July 06, 2006
THC Primes Rats For Heavier Heroin Abuse
Marijuana really does lead to higher risk of heavy duty drug abuse - at least in lab rats.
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 Delta-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.
I find this incredibly unsurprising. The developing brain develops differently if exposed to drugs that activate brain pleasure circuitry.
Decreased sensitivity leads to greater risk of addiction.
“At first, all the rats behaved the same and began to self-administer heroin frequently,” says Hurd. “But after a while, they stabilised their daily intake at a certain level. We saw that the ones that had been on THC as teenagers stabilised their intake at a much higher level than the others – they appeared to be less sensitive to the effects of heroin. And this continued throughout their lives.”
Hurd says reduced sensitivity to the heroin means the rats take larger doses, which has been shown to increase the risk of addiction.
Earlier use of alcohol in humans is associated with greater risk of alcoholism.
Data from a survey of 43,000 U.S. adults heighten concerns that early alcohol use, independent of other risk factors, may contribute to the risk of developing future alcohol problems. Those who began drinking in their early teens were not only at greater risk of developing alcohol dependence at some point in their lives, they were also at greater risk of developing dependence more quickly and at younger ages, and of developing chronic, relapsing dependence. Among all respondents who developed alcoholism at some point, almost half (47 percent) met the diagnostic criteria for alcohol dependence (alcoholism) by age 21.
The associations between early drinking and later problems held even after investigators controlled for other risk factors for dependence, adding to concerns that drinking at a young age might raise the risk of future alcohol problems rather than being an identifying feature of young people predisposed to risky behavior. The study appears in the July issue of Archives of Pediatrics & Adolescent Medicine, Volume 160, pages 739-746.
Timing of first alcohol use leads to a huge difference in risk
In results that echo earlier studies, of those individuals who began drinking before age 14, 47 percent experienced dependence at some point, vs. 9 percent of those who began drinking at age 21 or older. In general, each additional year earlier than 21 that a respondent began to drink, the greater the odds that he or she would develop alcohol dependence at some point in life. While one quarter of all drinkers in the survey started drinking by age 16, nearly half (46 percent) of drinkers who developed alcohol dependence began drinking at age 16 or younger.
New findings showed that among all drinkers, early drinking was associated not only with a higher risk of developing alcoholism at some point, but also within 10 years of first starting to drink, before age 25, and within any year of adult life. Early drinking was also associated with increased risk of having multiple episodes of alcoholism. Further, among respondents who had had alcohol dependence at some point, those who began drinking young had episodes of longer duration and with a wider range of symptoms than those who started later.
The developing brain gets altered by drug and alcohol use. We do not have free will. If legalization would increase the amount of teen drug use then legalization would lead to much more drug abuse and addiction.
Adolescent brains are at much higher risk because they are still developing. Industrialized societies need to do a better job of protected teenagers from subtstances that will mess up their brain development.
Also see my post Adolescence Is Tough On The Brain.
"Marijuana really does lead to higher risk of heavy duty drug abuse"
'Really', as in this supports steppingstone theory? I might as well draw compleatly opposite conclusion: if using marijuana makes heroine less effective then marijuana could make you less likely to use heroine in an environment where heroine is difficult and expensive to get.
Do you think a parallel case can be made with endogenous compounds as is made here for the exogenous?
Does being tossed up in the air, really scary high up into the air, as an infant by your cowboy father establish a later expressed preference, say, as it did in my case, to jump out of airplanes?
You wrote: "Industrialized societies need to do a better job of protected teenagers from subtstances that will mess up their brain development."
I couldn't agree more. Realizing that absolute prohibition often is counterproductive, in my family we instruct children; "No drugs or alcohol before you're 21. Then you're free to do as you choose." It's a time-limited absolute prohibition with a release point freedom clause.
It seems to me that the explanation for under-14 drinkers becoming alcoholics could just as well be that they were born that way and thus felt the need for a drink very early in life.
But the rat experiment shows that exposure (albeit to a different substance) changes brain development in ways that cause changes in cravings for addictive compounds. It seems likely that compounds aside from THC have this effect.
J i O,
My guess is that your thrill seeking desire is more due to genetic causes.
I am in general agreement with: "The developing brain develops differently if exposed to drugs that activate brain pleasure circuitry." I'll wager those same effects apply to "pain circuitry" as well, leading to avoidance components analogous to the attraction ones cited.
