or unsubstituted alkyl, substituted or unsubstituted carboxyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alcohol, and substituted or unsubstituted ethers, and R.sub.6 -R.sub.7 are H or methyl. In particular embodiments, there are no nitrogens in the rings, and/or no amino substitutions on the rings.

    In other embodiments, the cannabinoid is one of the following: ##STR8##

    where there can be 0 to 3 double bonds on the A ring, as indicated by the optional double bonds indicated by dashed lines on the A ring. The C ring is aromatic, and the B ring can be a pyran. Particular embodiments are dibenzo pyrans and cyclohexenyl benzenediols. Particular embodiments of the cannabinoids of the present invention may also be highly lipid soluble, and in particular embodiments can be dissolved in an aqueous solution only sparingly (for example 10 mg/ml or less). The octanol/water partition ratio at neutral pH in useful embodiments is 5000 or greater, for example 6000 or greater. This high lipid solubility enhances penetration of the drug into the CNS, as reflected by its volume of distribution (V.sub.d) of 1.5 L/kg or more, for example 3.5 L/kg, 7 L/kg, or ideally 10 L/kg or more, for example at least 20 L/kg. Particular embodiments may also be highly water soluble derivatives that are able to penetrate the CNS, for example carboxyl derivatives.

    R.sub.7-18 are independently selected from the group of H, substituted or unsubstituted alkyl, especially lower alkyl, for example unsubstituted C.sub.1 -C.sub.3 alkyl, hydroxyl, alkoxy, especially lower alkoxy such as methoxy or ethoxy, substituted or unsubstituted alcohol, and unsubstituted or substituted carboxyl, for example COOH or COCH.sub.3. In other embodiments R.sub.7-18 can also be substituted or unsubstituted amino, and halogen.

    The cannabinoid has substantially no binding to the NMDAr (for example an IC.sub.50 greater than or equal to 5 .mu.M or 10 .mu.M), has substantially no psychoactive activity mediated by the cannabinoid receptor (for example an IC.sub.50 at the cannabinoid receptor of greater than or equal to 300 nM, for example greater than 1 .mu.M and a K.sub.i greater than 250 nM, especially 500-1000 nM, for example greater than 1000 nM), and antioxidant activity, as demonstratable by the Fenton reaction or cyclic voltametry.

    In other particular embodiments, the cannabinoids are one of the following: ##STR9##

    where R.sub.19 is substituted or unsubstituted alkyl, such as lower alkyl (for example methyl), lower alcohol (such as methyl alcohol) or carboxyl (such as carboxylic acid) and oxygen (as in .dbd.O); R.sub.20 is hydrogen or hydroxy; R.sub.21 is hydrogen, hydroxy, or methoxy; R.sub.22 is hydrogen or hydroxy; R.sub.23 is hydrogen or hydroxy; R.sub.24 is hydrogen or hydroxy; R.sub.25 is hydrogen or hydroxy; and R.sub.26 is substituted or unsubstituted alkyl (for example n-methyl alkyl), substituted or unsubstituted alcohol, or substituted or unsubstituted carboxy.

    In yet other embodiments of the invention, the cannabinoids are ##STR10##

    wherein numbering conventions for each of the ring positions are shown, and R.sub.27, R.sub.28 and R.sub.29 are independently selected from the group consisting of H, unsubstituted lower alkyl such as CH.sub.3, and carboxyl such as COCH.sub.3. Particular examples of nonpsychoactive cannabinoids that fall within this definition are cannabidiol and ##STR11##

    and other structural analogs of cannabidiol.

    In more particular embodiments, the cannabinoid is used to prevent or treat an ischemic or neurodegenerative disease in the central nervous system of a subject, by administering to the subject a therapeutically effective amount of a cannabinoid to protect against oxidative injury to the central nervous system. The cannabinoid may be any of the compounds set forth above, or more specifically ##STR12##

    wherein R.sub.27, R.sub.28 and R.sub.29 are independently selected from the group consisting of H, lower alkyl such as CH.sub.3, and carboxyl such as COCH.sub.3, and particularly wherein a) R.sub.27 =R.sub.28 =R.sub.29 =H b) R.sub.27 =R.sub.29 =H; R.sub.28 =CH.sub.3 c) R.sub.27 =R.sub.28 =CH.sub.3 ; R.sub.29 =H d) R.sub.27 =R.sub.28 =COCH.sub.3 ; R.sub.29 =H e) R.sub.27 =H; R.sub.28 =R.sub.29 =COCH.sub.3

    When R.sub.27 =R.sub.28 =R.sub.29 =H, then the compound is cannabidiol. When R.sub.27 =R.sub.29 =H and R.sub.28 =CH.sub.3, the compound is CBD monomethyl ether. When R.sub.27 =R.sub.28 =CH.sub.3 and R.sub.29 =H, the compound is CBD dimethyl ether. When R.sub.27 =R.sub.28 =COCH.sub.3 and R.sub.29 =H, the compound is CBD diacetate. When R.sub.27 =H and R.sub.28 =R.sub.29 =COCH.sub.3, the compound is CBD monoacetate. The ischemic or neurodegenerative disease may be, for example, an ischemic infarct, Alzheimer's disease, Parkinson's disease, Down's syndrome, human immunodeficiency virus (HIV) dementia, myocardial infarction, or treatment and prevention of intraoperative or perioperative hypoxic insults that can leave persistent neurological deficits following open heart surgery requiring heart/lung bypass machines, such as coronary artery bypass grafts (CABG).

    The invention also includes an assay for selecting a cannabinoid to use in treating a neurological disease by determining whether the cannabinoid is an antioxidant. Once it has been determined that the cannabinoid is an antioxidant, an antioxidant effective amount of the cannabinoid is administered to treat the neurological disease, such as a vascular ischemic event in the central nervous system, for example the type caused by a neurovascular thromboembolism. Similarly, the method of the present invention includes determining whether a disease is caused by oxidative stress, and if the disease is caused by oxidative stress, administering the cannabinoid in a therapeutically effective antioxidant amount.

    The invention also includes identifying and administering antioxidant and neuroprotective compounds (such as cannabidiol) which selectively inhibit the enzyme activity of both 5- and 15-lipoxygenase more than the enzyme activity of 12-lipoxygenase. In addition, such compounds posses low NMDA antagonist activity and low cannabinoid receptor activity. Assays for selecting compounds with the desired effect on lipoxygenase enzymes, and methods for using identified compounds to treat neurological or ischemic diseases are also provided. Such diseases may include a vascular ischemic event in the central nervous system, for example a thromboembolism in the brain, or a vascular ischemic event in the myocardium. Useful administration of the compounds involves administration both during and after an ischemic injury.

    These and other objects of the invention will be understood more clearly by reference to the following detailed description and drawings.

    BRIEF DESCRIPTION OF THE FIGURES

    FIG. 1A is a graph showing NMDA induced cellular damage in a neuron (as measured by LDH release) in cells that were exposed to glutamate for 10 minutes, which demonstrates that increasing concentrations of cannabidiol in the cell culture protects against cellular damage.

    FIG. 1B is a graph similar to FIG. 1A, but showing that AMPA/kainate receptor mediated damage (induced by glutamate and the AMPA/kainate receptor potentiating agents cyclothiazide or concanavalin A) is also reduced in a concentration dependent manner by the presence of cannabidiol in the culture medium.

    FIG. 2A is a bar graph showing cellular damage (as measured by LDH release) in the presence of glutamate alone (100 .mu.M Glu), and in the presence of glutamate and 5 .mu.M cannabidiol (CBD) or 5 .mu.M THC, and demonstrates that CBD and THC were similarly protective.

