Health - Science Shows Cannabis is Harmful

[Perception Addict]

Science Shows Pot is Harmful

At least two Times-Argus letter writers have made false claims lately regarding the supposed harmlessness of marijuana. Walter Carpenter claims that "marijuana does far less harm than cigarettes," and Clancy DeSmit asserts that "We all know that alcohol and/or tobacco are far more harmful to individuals and society than marijuana."

We do? Actually, not. Contrary to perceived hippie lore, marijuana has been shown in numerous scientific studies to be both far more harmful to the lungs and immune system than cigarette smoke and more damaging to brain function and learning ability than comparable alcohol use.

A quick tour of health-related Web sites supported by many scientific studies and agencies, including the National Institute of Health and the British Lung Foundation, turned up these facts:

Marijuana smoke has 50 to 70 percent more cancer-causing hydrocarbons than cigarette smoke.

THC, the active ingredient in marijuana, impairs the immune system. Users get sick more seriously and more often than non-users.

Short-term brain effects include problems with memory, learning, thinking, and problem solving, and loss of coordination.

Longer term effects include depression, anxiety, and other serious personality disturbances.

I've known people who never became the engineers, physicians, scientists or other real problem-solvers they might have become had they not blown their minds on pot. And I think I know others who, for the same reason, can't seem to see the forest for the trees in their political opinions or their personal relationships.

I doubt that sending every confused and physically weakened pot head to jail is the answer. But I strongly support Gov. Douglas in sending a very clear message that pot is off limits. It has been shown to be a physical danger and a mental illness accelerator, and its more widespread use would be devastating to our adult citizens, to our young people, and to the progress and safety of our country.

http://www.timesargus.com/apps/pbcs....ON02/711230318

Reputation Comments on this post:

Interesting article opposing marijuana instead of supporting it

[Metomni]

SWIM believes all those problems are solved with the "Everything in Moderation" motto which every drug user should already be using.

" Marijuana smoke has 50 to 70 percent more cancer-causing hydrocarbons than cigarette smoke.

THC, the active ingredient in marijuana, impairs the immune system. Users get sick more seriously and more often than non-users.

Short-term brain effects include problems with memory, learning, thinking, and problem solving, and loss of coordination.

Longer term effects include depression, anxiety, and other serious personality disturbances."

First off, it may have more cancer-causing hydrocarbons, I don't know for sure, but so much less of it is smoked when compared to ciggarettes, so that number is misleading.

For one, of course there are going to be short-term effects, but after the body is used to the plant those short-term side effects are easily maneuvered around. As for the long term effects, SWIM would make the leap and assume that is for very heavily habitual users that are not keeping in mind their actual consumption.

Also, what about the good effects it has? Like for people with chronic stomach pain or eye problems that are helped along by the herb?

[Perception Addict]

People have argued the above many times, and for good reason. Unfortunately, such editorials as this one continue to appear.

[Metomni]

That's simply because there are people on both sides of the argument. No matter what, both sides are going to have scientists arguing for and against them.

SWIM believes the arguments opposing articles like this just make more sense. Not only do they work from a stoner's point of view, but the pro's work from a logical point of view and also a capitilist's point of view. That's why SWIM does not understand the current marijuana laws, they simply don't make much sense.

Out of curiosity, what is SWIY's stance on this topic? SWIY posted the editorial, but seems rather neutral on the subject.

[Perception Addict]

Originally Posted by Metomni

Out of curiosity, what is SWIY's stance on this topic? SWIY posted the editorial, but seems rather neutral on the subject.

Swim is in favor of legalization, of this substance as well as of substances in general. She likes to maintain neutrality when posting highly inflammatory or opinionated articles, as they ought to stand for themselves without being tainted by her personal viewpoint.

She did, however, find this article particularly ridiculous, and thinks that it sounds a lot like the DARE class she had to take in 5th grade (she thought it was fairly silly then too).

[Metomni]

Aye, it does sound like that indeed, SWIM only wishes he had seen the absurdity of it all back in elementary school.

[imyourlittlebare]

[quote=Metomni;340024]That's simply because there are people on both sides of the argument. No matter what, both sides are going to have scientists arguing for and against them.

i disagree with that. I have been in debate for several weeks about pot and i can link you up to my studies and what they show. Like, for starters, cannabis withdrawal. The intense anxiety one gets when one has been using for a long time. it hasnt been disproven by scientists. animal studies show the neuroscience behind it (gaba tolerance, dopamine and glutamate influx). from this data, one would hypothesize that there is intense anxiety when one quits. There is also data that shows collelation between thc leaving the body (less that a month for heavy smokers due to the half life of pot being about 12 days for them) and increase in anxiety (alot of smokers say they dont have a problem quitting and do so for a few days and go back. they start to experience the anxiety later). Im neutral here too. and i would like to debate this respectfully if you so chose.

[Nature Boy]

Marijuana smoke has 50 to 70 percent more cancer-causing hydrocarbons than cigarette smoke.

Yet not one definitive cancer diagnosis proven to have been caused by marijuana despite being widely used for hundreds of years.

THC, the active ingredient in marijuana, impairs the immune system. Users get sick more seriously and more often than non-users.

They might want to add a source for that claim as it sounds like a rather outlandish thing to prove.

Short-term brain effects include problems with memory, learning, thinking, and problem solving, and loss of coordination.

As does alcohol to far greater extremes.

Longer term effects include depression, anxiety, and other serious personality disturbances.

Again, just an empty statement with nothing to back it up.

[imyourlittlebare]

[quote=Nature Boy;340026]Yet not one definitive cancer diagnosis proven to have been caused by marijuana despite being widely used for hundreds of years.

funny, thats what tobacco lobbyists say


here is some info

Web of Science (ISI Citation Indexes) Title: Anandamide and Delta(9)-tetrahydrocannabinol directly inhibit cells of the immune system via CB2 receptors Author: Eisenstein, TK Add.Author / Editor: Meissler, JJ
Wilson, Q
Gaughan, JP
Adler, MW Citation: JOURNAL OF NEUROIMMUNOLOGY 189 (1-2): 17-22 SEP 2007 Year: 2007 Abstract: This study shows that two cannabinoids, Delta(9)-tetrahydrocannabinol (THC) and anandamide, induce dose-related immunosuppression in both the primary and secondary in vitro plaque-forming cell assays of antibody formation. The immunosuppression induced by both compounds could be blocked by SR144528, an antagonist specific for the CB2 receptor, but not by SR141716, a CB1 antagonist. These studies are novel in that they show that both anandamide and THC are active in the nanomolar to picomolar (for anandamide) range in these assays of immune function, and that both mediate their effects directly on cells of the immune system through the CB2 receptor. (C) 2007 Elsevier B.V. All rights reserved.

another

Cannabis, commonly known as marijuana, is the most frequently used illicit drug in Australia. Therefore, oral health care providers are likely to encounter patients who are regular users. An upward trend in cannabis use is occurring in Australia, with 40 per cent of the population aged 14 and above having used the drug. There are three main forms of cannabis: marijuana, hash and hash oil, all of which contain the main psychoactive constituent delta-9-tetrahydrocannabinol (THC). Cannabis is most commonly smoked, however it can be added to foods. THC from cannabis enters the bloodstream and exerts its effects on the body via interaction with endogenous receptors. Cannabis affects almost every system of the body, particularly the cardiovascular, respiratory and immune systems. It also has acute and chronic effects on the mental health of some users. Therefore, chronic abuse is a concern because of its negative effects on general physical and mental health. Cannabis abusers generally have poorer oral health than non-users, with an increased risk of dental caries and periodontal diseases. Cannabis smoke acts as a carcinogen and is associated with dysplastic changes and pre-malignant lesions within the oral mucosa. Users are also prone to oral infections, possibly due to the immunosuppressive effects. Dental treatment on patients intoxicated on cannabis can result in the patient experiencing acute anxiety, dysphoria and psychotic-like paranoiac thoughts.
The use of local anaesthetic containing epinephrine may seriously prolong tachycardia already induced by an acute dose of cannabis. Oral health care providers should be aware of the diverse adverse effects of cannabis on general and oral health and incorporate questions about patients' patterns of use in the medical history.

no offense, but all the people on the pro pot side just dismiss alot of studies. Like, offer your own. I dont care, but its not fair that the burden of proof is on us when we show alot of literature that supports our ideas and alot of what you say is just poking holes in the literature or taking eyes off pot to alcohol, mankinds greatest evil. We are not stupid. I believe alcohol is the worst and most destructive drug. However, that is not a warrant to dismiss any negative health findings on pot just because its not as bad as something. Thats like comparing two different agents of bio warfare. lets say one takes 24 hours to hurt someone and they will be permanently hurt by it neurologically, the other is anthrax. both have negative effects but i doubt anyone would dismiss the first one and say "its not as bad as the other one" My friend wrote a paper on pot use and goes into alot of the brain chemistry and such ill post that tomorrow. His findings in the research were very interesting and unbiased. he actually was kinda pro legalization before it. He found that the brain changes i found, but one of the hypothesized reason pot helps the hippocampus create new neurons is because it impedes working memory so much that new neurons are needed to pick up the slack. He also shows through fmri and other scans that years of pot cause you to use your brain in a different way. that is, instead of taking a main road to your pizza shop, you go in zigzags through side streets.

"here have also been small studies which show cannabis can increase learning potential in people with ADHD, which would contradict the outlandish claims the article tried to establish. In good news however, this article would indicate that perhaps the media has accepted that no one believes that whole amotivational syndrome thing and dropped it."

im open minded and would love to see that article. please post it. in respect to you disbelieving that pot can cause schizophrenia, i say to you it is true. If you have no family history of schizo, you need not worry. it is an assortment of factors that predispose you to schizo. Smoking pot alot and stopping does increase your chance of getting it if you had a chance of getting it. Why? because of an influx in the neurotransmitters dopamine and glutamate. all implicated in schizophrenia (the dopamine hypothesis and the glutamate hypotheses). also since your GABA tolerant, this influx is less likely to be stopped and can cause one to go over the edge and not come back. There are animal studies that are recreatable to prove this and since you could hypothosize that if someone was predisposed to schizo and smokes, you can say with some certainty there is a chance they will develop it

rain function is the one I find truly ludacris. There is no evidence to support any decreased intellectual capacity in the long term. Studies have shown that the average IQ level, let us call it n, is the base state prior to marijuana consumption. n-4 is the state when users are high on marijuana. n+1 is the average state after consumption has passed. The results show marijuana will not make anyone dumber in the long term, and may perhaps even allow the individual to operate at a higher effciency than once before, primarily because they become adept at functioning in two states of consciousness (in latent terms stoned and sober). Technically "alcoholics" could have the same thing happen, but its offset because it kills more brain cells and therefore nullifies the function.

here you are refering to state dependent learning. the way you worded this is misleading. Those who are THC naive and smoke would see significant drops in IQ. these scores are used with individuals who i guess since they NEED thc to acquire a certain level of IQ then they are addicted psychologically and need it to do better.