I'll wager further that early exposure to abnormally high levels of hyper-stimulated endocrine output also induces differences in the developing brain. That "thrill seeking desire" you speak of perhaps is an artifact of endogenously induced brain development differentials consequent to intense life experiences.
Genetics may incline toward outcomes, but experience induces outcomes.
I'm sorry - but this study seems to be the most rediculous kind of "science" to me, and I find the conclusions to be frankly ludicrous.
The conclusion - that is - that desensitization to pleasure producing drugs will lead to greater chances of their abuse.
Firstly I think all studies like this are urnealistic in that they always expose the test animals to "chronic" amounts of THC - an amount that not even heavy Human users would get close to.
Secondly, in this study, they then expose them to Heroin and show that the Chronic THC exposed animals require more Heroin to get high - something that I think is rather obvious based on previous research.
But then - to make the conclusion that these animals or their Human analogs would thusly be more likely to abuse harder drugs is utterly rediculous.
Like a previous poster said - the fact that their first exposure to Heroin would likely not be as pleasurable - as it would be to a non thc user - would produce the opposite effect - they would be less likely than the non thc user to try it again.
And - as this study showed - the non thc exposed animals became just as addicted to the Heroin as the thc exposed animals did.
I really like the interesting and varied information you put on your site here - but your blantant bias against the use of drugs for pleasure really seems to be a re-occuring theme in your posts.
I think we all know that drug or alchohol exposure is bad for developing teens - but as a teen user of marijuana myself - I can tell you that it was - by far - much less damaging to my development then Alcohol or Tobacco - so let us not allow federal propoganda or our personal hatred for the devestaing social and medical affects of addiction to cloud the real science on these issues.
The study may have just as easily come to the conclusion that THC-pretreated rats had greater tolerance to heroin and had an easier time quitting. After all, the THC pre-treated rats were NOT more disposed to become addicted to heroin, AND after the heroin had been withdrawn, the pre-treated rats gave up pushing the lever quicker than the vehicle rats. The only thing that the THC pretreated rats had as an increase was that they needed more heroin to get a buzz since they were already used to marijuana.
The fact that the study even used the word "gateway" is dishonest and very poor scientific procedure. They must have known that it would cause a bunch of ill-informed scare media headlines (and there were a bunch of them).
There could be something to actually learn from scientific studies such as this one, but not when they are so agenda-driven as to prevaricate about the results.
Remember that in popular media (and political) use, the gateway theory implies that the mere use of marijuana leads to actual abuse of hard drugs. However, the numbers do not bear this out. If we take the government's own numbers...
According to White House's Drug Facts, 96.8 million Americans have used marijuana in their lifetime. According to the ONDCP-commissioned 1999 IoM's Marijuana as Medicine report, 23% of heroin users have ever became dependent in their lifetime. Now running some numbers through NSDUH 2004 dataset at SAMHDA, you get the result that 3.1% of marijuana users have used heroin. Hence 23% of that i.e. 0.71% have been addicted to heroin. Hence, 99.29% of marijuana users have never been addicted to heroin. Some gateway effect, huh?
my criticisms are here.
Bias on my part? As Neil Young put it "I've seen the needle and the damage done". I've known too many people who've been damaged by their drug use, people close to me. Am I biased against recreational drugs? Perhaps. But my bias is not irrational.
But THC really does make lasting changes in the brain's reward circuitry.
Teenagers simultaneously lack the emotional maturity to handle recreational drugs plus their brains are still developing and therefore are more plastic and susceptible to lasting changes as a result of recreational drug use.
As for the incidence of heroin use: But it is not the only drug that does damage to the brain. This particular study just happened to use THC and heroin. What might the results have been had the researchers used THC and cocaine or THC and alcohol or THC and methamphetamine?
Also, not everyone who first used marijuana did so as a teenager or frequently as a teenager. So not all got much effects from THC rewiring their brain pleasure centers.
This is bad science driving politics Randall.
We have massive doses of drugs being fed to mammals with very small brains and social networks that are, ah, not exactly isomorphic to human developments.
"The developing brain gets altered by drug and alcohol use. We do not have free will. If legalization would increase the amount of teen drug use then legalization would lead to much more drug abuse and addiction."
This doesn't follow. Legalization doesn't necissarily imply greater teen drug use, and this study says very little about marijuana use among US teens.