    FIG. 2B is a bar graph similar to FIG. 2A, but showing the cellular damage assessed in the presence of the cannabinoid receptor antagonist SR 141716A (SR), which was not found to alter the neuroprotective effect of CBD (5 .mu.M) or THC (5 .mu.M), indicating the effect is not a typical cannabinoid effect mediated by the cannabinoid receptor.

    FIG. 3 is a graph showing the reduction oxidation potentials determined by cyclic voltametry for some natural and synthetic cannabinoids, the antioxidant BHT, and the non-cannabinoid anandamide (arachidonyl ethanolamide) which is a ligand for the cannabinoid receptor. The voltage at which initial peaks occur is an indication of antioxidant activity.

    FIG. 4 is a graph that demonstrates the antioxidant properties of BHT, CBD and THC, by plotting the fluorescence of a fluorescent dye against concentrations of these substances, where declining fluorescence is an indication of greater antioxidant activity.

    FIG. 5A is a graph illustrating decreased t-butyl peroxide induced toxicity (as measured by LDH release) in the presence of increasing concentrations of cannabidiol, demonstrating that cannabidiol is an effective antioxidant in living cells.

    FIG. 5B is a bar graph comparing the antioxidant activity of several antioxidants against glutamate induced toxicity in neurons, showing that CBD has superior antioxidant activity.

    FIG. 6A is a graph showing the effect of CBD (as measured by the change in absorbance at 234 nm) on the enzymatic activity of two lipoxygenase enzymes, rabbit 15-LO and porcine 12-LO, which demonstrates that CBD inhibits 15-LO, but not 12-LO enzyme.

    FIG. 6B is a graph demonstrating that inhibitory effect of CBD on 15-LO is competitive.

    FIG. 7A is a graph similar to FIG. 6A, but was performed in whole cells rather than purified enzyme preparations, and shows the effect of CBD (as measured by the change in absorbance at 236 nm) on the enzymatic activity of 5-LO from cultured rat basophillic leukemia cells (RBL-2H3), which demonstrates that CBD inhibits 5-LO.

    FIG. 7B is a graph showing the effect of CBD (as measured by the change in absorbance at 236 nm) on the formation of 12-HETE (the product of 12-LO) by human leukocytes (12-LO type 1).

    FIG. 7C is a graph similar to FIG. 7B, showing the effect of CBD (as measured by the change in absorbance at 236 nm) on the formation of 12-HETE by human platelets (12-LO type 2).

    FIG. 8 is a bar graph demonstrating that 12-HETE can protect cortical neurons from NMDAr toxicity most effectively when administered during and post ischemia.

    DETAILED DESCRIPTION OF SOME SPECIFIC EMBODIMENTS

    This invention provides antioxidant compounds and compositions, such as pharmaceutical compositions, that include cannabinoids that act as free radical scavengers for use in prophylaxis and treatment of disease. The invention also includes methods for using the antioxidants in prevention and treatment of pathological conditions such as ischemia (tissue hypoxia), and in subjects who have been exposed to oxidant inducing agents such as cancer chemotherapy, toxins, radiation, or other sources of oxidative stress. The compositions and methods described herein are also used for preventing oxidative damage in transplanted organs, for inhibiting reoxygenation injury following reperfusion of ischemic tissues (for example in heart disease), and for any other condition that is mediated by oxidative or free radical mechanisms of injury. In particular embodiments of the invention, the compounds and compositions are used in the treatment of ischemic cardiovascular and neurovascular conditions, and neurodegenerative diseases. However the present invention can also be used as an antioxidant treatment in non-neurological diseases.

    Molecular oxygen is essential for aerobic organisms, where it participates in many biochemical reactions, including its role as the terminal electron acceptor in oxidative phosphorylation. However excessive concentrations of various forms of reactive oxygen species and other free radicals can have serious adverse biological consequences, including the peroxidation of membrane lipids, hydroxylation of nucleic acid bases, and the oxidation of sulfhydryl groups and other protein moieties. Biological antioxidants include tocopherols and tocotrieneols, carotenoids, quinones, bilirubin, ascorbic acid, uric acid, and metal binding proteins. However these endogenous antioxidant systems are often overwhelmed by pathological processes that allow permanent oxidative damage to occur to tissue.

    Free radicals are atoms, ions or molecules that contain an unpaired electron, are usually unstable, and exhibit short half-lives. Reactive oxygen species (ROS) is a collective term, designating the oxygen radicals (e.g. .O.sub.2.sup.- superoxide radical), which by sequential univalent reduction produces hydrogen peroxide (H.sub.2 O.sub.2) and hydroxyl radical (.OH). The hydroxyl radical sets off chain reactions and can interact with nucleic acids. Other ROS include nitric oxide (NO.) and peroxy nitrite (NOO.), and other peroxyl (RO.sub.2.) and alkoxyl (RO.) radicals. Increased production of these poisonous metabolites in certain pathological conditions is believed to cause cellular damage through the action of the highly reactive molecules on proteins, lipids and DNA. In particular, ROS are believed to accumulate when tissues are subjected to ischemia, particularly when followed by reperfusion.

    The pharmaceutical compositions of the present invention have potent antioxidant and/or free radical scavenging properties, that prevent or reduce oxidative damage in biological systems, such as occurs in ischemic/reperfusion injury, or in chronic neurodegenerative diseases such as Alzheimer's disease, HIV dementia, and many other oxidation associated diseases.

    DEFINITIONS

    "Oxidative associated diseases" refers to pathological conditions that result at least in part from the production of or exposure to free radicals, particularly oxyradicals, or reactive oxygen species. It is evident to those of skill in the art that most pathological conditions are multifactorial, and that assigning or identifying the predominant causal factors for any particular condition is frequently difficult. For these reasons, the term "free radical associated disease" encompasses pathological states that are recognized as conditions in which free radicals or ROS contribute to the pathology of the disease, or wherein administration of a free radical inhibitor (e.g. desferroxamine), scavenger (e.g. tocopherol, glutathione) or catalyst (e.g. superoxide dismutase, catalase) is shown to produce detectable benefit by decreasing symptoms, increasing survival, or providing other detectable clinical benefits in treating or preventing the pathological state.

    Oxidative associated diseases include, without limitation, free radical associated diseases, such as ischemia, ischemic reperfusion injury, inflammatory diseases, systemic lupus erythematosis, myocardial ischemia or infarction, cerebrovascular accidents (such as a thromboembolic or hemorrhagic stroke) that can lead to ischemia or an infarct in the brain, operative ischemia, traumatic hemorrhage (for example a hypovolemic stroke that can lead to CNS hypoxia or anoxia), spinal cord trauma, Down's syndrome, Crohn's disease, autoimmune diseases (e.g. rheumatoid arthritis or diabetes), cataract formation, uveitis, emphysema, gastric ulcers, oxygen toxicity, neoplasia, undesired cellular apoptosis, radiation sickness, and others. The present invention is believed to be particularly beneficial in the treatment of oxidative associated diseases of the CNS, because of the ability of the cannabinoids to cross the blood brain barrier and exert their antioxidant effects in the brain. In particular embodiments, the pharmaceutical composition of the present invention is used for preventing, arresting, or treating neurological damage in Parkinson's disease, Alzheimer's disease and HIV dementia; autoimmune neurodegeneration of the type that can occur in encephalitis, and hypoxic or anoxic neuronal damage that can result from apnea, respiratory arrest or cardiac arrest, and anoxia caused by drowning, brain surgery or trauma (such as concussion or spinal cord shock).