Does this make cannabis harmful, I'd say no. Also regardless of the tar, marijuana smoke is thicker, which is probably where they get that information from to support it being more carcinogenic, but as such it cannot pass through whatever little 'doorway' smoke goes down to cause emphysema, so that is helpful.

since pot is a broncodialator, im sure as you smoke more and more is getting in. However, im sure tahts not the main concern at least with me. I know alot of potheads smoke cigs and have two when they smoke a bowl. when they do, the smoke goes much deeper and causes much more damage in my opinion

Did i miss anything? I want to do this respectfully guys. I have my opinion and science to back it up. You have your opinion. Lets do this like gentlemen, ive seen too many people get all wilded up including myself. Im an open guy. Im all for legalization. Just not ignoring facts and ignoring health risks.

[Nature Boy]

Originally Posted by imyourlittlebare

funny, thats what tobacco lobbyists say

Yeah, in the 1950's.

There's plenty of evidence that tobacco has caused cancer, both directly and indirectly. There is nothing of the same nature linked with cannabis.

[imyourlittlebare]

Originally Posted by Nature Boy

Yeah, in the 1950's.

There's plenty of evidence that tobacco has caused cancer, both directly and indirectly. There is nothing of the same nature linked with cannabis.

like i told you the one day. there is no direct evidence persay. Those lobbyists are clever. the only way its every going to say smoking causes cancer on a box of smokes is if they expose 100 newborns to ciggerettes and directly find its the cause of cancer. Which isnt going to happen

I dont think marijuana causes lung cancer or other cancers at the alarming rate ciggerettes do. however, it does contain carcinogens. And to deny you are breathing those in and that there is risk of certain types of cancers is wrong.

[entheogensmurf]

Originally Posted by Nature Boy

Yet not one definitive cancer diagnosis proven to have been caused by marijuana despite being widely used for hundreds of years.

Thousands of years

[Pino]

Swim immediately believes the claim it is damaging to the lungs (unless smoked in a vaporizer), but he would like to know more about the frequency of use those long term effects occur. Swim knows for example that coffee can trigger the same, but the use has to be insanely high.

[candy_kid]

"50 to 70 percent more cancer-causing hydrocarbons" -- are these carcinogenic hydrocarbons truly the reason tobacco causes cancer?

"The fact is, although insoluble tars are a contributing factor to thelung cancer danger present in today's cigarettes, the real danger is radioactivity. According to U.S. Surgeon General C. Everette Koop (on national television, 1990) radioactivity, not tar," accounts for at least 90% of all smoking related lung cancer.

Tobacco crops grown in the United States are fertilized by law with phosphates rich in radium 226. In addition, many soils have a natural radium 226 content. Radium 226 breaks down into two long lived 'daughter' elements -- lead 210 and polonium 210. These radioactive particles become airborne, and attach themselves to the fine hairs on tobacco leaves."
http://www.erowid.org/plants/cannabi..._health2.shtml

Besides, even if they were cancer causing, using this as 'proof' marijuana causes cancer is bad science. They should be using studies showing more people actually caught cancer, although perhaps they don't like those results?...

"The largest study of its kind has unexpectedly concluded that smoking marijuana, even regularly and heavily, does not lead to lung cancer.

The new findings "were against our expectations," said Donald Tashkin of the University of California at Los Angeles, a pulmonologist who has studied marijuana for 30 years.

"We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use," he said. "What we found instead was no association at all, and even a suggestion of some protective effect.""
http://www.washingtonpost.com/wp-dyn...052501729.html

How about the claim that marijuana impairs the immune system? What quantities were these results measured in anyway? not mentioned? hrm...

"Myth 4. Marijuana suppresses the immune system Like the studies claiming to show damage to the reproductive system, this myth is based on studies where animals were given extremely high -- in many cases, near-lethal -- doses of cannabinoids. These results have never been duplicated in human beings. Interestingly, two studies done in 1978 and one done in 1988 showed that hashish and marijuana may have actually stimulatedthe immune system in the people studied."
http://www.erowid.org/plants/cannabi...s_info14.shtml

Short term brain effects? look at alcohol, look at prescription pain medications, I mean common, keep in mind these are to some extent why these drugs are used; read: short term...

Depression seems possible, we've all known a few depressed stoners, but there are also dozens of stoners who are happy and cheerful all the time... Kinda like how we all know a few depressed non stoners, and a whole bunch of happy abstaining kids. The statistics don't seem to really say much right now in anycase, maybe a study showing the biochemical process linking marijuana and depression would be in order before these accusations start getting thrown out.

anyway, I'm not saying marijuana is perfect- just that this article is bull it would explain a lot if these quick searches the author speaks of were to freevibe?

Reputation Comments on this post:

	Awesome information on the radioactivity
	Information was clear and thought out, links were good and made me learn a lot.

[Nature Boy]

Originally Posted by Perception Addict

and more damaging to brain function and learning ability than comparable alcohol use.

Nearly forgot, how is marijuana more damaging to brain function than alcohol when it cannot actively destroy braincells like alcohol can?

[OccularFantasm]

There have been studies which show an immuno-suppressive response from marijuana. They have used synthetic cannabinoid compounds to suppress the immune system to help assist organ transplant. (it was from blackwell-synergy, do not still have article) But then again I think this study was done on rats, and never made it to the human stage. Results undoubtedly could be very different as the two species are not intensely similar.

Does this make cannabis harmful, I'd say no. Also regardless of the tar, marijuana smoke is thicker, which is probably where they get that information from to support it being more carcinogenic, but as such it cannot pass through whatever little 'doorway' smoke goes down to cause emphysema, so that is helpful.

It is also funny they tried to link cannabis use to lung cancer, as cannabis has hundreds of compounds that have been shown to be tumor-fighting, namely against breast cancer, lung cancer, and virus-induced-lukemia.

As for making people sick, that is most unlikely. Although there is a recorded immunosuppressive effect, the impairment of the immune system from other variables such as anxiety, loss of sleep, malnutrition, and psychosis are much more pronounced, and would more than offset the suppression caused by marijuana. In fact, one could argue that for a person with chronic symptoms which cannabis can alleviate, the immune system is actually strengthened.

Also any smoking will hamper the immune system, it just makes your body need to detox more things at once, which by definition impairs it (slightly).

As for current marijuana laws, it is more of a cultural and political issue, not so much scientific. I mean, the Nixon administration did a whole congressional report that showed even long term marijuana smoking causes no ill effects in the short or long term.(which is openly available I'd guess somewhere on this forum, if not google it)

Brain function is the one I find truly ludacris. There is no evidence to support any decreased intellectual capacity in the long term. Studies have shown that the average IQ level, let us call it n, is the base state prior to marijuana consumption. n-4 is the state when users are high on marijuana. n+1 is the average state after consumption has passed. The results show marijuana will not make anyone dumber in the long term, and may perhaps even allow the individual to operate at a higher effciency than once before, primarily because they become adept at functioning in two states of consciousness (in latent terms stoned and sober). Technically "alcoholics" could have the same thing happen, but its offset because it kills more brain cells and therefore nullifies the function.

I hadn't heard about the radium in tobacco fields, but that is rather disturbing. I wonder which diseases that have increased exponentially in recent history can be attributed to that. One can only imagine (for now).

Hell, in Ayurdevic medicine a powdered extract is made form the entire cannabis plant, which is given to all inhabitants (from age 6 until death), and yet they seem to turn out more doctors and scholars than most any nation.

"I've known people who never became the engineers, physicians, scientists or other real problem-solvers they might have become had they not blown their minds on pot."

This part of the article is actually laughable. If the person cannot handle a soft drug such as marijuana, their brain is obviously not strong enough to do anything useful for itself or society. I'm just glad for once it didn't try to throw that bogus schizophrenic down our throats, as most proWOD scientists (either corrupted or not the sharpest knives in the drawer) would try to argue.

There have also been small studies which show cannabis can increase learning potential in people with ADHD, which would contradict the outlandish claims the article tried to establish. In good news however, this article would indicate that perhaps the media has accepted that no one believes that whole amotivational syndrome thing and dropped it.

[candy_kid]

^^ you seem to have skipped over my quote and a link to the article on the largest study looking at cancer and marijuana to date, which of course was expecting marijuana to correlate with cancer- and "What we found instead was no association at all, and even a suggestion of some protective effect." -- scroll up, I have a larger whole quote and a link to the article

I'm not saying marijuana is perfect, and it most definitely reduces lung capacity if smoked as often as some smoke cigarettes for example-- but it appears in the case of cancer, marijuana is either neutral or slightly preventative- whatever the reason. Maybe the ability for carcinogens from smoking non radioactive materials to cause cancer has been overstated due to the original belief that it's tar from the smoke that cause cigarettes to lead to lung cancer? or perhaps THC's cancer preventative function combats the carcinogens? its really hard to say the why, but I think the study speaks for itself on the what.

[imyourlittlebare]

no i saw the article. but evidence is inconclusive either way. for every 2 articles that say it causes cancer, there is 1 that says it doesnt which seems inconclusive to me. So my opinion is that marijuana can and does cause lung cancer, due to its carcinogens, however, i believe there may be some protective factor that prevents it from being an epidemic like smoking cigs.

edit: i just reread everything and it seems we are on the same page but with different stances so were cool. I really like debates like this. noone has to get hostle and we are all friendly yet aggressive. It makes for nice intellectual conversation

[Nature Boy]

Originally Posted by imyourlittlebare

however, i believe there may be some protective factor that prevents it from being an epidemic like smoking cigs.

I believe that this protective factor may be more significant than we even realise at this stage. A study was done on Rastafarian Jamaicans who smoke cannabis heavily on a daily basis. Interestingly, there is no noticeable increase in cancer cases amongst them. I even think the rates were lower than average worldwide, whether this is due to genetic conditioning or the protective factor really is significant. I'll post a link if I can find it again.

