Rats taking cannabis get taste for heroin

news@nature.com ^ | 5 July 2006 | Michael Hopkin

[neverdem]

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Published online: 5 July 2006; | doi:10.1038/news060703-9

Rats taking cannabis get taste for heroin

Study suggests cannabis-users may be vulnerable to harder drugs.

Michael Hopkin

Neuroscientists have found that rats are more likely to get hooked on heroin if they have previously been given cannabis. The studies suggest a biological mechanism — at least in rats — for the much-publicized effect of cannabis as a 'gateway' to harder drugs.

The discovery hints that the brain system that produces pleasurable sensations when exposed to heroin may be 'primed' by earlier exposure to cannabis, say researchers at the Karolinska Institute in Stockholm, Sweden, who carried out the study.

There has long been a debate about whether exposure to drugs such as nicotine or marijuana might lead to harder habits. Many argue that the most important factors in the equation are social ones: people who get one drug from a dealer are probably more inclined to try another. But researchers are still interested to know whether there is any physiological effect that might additionally predispose users of so-called soft drugs to harder-drug addiction.

To rule out social factors, the researchers turned to an animal model. They dosed some rats with the active ingredient of cannabis and others with a neutral compound during their adolescence (when they were about four to six weeks old). After that, they gave the rats intermittent access to heroin for several weeks, obtained by pressing a lever.

Although all rats helped themselves to heroin, the ones given cannabis's key compound, called -9-tetrahydrocannabinol (THC), during their formative years showed a greater escalation in their self-dosing during the experiment. By the end, rats that'd had cannabis in their 'teens' were pressing the lever that delivered heroin about 1.5 times more than the rats that had previously been drug-free.

We now know that these drugs have an impact on behaviour later in life.  Yasmin Hurd, Mount Sinai School of Medicine, New York

The researchers report the findings in the journal Neuropsychopharmacology¹.

Hard to kick

"It's a nice study, although somewhat preliminary," comments Ian Stolerman, a psychopharmacologist at Kings College London. "It's too early to say there's a consensus, but a small number of studies like this suggest that there is a physiological basis for this effect."

The rat results may be due to the fact that both THC and heroin act on a pleasure pathway in the brain called the opioid system, explains study leader Yasmin Hurd, now at Mount Sinai School of Medicine in New York. Exposure to opiates such as heroin triggers the release of chemical messengers in the brain called opioids that stimulate pleasant sensations.

The receptor molecule to which THC binds is also found on brain cells in the opioid system, Hurd adds. Over-stimulation of these receptors through exposure to cannabis may alter these cells so that the brain either feels intensely rewarded by subsequent heroin exposure, or needs an ever-increasing dose to feel the same pleasure — both of which could lead to addiction.

If so, a similar effect may be seen with drugs such as cocaine and amphetamines, which involve another brain pathway called the dopaminergic system, Stolerman adds. Cells involved in this pathway also have THC receptors, possibly indicating that they could also be modified by cannabis exposure.

A slippery slope

But even if the gateway effect is one day found to also have a biological basis in humans, the effect is undoubtedly complicated by social factors. Some social commentators have ascribed the perceived gateway effect to the simple fact that cannabis is cheaper than many other illegal drugs, meaning that adolescents are more likely to use it before graduating to other substances.

Hurd, however, feels that softening the law against marijuana at this point would be "ridiculous", given the number of unknowns about its effects. She adds that two other drugs that also stimulate opioid cells, and could therefore also feasibly cause a gateway effect, are nicotine and alcohol. "If we turned back the clock with the knowledge we have now, these two drugs would never have been legalized," Hurd says.

The discovery also warns against complacency that cannabis does not have any lasting effect in young people who use the drug. "Lots of mothers say 'oh well, at least it's not cocaine'," Hurd says. "But this is not about the short-term effects. For adults to do it is one thing, but we have to consider the effects on children."

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References

1. Ellgren M.,

   Spano S. M.&

   Hurd Y. L. . Neuropsychopharmacology, . - doi:10.1038/sj.npp.1301127

[neverdem]

Scientific proof that reading BS will make you want to try heroin.