    As used herein, an "antioxidant" is a substance that, when present in a mixture containing an oxidizable substrate biological molecule, significantly delays or prevents oxidation of the substrate biological molecule. Antioxidants can act by scavenging biologically important reactive free radicals or other reactive oxygen species (.O.sub.2.sup.-, H.sub.2 O.sub.2, .OH, HOCl, ferryl, peroxyl, peroxynitrite, and alkoxyl), or by preventing their formation, or by catalytically converting the free radical or other reactive oxygen species to a less reactive species. Relative antioxidant activity can be measured by cyclic voltametry studies of the type disclosed in Example 5 (and FIG. 3), where the voltage (x-axis) is an index of relative antioxidant activity. The voltage at which the first peak occurs is an indication of the voltage at which an electron is donated, which in turn is an index of antioxidant activity.

    "Therapeutically effective antioxidant doses" can be determined by various methods, including generating an empirical dose-response curve, predicting potency and efficacy of a congener by using quantitative structure activity relationships (QSAR) methods or molecular modeling, and other methods used in the pharmaceutical sciences. Since oxidative damage is generally cumulative, there is no minimum threshold level (or dose) with respect to efficacy. However, minimum doses for producing a detectable therapeutic or prophylactic effect for particular disease states can be established.

    As used herein, a "cannabinoid" is a chemical compound (such as cannabinol, THC or cannabidiol) that is found in the plant species Cannabis saliva (marijuana), and metabolites and synthetic analogues thereof that may or may not have psychoactive properties. Cannabinoids therefore include (without limitation) compounds (such as THC) that have high affinity for the cannabinoid receptor (for example K.sub.i <250 nM), and compounds that do not have significant affinity for the cannabinoid receptor (such as cannabidiol, CBD). Cannabinoids also include compounds that have a characteristic dibenzopyran ring structure (of the type seen in THC) and cannabinoids which do not possess a pyran ring (such as cannabidiol). Hence a partial list of cannabinoids includes THC, CBD, dimethyl heptylpentyl cannabidiol (DMHP-CBD), 6,12-dihydro-6-hydroxy-cannabidiol (described in U.S. Pat. No. 5,227,537, incorporated by reference); (3S,4R)-7-hydroxy-.DELTA..sup.6 -tetrahydrocannabinol homologs and derivatives described in U.S. Pat. No. 4,876,276, incorporated by reference; (+)-4-[4-DMH-2,6-diacetoxy-phenyl]-2-carboxy-6,6-dimethylbicyclo[3.1. 1]hept-2-en, and other 4-phenylpinene derivatives disclosed in U.S. Pat. No. 5,434,295, which is incorporated by reference; and cannabidiol (-)(CBD) analogs such as (-)CBD-monomethylether, (-)CBD dimethyl ether; (-)CBD diacetate; (-)3'-acetyl-CBD monoacetate; and .+-.AF11, all of which are disclosed in Consroe et al., J. Clin. Phannacol. 21:428S-436S, 1981, which is also incorporated by reference. Many other cannabinoids are similarly disclosed in Agurell et al., Pharmacol. Rev. 38:31-43, 1986, which is also incorporated by reference.

    As referred to herein, the term "psychoactivity" means "cannabinoid receptor mediated psychoactivity." Such effects include, euphoria, lightheadedness, reduced motor coordination, and memory impairment. Psychoactivity is not meant to include non-cannabinoid receptor mediated effects such as the anxiolytic effect of CBD.

    The "lipoxygenase enzyme activity" refers to the relative level of lipoxygenase enzyme activity for a particular lipoxgenase, such as 5-, 15- or 12-lipoxygenase, as measured in Example 8. A compound would be said to "selectively inhibit a lipoxgenase enzyme" if the concentration of inhibitor required to reduce enzyme activity by 50% was at least about 5 times less than the amount required to reduce activity of a second lipoxgenase enzyme by the same degree (under the same conditions, i.e. temperature, substrate concentration, etc.)

    An "antagonist" is a compound that binds and occupies a receptor without activating it. In the presence of a sufficient concentration of antagonist, an agonist cannot activate its receptor. Therefore, antagonists may decrease the neurotoxicity mediated by NMDA (as described in Example 3) or AMPA and Kainate (as described in Example 4).

    An "agonist" is a compound that activates a receptor. When the receptor is activated for a longer than normal period of time, this may cause neurotoxicity, as in the case of NMDA, AMPA and kainate receptors (see Examples 3 and 4).

    The term "alkyl" refers to a cyclic, branched, or straight chain alkyl group containing only carbon and hydrogen, and unless otherwise mentioned contains one to twelve carbon atoms. This term is further exemplified by groups such as methyl, ethyl, n-propyl, isobutyl, t-butyl, pentyl, pivalyl, heptyl, adamantyl, and cyclopentyl. Alkyl groups can either be unsubstituted or substituted with one or more substituents, e.g. halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, acyloxy, hydroxy, mercapto, carboxy, aryloxy, aryloxy, aryl, arylalkyl, heteroaryl, amino, alkylamino, dialkylamino, morpholino, piperidino, pyrrolidin-1-yl, piperazin-1-yl, or other functionality.

    The term "lower alkyl" refers to a cyclic, branched or straight chain monovalent alkyl radical of one to seven carbon atoms. This term is further exemplified by such radicals as methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl (or 2-methylpropyl), cyclopropylmethyl, i-amyl, n-amyl, hexyl and heptyl. Lower alkyl groups can also be unsubstituted or substituted, where a specific example of a substituted alkyl is 1,1-dimethyl heptyl.

    "Hydroxyl" refers to --OH.

    "Alcohol" refers to R--OH, wherein R is alkyl, especially lower alkyl (for example in methyl, ethyl or propyl alcohol). An alcohol may be either linear or branched, such as isopropyl alcohol.

    "Carboxyl" refers to the radical --COOH, and substituted carboxyl refers to --COR where R is alkyl, lower alkyl or a carboxylic acid or ester.

    The term "aryl" or "Ar" refers to a monovalent unsaturated aromatic carbocyclic group having a single ring (e.g. phenyl) or multiple condensed rings (e.g. naphthyl or anthryl), which can optionally be unsubstituted or substituted with, e.g., halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, acyloxy, hydroxy, mercapto, carboxy, aryloxy, aryl, arylalkyl, heteroaryl, amino, alkylamino, dialkylamino, morpholino, piperidino, pyrrolidin-1-yl, piperazin-1-yl, or other functionality.

    The term "alkoxy" refers to a substituted or unsubstituted alkoxy, where an alkoxy has the structure --O--R, where R is substituted or unsubstituted alkyl. In an unsubstituted alkoxy, the R is an unsubstituted alkyl. The term "substituted alkoxy" refers to a group having the structure --O--R, where R is alkyl which is substituted with a non-interfering substituent. The term "arylalkoxy" refers to a group having the structure --O--R--Ar, where R is alkyl and Ar is an aromatic substituent. Arylalkoxys are a subset of substituted alkoxys. Examples of useful substituted alkoxy groups are: benzyloxy, naphthyloxy, and chlorobenzyloxy.

    The term "aryloxy" refers to a group having the structure --O--Ar, where Ar is an aromatic group. A particular aryloxy group is phenoxy.

    The term "heterocycle" refers to a monovalent saturated, unsaturated, or aromatic carbocyclic group having a single ring (e.g. morpholino, pyridyl or faryl) or multiple condensed rings (e.g. indolizinyl or benzo[b]thienyl) and having at least one heteroatom, defined as N, O, P, or S, within the ring, which can optionally be unsubstituted or substituted with, e.g. halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, acyloxy, hydroxy, mercapto, carboxy, aryloxy, aryl, arylakyl, heteroaryl, amino, alkylamino, dialkylamino, morpholino, piperidino, pyrrolidin-1-yl, piperazin-1-yl, or other functionality.