[candy_kid]

@imyourlittlebear : can you link a study that is comparably large to the one I linked, showing a correlation between marijuana and cancer? Not that I doubt you, but your argument seemed a little weak without anything backing it up.

I'm actually kinda curious what you've found though, a while back I had an argument about marijuana with a very anti drug computer savvy girl (no limitations there). I told her to link me any study that showed it did something long term beyond tarring up your lungs and she'd win the argument. Not that I didn't believe anything was out there, I was more curious what she could find..- Anyway, she spent quite a while searching for articles and finally sent a huge email off to me; unfortunately, all the articles were related to triggering schizophrenic episodes in one direction or another -- nothing even in the typical BS direction... anyway, I'd kinda assumed there wasn't much in the way of actual studies since then, but maybe you can change my mind littlebear

before you go too crazy btw, keep in mind that a lot of the information suggesting marijuana causes cancer is based on the reasoning that marijuana has more tar than cigarettes. Tar is now known not to be the main cancer causing agent in cigarettes, this actually being radioactivity-- so you might wanna check and make sure this isn't the basis you know... like find something that actually correlates cancer, not tar levels

I look forward to your follow up!

[imyourlittlebare]

Here we go. I will make this as easy as possible to understand. If you dont have a basic understanding of scienctific deduction, how to read results, or a basic understanding of neuroscience then this may get confusing.

this article is alot of what im talking about. glutamate inhibition= influx with discontinuation=anxiety and risk of getting mood disorder. produces tolerance to GABA. Key to anxiety disorders. Also, pot inhibits glutamate while high and when thc exposure is done, an influx of glutamate occurs along with dopamine (later source) so this is biological evidence that if humans were to consume thc, those predisposed to getting schizophrenia are more likely to get it and there would be great anxiety if one discontinued smoking pot after heavy use.

Title: Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation.
Author: Hoffman, Alexander F; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H; Lupica, Carl R
Institution: United States Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurobiology Branch, Electrophysiology Research Unit, Baltimore, Maryland 21224, USA.
Appears In: Learning & memory (Cold Spring Harbor, N.Y.). vol. 14, no. 1-2 (2007): 63-74.
Journal Info: Abbreviation: Learn Mem. Journal Subset: IM.. Country of Publication: United States.
Abstract: Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for learning and memory, the consequences of prolonged exposure to Delta(9)-THC for hippocampal function are poorly understood. Rats were injected with Delta(9)-THC (10 mg/kg, i.p., q.d.) for 1, 3, or 7 d, and electrophysiological recordings were performed in hippocampal slices 1d after the final injection. At this time, Delta(9)-THC was undetectable in hippocampus using liquid chromatography-mass spectrometry (LC-MS). Hippocampal LTP generated using high-frequency (HFS) or theta burst stimulation was not observed in brain slices from the 7-d Delta(9)-THC-treated animals. Delta(9)-THC also blocked HFS-LTP after 3 d, but not 1 d of treatment. The complete blockade of LTP persisted for 3 d after the last Delta(9)-THC injection, and full reversal of the LTP deficit was not observed up to 14 d following Delta(9)-THC withdrawal. The cannabinoid antagonist AM251 (2 mg/kg), administered before each Delta(9)-THC injection prevented the blockade of LTP, and 7-d treatment with AM251 alone significantly increased the level of LTP. Chronic Delta(9)-THC also produced tolerance to the inhibition of synaptic GABA, but not glutamate release by the agonist WIN55,212-2. These data define consequences of repeated Delta(9)-THC exposure for synaptic plasticity in the hippocampus that may help explain memory impairments in humans following chronic marijuana use.


This article talks about the role of cannabinoid systems normally. It modulates fear and anxiety. However, since GABA tolerance is increased, and there is a glutamate and dopamine influx when one discontinues pot, it could be hypothesized that the cannabinoid system is less capable of modulating fear and anxiety. If that were the case, then again those predisposed to getting schizophrenia are more likely to get it and there would be great anxiety if one discontinued smoking pot after heavy use.

Title: Modulation of fear and anxiety by the endogenous cannabinoid system.
Author: Chhatwal, Jasmeer P; Ressler, Kerry J
Institution: Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA.
Appears In: CNS spectrums. vol. 12, no. 3 (2007 Mar): 211-20.
Journal Info: Abbreviation: CNS Spectr. Journal Subset: IM.. Country of Publication: United States.
Abstract: The last decade has witnessed remarkable progress in the understanding of the mammalian cannabinoid system, from the cloning of the endogenous cannabinoid receptor to the discovery of new pharmacologic compounds acting on this receptor. Current and planned studies in humans include compounds with effects ranging from direct antagonists to inhibitors of reuptake and breakdown. This progress has been accompanied by a much greater understanding of the role of the cannabinoid system in modulating the neural circuitry that mediates anxiety and fear responses. This review focuses on the neural circuitry and pharmacology of the cannabinoid system as it relates to the acquisition, expression, and extinction of conditioned fear as a model of human anxiety. Preclinical studies suggest that these may provide important emerging targets for new treatments of anxiety disorders.

While you need not understand everything this article is saying, i highlighted the passage you should all read. It states that there were changes that happened to the cannabinoid system receptors (receptors are areas of the neuron that respond to things called neurotransmitters. A neurotransmitter can excite the neuron or inhibit. Main inhibitory NT is GABA. as stated earlier, GABA becomes less effective to stop synaptic transmission after heavy pot use. This article goes a step further and did an assay and looked at the brain. It found that not only were there less receptors, but the receptors left would not function right. Normal neurotransmitter communication in this system would be crippled. The normal thing that would cause activation in the receptor wont, it would require more of an agonist action on it to activate it. So, since the cannabinoid system modulates fear and anxiety, one could hypothesize that since the system itself has less receptors and the ones left dont work as well, since GABA tolerance occurs and this causes even more of a problem with synaptic transmission, this would effect the system negatively even more. f that were the case, then again those predisposed to getting schizophrenia are more likely to get it and there would be great anxiety if one discontinued smoking pot after heavy use.


Title: The effects of delta9-tetrahydrocannabinol physical dependence on brain cannabinoid receptors.
Author: Breivogel, Christopher S; Scates, Susan M; Beletskaya, Irina O; Lowery, Olivia B; Aceto, Mario D; Martin, Billy R
Institution: Department of Pharmaceutical Sciences, Campbell University School of Pharmacy, P.O. Box 1090, Buies Creek, NC 27506, USA. breivogel@mailcenter.campbell.edu
Appears In: European journal of pharmacology. vol. 459, no. 2-3 (2003 Jan 17): 139-50.
Journal Info: Abbreviation: Eur J Pharmacol. Journal Subset: IM.. Country of Publication: Netherlands.
Date Revised: 20061115
Abstract: The effects of chronic Delta(9)-tetrahydrocannabinol on cannabinoid receptor levels and receptor-G-protein coupling were investigated. Male Sprague-Dawley rats were infused continuously with low or high dose regimens of Delta(9)-tetrahydrocannabinol or vehicle for 4 days. Following treatment, rats were sacrificed for cannabinoid CB(1) receptor binding analysis or challenged with the cannabinoid CB(1) receptor antagonist, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A). The rats receiving Delta(9)-tetrahydrocannabinol exhibited antagonist-precipitated withdrawal signs. Each brain region (cerebellum, cortex, hippocampus and basal ganglia) from high-dose rats showed 30-70% decreases in [3H] (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxyphenyl)cyclohexanol (WIN55212-2) B(max) values, indicating receptor down-regulation. Most regions showed decreased WIN55212-2-stimulated[35S]guanosine-5'-O-3-thiotriphosphate (GTPgammaS) binding, indicating desensitization of cannabinoid CB(1) receptors. Additional receptor binding assays in cerebellar membranes showed a significantly greater decrease in agonist than in antagonist B(max) values, indicating a lower fraction of coupled receptors after treatment. Concentration-effect analysis of five agonists revealed that the treatment resulted in greater decreases in the efficacy of low-efficacy agonists.

This shows pot does effect Dopamine. dopamine and glutamate are both inhibited by thc. once the mechanism of thc is over, there is an influx of both neurotransmitters causing anxiety and, if the circumstances are right and there is a biological predisposition, schizophrenia.

Abstract: The principal psychoactive component of marijuana, delta-9-tetrahydrocannabinol (Delta9-THC), suppresses nausea and vomiting in cancer patients caused by chemotherapeutics such as cisplatin. Cisplatin induces vomiting via a number of emetic stimuli, including dopamine. Currently, there is controversy as to whether Delta9-THC can prevent emesis produced by dopaminergic agonists such as apomorphine. The present investigation utilizes the least shrew to evaluate the antiemetic potential and the cannabinoid receptor by which Delta9-THC may prevent emesis produced by four dopamine receptor agonists with differing selectivity for D2 and D3 receptors, i.e., a nonselective dopamine receptor agonist (apomorphine), a D2-preferring receptor agonist (quinpirole), and two D3-preferring receptor agonists (quinelorane and 7-OH DPAT). In addition, relative to its antiemetic doses, the motor suppressive doses of Delta9-THC in dopamine D2/D3-receptor-agonist-treated shrews were also evaluated. Thus, different groups of shrews were injected with either vehicle (V) or varying doses of Delta9-THC [0.5, 1, 2.5, 5, or 10 mg/kg, intraperitoneal (i.p.)] 10 min prior to administration of a 2 mg/kg dose of one of the four cited D2/D3 agonists. Immediately after the last injection, the frequency of vomiting for each shrew was recorded for the next 30 min. To investigate which cannabinoid receptor is involved in the antiemetic action of Delta9-THC, various doses of the CB1 receptor antagonist SR 141716A [0, 5, 10, and 20 mg/kg, subcutaneous (s.c.)] were administered to shrews 10 min prior to an injection of a fully effective antiemetic dose of Delta9-THC (5 mg/kg, i.p.). Ten minutes later, each treated shrew was administered with a 2 mg/kg dose of apomorphine. The emesis frequency was recorded for the next 30 min. For locomotor studies, different groups of shrews received either vehicle or various doses of Delta9-THC (0, 5, 10, 20, or 30 mg/kg) 10 min prior to an injection of vehicle or a 2 mg/kg dose of one of the four D2/D3 receptor agonists. The triad of motor behaviors (spontaneous locomotor activity, total duration of movement, and rearing frequency) were recorded for the next 30 min by a computerized video tracking system. Delta9-THC dose-dependently attenuated the frequency of emesis as well as fully protecting shrews from vomiting produced by each one of the four cited dopamine D2/D3 receptor agonists with ID50s ranging from 1 to 4 mg/kg. SR 141716A reversed the antiemetic activity of Delta9-THC against apomorphine-induced emesis. Delta9-THC also differentially suppressed the triad of motor activities in dopamine D2/D3-receptor-agonist-treated shrews with ID50s ranging from 7 to 21 mg/kg. The results suggest that Delta9-THC prevents emesis via cannabinoid CB1 receptors in a potent and dose-dependent manner in D2/D3-receptor-agonist-treated shrews at doses well below those which cause significant motor depression.