Please elaborate. Did you read the whole thread?

[Reform4Bush]

I read every comment.

Not much to elaborate on, unless you are looking for me to expand on the delivery method of the heroin I feel the need to use after reading this garbage article.

[TheSpottedOwl]

I was thinking of fly paper, but dammit...they're so cute. I'm just going to have to grab them by the tails and move them under a bush. They are starting to trust me...

[Know your rights]

More like: Give me liberty, including the liberty to decide for myself whether or not to use drugs, or give me death.

Move to Amsterdam

You move to anti-drug Sweden and enjoy the big government you crave ... I'll stick with the Land of the Free.

[Moonman62]

But according to your posts shouldn't I assume that the Land of the Free is also anti-drug? You remember the Drug War don't you?

[Know your rights]

shouldn't I assume that the Land of the Free is also anti-drug?

Currently the Drug War stains this land's principles of liberty and limited government ... which is why I'm going to stay here and work to remove that stain.

[oxcart]

Here is my 2 penny's worth;

The role of liver tryptophan pyrrolase in the opposite effects of chronic administration and subsequent withdrawal of drugs of dependence on rat brain tryptophan metabolism.

A A Badawy, N F Punjani, and M Evans

1. Chronic administration of morphine, nicotine or phenobarbitone has previously been shown to inhibit rat liver tryptophan pyrrolase activity by increasing hepatic [NADPH], whereas subsequent withdrawal enhances pyrrolase activity by a hormonal-type mechanism. 2. It is now shown that this enhancement is associated with an increase in the concentration of serum corticosterone. 3. Chronic administration of the above drugs enhances, whereas subsequent withdrawal inhibits, brain 5-hydroxytryptamine synthesis. Under both conditions, tryptophan availability to the brain is altered in the appropriate direction. 4. The chronic drug-induced enhancement of brain tryptophan metabolism is reversed by phenazine methosulphate, whereas the withdrawal-induced inhibition is prevented by nicotinamide. 5. The chronic morphine-induced changes in liver [NADPH], pyrrolase activity, tryptophan availability to the brain and brain 5-hydroxytryptamine synthesis are all reversed by the opiate antagonist naloxone. 6. It is suggested that the opposite effects on brain tryptophan metabolism of chronic administration and subsequent withdrawal of the above drugs of dependence are mediated by the changes in liver tryptophan pyrrolase activity. 6. Similar conclusions based on similar findings have previously been made in relation to chronic administration and subsequent withdrawal of ethanol. These findings with all four drugs are briefly discussed in relation to previous work and the mechanism(s) of drug dependence.

FULL TEXT; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=7197926

[oxcart]

Please see post #47

[PaxMacian]

If an herb can be banned for being a gateway drug then porn
should be banned for causing rape because all rapists started
their deviation from the norm with it.

[Moonman62]

That's because there is nowhere to move. No functioning society has had unlimited liberty.

If you don't like Amsterdam try Vancouver. I've heard it's beautiful. I've also heard that the area where people have the liberty to do drugs isn't so nice.

[PaxMacian]

There is no such thing as unlimited liberty as it is always
limited by the natural rights of others.

[bigfootbob]

I've been looking for this study I read about a couple of weeks ago from France that showed cannabis in the test showed it could inhibit and reverse hepatic fibrosis. If I recall the study correctly, the cannabis attached itself to the CB1 receptor and acted as an antagonist reducing the effects of fibrosis.

They also used Sativex in the study and it wasn't as effective and the discussion I read centered on the ethanol content. I don't care if a beer has 50 time more ethanol, by your reported study, any ethanol/alcohol content for a cirrhotic liver isn't therapeutic.

Why the hell did GW Pharmaceuticals insert the ethanol into Sativex in the first place?

[neverdem]

I've been looking for this study I read about a couple of weeks ago from France that showed cannabis in the test showed it could inhibit and reverse hepatic fibrosis. If I recall the study correctly, the cannabis attached itself to the CB1 receptor and acted as an antagonist reducing the effects of fibrosis.