    "Arylalkyl" refers to the groups --R--Ar and --R--HetAr, where Ar is an aryl group. HetAr is a heteroaryl group, and R is a straight-chain or branched chain aliphatic group. Example of arylaklyl groups include benzyl and furfuryl. Arylalkyl groups can optionally be unsubstituted or substituted with, e.g., halogen, alkyl, alkoxy, alkylthio, trifluoromethyl, acyloxy, hydroxy, mercapto, carboxy, aryloxy, aryl, arylalkyl, heteroaryl, amino, alkylamino, dialkylamino, morpholino, peperidino, pyrrolidin-1-yl, piperazin-1-yl, or other functionality.

    The term "halo" or "halide" refers to fluoro, bromo, chloro and iodo substituents.

    The term "amino" refers to a chemical functionality --NR'R" where R' and R" are independently hydrogen, alkyl, or aryl. The term "quaternary amine" refers to the positively charged group --N.sup.+ R'R", where R'R" and R" are independently selected and are alkyl or aryl. A particular amino group is --NH.sub.2.

    A "pharmaceutical agent" or "drug" refers to a chemical compound or composition capable of inducing a desired therapeutic or prophylactic effect when properly administered to a subject.

    All chemical compounds include both the (+) and (-) stereoisomers, as well as either the (+) or (-) stereoisomer.

    Other chemistry terms herein are used according to conventional usage in the art, as exemplified by The McGraw-Hill Dictionary of Chemical Terms (1985) and The Condensed Chemical Dictionary (1981).

    The following examples show that both nonpsychoactive cannabidiol, and psychoactive cannabinoids such as THC, can protect neurons from glutamate induced death, by a mechanism independent of cannabinoid receptors. Cannabinoids are also be shown to be potent antioxidants capable of preventing ROS toxicity in neurons.

    EXAMPLE 1

    Preparation of Cannabinoids and Neuronal Cultures

    Cannabidiol, THC and reactants other than those specifically listed below were purchased from Sigma Chemical, Co. (St. Louis, Mo.). Cyclothiazide, glutamatergic ligands and MK-801 were obtained from Tocris Cookson (UK). Dihydrorhodamine was supplied by Molecular Probes (Eugene, Oreg.). T-butyl hydroperoxide, tetraethylammonium chloride, ferric citrate and sodium dithionite were all purchased from Aldrich (WI). All culture media were Gibco/BRL (MD) products.

    Solutions of cannabinoids, cyclothiazide and other lipophiles were prepared by evaporating a 10 mM ethanolic solution (under a stream of nitrogen) in a siliconized microcentrifuge tube. Dimethyl sulfoxide (DMSO, less than 0.05% of final volume) was added to ethanol to prevent the lipophile completely drying onto the tube wall. After evaporation, 1 ml of culture media was added and the drug was dispersed using a high power sonic probe. Special attention was used to ensure the solution did not overheat or generate foam. Following dispersal, all solutions were made up to their final volume in siliconized glass tubes by mixing with an appropriate quantity of culture media.

    Primary neuronal cultures were prepared according to the method of Ventra et al. (J. Neurochem. 66:1752-1761, 1996). Fetuses were extracted by Cesarian section from a 17 day pregnant Wistar rat, and the feral brains were placed into phosphate buffered saline. The cortices were then dissected out, cut into small pieces and incubated with papain for nine minutes at 37.degree. C. After this time the tissue was dissociated by passage through a fire polished Pasteur pipette, and the resultant cell suspension separated by centrifugation over a gradient consisting of 10 mg/ml bovine serum albumin and 10 mg/ml ovomucoid (a trypsin inhibitor) in Earls buffered salt solution. The pellet was then re-suspended in high glucose, phenol red free Dulbeco's modified Eagles medium containing 10% fetal bovine serum, 2 mM glutamine, 100 IU penicillin, and 100 .mu.g/ml streptomycin (DMEM). Cells were counted, tested for vitality using the trypan blue exclusion test and seeded onto poly-D-lysine coated 24 multiwell plates. After 96 hours, 10 .mu.M fluoro-deoxyuridine and 10 .mu.M uridine were added to block glial cell growth. This protocol resulted in a highly neuron-enriched culture.

    EXAMPLE 2

    Preparation of Astrocytes and Conditioned Media

    Astrocyte conditioned DMEM was used throughout the AMPA/kainate toxicity procedure and following glutamate exposure in the NMDAr mediated toxicity protocol. Media was conditioned by 24 hour treatment over a confluent layer of type I astrocytes, prepared from two day old Wistar rat pups. Cortices were dissected, cut into small pieces, and enzymatically digested with 0.25% trypsin. Tissue was then dissociated by passage through a fire polished Pasteur pipette and the cell suspension plated into untreated 75 cm.sup.2 T-flasks. After 24 hours the media was replaced and unattached cells removed. Once astrocytes achieved confluence, cells were divided into four flasks. Media for experiments was conditioned by a 24 hour exposure to these astrocytes, after which time it was frozen at -20.degree. C. until use. Astrocyte cultures were used to condition DMEM for no longer than two months.

    EXAMPLE 3

    NMDA Mediated Toxicity Studies

    Glutamate neurotoxicity can be mediated by NMDA, AMPA or kainate receptors. To examine NMDAr mediated toxicity, cultured neurons (cultured for 14-18 days) were exposed to 250 .mu.M glutamate for 10 minutes in a magnesium free saline solution. The saline was composed of 125 mM NaCl, 25 mM glucose, 10 mM HEPES (pH 7.4), 5 mM KCl, 1.8 mM calcium chloride and 5% bovine serum albumin. Following exposure, cells were washed twice with saline, and incubated for 18 hours in conditioned DMEM. The level of lactate dehydrogenase (LDH) in the media was used as an index of cell injury.

    Toxicity was completely prevented by addition of the NMDAr antagonist, MK-801 (500 nM, data not shown). However, FIG. 1A shows that cannabidiol also prevented neurotoxicity (maximum protection 88.+-.9%) with an EC.sub.50 of 2-4 .mu.M (specifically about 3.5 .mu.M).

    EXAMPLE 4

    AMPA and Kainate Receptor Mediated Toxicity Studies

    Unlike NMDA receptors, which are regulated by magnesium ions, AMPA/kainate receptors rapidly desensitize following ligand binding. To examine AMPA and kainate receptor mediated toxicity, neurons were cultured for 7-13 days, then exposed to 100 .mu.M glutamate and 50 .mu.M cyclothiazide (used to prevent AMPA receptor desensitization). Cells were incubated with glutamate in the presence of 500 nM MK-801 (an NMDAr antagonist) for 18-20 hours prior to analysis. Specific AMPA and kainate receptor ligands were also used to separately examine the effects of cannabinoids on AMPA and kainate receptor mediated events. Fluorowillardiine (1.5 .mu.M) was the AMPA agonist and 4-methyl glutamate (10 .mu.M) was the kainate agonist used to investigate receptor mediated toxicity. When specifically examining kainate receptor activity, cyclothiazide was replaced with 0.15 mg/ml Concanavalin-A.

    Cannabidiol protection against AMPA/kainate mediated neurotoxicity is illustrated in FIG. 1B, where LDH in the media was used as an index of cell injury. The neuroprotective effect of cannabidiol was similar to that observed in the NMDA mediated toxicity model (FIG. 1A). Cannabidiol prevented neurotoxicity (maximum protection 80.+-.17%) with an EC.sub.50 of 2-4 .mu.M (specifically about 3.3 .mu.M). Comparable results were obtained with either the AMPA receptor ligand, fluorowillardiine or the kainate receptor specific ligand, 4-methyl-glutamate (data not shown). Hence cannabidiol protects similarly against toxicity mediated by NMDA, AMPA or kainate receptors.