I will not repost my data again. I typed the best summary of the neuroscience data above.



^ Johansson E, Halldin MM, Agurell S, Hollister LE, Gillespie HK. (1989). "Terminal elimination plasma half-life of delta 1-tetrahydrocannabinol (delta 1-THC) in heavy users of marijuana.". European Journal of Clinical Pharmacology 37 (3): 273-7. PMID 2558889. Retrieved on 2007-10-27.

this study shows that the half life of marijuana, which is plasma peak of the drug is anywhere from 3 to 12 days. This coincides with the onset of the peak of anxiety for most people who experience cannabis withdrawal. Heavy users take about a month for pot to get out of their system (12 days is for one half life which is the time where plasma levels of a drug reach their peak). so after smoking, there is still an effect even if a user is unaware and once the thc is out, anxiety is at its worst. great correlative data. here is real data. This relates back to the neuroscience evidence.

Cannabinoids may have a role in reducing fear-related memories. Author: Lawrence, David Citation: Lancet 8/3/2002, Vol. 360 Issue 9330, p392 Year: 2002 Abstract: Reports that scientists may have discovered a link between endogenous cannabinoids and the processing of memories. Study which focused on fear responses in mice; Physiological role for endogenous cannabinoid system in memory processing; Relationship between marijuana abuse and severe mental disorders; Behavioral response which is due to the release of an endogenous cannabinoid. Subject: CANNABINOIDS
FEAR
MEMORY
MARIJUANA abuse ISSN: 0099-5355 External: http://content.epnet.com/ContentServer.asp?T=P& P=AN& K=7079422& EbscoContent=dGJyMMTo50Seqa44zOX0OLCmrk%2Bepq9Sr6a 4SbKWxWXS& ContentCustomer=dGJyMO3e54fq3%2ByDuePfgeyx%2BEu3q6 4A& D=pbh Text: ------------------------------------------
Source: Lancet, 8/3/2002
Section: NEWS
Cannabinoids may have a role in reducing fear-related memories
The discovery of two types of cannabinoid receptors in the 1990s has spurred research into the physiological and pharmacological effects of endogenous cannabinoids, which are similar to tetrahydrocannabinol, the primary psychotropic ingredient in the plant Cannabis sativa. This week, a team of German and Italian researchers announced that they have discovered a physiological link between endogenous cannabinoids and the processing of memories.
The researchers conditioned mice to associate a tone with a foot shock. Conditioned mice showed classic signs of fear upon hearing the tone. Wild-type mice eventually failed to show any sign of fear after a period in which tones arrived without shocks. However, knockout mice that lack cannabinoid receptor 1 (CB1), as well as wild-type mice treated with a CB1 antagonist, SR141716A, showed only a slight reduction in the fearful response (Nature 2002; 418: 530-34).
"The study shows for the first time a physiological role of the endogenous cannabinoid system in memory processing", says Beat Lutz (Max Planck Institute of Psychiatry, Munich, Germany), the study's senior researcher. Lutz says that the pharmacological effects of cannabinoids have been extensively studied in the past, but that it could be difficult to relate the pharmacological effects with underlying physiology. "Only recently, electrophysiological experiments were performed showing a functional role of the endogenous cannabinoid system", he says. "In the present investigation, cellular, genetic, biological chemistry, and behavioural studies have converged in order to prove the existence of such physiological functions."
The researchers claim the results show that endogenous cannabinoids may have a role in helping humans overcome fears, and suggest that the cannabinoid system could be harnessed to help patients recover from conditions such as phobias, post-traumatic stress disorder, and some types of chronic pain.
"Extinction of aversive memory is impaired in several pathological states, such as post-traumatic stress disorders", Lutz says. "However, whether it is possible to obtain the reverse effect--ie, enhancing extinction--by interfering with the endogenous cannabinoid system, is still to be proven."
For instance, Pankaj Sah (John Curtin School of Medical Research, Australian National University, Canberra, Australia) says that there is a widely recognised relationship between marijuana abuse and several mental disorders; however, he points out that no-one is sure whether marijuana contributes to the disorders or whether it is part of a self-medication regimen to help cope with the trauma of the disorder. Sah, who wrote an accompanying commentary (Nature 2002; 418: 488-89), suggests that the latter scenario is a plausible explanation.
"It's a reasonable area to study", Sah told The Lancet. "Sure, [marijuana] has other effects as well, but this is the first study to show a well understood behavioural response that is due to the release of an endogenous cannabinoid."

this study just shows that marijuana causes deficits in memory while your high


Effects of marijuana on neurophysiological signals of working and episodic memory. Author: Ilan, Aaron B. Add.Author / Editor: Smith, Michael E.
Gevins, Alan Citation: Psychopharmacology 2004, Vol. 176 Issue 2, p214-222 Year: 2004
Rationale: The primary psychoactive constituent of marijuana, Δ₉-THC, activates cannabinoid receptors, which are especially abundant in the frontal cortex and hippocampus. Acute marijuana smoking can disrupt working memory (WM) and episodic memory (EM) functions that are known to rely on these regions. However, the effects of marijuana on the brain activity accompanying such cognitive processes remain largely unexplored. Objectives: To examine such effects on performance and neurophysiological signals of these functions, EEG recordings were obtained from ten subjects (5M, 5F) performing cognitive tasks before and after smoking marijuana (3.45% Δ₉-THC) or a placebo. WM was assessed with a spatial N-back task, and EM was evaluated with a test requiring recognition of words after a 5-10 min delay between study and test. Results: Marijuana increased heart rate and decreased global theta band EEG power, consistent with increased autonomic arousal. Respon
ses in the WM task were slower and less accurate after smoking marijuana, accompanied by reduced alpha band EEG reactivity in response to increased task difficulty. In the EM task, marijuana was associated with an increased tendency to erroneously identify distracter words as having been previously studied. In both tasks, marijuana attenuated stimulus-locked event-related potentials (ERPs). Conclusions: The results suggest that marijuana disrupted both sustained and transient attention processes resulting in impaired memory task performance. In subjects most affected by marijuana a pronounced ERP difference between previously studied words and new distracter words was also reduced, suggesting disruption of neural mechanisms underlying memory for recent study episodes. [ABSTRACT FROM AUTHOR] of words after a 5-10 min delay between study and test. Results: Marijuana increased heart rate and decreased global theta band EEG power, consistent with increased autonomic arousal. Respon

This study is interesting. It supports the theory that pot not only screws memory while high but sober as well. This is a documented phenomenon, although its disputed, the neuroscience evidence highly supports that cannabis changes the brain to work less efficiently and working memory does get impaired by this.
Cannabinoid-mediated disinhibition and working memory: Dynamical interplay of multiple feedback mechanisms in a continuous ativactor mode of prefrontal cortex Author: Carter, E Add.Author / Editor: Wang, X Citation: CEREBRAL CORTEX 17: I16-I26 Suppl. 1 SEP 2007 Year: 2007 Abstract: Recurrent excitation is believed to underlie persistent neural activity observed in the prefrontal cortex and elsewhere during working memory. However, other positive and negative feedback mechanisms, operating on disparate timescales, may also play significant roles in determining the behavior of a working memory circuit. In this study, we examined dynamical interactions of multiple feedback mechanisms in a biophysically based neural model of spatial working memory. In such continuous attractor networks, a self-sustained activity pattern tends to drift randomly, resulting in a decreased accuracy of memory over time. Moreover, attractor states become unstable when spike-frequency adaptation reduces the excitability of persistently firing pyramidal neurons. Here, we show that a slow activity-dependent local disinhibition, namely cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), can counteract these destabilizing effects, rendering working memory function more robust. In addition, the slow DSI effect gives rise to trial-to-trial correlations of memoryguided behavioral responses. On the other hand, computer simulations revealed that a global cannabinoid agonist (mimicking the effect of drug intake) yields the opposite effect. Thus, this work suggests a circuit scenario according to which endogenous DSI is beneficial for, whereas an exogenous drug such as marijuana is detrimental to, working memory and possibly other prefrontal functions.











Finally, here is the bread and butter of the whole theory. Let me summarize. Biological evidence supports that cannabis "It found that not only were there less receptors, but the receptors left would not function right. Normal neurotransmitter communication in this system would be crippled. The normal thing that would cause activation in the receptor wont, it would require more of an agonist action on it to activate it. So, since the cannabinoid system modulates fear and anxiety, one could hypothesize that since the system itself has less receptors and the ones left dont work as well, since GABA tolerance occurs and this causes even more of a problem with synaptic transmission, this would effect the system negatively even more. f that were the case, then again those predisposed to getting schizophrenia are more likely to get it and there would be great anxiety if one discontinued smoking pot after heavy use." Furthermore, correlational data supported the theory of cannabis anxiety because as thc leaves the body, anxiety increases because thc is still exherting an effect. Once its left, the system that modulates fear, and anxiety and deals with anxiety memories becomes haywire. pot also effects working memory through this and causes problems with memory while high. why a person doesnt realize it? They are doing state dependant learning so it doesnt seem like it. If they quit pot for 3 months probably they would notice. So after all this evidence, does human studies support the hypotheses? The answer is yes