"Adolescent brains are at much higher risk because they are still developing. Industrialized societies need to do a better job of protected teenagers from subtstances that will mess up their brain development."
Through what? More laws and powers to a nanny state?
Some drugs simply are fun. Because some individuals can't manage themselves we should restrict liberty on everyone?
Who has actually read the damn report?
There, clear as day, after all detailed explanations, on p.7, it sums up:
"The periodic exposure to low-dose THC during adolescence did not appear to predispose animals to an increased sensitivity to initiate heroin self-administration."
Is someone having trouble understanding the above sentence?
If you're have language problems, let me translate: It says marijuana is NOT a gateway drug, accoring to the findings of this report.
So how is it that its authors draw a conclusion IN DIRECT OPPOSTION to their own findings? Does this not show up their bias and their Prohibitionist agenda? Might as well say:- "We don't care what the findings show, we'll just say what we want to anyway!"
Ms Hurd is a disgrace to herself and her profession.
Mr. Randall, I think I appreciate where you're coming from, because I too "have seen the needle and the damage done", but to give credence to puppet "scientists" working under agendas of personal bias, or worse, is definitely not helpfull in this case.
PS. All the junkies I've known stared off on alcohol. A gateway drug, then, is it?
I can not conclude anything from a single sentence. Here are some other sentences from the paper:
Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mug/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mug/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mug/kg/injection).
One of the ways that humans differ from rats is very important: Humans can know what it was they were taking and can engage in much more complex activities to get access to it once again. They can know when they are starting to administer it. A rat has to notice the effect in order to know that some dispensing machine is once again delivering heroin.
Thanks for replying to my comment Randall.
The rats were noticing the effect during self-administration at the "addiction" stage. Both groups reacted exactly the same way. "Gateway" implies that cannabis could lead to addiction. This Hurd did not find anywhere.
However, the absence of data wasn't going to stop her from spouting off, apparently. She seems to have employed some sleight-of-hand by conveniently changing the definition of "gateway" to something you or me would not recognise. Most scientists noticed this and are already laughing. This is unforgiveable sloppiness on the part of the researchers, IMHO. But of course, it's not really slopiness, is it? Looks more like deliberate skewing. If you've already drawn your conclusion before you even start the experiment, why bother?
Note that the non-THC rats were more anxious and behaved more in what we'd call a "junkie-like" way than the THC group, if we were to anthropomorphise:
Since you quote the report, did you notice the bit that says:
"Vehicle-exposed animals had a higher percent increase than the THC-pretreated rats in the number of active lever responses (328758.3 vs 151713.6%; po0.05); the vehicle group also had a higher number of inactive lever presses"
Why is it not clearly stated in the media that the non-THC rats were pressing the levers more often than their contented cousins? Perhaps because that would demostrate that the THC group of rats displayed much higher intelligence? We wouldn't want that, would we?
Nevertheless, since the administration of the heroin was intelligence dependant (they had to notice that a light was on) the smarter rats got more (with less effort). The ones not exposed to THC couldn't figure out when the dispenser was active. Why not publicise that "Cannabis is a gateway to intelligence", then?
I'm sorry, but this report is as bad science as you can get, and the fact that it was published unquestioningly by News@Nature makes me wonder what other little deals were going on behind the scenes.
What is meant by "inactive lever pressers"? Doesn't that mean they did not press the lever?
You say "The ones not exposed to THC couldn't figure out when the dispenser was active". Really? Or were they less likely to want what was being dispensed?
I've found with dogs that they do things I do not expect and I can come up with multiple theories for what might be their motivations. So I do take the animal studies with a large grain of salt.
>>What is meant by "inactive lever pressers"? Doesn't that mean they did not press the lever?
No, it doesn't mean they didn't press the lever. There was a light which switched on when the dispenser was active. The lever could be pressed anytime, it just didn't dispense when it was inactivce.
So the way I read it, the non-THC rats were agitated and trying to get a fix by pressing the lever all the time, even when there was nothing there. It is interesting that the THC rats figured this out, and it was quite probably a factor in their being able to get more (with less effort, as I said before). How do you explain this? I cannot find any way to interpret it other than that the THC group was displaying higher intelliugence. Can you present a different take?