    Unlike cannabidiol, THC is a ligand (and agonist) for the brain cannabinoid receptor. The action of THC at the cannabinoid receptor has been proposed to explain the ability of THC to protect neurons from NMDAr toxicity in vitro. However in AMPA/kainate receptor toxicity assays, THC and cannabidiol were similarly protective (FIG. 2A), indicating that cannabinoid neuroprotection is independent of cannabinoid receptor activation. This was confirmed by inclusion of cannabinoid receptor antagonist SR-141716A in the culture media (SR in FIG. 2B). See Mansbach et al., Psychopharmacology 124:315-22, 1996, for a description of SR-141716A. Neither THC nor cannabidiol neuroprotection was affected by cannabinoid receptor antagonist (FIG. 2B).

    EXAMPLE 5

    Cyclic Voltametery Studies or ReDox Potentials

    To investigate whether cannabinoids protect neurons against glutamate damage by reacting with ROS, the antioxidant properties of cannabidiol and other cannabinoids were assessed. Cyclic voltametry, a procedure that measures the ability of a compound to accept or donate electrons under a variable voltage potential, was used to measure the oxidation potentials of several natural and synthetic cannabinoids. These studies were performed with an EG&G Princeton Applied Research potentiostat/galvanostat (Model 273/PAR 270 software, NJ). The working electrode was a glassy carbon disk with a platinum counter electrode and silver/silver chloride reference. Tetraethylammonium chloride in acetonitrile (0.1 M) was used as an electrolyte. Cyclic voltametry scans were done from +0 to 1.8 V at scan rate of 100 mV per second. The reducing ability of cannabidiol (CBD), THC, HU-211, and BHT were measured in this fashion. Anandamide, a cannabinoid receptor ligand without a cannabinoid like structure, was used as a non-responsive control. Each experiment was repeated twice with essentially the same results.

    Cannabidiol, THC and the synthetic cannabinoid HU-211 all donated electrons at a similar potential as the antioxidant BHT. Anandamide (arachidonyl ethanolamide) did not undergo oxidation at these potentials (FIG. 3). Several other natural and synthetic cannabinoids, including cannabidiol, nabilone, and levanantrodol were also tested, and they too exhibited oxidation profiles similar to cannabidiol and THC (data not shown).

    EXAMPLE 6

    Iron Catalyzed Dihydrorhodamine Oxidation (Fenton Reaction)

    The ability of cannabinoids to be readily oxidized, as illustrated in Example 5, indicated they possess antioxidant properties comparable to BHT. The antioxidant activity of BHT was examined in a Fenton reaction, in which iron is catalyzed to produce ROS. Cannabidiol (CBD) and tetrahydrocannabinol (THC) were evaluated for their ability to prevent oxidation of dihydrorhodamine to the fluorescent compound rhodamine. Oxidant was generated by ferrous catalysis (diothionite reduced ferric citrate) of t-butyl hydroperoxide in a 50:50 water:acetonitrile (v/v) solution. Dihydrorhodamine (50 .mu.M) was incubated with 300 .mu.M t-butyl hydroperoxide and 0.5 .mu.M iron for 5 minutes. After this time, oxidation was assessed by spectrofluorimetry (Excit=500 nm, Emiss=570 nm). Various concentrations of cannabinoids and BHT were included to examine their ability to prevent dihydrorhodiamine oxidation.

    Cannabidiol, THC and BHT all prevented dihydrorhodamine oxidation in a similar, concentration dependent manner (FIG. 4), indicating that cannabinoids have antioxidant potency comparable to BHT.

    To confirm that cannabinoids act as antioxidants in the intact cell, neurons were also incubated with the oxidant t-butyl hydroperoxide and varying concentrations of cannabidiol (FIG. 5A). The t-butyl hydroperoxide oxidant was chosen for its solubility in both aqueous and organic solvents, which facilitates oxidation in both cytosolic and membrane cell compartments. Cell toxicity was assessed 18-20 hours after insult by measuring lactate dehydrogenase (LDH) release into the culture media. All experiments were conducted with triple or quadruple values at each point and all plates contained positive (glutamate alone) and baseline controls. The assay was validated by comparison with an XTT based metabolic activity assay. As shown in FIG. 5A, cannabidiol protected neurons against ROS toxicity in a dose related manner, with an EC.sub.50 of about 6 .mu.M. The maximum protection observed was 88.+-.9%.

    Cannabidiol was also compared with known antioxidants in an AMPA/kainate toxicity protocol. Neurons were exposed to 100 .mu.M glutamate and equimolar (5 .mu.M) cannabidiol, .alpha.-tocopherol, BHT or ascorbate (FIG. 5B). Although all of the antioxidants attenuated glutamate toxicity, cannabidiol was significantly more protective than either .alpha.-tocopherol or ascorbate. The similar antioxidant abilities of cannabidiol and BHT in this chemical system (FIG. 4), and their comparable protection in neuronal cultures (FIG. 5B), implies that cannabidiol neuroprotection is due to an antioxidant effect.

    EXAMPLE 7

    In vivo Rat Studies

    The middle cerebral artery of chloral hydrate anesthetized rats was occluded by insertion of suture thread into it. The animals were allowed to recover from the anesthetic and move freely for a period of two hours. After this time the suture was removed under mild anesthetic and the animals allowed to recover for 48 hours. Then the animals were tested for neurological deficits, sacrificed, and the infarct volume calculated. To examine the infarct volume, animals were anesthetized, ex-sanguinated, and a metabolically active dye (3-phenyl tetrazolium chloride) was pumped throughout the body. All living tissues were stained pink by the dye, while morbid regions of infarcted tissue remained white. Brains were then fixed for 24 hours in formaldehyde, sliced and the infarct volumes measured.

    One hour prior to induction of ischemia 20 mg/kg of cannabidiol was administered by intra-peritoneal injection (ip) in a 90% saline:5% emulphor 620 (emulsifier):5% ethanol vehicle. A second ip 10 mg/kg dose of cannabidiol was administered 8 hours later using the same vehicle. Control animals received injections of vehicle without drug. IV doses would be expected to be 3-5 times less because of reduction of first pass metabolism.

    The infarct size and neurological assessment of the test animals is shown Table 1.

    TABLE 1 Cannabidiol protects rat brains from ischemia damage Volume of Infarct Behavioral Deficit (mm3) Score Animal Drug Control Drug Control 1 108.2 110.5 3 2 2 83.85 119.6 4 4 3 8.41 118.9 3 4 4 75.5 177.7 1 4 5 60.53 33.89 1 3 6 27.52 255.5 1 5 7 23.16 143 1 4 Mean 55.3 137.0 2.0 3.7 SEM 13.8 25.7 0.5 0.4 p = 0.016 significant p = 0.015 significant *Neurological scoring is performed on a subjective 1-5 scale of impairment. 0 = no impairment, 5 = severe (paralysis)

    This data shows that infarct size was approximately halved in the animals treated with cannabidiol, which was also accompanied by a substantial improvement in the neurological status of the animal.

    These studies with the nonpsychotropic marijuana constituent, cannabidiol, demonstrate that protection can be achieved against both glutamate neurotoxicity and free radical induced cell death. THC, the psychoactive principle of cannabis, also blocked glutamate neurotoxicity with a potency similar to cannabidiol. In both cases, neuroprotection is unaffected by the presence of a cannabinoid receptor antagonist. These results therefore surprisingly demonstrate that cannabinoids can have useful therapeutic effects that are not mediated by cannabinoid receptors, and therefore are not necessarily accompanied by psychoactive side effects. Cannabidiol also acts as an anti-epileptic and anxiolytic, which makes it particularly useful in the treatment of neurological diseases in which neuroanatomic defects can predispose to seizures (e.g. subarachnoid hemorrhage).