Copy and paste marijuana and hepatic fibrosis into the query box at PubMed. Maybe that first link was the study that you saw, but check the others.

They also used Sativex in the study and it wasn't as effective and the discussion I read centered on the ethanol content. I don't care if a beer has 50 time more ethanol, by your reported study, any ethanol/alcohol content for a cirrhotic liver isn't therapeutic.

Here's the statement from the first link in comment# 37:

"SATIVEX®contains approximately 50% v/v of ethanol. Each dose contains up to 0.04 g of ethanol. The median daily dose of 5 sprays would be up to 0.2 g ethanol."

It is an excerpt from Sativex's PRODUCT MONOGRAPH for Canada. That was from the cached HTML version of the original Sativex portable data file(pdf) document. It appears to be the equivalent of the product information insert provided with prescription medicines in their original packaging in the USA.

I found it and the amount of ethanol in a standard drink because I thought that the relative and absolute amount of ethanol was relevant.

As an aside, it's my experience that excerpting the relevant statements from either original pdf or cached HTML articles is a reliable pain in the butt.

Why the hell did GW Pharmaceuticals insert the ethanol into Sativex in the first place?

Governments usually won't approve anybody smoking anything, and ethanol is a great organic solvent.

Full disclosure: I'm a physician. My undergraduate major was chemistry. I'm limited in doing literature searches and using the internet as I have had no formal training in either. I had an informal introduction to the internet at a local library six years ago. I originally started searching Medline on CD-ROM over a decade ago. Now I go to PubMed to find citations in the medical literature all the time. Understanding how to use the Boolean operators, AND, OR, NOT greatly facilitates using PubMed. P.S. At PubMed, it's my experience that you don't have to capitalize and, or and not. If you use any other service/function of the National Center for Biotechnology Information, I would capitalize.

[neverdem]

Not much to elaborate on, unless you are looking for me to expand on the delivery method of the heroin I feel the need to use after reading this garbage article.

Here's another take on the same study.

Gone to Pot?

"Rats that had been exposed to THC as "teens" took about 25% more heroin than did their just-say-no peers. Biochemical tests of the adult animals showed that THC-doused brains had the same number of receptors that responded to THC as unexposed rat brains, but more receptors for heroin and more of a compound associated with reward behavior in their neurons, the team reports online 5 July in Neuropsychopharmacology. Whether this indicates marijuana is a "gateway" drug depends on the definition of "gateway," says Hurd. She says both groups of animals took the same amount of time to start taking heroin, suggesting THC use doesn't start them on the path to hedonism, but the THC-primed rats got more into it, suggesting it paves the way for increased use."

[SupplySider]

"Give me drugs or give me death"?

"Give me cannabis or give me meth!"

[Know your rights]

Currently the Drug War stains this land's principles of liberty and limited government ... which is why I'm going to stay here and work to remove that stain.

That's because there is nowhere to move.

No, that's because no other country was founded on the principle of liberty.

No functioning society has had unlimited liberty.

Who wants "unlimited" liberty? Each adult's liberty should be limited by the rights of others ... and by nothing else.

If you don't like Amsterdam try Vancouver.

No, as I said, you go try anti-drug Sweden.

I've heard it's beautiful. I've also heard that the area where people have the liberty to do drugs isn't so nice.

Of course not ... the liberty to do drugs only in a limited area and in the absence of the liberty to sell them is a bad idea.

[Moonman62]

No, that's because no other country was founded on the principle of liberty.

Our country was founded on the principle of self rule. The Constitution was initiated to establish the federal government. The Bill of Rights was implemented to balance the rights of the government with the rights of individuals.

Of course not ... the liberty to do drugs only in a limited area and in the absence of the liberty to sell them is a bad idea.

The liberty to do drugs and sell drugs in an unlimited area is a worse idea.

Our country is still a fairly nice and prosperous place. We don't want Anarchists, Libertarians, Liberals, drug users, and criminals to make it any worse than they already have. That's why the Libertarian Party can't even crack a half percent in a national election these days.

[Know your rights]

no other country was founded on the principle of liberty.