Source: Addiction, Oct96 Section: RESEARCH REPORT AN EVALUATION OF THE HISTORY OF A MARIJUANA WITHDRAWAL SYNDROME IN A LARGE POPULATION Abstract Case reports and laboratory research indicate the existence of a cannabis withdrawal syndrome. However, the data tell us little about the prevalence and clinical characteristics of a marijuana withdrawal syndrome in people who have used the drug but who did not enter treatment for cannabis dependence. Face-to-face semi-structured interviews applying standard diagnostic criteria were used in the present study to gather data from 5611 men and women, recruited between 1991 and 1995 through the Collaborative Study of the Genetics of Alcoholism (COGA). Almost 41% of the sample had no history of marijuana use (Group I), 28% had consumed this drug less than 21 times in any single year (Group 2), and 31% used it at least that frequently (Groups 3 and 4). Almost 16% of the more frequent marijuana users related a history of a marijuana withdrawal syndrome, and these Group 4 subjects had used the drug almost daily for an average of almost 70 months. The typical withdrawal symptoms included "nervous, tense, restlessness", "sleep disturbance" and "appetite change". While Group 4 subjects were more likely to have developed dependence on most types of drugs, even when alcohol and drug use patterns were statistically taken into account, marijuana use was still significantly related to a self-report of a history of marijuana withdrawal. Introduction


Addiction Sep99, Vol. 94 Issue 9, p1311 Year: 1999 Abstract: Aims. The clinical relevance of marijuana withdrawal has not been established. This study is the first to document the incidence and severity of perceived marijuana withdrawal symptoms in a clinical sample of marijuana-dependent adults. Measurements. Fifty-four people seeking outpatient treatment for marijuana dependence completed a 22-item Marijuana Withdrawal Symptom checklist based on their most recent period of marijuana abstinence. Findings. The majority (57%.) indicated that they had experienced >/= six symptoms of at least moderate severity and 47% experienced >/= four symptoms rated as severe. Withdrawal severity was greater in those with psychiatric symptomatology and more frequent marijuana use. Conclusions. This study provides further support for a cluster of withdrawal symptoms experienced following cessation of regular marijuana use. The affective and behavioral symptoms reported were consistent with those observed in previous laboratory and interview studies. Since withdrawal symptoms are frequently a target for clinical intervention with other substances of abuse, this may also be appropriate for marijuana. [ABSTRACT FROM AUTHOR]

Purpose of review The demand for treatment for cannabis dependence has grown dramatically. The majority of the people who enter the treatment have difficulty in achieving and maintaining abstinence from cannabis. Understanding the impact of cannabis withdrawal syndrome on quit attempts is of obvious importance. Cannabis, however, has long been considered a 'soft' drug, and many continue to question whether one can truly become dependent on cannabis. Skepticism is typically focused on whether cannabis use can result in 'physiological' dependence or withdrawal, and whether withdrawal is of clinical importance. Recent findings The neurobiological basis for cannabis withdrawal has been established via discovery of an endogenous cannabinoid system, identification of cannabinoid receptors, and demonstrations of precipitated withdrawal with cannabinoid receptor antagonists. Laboratory studies have established the reliability, validity, and time course of a cannabis withdrawal syndrome and have begun to explore the effect of various medications on such withdrawal. Reports from clinical samples indicate that the syndrome is common among treatment seekers. Summary A clinically important withdrawal syndrome associated with cannabis dependence has been established. Additional research must determine how cannabis withdrawal affects cessation attempts and the best way to treat its symptoms. Subject: cannabis


THERAPEUTIC DRUG MONITORING 20 (5): 570-576 OCT 1998 Year: 1998 Abstract: The excretion of marijuana metabolites occurs over an extended period of time. yet few studies have been designed for accurate estimation of excretion half-lives. The authors monitored excretion of the primary urinary metabolite of marijuana, 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THCCOOH), by gas chromatography-mass spectrometry in a controlled clinical study of marijuana smoking that included measurement of the drug in each urine void collected during the 3-week study. Terminal excretion half-lives of THCCOOH were determined in six healthy male subjects with histories of marijuana smoking; the study was conducted on the clinical research unit of a major medical institution. Subjects smoked a single marijuana cigarette (placebo, 1.75% or 3.55% THC) each week. Urine specimens (N = 953) were analyzed under blind conditions for THCCOOH by gas chromatography-mass spectrometry. Mean +/- SEM half-lives calculated by the amount remaining to be excreted method after the low and high doses were 31.5 +/- 1.0 hours (range, 28.4 to 35.3 hours) and 28.6 +/- 1.5 hours (range, 24.9 to 34.5 hours), respectively, when a 7-day monitoring period was used. The amounts of THCCOOH excreted over a 7-day period were 93.9 +/- 24.5 mu g (range, 34.6 to 171.6 mu g) and 197.4 +/- 33.6 mu g after the low- and high-dose sessions. Longer half-lives, 44.3 to 59.9 hours, were obtained with a 14-day sample collection.

and there are plenty of other studies as well as the case studies of not only my friends, not only alot of people who will admit it on this site, but swim as well. Thank you.

[purplehaze]

Swim thinks while both substance's have there downfalls alcohol for some reason was chosen to be legal.

Let's think what has alcohol done for our world? Exploration? Maybe. But it's brought great men down with it's time too. Today it causes family's to no longer be together, men to beat women. Violence, amongst other negative effect's.

Marijuana on the other hand doesn't seem to be causing people to lose there better since of judgment.

Swim believes marijuana should be made legal, imagine some of the greatest men remembered in history stimulated by marijuana.

Alexander Gram Bell invented the telephone, maybe he would have invented the internet as well soon after. Although you might say, there were no computer's. Maybe another inventor would have invented something better, swim believes with marijuana humans have deeper thought's possibly resulting in faster advancement in technology.

All around you can't convince swim that there is a reason to have alcohol legal and marijuana illegal unless you wish for him to believe in your double standards.

[imyourlittlebare]

btw, read my replies about cancer already. I know its disputed and i believe a combination of what i say and nature boy say is correct but i have no idea.

[imyourlittlebare]

here is the ultimate study on memory for humans and there is many more like it. this shows that marijuana users, in order to to tasks the same as a normal person, needs to use MORE of their brain to do it. This shows that there is in fact cognitive and neurological problems from pot

Psychopharmacology (2004) 176: 239–247 DOI 10.1007/s00213-004-1885-8
ORIGINALINVESTIGATIONGen Kanayama . Jadwiga Rogowska . Harrison G. Pope . Staci A. Gruber . Deborah A. Yurgelun-Todd

Spatial working memory in heavy cannabis users: a functional
magnetic resonance imaging study

Received: 26 March 2003 / Accepted: 19 March 2004 / Published online: 16 June 2004
# Springer-Verlag 2004

Abstract Rationale: Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. Objective: We assessed brain function among recent heavy cannabis users while they performed a working memory task. Methods: Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6–36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques.


Results: Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex
and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings
remained essentially unchanged when re-analyzed using subjects’ ages as a covariate. Brain activation showed little or no significant correlation with subjects’ years of
education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning.

Conclusions: Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory
task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by “working
harder”—calling upon additional brain regions to meet the demands of the task.


Introduction
Cannabis is the most widely used illicit drug in the United States (Substance Abuse and Mental Health Services Administration 2002), yet the cognitive effects of long-
term cannabis use remain largely unknown. Several lines of evidence suggest that long-term cannabis use may produce working memory impairments and attentional
dysfunction (Block and Ghoneim 1993; Pope and Yurgelun-Todd 1996; Fletcher et al. 1996; Pope et al. 2001; Solowij et al. 2002; Bolla et al. 2002). These deficits
seem to persist for at least several days after the drug is stopped (Pope et al. 2001). For example, we have previously reported evidence of impaired performance
on spatial working memory—short-term memory used to maintain and manipulate spatial information for a brief period—in chronic, heavy cannabis smokers compared
with normal control subjects (Pope et al. 2001). These findings complement our previous reports of cognitive deficits in heavy cannabis smokers on other tests sensitive
to frontal functions. However, little is known about the functional changes in
cerebral activation that underlie these deficits. Several studies have examined cerebral blood volume, cerebral blood flow, and/or glucose metabolism in recently
abstinent chronic cannabis users, or in subjects acutely ntoxicated with either cannabis or its active component, .-9-tetrahydrocannabinol (.9-THC) (Mathew et al. 1989,
1992, 1997; Volkow et al. 1996; Yurgelun-Todd et al. 2001; see also review by Loeber and Yurgelun-Todd 1999). These investigations have reported that abstinence
from cannabis results in depressed cerebral metabolism among chronic users, whereas very recent or acute cannabis exposure increases cerebral activation as measured by increased blood flow. These studies, however, examined intoxicated cannabis users at a resting state rather than during the performance of a specific cognitive task. Two studies by O’Leary et al. (2000, 2002), utilizing an auditory attention task, found increased regional cerebral blood flow in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, and cerebellum, but decreased blood flow in temporal lobe auditory regions, visual cortex, and regions associated with attention (parietal lobe,frontal lobe, and hypothalamus). The same group (O’Leary et al. 2003) found increased forebrain and cerebellar blood flow, but decreased frontal lobe blood flow, in acutely intoxicated cannabis users performing a counting task. In a pilot study in our laboratory using functional magnetic resonance imaging (fMRI) (Yurgelun-Todd et al. 1998), we found increased anterior cingulate activity but decreased dorsolateral prefrontal cortex (DLPFC) activity in eight recent cannabis users compared with eight control subjects during the performance of a working memory task. This pilot investigation represents the only study, to our knowledge, that has used fMRI to measure blood oxygenation level in specific brain regions of cannabis users. Images in this pilot study were analyzed by manually identifying brain regions of interest and then averaging the MR signal of all pixels in that region—a less sophisticated method than the statistical parametric mapping (SPM) method used in the present study and most other modern studies. In order to extend these findings, the present investigation used fMRI to examine brain function of long-term cannabis users while they performed a spatial working