    A particular advantage of the cannabinoid compounds of the present invention is that they are highly lipophilic, and have good penetration into the central nervous system. The volume of distribution of some of these compounds is at least 100 L in a 70 kg person (1.4 L/kg), more particularly at least 250 L, and most particularly 500 L or even 700 L in a 70 kg person (10 L/kg). The lipophilicity of particular compounds is also about as great as that of THC, cannabidiol or other compounds that have excellent penetration into the brain and other portions of the CNS.

    Cannabinoids that lack psychoactivity or psychotoxicity are particularly useful embodiments of the present invention, because the absence of such side effects allows very high doses of the drug to be used without encountering unpleasant side effects (such as dysphoria) or dangerous complications (such as obtundation in a patient who may already have an altered mental status). For example, therapeutic antioxidant blood levels of cannabidiol can be 5-20 mg/kg, without significant toxicity, while blood levels of psychoactive cannabinoids at this level would produce obtundation, headache, conjunctival irritation, and other problems. Particular examples of the compounds of the present invention have low affinity to the cannabinoid receptor, for example a K.sub.i of greater than 250 nM, for example K.sub.i.gtoreq.500-1000 nM. A compound with a K.sub.i.gtoreq.1000 nM is particularly useful, which compound has essentially no psychoactivity mediated by the cannabinoid receptor.

    Cannabidiol blocks glutamate toxicity with equal potency regardless of whether the insult is mediated by NMDA, AMPA or kainate receptors. Cannabidiol and THC have been shown to be comparable to the antioxidant BHT, both in their ability to prevent dihydrorhodamine oxidation and in their cyclic voltametric profiles. Several synthetic cannabinoids also exhibited profiles similar to the BHT, although anandamide, which is not structurally related to cannabinoids, did not. These findings indicate that cannabinoids act as antioxidants in a non-biological situation, which was confirmed in living cells by showing that cannabidiol attenuates hydroperoxide induced neurotoxicity. The potency of cannabidiol as an antioxidant was examined by comparing it on an equimolar basis with three other commonly used compounds.

    In the AMPA/kainate receptor dependent neurotoxicity model, cannabidiol neuroprotection was comparable to the potent antioxidant, BHT, but significantly greater than that observed with either .alpha.-tocopherol or ascorbate. This unexpected superior antioxidant activity (in the absence of BHT tumor promoting activity) shows for the first time that cannabidiol, and other cannabinoids, can be used as antioxidant drugs in the treatment (including prophylaxis) of oxidation associated diseases, and is particularly useful as a neuroprotectant. The therapeutic potential of nonpsychoactive cannabinoids is particularly promising, because of the absence of psychotoxicity, and the ability to administer higher doses than with psychotropic cannabinoids, such as THC. Previous studies have also indicated that cannabidiol is not toxic, even when chronically administered to humans or given in large acute doses (700 mg/day).

    EXAMPLE 8

    Effect of Cannabidiol on Lipoxygenase Enzymes

    This example describes in vitro and in vivo assays to examine the effect of cannabidiol (CBD) on three lipoxygenase (LO) enzymes: 5-LO, 12-LO and 15-LO.

    In vitro Enzyme Assay

    The ability of CBD to inhibit lipoxygenase was examined by measuring the time dependent change in absorption at 234 nM following addition of 5 U of each lipoxygenase (rabbit 15-LO purchased from Biomol (PA), porcine 12-LO purchased from Cayman chemicals (MI)) to a solution containing 10 .mu.M (final concentration) linoleic acid.

    Enzyme studies were performed using a u.v. spectrophotometer and a 3 ml quartz cuvette containing 2.5 ml of a stirred solution of 12.5 .mu.M sodium linoleic acid (sodium salt) in solution A (25 mM Tris (pH 8.1), 1 mM EDTA 0.1% methyl cellulose). The reaction was initiated by addition of 0.5 ml enzyme solution (10 U/ml enzyme in solution A) and recorded for 60 seconds. Lipoxygenase exhibits non-Michaelis-Menten kinetics, an initial "lag" (priming) phase followed by a linear phase which is terminated by product inhibition. These complications were reduced by assessing enzyme activity (change in absorption) over the "steepest" 20 second period in a 60 second run time. Recordings examined the absorption at 234 nm minus the value at a reference wavelength of 280 nm. Linoleic acid was used as the substrate rather than arachidonic acid, because the products are less inhibitory to the enzyme, thereby providing a longer "linear phase".

    Cell Purification and Separation

    Human platelets and leukocytes were purified from buffy coat preparations (NIH Blood Bank) using a standard Ficoll based centrifugation method used in blood banks. Prior to use, cells were washed three times to eliminate contaminating cell types. Cultured rat basophillic leukemia cells (RBL-2H3) were used as a source of 5-lipoxygenase.

    In vivo Determination of Lipoxygenase Activity

    Cells were incubated with arachidonic acid and stimulated with the calcium ionophore A23187. Lipids were extracted and separated by reverse phase HPLC. Product formation was assessed as the area of a peak that co-eluted with an authentic standard, had a greater absorbance at 236 nm than at either 210 or 280 nm, and the formation of which was inhibited by a lipoxygenase inhibitor.

    Cell pellets were triturated in DMEM culture media, aliquoted and pre-incubated for 15 minutes with 20 .mu.M arachidonic acid and varying concentrations of cannabidiol and/or 40 .mu.M nordihydroguaiaretic acid (a lipxygenase inhibitor). Platelets and leukocytes were also pre-incubated with 80 .mu.M manoalide (Biomol) to prevent phospholipase A2 activation. Product formation was initiated by addition of 5 .mu.M A23187 and incubation for 10 minutes at 37.degree. C. At the end of the incubation, the reaction was stopped by addition of 15% 1M HCl and 10 ng/ml prostaglandin B2 (internal standard). Lipids were extracted with 1 volume of ethyl ether, which was dried under a stream of nitrogen. Samples were reconstituted in 50% acetonitrile:50% H.sub.2 O and separated by reverse phase HPLC using a gradient running from 63% acetonitrile: 37% H.sub.2 O:0.2% acetic acid to 90% acetonitrile (0.2% acetic acid) over 13 minutes.

    Measurement of NMDAr Toxicity

    The ability of 12-HETE (12-(s)-hydroxy-eicosatetraenoic acid, the product of the action of 12-lipoxygenase on arachidonic (eicosatetraenoic) acid) to protect cortical neurons from NMDAr toxicity was measured as described in Example 3. The 12-HETE (0.5 .mu.g/ml) was added either during ischemia (co-incubated with the glutamate), during post-ischemia (co-incubated with the DMEM after washing the cells), or during both ischemia and post-ischemia.

    Results

    Using semi-purified enzyme preparations, the effect of CBD on rabbit 15-LO and porcine 12-LO was compared. As shown in FIGS. 6A and B, CBD is a potent competitive inhibitor of 15-LO with an EC.sub.50 of 598 nM. However, CBD had no effect on the 12-LO enzyme.

    Using whole cell preparations, the effect of CBD on 5- and 12-LO enzymes was investigated. As shown in FIG. 7A, CBD inhibited 5-LO in cultured rat basophillic leukemia cells (RBL-2H3) with an EC.sub.50 of 1.92 .mu.M. However, CBD had no effect on 12-LO, as monitored by the production of 12-HETE (the product of 12-LO), in either human leukocytes or platelets (FIGS. 7B and C). The leukocyte 12-LO is similar, while the platelet 12-LO is structurally and functionally different, from the porcine 12-LO used in the in vitro enzyme study.