Our country was founded on the principle of self rule.

The phrase "life, liberty, and the pursuit of happiness" is not familiar to you?

The Constitution was initiated to establish the federal government. The Bill of Rights was implemented to balance the rights of the government with the rights of individuals.

No, the body of the Constitution grants the federal government the only powers (not "rights") it has, with the rest being retained by the states and the people ... which is why some Founding Fathers opposed the Bill of Rights on grounds of redundancy.

Of course not ... the liberty to do drugs only in a limited area and in the absence of the liberty to sell them is a bad idea.

The liberty to do drugs and sell drugs in an unlimited area is a worse idea.

Nonsense ... the liberty to do and sell the deadly addictive violence-inducing drug alcohol has proved to be a better idea than trying to ban it. Eventually we'll grasp that the same is true of other drugs, particularly marijuana.

[Moonman62]

The phrase "life, liberty, and the pursuit of happiness" is not familiar to you?

Yes, it is in the Declaration of Independence, and it was a great rallying cry, but when it came to founding our country by codifying the laws it is not to be found. According to Wiki the phrase was only used once in a Supreme Court case.

No, the body of the Constitution grants the federal government the only powers (not "rights") it has, with the rest being retained by the states and the people ...

Call it what you want, but the Supreme Court still decides where the "powers" of the government end, and the rights of the people begin. Your redefinition is meaningless.

which is why some Founding Fathers opposed the Bill of Rights on grounds of redundancy.

Their argument was that specifying people's rights would actually limit them. But since it was Federalists like Hamilton who held that view I have to wonder what their true motivation was.

Nonsense ... the liberty to do and sell the deadly addictive violence-inducing drug alcohol has proved to be a better idea than trying to ban it.

Alcohol was never banned. During Prohibition possession was legal, doctors could prescibe it, low alcohol beer was legal that could be turned into high alcohol beer, and law enforcement was not allowed to enter businesses that were serving alcohol to investigate.

Eventually we'll grasp that the same is true of other drugs, particularly marijuana.

One of these days maybe you'll realize that people don't want to live in neighborhoods where drugs are sold and used freely, and that groups like the Libertarian Party that espouse such nonsense are losers.

[Know your rights]

The phrase "life, liberty, and the pursuit of happiness" is not familiar to you?

Yes, it is in the Declaration of Independence, and it was a great rallying cry, but when it came to founding our country by codifying the laws it is not to be found.

Incorrect as usual; the U.S. Constitution, the "supreme law of the land, states as one of its purposes to "secure the Blessings of Liberty".

No, the body of the Constitution grants the federal government the only powers (not "rights") it has, with the rest being retained by the states and the people ...

Call it what you want, but the Supreme Court still decides where the "powers" of the government end, and the rights of the people begin.

So you think Roe v Wade and Lawrence v Texas were properly decided? Conservatives don't.

which is why some Founding Fathers opposed the Bill of Rights on grounds of redundancy.

Their argument was that specifying people's rights would actually limit them. But since it was Federalists like Hamilton who held that view I have to wonder what their true motivation was.

The views of Federalists are automatically suspect? How is that a conservative point of view?

Nonsense ... the liberty to do and sell the deadly addictive violence-inducing drug alcohol has proved to be a better idea than trying to ban it.

Alcohol was never banned. During Prohibition possession was legal,

A distinction without a difference, as manufacture, sale, or transportation was prohibited.

doctors could prescibe it, low alcohol beer was legal that could be turned into high alcohol beer, and law enforcement was not allowed to enter businesses that were serving alcohol to investigate.

Mighty thin reeds on which to hang your distinction. Cocaine is prescribable ... does that mean it's not banned?

Eventually we'll grasp that the same is true of other drugs, particularly marijuana.

One of these days maybe you'll realize that people don't want to live in neighborhoods where drugs are sold and used freely,

The sale and circumstances of use of the drug alcohol are regulated, and I would expect and support comparable laws regarding other drugs.

and that groups like the Libertarian Party that espouse such nonsense are losers.

Empty namecalling.