memory task. Evidence from imaging studies of normal subjects indicates that the functional processes involved in spatial working memory are mediated by a neural network linking the prefrontal cortex (PFC), including both dorsal
PFC (Brodmann’s area 46/9) and ventral PFC (BA 44, 45,
47), and the parietal cortex, temporal cortex, and anterior
cingulate cortex (BA 24/32) (Goldman-Rakic 1995;
D’Esposito et al. 1995, 1999; Rowe and Passingham
2001; Wagner et al. 2001; Munk et al. 2002). In particular,
working memory tasks appear to activate Brodmann’s area
46/9, as well as ventral PFC (BA 44, 45, 47), and
supplementary motor and premotor cortices (BA 6) (Smith
et al. 1996; Braver et al. 1997; Courtney et al. 1997, 1998;
Rowe and Passingham 2001). Working memory studies
have suggested that BA6 is activated regardless of the type
of information being processed (Baker et al. 1996;
D’Esposito et al. 1998).
Based on findings from healthy control subjects, we
designed a protocol to extend our understanding of
cannabis-induced working memory deficits by examining
cerebral activation in specific frontal cortical regions of
heavy cannabis users. We hypothesized that, in response to
a spatial working memory task, heavy cannabis users
would demonstrate significantly lower activation than
normal controls, particularly in the DLPFC (BA 46/9),
ventral PFC (BA 44, 45, 47), and more posterior regions
such as Brodmann’s area eight and premotor cortex (BA 6).
Methods
Subjects
We enrolled 12 heavy cannabis users and 10 control subjects. The
cannabis users were recruited in the course of a larger study of the
residual neuropsychological effects of cannabis use; full details of
subject selection criteria and study procedures have been published
previously (Pope et al. 2001). Briefly, the heavy cannabis users were
30–55 years old, had all smoked cannabis at least 5000 times and
were currently smoking at least seven times per week at the time of
entry into the study. Imaging data were collected between 6 h and
36 h after the subject’s last reported cannabis use. Subjects were
excluded if they reported lifetime use of any category of illicit drugs
[such as cocaine, hallucinogens, or 3,4-methylenedioxymethamphetamine
(MDMA; “ecstasy”)] more than 100 times or any lifetime
history of DSM-IV alcohol abuse or dependence (American
Psychiatric Association 1994). We also excluded subjects reporting
any current DSM-IV Axis-I disorder, as determined by the
Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID;
First et al. 1996); a history of head injury with loss of consciousness
requiring hospitalization; current use of any psychoactive medication;
or any other medical condition that might affect cognitive
function. We estimated the verbal IQ of each subject using the
vocabulary subscale of the Wechsler adult intelligence test as
described previously (Pope et al. 2001).
At the time of imaging, we also obtained subjects’ urine samples,
collected under observation, which we screened by immunoassay
(EMIT II, Behring Diagnostics, Cupertino, CA) for 11-nor-9carboxy-
delta 9-tetrahydrocannabinol (THCCOOH), creatinine, cocaine
metabolites, benzodiazepines, barbiturates, phencyclidine,
opioids, and amphetamines, and by enzymatic assay (EA) for
ethanol. We obtained quantitative THCCOOH and creatinine
concentrations by gas chromatography–mass spectroscopy; we
then used urinary creatinine levels to adjust for differences in the
concentration of subjects’ urine samples. In the results below, we
report subjects’ THCCOOH levels normalized to an assumed
uniform urinary creatinine concentration of 100 ng/ml. These
normalized urinary THCCOOH levels likely provided a better
reflection of subjects’ recent cannabis use than the simple measure
of hours since last use, since subjects smoked cannabis of widely
varying potency in widely varying patterns. Thus, a subject who
smoked a large amount of potent cannabis 30 h prior to testing might
have higher cannabinoid levels than a subject who smoked a small
amount of lower potency cannabis 6 h prior to testing.
The control subjects were individuals who reported no history of
cannabis abuse or dependence, no history of abuse of or dependence
on any other illicit drug or alcohol, and no current or past DSM-IV
Axis-I disorder on the SCID. Controls were neither tested for verbal
IQ nor required to undergo urinary drug testing. As with the
cannabis users, controls were excluded if they reported a history of
head injury with loss of consciousness, medical or neurological
conditions likely to affect cognitive functioning, or usage of
psychotropic medication(s).
Task paradigm
While undergoing imaging, all subjects completed a spatial working
memory paradigm that included two tasks: a perception task and a
short-delay working memory task. This paradigm was adapted from
one previously used in a positron emission tomography (PET) study
of spatial working memory by Jonides et al. (1993). The tasks were
as follows.
Perception task Subjects were presented with a fixation cross in the
center of the screen for 0.2 s; the cross was then supplanted by three
dots appearing on the circumference of an imaginary circle centered
on the cross, presented for 4.3 s. This was followed by an interval of
1.5 s, during which the three dots remained present and a probe for

location memory was added. The probe consisted of a single open
circle that either did or did not encircle the location of one of the
dots (probability was set at 0.5). Subjects pressed a button once or
twice to indicate whether the probe encircled a dot.
Short-delay response task Subjects focused on a cross in the center
of the screen for 0.2 s. This cross was then supplanted by three dots.
The dots remained on the screen for 1.3 s and were again replaced
by the fixation cross alone for a 3-s delay period (with fixation). The
probe circle then appeared for 1.5 s, and subjects were asked to press
a button once or twice to indicate whether or not the probe circle
marked the location where a dot had previously been present.
Five alternating rest/activation cycles (off–on–off–on–off) comprised
each condition. An activation cycle contained five trials of
6 s. Thus, for both the perception and short-delay tasks, the time
required was 30 s/cycle and 150 s for the full condition. The visual
stimuli were presented by a Macintosh controlled video display.
Task instructions were presented on the computer screen and were
also explained to subjects by trained administrators before scanning.
Imaging techniques
Functional scanning Scanning was performed on a 1.5-Tesla GE
whole-body scanner using a quadrature head coil. Head movement
was minimized by padding and restraints. After acquisition of high-
resolution T1-weighted images for fMRI anatomic localization, 50
sequential gradient-echo echoplanar images (EPIs) sensitive to
blood oxygenation level-dependent (BOLD) signal were collected in
contiguous slices of 6-mm thickness, with 3000-ms repetition time
(TR), 40-ms echo time (TE), 20×20-cm field of view (FOV), a
64×64 image matrix, 70° flip angle, and an in-plane resolution of
3×3 mm. The slices were oriented to cover the entire frontal cortex,
and parts of the temporal and parietal lobes, but not the cerebellum.
Image processing and statistical analysis The functional imaging
and statistical analyses were performed using SPM99 (Wellcome
Department of Cognitive Neurology, London, UK). Functional
images were realigned to correct for motion-related variance
components, normalized to the standard Montreal Neurological
Institute (MNI) EPI template (Talairach and Tournoux 1988; Friston
et al. 1995a) and spatially smoothed with an 8-mm full width at half
maximum (FWHM) isotropic Gaussian kernel to allow for anatomical
variation among subjects. The statistical parametric maps were
generated using the general linear model in SPM99 (Friston et al.
1995b). Low-frequency noise was removed with a high-pass filter
with a cutoff of 127 s applied to the fMRI time series at each voxel.
Data from each subject for each task condition were first analyzed
with a fixed box-car function convolved with a model hemodynamic
response function. For individual subjects, regions formed by more
than ten contiguous voxels with significant activations (P<0.001
uncorrected for multiple comparisons) were considered to represent
areas of significant response. Predetermined condition effects at
each voxel were calculated by the fixed model, creating a single
image of mean activation for the short-delay task minus the
perception control task in each subject for the group analysis. The
group data were then analyzed using a random-effects model on a
second level to account for interindividual variance. Comparisons
within groups were performed on a voxel-wise basis using a one-
sample t-test (P<0.001 uncorrected), and comparisons between
groups were performed using a two-sample t-test (P<0.005
uncorrected).
Finally, because of age differences between the cannabis and
control groups (see below), we repeated our comparison between
groups while using age as a covariate. We also tested correlations
between brain activation and (1) age and (2) years of education
within the cannabis group and the comparison group. In addition,
within the cannabis group alone, we assessed correlations between
brain activation and (3) verbal IQ, (4) lifetime episodes of cannabis
use, and (5) normalized urinary THCCOOH levels (as described
above) at the time of imaging. (As noted above, we examined
urinary THCCOOH levels, rather than hours since last use, since the
former measure appeared likely to be a better reflection of recent
cannabis use). These correlations were also performed using
activation in the short-delay task minus the perception task as the
outcome variable, the same 8-mm FWHM Gaussian kernel, and a
significance level of P<0.005 uncorrected.
Results
Subject characteristics
The 12 cannabis users were older than the 10 controls;
however, the groups did not differ significantly on other
demographic measures (Table 1). Cannabis users reported
that they had smoked cannabis on a mean of 19,200
occasions in their lives (range 5100–54,000). Their mean
±SD urinary THCCOOH level at the time of scanning
(normalized to a urinary creatinine concentration as
described above) was 497±515 ng/ml (range 35–
1470 ng/ml). All subjects in both groups performed the
perception task without errors; on the short-delay task,
subjects displayed only a few performance errors, with no
significant difference between groups (correct performance
in 86±25% of trials among the cannabis users
and 93±16% of trials among control subjects; P=0.46).
Perception task
During the simple perception task (in which no working
memory was involved), both the control subjects and
cannabis users activated the inferior frontal gyrus and
middle frontal gyrus bilaterally (BA9 and 44; Table 2).
The cannabis subjects also showed activation in several
other areas, including right superior frontal gyrus, right
caudate, and bilateral anterior cingulate.
Short-delay response task
In the short-delay task, control subjects again displayed
prominent activation bilaterally in the middle and inferior
Table 1 Demographic features Heavy cannabis users Control subjects Pa
of cannabis users and control
subjects N=12 N=10
Male, N (%) 10 (83) 6 (60) 0.35
Caucasian, N (%) 10 (83) 10 (100) 0.48
aSignificance of differences cal-Age (years), mean (SD) 37.9 (7.4) 27.8 (7.9) 0.006
culated using Fisher’s exact test, Education (years), mean (SD) 14.8 (2.1) 15.9 (1.9) 0.22
two-tailed and t-test, two-tailed