    The ability of 12-HETE to protect cortical neurons from NMDAr toxicity is shown in FIG. 8. To achieve best protection from NMDAr toxicity, 12-HETE was administered both during and post ischemia.

    Therefore, CBD serves as a selective inhibitor of at least two lipoxygenase enzymes, 5-LO and 15-LO, but had no effect on 12-LO. Importantly, this is the first demonstration (FIG. 8) that the 12-LO product 12-HETE can play a significant role in protecting neurons from NMDAr mediated toxicity. Although the mechanism of this protection is unknown at the present time, 12-HETE is known to be an important neuromodulator, due to its ability to influence potassium channel activity.

    EXAMPLE 9

    Methods of Treatment

    The present invention includes a treatment that inhibits oxidation associated diseases in a subject such as an animal, for example a rat or human. The method includes administering the antioxidant drugs of the present invention, or a combination of the antioxidant drug and one or more other pharmaceutical agents, to the subject in a pharmaceutically compatible carrier and in an effective amount to inhibit the development or progression of oxidation associated diseases. Although the treatment can be used prophylactically in any patient in a demographic group at significant risk for such diseases, subjects can also be selected using more specific criteria, such as a definitive diagnosis of the condition. The administration of any exogenous antioxidant cannabinoid would inhibit the progression of the oxidation associated disease as compared to a subject to whom the cannabinoid was not administered. The antioxidant effect, however, increases with the dose of the cannabinoid.

    The vehicle in which the drug is delivered can include pharmaceutically acceptable compositions of the drugs of the present invention using methods well known to those with skill in the art. Any of the common carriers, such as sterile saline or glucose solution, can be utilized with the drugs provided by the invention. Routes of administration include but are not limited to oral, intracranial ventricular (icv), intrathecal (it), intravenous (iv), parenteral, rectal, topical ophthalmic, subconjunctival, nasal, aural, sub-lingual (under the tongue) and transdermal. The antioxidant drugs of the invention may be administered intravenously in any conventional medium for intravenous injection such as an aqueous saline medium, or in blood plasma medium. Such medium may also contain conventional pharmaceutical adjunct materials such as, for example, pharmaceutically acceptable salts to adjust the osmotic pressure, lipid carriers such as cyclodextrins, proteins such as serum albumin, hydrophilic agents such as methyl cellulose, detergents, buffers, preservatives and the like. Given the low solubility of many cannabinoids, they may be suspended in sesame oil.

    Given the excellent absorption of the compounds of the present invention via an inhaled route, the compounds may also be administered as inhalants, for example in pharmaceutical aerosols utilizing solutions, suspensions, emulsions, powders and semisolid preparations of the type more fully described in Remington: The Science and Practice of Pharmacy (19.sup.th Edition, 1995) in chapter 95. A particular inhalant form is a metered dose inhalant containing the active ingredient, in a suspension or a dispersing agent (such as sorbitan trioleate, oleyl alcohol, oleic acid, or lecithin, and a propellant such as 12/11 or 12/114).

    Embodiments of the invention comprising pharmaceutical compositions can be prepared with conventional pharmaceutically acceptable carriers, adjuvants and counterions as would be known to those of skill in the art. The compositions are preferably in the form of a unit dose in solid, semi-solid and liquid dosage forms such as tablets, pills, powders, liquid solutions or suspensions, injectable and infusible solutions, for example a unit dose vial, or a metered dose inhaler. Effective oral human dosage ranges for cannabidiol are contemplated to vary from about 1-40 mg/kg, for example 5-20 mg/kg, and in particular a dose of about 20 mg/kg of body weight.

    If the antioxidant drugs are to be used in the prevention of cataracts, they may be administered in the form of eye drops formulated in a pharmaceutically inert, biologically acceptable carrier, such as isotonic saline or an ointment. Conventional preservatives, such as benzalkonium chloride, can also be added to the formulation. In ophthalmic ointments, the active ingredient is admixed with a suitable base, such as white petrolatum and mineral oil, along with antimicrobial preservatives. Specific methods of compounding these dosage forms, as well as appropriate pharmaceutical carriers, are known in the art. Remington: The Science and Practice of Pharmacy, 19th Ed., Mack Publishing Co. (1995), particularly Part 7.

    The compounds of the present invention are ideally administered as soon as a diagnosis is made of an ischemic event, or other oxidative insult. For example, once a myocardial infarction has been confirmed by electrocardiograph, or an elevation in enzymes characteristic of cardiac injury (e.g. CKMB), a therapeutically effective amount of the cannabinoid drug is administered. A dose can also be given following symptoms characteristic of a stroke (motor or sensory abnormalities), or radiographic confirmation of a cerebral infarct in a distribution characteristic of a neurovascular thromboembolic event. The dose can be given by frequent bolus administration, or as a continuous IV dose. In the case of cannabidiol, for example, the drug could be given in a dose of 5 mg/kg active ingredient as a continuous intravenous infusion; or hourly intramuscular injections of that dose.

    EXAMPLE 10

    The following table lists examples of some dibenzopyran cannabinoids that may be useful as antioxidants in the method of the present invention.

    ##STR13## ##STR14## Compound R.sub.19 R.sub.20 R.sub.21 R.sub.22 R.sub.23 R.sub.24 R.sub.25 R.sub.26 H 5 7-OH-.DELTA..sup.1 -THC CH.sub.2 OH H H H H H H C.sub.5 H.sub.11 H 6 6.alpha.-OH-.DELTA..sup.1 -THC CH.sub.3 .alpha.-OH H 7 6.beta.-OH-.DELTA..sup.1 -THC CH.sub.3 .beta.-OH 8 1"-OH-.DELTA..sup.1 -THC CH.sub.3 OH H 9 2"-OH-.DELTA..sup.1 -THC CH.sub.3 OH 10 3"-OH-.DELTA..sup.1 -THC CH.sub.3 OH 11 4"-OH-.DELTA..sup.1 -THC CH.sub.3 OH H 12 6.alpha.,7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH .alpha.-OH H 13 6v,7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH .beta.-OH 14 1",7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH OH H 15 2",7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH OH H 16 3",7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH OH H 17 4",7-diOH-.DELTA..sup.1 -THC CH.sub.2 OH OH 18 1",6.beta.-diOH-.DELTA..sup.1 -THC CH.sub.3 .beta.-OH OH 19 1",3"-diOH-.DELTA..sup.1 -THC CH.sub.3 OH OH 20 1",6.alpha.,7-triOH-.DELTA..sup.1 -THC CH.sub.2 OH .alpha.-OH OH H 21 .DELTA..sup.1 -THC-6-one CH.sub.3 .dbd.O 22 Epoxyhexahydrocannabinol CH.sub.3 (EHHC)* 23 7-oxo-.DELTA..sup.1 -THC CHO H 24 .DELTA..sup.1 -THC-7"-oic acid COOH H 25 .DELTA..sup.1 -THC-3"-oic acid CH.sub.3 C.sub.2 H.sub.4 COOH H 26 1"-OH-.DELTA..sup.1 -THC-7"-oic acid COOH OH H 27 2"-OH-.DELTA..sup.1 -THC-7"-oic acid COOH OH H 28 3"-OH-.DELTA..sup.1 -THC-7"-oic acid COOH OH H 29 4"-OH-.DELTA..sup.1 -THC-7"-oic acid COOH OH H 30 3",4",5"-trisnor-2"-OH-.DELTA..sup.1 - COOH C.sub.2 H.sub.4 OH THC-7-oic acid H 31 7-OH-.DELTA..sup.1 -THC-2"-oic acid CH.sub.2 OH CH.sub.2 COOH H 32 6.beta.-OH-.DELTA..sup.1 -THC-2"-oic acid CH.sub.3 .beta.-OH CH.sub.2 COOH H 33 7-OH-.DELTA..sup.1 -THC-3"-oic acid CH.sub.2 OH C.sub.2 H.sub.4 COOH H 34 6.beta.-OH-.DELTA..sup.1 -THC-3"-oic acid CH.sub.3 .beta.-OH C.sub.2 H.sub.4 COOH H 35 6.alpha.-OH-.DELTA..sup.1 -THC-4"-oic acid CH.sub.3 .alpha.-OH C.sub.3 H.sub.6 COOH H 36 2",3"-dehydro-6U-OH-.DELTA..sup.1 - CH.sub.3 .alpha.-OH C.sub.3 H.sub.4 COOH THC-4"-oic acid H 37 .DELTA..sup.1 -THC-1",7-dioic acid COOH COOH H 38 .DELTA..sup.1 -THC-2",7-dioic acid COOH CH.sub.2 COOH H 39 .DELTA..sup.1 -THC-3",7-dioic acid COOH C.sub.2 H.sub.4 COOH H 40 .DELTA..sup.1 -THC-4",7-dioic acid COOH C.sub.3 H.sub.6 COOH H 41 1",2"-dehydro-.DELTA..sup.1 -THC-3",7- COOH C.sub.2 H.sub.2 COOH dioic acid H 42 .DELTA..sup.1 -THC-glucuronic acid CH.sub.3 gluc.sup..dagger. H 43 .DELTA..sup.1 -THC-7-oic acid COO gluc.sup..dagger. glucuronide *Epoxy group in C-1 and C-2 positions .sup..dagger. Glucuronide Note: R-group substituents are H if not indicated otherwise.