It's a real pity that the media got itself into such a lather about "cannabis leads to heroin" that it didn't take the trouble to explain these "bothersome" little details. And you can hardly blame them, since it was the study authors (Hurd in particular) that misled them in the first place.
This is quite a good example of why people (myself included) get a bit frustrated with the media, so I must apologise if I've sounded irritated. However, as you can plainly see we have a situation where at the VERY least it's clear that cannabis DOESN'T lead to heroin (this is one of the sutdy's own findings!), at the worst where some very interesting results relating to THC and intelligence are deliberately suppressed or sidelined. And the media is presented with a LIE, just to feed a Prohibitonist agenda.
So it's clearly a case of damned if you do and damned if you don't. What would it take for these people to produce an unbiased report on cannabis, perhaps even mention some of the positive medical results (eg. fighting Alzheimer's, cancer, etc)? God only knows - I imagine only at gunpoint would they concede :D :D :D
But it is important that the general public realise that such "academics"' credibility is close to nil, and that they are most unhelpful to anyone interested in some real education about cannabis.
We had the same thing a couple of weeks ago when that Stalinist moron from the UN, Costa, was spouting off that "new strains" of cannabis are more dangerous than heroin. A total fabrication of the Christian Right lobby, incidentally, funny how Stalinism and the Right wing get on just fine when they need to. The man is supposed to be an engineer, yet he did not verify a single item of his data. Hope he didn't build any bridges the same way, for all our sakes. Hell's Bells, if all this rubbish they were saying was true, why worry about cannabis leading to heroin? Heroin is less dangerous... :D
It is, however, more than disgraceful that the premier international organisation, supposedly dedicated to peace, is instead pursuing a cultural witch-hunt, with Costa regularly dining at Walters' table, etc, etc. Shameful.
In correction to the above, and having re-re-read the report: There were two levers, an active one and an inactive one. The inactive one did nothing. The active one dispensed heroin, but only when the light was on. And of course the report talks of lever "presses", not lever "pressers".
The report seems to leave out a few details, but I'll read it one more time, to be completely sure - much is hidden behind the scientific jargon....
It could be the THC calmed the rats and made them less likely to engage in activity in general, including pressing levers when the light was not on. They may have required a higher level of stimulus to pass the threshold of engaging in activity.
I could probably come up with other hypotheses to explain the difference. But I wouldn't have confidence in any of the hypotheses. I'm skeptical of the intelligence raising hypothesis only because it is hard to raise intelligence. Plus, stoner roommates I had in college were not exactly walking advertisements for the idea that THC makes you smarter. "Oh wow, I forgot to go to class."
I'm happy to see you're now approaching it all with a sense of humour, rather than unquestioning acceptance.
I agree completely with your remark that animal experiments of this sort should be taken a grain (or more) of salt.
Just for startets, I understand that rats, unlike humans are not at all fond of cannabis.
My remark about raising intelligence was meant to be humorous, but could certainly be seen as a more valid conclusion to the (quite possibly mercenary) claptrap Ms. Hurd and News@Nature came up with.
This was, I think, the issue that most people objected to. The study itself, as you said, was a bit of a joke. 6 rats, for crying out loud - wow, that's some conclusive population!. However, that this came to be trumpetted in all the international media as the final conclusive proof of the gateway thoery (even when the findings themselves were totally contradictory!), can only demonstrate the unbelievable amount of prejudice and ignorance - as well as the schedule of the agents who are determined to keep it that way.
I would also agree with you (from my own experience) that the abuse of cannabis leads to stupidity, certainly not intelligence - but that's the key word - ABUSE.
I have personally managed to solve really dificult intellectual problems on which I had been stuck for a long time (including mathematical problems) by the judicious use of cannabis. The trouble is that while "Reefer Madness" rules, not many are likely to find out what the judicious use of cannabis is, are they? Not unless they're wiling to break the law, and why should such a high demand be placed on them?
It is for this reason that I, and many other people, get so indignant when ignorance is perpetuated in the name of science. I am sure you will understand this.
Best - adt
i believe we are all responsible for our own actions and will not stop people from doing these things. the government is effectively losing the war on drugs, thus making a compromise with the substances necessary. A study has shown that legalizing marijuana has lessened the likelihood of the steppingstone theory in which that those users who had previously taken harder drugs will now move to a cheaper more legal high for the sake of their situation. these studies bashing the drugs are ineffective vessels of information and cannot effectively stop anyone from anything.