Table 2 Foci of maximally
activated brain regions for the
Regions of activation Laterality Brodmann’s area x y z t-value
perception task. L left hemisphere,
M midline, R right
hemisphere. Atlas coordinates
Control subjects
Inferior frontal gyrus L 44 -62 12 12 4.04
from the MNI standard atlas, R 9 46 12 22 3.41 such that x reflects the distance (mm) to the right or left of midline, y reflects the distance anterior or posterior to the an-Middle frontal gyrus Heavy cannabis users
R
L
9
9
46
-52
16
8
36
36
3.74
3.41
terior commissure, and z reflects
the distance superior or inferior
to the horizontal plane through
the AC–PC line. Coordinates
Inferior frontal gyrus
Caudate Middle frontal gyrus
R
R
R
38
9
50
14
50
22
-2
22
-12
14
32
5.59
5.35
5.11
and t-values are reported for the L 46 -48 36 28 5.43 clusters in each lateral region with the largest number of activated voxels and t-values Superior frontal gyrus Anterior cingulate gyrus
R
L
8
32
-30
-2
36
22
50
42
3.92
4.38
significant beyond P<0.001. R 32 2 52 50 3.38
frontal gyri (BA 46/9 and BA 47, respectively), with
additional areas of activation in the right anterior cingulate
(BA 32) and bilateral caudate (Table 3). Cannabis users
also showed activation of middle frontal and inferior
frontal gyrus, left anterior cingulate, and right caudate
together with additional foci of less prominent activation
in left superior frontal and right parahippocampal gyrus.
Short-delay response task minus perception task
In order to determine areas of activation specific to the
working memory process, we examined activation in the
short-delay task minus that in the perception task. In the
control group, this subtraction exercise demonstrated
widespread activation bilaterally in the middle frontal
gyrus (BA 46/9 and BA6), bilateral inferior frontal gyrus
(BA47), and right anterior cingulate (BA32). The cannabis
users showed activation generally in these same regions,
but it was more prominent than in the controls, with larger
numbers of foci of activation. Additionally, cannabis users
showed activation in three areas of the right lentiform
nucleus and one area of right superior frontal gyrus.
Figure 1 illustrates the more prominent and widespread
brain activation of the cannabis users relative to the
controls during the working memory task. The differences
between groups are visible both on rendered brain images
(top of figure) and on sagittal, coronal, and axial slices
displaying the regions of maximal mean activation in each
study group (bottom of figure).
Activation in cannabis subjects minus control subjects
The above observations suggest that contrary to our
hypothesis, the cannabis users exhibited more pronounced
and more widespread activation than the control subjects
in response to the working memory task. To further
characterize these differences, we subtracted the results of
the short-delay response task minus perception task in
controls from that of the cannabis users (Table 4). This
comparison demonstrated that, during the working memory
task, the cannabis users showed significantly greater
Table 3 Foci of maximally
activated brain regions for the
Activation area Laterality Brodmann’s area x y z t-value
short-delay response task. L left
hemisphere, M midline, R right
hemisphere. Atlas coordinates
Control subjects
Middle frontal gyrus R 46 54 20 32 6.66
are from the MNI standard atlas, L 9 -48 8 36 5.60
such that x reflects the distance
(mm) to the right or left of
midline, y reflects the distance
anterior or posterior to the an-
Anterior cingulate gyrus
Inferior frontal gyrus
L
R
R
6
32
47
-36
2
50
8
12
24
56
52
-14
5.09
6.36
4.65
terior commissure, and z reflects Caudate R 12 -4 14 4.04
the distance superior or inferior
to the horizontal plane through
the AC-PC line. Coordinates Heavy cannabis users
L -12 -6 14 3.77
and t-values are reported for the Middle frontal gyrus R 9 54 22 32 9.14
clusters in each lateral region L 9 -46 16 34 6.21
with the largest number of
activated voxels and t-values
significant beyond P <0.001
Anterior cingulate gyrus
Caudate
L
R
32 -2
12
18
-2
46
12
8.77
7.16
Inferior frontal gyrus L 47 -42 20 -4 5.40
Superior frontal gyrus L 6 -26 10 60 4.70
Parahippocampus R 32 -22 -4 3.65

Fig. 1 Foci of maximal activation for the short-delay response task
minus the perception task in control subjects (left) and long-term
heavy cannabis users (right). The more prominent and widespread
brain activation of the cannabis users is visible both on rendered
brain images (top) and on sagittal, coronal, and axial slices
displaying the regions of maximal mean activation in each study
activation than controls in a number of regions, including
superior, middle, and inferior frontal gyrus; right superior
temporal gyrus; anterior cingulate gyrus bilaterally; right
precentral gyrus; and regions of caudate and putamen. By
contrast, activation in the controls exceeded that of the
cannabis users in only two small regions of the middle
frontal cortex.
group (bottom). Note that the color scale for levels of activation
differs between study groups; e.g., a yellow color corresponds to a T
score of about 3.5 for the controls, but represents a T score of about
5.0 for the cannabis users. Thus, the difference between cannabis
users and controls is actually greater than it first appears
Secondary analyses
A possible limitation of the above analyses is the
difference in mean age between the groups (Table 1). To
address this issue, we repeated the analysis in Table 4
while introducing subjects’ ages as a covariate This
analysis demonstrated that age produced very little effect
on the differences between cannabis and control subjects;
after adjustment for age, the regions of increased activation
among the cannabis users remained virtually the
same, and the magnitude of the differences between the

Table 4 Foci of maximally
activated brain regions for
Regions of activation Laterality Brodmann’s area x y z t-value
short-delay response minus perception.
L left hemisphere, M
midline, R right hemisphere.
Heavy cannabis users minus controls
Superior temporal gyrus R 38 34 12 -26 3.49
Atlas coordinates are from the Anterior cingulate gyrus R 24 16 6 28 3.38
MNI standard atlas, such that x
reflects the distance (mm) to the
right or left of midline, y reflects
the distance anterior or posterior
Inferior frontal gyrus
L
R
R
32
47
-18
36
42
16
26
32
34
8
4
2.96
3.35
3.28
to the anterior commissure, and Caudate R 14 24 12 3.29
z reflects the distance superior or
inferior to the horizontal plane
through the AC–PC line. Co-Middle frontal gyrus
L
L
-6
-22
18
38
6
14
2.84
3.26
ordinates and t-values are re-R 10 16 38 -8 2.97
ported for the clusters in each
lateral region with the largest
number of activated voxels and
Superior frontal gyrus
Precentral gyrus
R
R 6
18
54
46
6
-12
18
3.11
3.00
t-values significant beyond P Lentiform nucleus R Putamen 26 8 18 2.94
<0.005 Controls minus heavy cannabis users
Middle frontal cortex L 6 -42 14 50 3.33
R 9 44 42 34 2.97
groups actually increased slightly in most of these regions
(details available from the authors on request). As a further
check on the effects of age, we also assessed the
correlation between age and activation in the short-delay
minus perception conditions among both the cannabis
users and comparison subjects; we again found virtually
no significant associations between age and activation.
Finally, we repeated the analysis in Table 4 while
eliminating the two oldest cannabis users and the four
youngest control subjects, leaving ten cannabis users and
six controls closely matched on age (mean±SD age 35.1
±3.6 years versus 31.7±8.2 years, respectively). This
analysis again produced findings very similar to those of
the primary analysis (details available from the authors on
request).
In a series of correlational analyses, we found few
significant correlations between years of education and
brain activation in either group, and again none of these
was associated with the regions of interest activated by the
working memory task. Also, within the cannabis group
alone, we found virtually no significant correlations
between activation and verbal IQ, lifetime episodes of
cannabis use, or normalized urinary THCCOOH levels
(details available from the authors on request).
Discussion
Using the fMRI BOLD technique, we measured cortical
activation in response to a spatial working memory task in
12 recent heavy cannabis users who had last smoked
between 6 h and 36 h prior to study. We also measured
activation in 10 control subjects with no recent cannabis
use and no history of cannabis abuse or dependence. The
two groups exhibited no performance errors on the
perception task, and few errors on the short-delay task,
with no significant difference between groups; this
phenomenon may have represented a ceiling effect due
to the relative simplicity of the tasks. When examining the
fMRI results, however, we found that cannabis users
displayed greater and more widespread brain activation
than controls during task performance. This finding
remained essentially unchanged (and indeed was slightly
reinforced) when we repeated our analysis while introducing
subjects’ ages as a covariate. We found very few
significant correlations between brain activation and age
or years of education in either group, nor between
activation and verbal IQ or lifetime episodes of cannabis
use within the cannabis group. Furthermore, none of the
clusters showing significant correlations in these exercises
was located in the regions of interest activated by the
working memory task. The absence of such correlations
supports the conclusion that the differences between the
cannabis and comparison groups are indeed an effect of
recent cannabis use, rather than an artifact caused by
confounding variables.
Perhaps surprisingly, we also found no significant
correlations between brain activation and normalized
urinary THCCOOH concentrations at the time of imaging.
However, urinary THCCOOH concentrations may be only
weakly associated with brain cannabinoid levels, and brain
cannabinoid levels, in turn, may not be tightly correlated
with levels of brain activation. Further studies will be
required to explore these issues.
Looking at the results in more detail, the findings in our
control subjects indicated that the regions activated in the
perception condition were generally similar to those
observed in previous studies using visual perception
tasks (Calhoun et al. 2001). When the perception condition
was subtracted from the short-delay response condition in
order to isolate activation specific to spatial working
memory itself, the results in controls were again generally
similar to those found in many recent neuroimaging
studies (fMRI or PET) that have examined working
memory processes in the frontal lobes (D’Esposito et al.
1998; Smith and Jonides 1999). For example, Rowe and
Passingham (2001) used a spatial memory task similar to
ours to examine prefrontal activation in six normal