    Chemical structures of some of the dibenzopyran cannabinoids are shown below. ##STR15## ##STR16## ##STR17##

    EXAMPLE 11

    Examples of Structural Analogs of Cannabidiol

    The following table lists examples of some cannabinoids which are structural analogs of cannabidiol and that may be useful as antioxidants in the method of the present invention. A particularly useful example is compound CBD, cannabidiol.

    Compound R.sub.19 R.sub.20 R.sub.21 R.sub.22 R.sub.23 R.sub.24 R.sub.25 R.sub.26 ##STR18## ##STR19## 44 CBD CH.sub.3 H H H H H H C.sub.5 H.sub.11 45 7-OH--CBD CH.sub.2 OH 46 6.alpha.- CH.sub.3 .alpha.-OH 47 6.beta.- CH.sub.3 .beta.-OH 48 1"- CH.sub.3 OH 49 2"- CH.sub.3 OH 50 3"- CH.sub.3 OH 51 4"- CH.sub.3 OH 52 5"- CH.sub.3 C.sub.4 H.sub.8 CH.sub.2 OH 53 6,7-diOH--CBD CH.sub.2 OH OH 54 3",7-diOH--CBD CH.sub.2 OH OH 55 4",7-diOH--CBD CH.sub.2 OH OH 56 CBD-7-oic acid COOH 57 CBD-3"-oic acid CH.sub.3 C.sub.2 H.sub.4 COOH ##STR20## ##STR21## 58 CBN CH.sub.3 H H H H H H C.sub.5 H.sub.11 59 7-OH--CBN CH.sub.2 OH 60 1"-OH--CBN CH.sub.3 OH 61 2"-OH--CBN CH.sub.3 OH 62 3"-OH--CBN CH.sub.3 OH 63 4"-OH--CBN CH.sub.3 OH 64 5"-OH--CBN CH.sub.3 C.sub.4 H.sub.8 CH.sub.2 OH 65 2"-7-diOH--CBN CH.sub.2 OH OH 66 CBN-7-oic acid COOH 67 CBN-1"-oic acid CH.sub.3 COOH 68 CBN-3"-oic acid CH.sub.3 C.sub.2 H.sub.4 COOH Note: R-group substituents are H if not indicated otherwise.

    The invention being thus described, variation in the materials and methods for practicing the invention will be apparent to one of ordinary skill in the art. Such variations are to be considered within the scope of the invention, which is set forth in the claims below.
    Last edited by Hardrock69; 09-30-2012 at 12:48 AM.

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    Dupe post.
    Last edited by Hardrock69; 09-30-2012 at 12:54 AM.

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    CBD kills cancer (more like arrests and reverses, but whatevs), there's a study that pretty much proves it, and there's a call for further testing. Unfortunately you could never get enough into your system to appreciate the effects via smoking alone, it'll need to be synthesized...

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    Yes, but the point is, the government itself admitted that cannabis had many medical uses in the patent application which was filed in 2001.

    And they are raiding pot dispensaries?

    The government cannot have it both ways. Either they withdraw the patent, and continue with pot on Schedule 1, and continue raiding dispensaries, OR they admit they have no valid reason for pot to be on Schedule 1 and remove it, and stop raiding dispensaries. But they cannot withdraw the patent. The horse is already out of the barn and is flying high like a motherfucker.

    These studies we have been seeing the results of lately are RECENT studies. The government did not publicize this patent filing when they did it. They probably hoped nobody would notice.

    This is the ammo the dispensaries needed to have the cases thrown out, and to prohibit the Feds from raiding the dispensaries.

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    http://nationalcannabiscoalition.com...ify-marijuana/

    Here we go......a good solid attempt to get Cannabis off of schedule I.
    US Court to Hear Arguments to Re-classify Marijuana

    This week, on October 16th, the U.S. Court of Appeals in Washington, D.C. will begin hearing oral arguments in Americans for Safe Access v. Drug Enforcement Administration, a lawsuit challenging the federal government’s current status of cannabis alongside LSD and heroin as a Schedule I substance, which identifies cannabis has having “no medicinal value.”

    The hypocrisy is egregious and obvious: on top of the countless scientific studies which have been done over the last several years showing cannabis as an effective medicine for everything from Alzheimer’s to MS to cancer, nearly three quarters of Americans recognize this truth and support the doctors and patients who feel the same. Marinol, a synthetic form of THC, which is found in the cannabis plant, is classified as Schedule III – meaning it is recognized to have medicinal value. In December, 2011, the federal government granted a patent on medical cannabis to a private firm called KannaLife In 2002, my state university college textbook in pharmacology cited “cannabis” as being the model anti-emetic drug – meaning cannabis controls nausea better than any other known compound on the planet.

    For the first time in 20 years, federal courts will have to address this inconsistency, despite their blatant tactics to delay these discussions. And there’s a good chance they will be forced to put policy more in line with science. Unfortunately, there’s a good chance this change will do much meaningful for the thousands of cannabis patients and consumers in this country. If cannabis is rescheduled to Schedule II, it will come to sit alongside cocaine in its designation. Yes, doctors can prescribe cocaine. But we all know this doesn’t happen in real practice. Furthermore, rescheduling means the FDA is still in control, and they don’t let anyone but Big Pharma produce medicines.

    I applaud Americans for Safe Access and the excellent work they are doing – pushing the envelope and demanding that we have the conversation and hold our policies to a scientific standard. But although I welcome our court system finally attempting to address the contradiction of our policies with science, I caution anyone from getting their hopes up or from thinking that the battle is over should marijuana be re-scheduled.

    The fact is, cannabis needs to be removed from the scheduling system altogether. Period. Only then will the civil liberties aspect of this issue be resolved. Only then will opportunities open for entrepreneurship and local businesses in this emerging industry. Only then will the ugliness of the illegal market completely be addressed. And most importantly, only then will all the patients who need their medicine have access to it.

    I sincerely hope that Americans for Safe Access is successful this week in their court hearings – the truth is with them. But the battle does not stop there; we need to de-schedule, not just re-schedule marijuana.


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