subjects using event-related fMRI. In the experimental
task, subjects were required to remember the location of
three red dots, presented on three successive trials.
Following a delay of 8.5–17.5 s, subjects were shown
the number of one of the three dots and asked to indicate
where the dot had been located. In agreement with their
previous study (Rowe et al. 2000), these investigators
found that when the subject was asked to select the
location from memory, area 46 in the DLPFC was
activated bilaterally, together with the neighboring area
9/46 in the mid-DLPFC. Areas in ventrolateral PFC and
anterior cingulate cortex were also activated. Our findings
in normal controls are consistent with these results.
Heavy cannabis users, however, in contrast to our
predictions, exhibited greater and more widespread activation
than controls in response to the perception task, the
short-delay task, and in the analysis of short-delay minus
perception. In particular, the cannabis users responded to
the working memory task with widespread activation of
numerous regions, including not only regions typically
used for spatial working memory, but other regions as well
(Table 4). These findings suggest that cannabis users
generate greater activation in the usual regions but also
recruit ancillary regions to meet the demands of the task. It
is of note that the anterior cingulate, a region known to be
involved in attentional monitoring (Luks et al. 2002;
Gruber et al. 2002), was more strongly activated in the
cannabis users, due perhaps to an attempt to coordinate
activity from the unusually wide range of regions recruited
for the task.
The notion that increased activation of the anterior
cingulate among cannabis users may be attributable to
attentional dysfunction is consistent with other studies of
cognitive effects of cannabis. Several studies have
detected attentional dysfunction in long-term cannabis
users (Block and Ghoneim 1993; Pope and Yurgelun-Todd
1996; Fletcher et al. 1996; Pope et al. 2001; Solowij et al.
2002; Bolla et al. 2002), and others have shown activation
of the anterior cingulate in tasks requiring attentional
function (Posner and Petersen 1990; Corbetta et al. 1991;
Luks et al. 2002). In addition, the recent PET studies of
O’Leary et al. (2000, 2002) found increased regional
cerebral blood flow to the anterior cingulate during an
auditory attention task. Therefore, the increased activation
of the anterior cingulate of the users of this study may
reflect an increased effort to overcome a cannabis-induced
attentional impairment.
Our fMRI findings of widely increased activation
among very recently abstinent cannabis users appear
consistent with previous studies that have found increased
cerebral blood flow and glucose metabolism in acutely
intoxicated or very recently abstinent users (Loeber and
Yurgelun-Todd 1999). However, with the exception of the
studies of O’Leary et al. (2000, 2002, 2003), these
previous studies are not directly comparable to ours in that
they examined subjects at rest, rather than during the
performance of a cognitive task. Our own preliminary
fMRI investigation of working memory (Yurgelun-Todd et
al. 1998) found increased cingulate activation in cannabis
users relative to controls, in agreement with the present
study, but decreased activity among cannabis users in the
DLPFC, in disagreement. However, as previously mentioned,
our previous study used an older and imprecise
method, where we manually examined only four pixels in
the relatively large region of the DLPFC. The more
sophisticated SPM method, used in the present paper, is
likely to be more reliable, since it corrects for temporal and
spatial autocorrelations in the fMRI data using multivariate
regression analysis.
Our hypothesis of increased utilization of brain reserve
among cannabis users is consistent with the findings of
studies on other types of patients with neurophysiological
and behavioral syndromes. For example, patients with
early human immunodeficiency virus (HIV) infection may
show little or no deficit on neuropsychological tests of
working memory, yet they display significantly greater
and more widespread brain activation than controls while
performing such tests, suggesting that they recruit
additional brain regions to compensate for neural changes
(Ernst et al. 2002). Similarly, another study found that
alcoholic subjects performed at a comparable level to
matched controls on a verbal working memory task, but
the alcoholics displayed greater activation in left frontal
and superior cerebellar regions—suggesting a compensatory
increase in brain activation in order to maintain the
same performance as controls (Desmond et al. 2003).
Few studies have examined cortical activation during
spatial working memory tasks in subjects with substance
abuse, and none, to our knowledge, has examined
cannabis users. In a study of alcoholics, Pfefferbaum et
al. (2001) employed an experimental design similar to
ours, examining brain activation in a somewhat more
difficult (match 2-back) spatial working memory task.
When compared with the ten controls, the seven detoxified
chronically alcoholic men showed diminished activation
of frontal cortical systems, but greater activation of
posterior and inferior frontal cortex. By contrast, the
cannabis users in our study displayed increased activation
of frontal cortical systems. However, the cannabis users,
like the alcoholics, displayed increased activation of
ancillary regions. In a recent imaging study of alcoholic
women, Tapert et al. (2001) found significantly lower
brain activation in patients than in controls across a variety
of frontal and parietal regions with little evidence of
compensatory activation elsewhere. Future studies are
needed to clarify such contradictory findings.
Several possible limitations of our study should be
considered. The first is the difference in mean age between
the cannabis users and control subjects. However, our
findings remained essentially the same when we repeated
our analysis while using subjects’ ages as a covariate.
Moreover, when we repeated our analyses with a restricted
sample of subjects matched for age and gender distribution,
the results again remained essentially the same. These
observations suggest that our findings are unlikely to
represent an artifact of age or gender. A second possible limitation is that the drug use among the control subjects
was not assessed as systematically as the drug use among

the cannabis users. Although we excluded controls with a
history of alcohol or other substance abuse or dependence,
the possibility remains that some control subjects had used
substantial amounts of cannabis without qualifying for
abuse or dependence. If this were the case, however, it
would likely have narrowed the difference between
cannabis users and controls, making our results a more
conservative estimate of the effects of cannabis. Third, the
cannabis users had ingested varying amounts of active
drug (depending on the potency of the preparation used
and the amount smoked), and had last smoked at varying
times (6–36 h) prior to the time of imaging. As noted
above, we have attempted to explore this variability by
examining the correlation between brain activation and
subjects’ urinary THCCOOH levels. This analysis found
virtually no voxels showing a significant correlation
between activation and THCCOOH levels—but we cannot
exclude the possibility that there might nevertheless be an
association between brain activation and time since last
cannabis use within the 6-to 36-h range. At present,
speculation on this point must be limited, since we are not
aware of any studies that have used fMRI to examine task-
related neuronal activation in subjects who were directly
administered cannabinoids—or, for that matter, comparable
studies with any other drugs of abuse, with the
exception of one study showing increased task-related
neuronal activity with amphetamine administration (Uftring
et al. 2001).
We also cannot exclude the possibility that some
confounding variable, rather than cannabis use itself,
accounted for the differences between groups. Although
the groups were carefully screened to exclude subjects
with substantial use of other drugs or alcohol, current
psychiatric or medical disorders, and use of psychoactive
medications, the possibility remains that the cannabis
users possessed some attribute other than cannabis use
associated with the greater cortical activation during the
working memory task. Notably, however, we found
virtually no voxels showing a significant correlation
between activation and years of education, suggesting
that this variable was not an important confounder.
Finally, we examined cortical activation only within the first 36 h after last cannabis use. Subsequent studies should attempt to examine brain activation during a working memory task in cannabis users after a prolonged period of abstinence to assess whether our findings represent a temporary or more persistent effect. Data from our earlier neuropsychological testing study suggest generally that neuropsychological test performance in cannabis users remains compromised at 7 days, but improves by 28 days of abstinence. It is unclear, however, whether these changes in performance are paralleled by changes in patterns of cerebral activation. In summary, our findings suggest that long-term, heavy cannabis users, like individuals with alcoholism or early HIV infection, display increased cortical activation and even recruit ancillary brain regions during the performance of a working memory task. This finding raises the possibility that long-term cannabis users suffer from subtle neurophysiological changes, at least during the immediate period after discontinuing cannabis use. Furthermore, this change may be greater than that suggested by studies using conventional neuropsychological tests, since users may superficially perform as well as control subjects but only at the cost of “working harder,” activating brain regions more strongly and more broadly than normally required. Such observations highlight the importance of supplementing neuropsychological findings with fMRI imaging data in cannabis users.


Acknowledgments Supported in part by NIDA Grant R01 12483
(to Dr. Yurgelun-Todd) and NIDA Grant 5 R37 DA-10346 (to Dr.
Pope).
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Reputation Comments on this post:

You need to find a different way for formatting because this is blinding and hard to understand (because of formatting i...

[OccularFantasm]

So lets back up for a second. Wouldn't it logically be sound to say that smoking causes cancer. no smoking tobacco, not smoking cannabis, but just smoking. Cannabis has anti-tumor fighting properties, but I do not see how anything that is combusted at a high temperature including much cellulose and any bug killers or any other chemicals spread on crops, like the radium on tobacco. to me it seems far more likely that there are indeed cancer fighting agents in cannabis, but smoking it also releases cancer causing carcinogens. The combination of this would also account for the varying studies. I can attest to the anti-tumor and cancer fighting effects though. But I will keep this short as I just wrote in the other pot something something harmful thread.

Meh, its a *.pdf, I'll make an attachment of it then I guess.

Marijuana does not dent IQ permanently

• 17:50 08 April 2002
• NewScientist.com news service
• Alison Motluk

As for the IQ portion, I believe the reference I used there was the report done up by the Nixon commission, but as I am too lazy to go and find it I just Googled it quick and found a different one. This one is fromt he Canadian Medical Journal.

Smoking marijuana does not have a long-term effect on intelligence, say researchers in Canada who have followed volunteers from before birth to early adulthood.
Heavy pot smokers did experience a dip in their intelligence quotient (IQ). But people who had once smoked heavily and then given up were right back up to normal, the study found. Light smokers appeared no different from non-smokers.
What the researchers do not know is if decades of pot-smoking could have a more lasting impact. Looking at long-term users in their 30s or 40s could show different results, admits Peter Fried, at Carleton University in Ottawa, who led the study. "Perhaps the nervous system isn't as flexible then," he says.
"You can't argue with what they're saying," says William Campbell, President of the Canadian Society of Addiction Medicine. "It doesn't surprise me or disappoint me."

[top]Urine test

Fried and his team followed 70 middle-class kids from the womb. IQ tests were taken at around age 10 and then again between 18 and 20. As adults, the participants were asked about a range of behaviours, including pot smoking. They also under went urine analysis to check their answers.
At the time of the second questionnaire, nine had been heavy users in the past but had not smoked for over three months. Fifteen were still smoking cannabis heavily - at least five joints a week and nine were current light users who smoked a few joints weekly. The rest of the volunteers had never been regular users, so had either never smoked marijuana or had done so less than once a week.
Only the heavy current users had experienced a decline in their IQ scores over the 10-year period - about four points. Light users, former users and abstainers all saw their IQ scores climb between two and six points.
Fried concedes that while IQ may be spared, memory and attention may be harder hit and is examining the effect now: "The most-often stated reason for quitting was they felt their short-term memory was affected."
Canadian Medical Association Journal (vol 166, p 887)




I'll put a more comprehensive study on here too as well. The following quote is from it. (although I don't know why it switches f's to those restricted signs.)

"Although there have been claims that chronic cannabis use may permanently damage the brain, there is little scienti®c evidence to support these claims (for reviews see Dornbush et al., 1976; Hollister, 1986, 1998; Zimmer and Morgan, 1997). As described above, some studies have revealed a modestly impaired ability to focus attention and ®lter out irrelevant information in ex-cannabis users (Solowij, 1998), but other studies failed to ®nd any impairments in cognitive function (Pope et al., 2001). There is little evidence that cannabis use impairs work performance or leads to an `amotivational syndrome' (Dornbush et al., 1976; Hollister, 1986; Abood and Martin, 1992), nor is there any convincing evidence for neuropathological changes in the brains of cannabis users (Hollister, 1986)."

The nice thing about this study, is it doesn't take an objective side. It simply evaluates all aspects, not just chemistry or one specific trait, from which I suppose any side could find supporting evidence for certain ideas.