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Pot's antidepressant effects reverse at high doses

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Date: Tuesday Oct. 23, 2007 5:12 PM ET

A new study finds that a synthetic form of THC, the active ingredient in marijuana, is an effective antidepressant at low doses. But, at higher doses, the effect reverses itself and can actually worsen depression.

This study offers the first evidence that cannabis can -- at least at lower doses - increase serotonin, an important neurotransmitter that regulates mood.

The study, published in The Journal of Neuroscience, was led by Dr. Gabriella Gobbi of McGill University and Le Centre de Recherche Fernand Seguin. She says she was prompted to explore marijuana's potential as an antidepressant through her work as a psychiatrist, where she noticed that several of her patients suffering from depression smoked pot.

"And in the scientific literature, we had some evidence that people treated with cannabis for multiple sclerosis or AIDS showed a big improvement in mood disorders," Gobbi said in a statement. "But there were no laboratory studies demonstrating the antidepressant mechanism of action of cannabis."

To conduct their study, Gobbi's team injected the synthetic cannabinoid WIN55,212-2 into laboratory rats and then had them perform a test to measure their "depression."

The rats were placed in a water tank that was impossible to escape. Typically, the animals will swim hard for 10 minutes, trying to find a way out, then give up and float until researchers remove them. The next day, the rats are put back in the water, whereupon they give up much faster, usually after two minutes. This, researchers say, illustrates the "learned helplessness" model of depression.

Gobbi's team observed that when the rats were given small doses of the synthetic canniboid, the rats showed no depression and once again swam hard, nearly as fast on the second day as they did on the first.

The research team also used electrodes to monitor brain activity and noticed a parallel effect of an increased activity in the neurons that produce serotonin.

Gobbi believes that the antidepressant effects of cannabis are due to its chemical similarity to natural substances in the brain known as "endo-cannabinoids," which are released under conditions of stress or pain.

However, increasing the cannabinoid dose beyond a set point completely undid the benefits, with the serotonin in the rats' brains actually dropping below the level of those rats in the control group, who were simply typically "depressed."

"So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed," says Gobbi.

For this reason, Gobbi's team calls cannabis "a double-edged sword."

Gobbi's team concludes that there are risks associated with using cannabis directly as an anti-depressant, since it could worsen depression - especially since controlling the dosage of natural cannabis is difficult when it is smoked in the form of marijuana joints.

Instead, she and her colleagues are focusing their research on a new class of drugs which enhance the effects of the brain's natural endo-cannabinoids.

Comments are now closed for this story

Von Autoban
said

Rats. How credible is this? Rats being depressed. Just like humans aren't they. For mental disorders examining the effects of a drug on a rat is a first step. Drawing such concrete conclusions off rats seems a bit fuzzy eh.


Mark
said

Dear Tessa
Information that's been released in the past year has shown that marijuana smoke is 2.5-6 times more harmful than tobacco smoke. Please update YOUR facts.


NN
said

A growing minority of cannabis users do use a vaporiser rather than smoking, myself included. I have no experience with tobacco and find smoking a joint or pipe intolerable. The vaporiser does seem to provide more precise dose control as well, though I'd still call it tricky to get an exact dose (not that any real guidelines exist).

As Allan M notes, this isn't an unexpected result for any substance that can act as an antidepressant.

Based on my own mild experience I still wouldn't recommend self-prescribing for depression, but realistically that's how most people treat it, whether with alcohol, St. John's Wort, or behaviour.



Full Disclosure
said

Note that the article conspicuously avoids the issue of how much THC needs to be administered in order to cause the serotonin levels to drop. Other than stating that "increasing the cannabinoid dose beyond a set point" causes the serotonin levels to fall. Normally with these types of studies, the amounts of THC given to the animal test subjects in order to cause the stated negative effects are far beyond the levels attained by even the heaviest daily pot smokers.
Oh, and Tessa is right John, you need to review the facts surrounding the physical effects of smoking marijuana on the lungs because this is another half-truth (or half-lie depending on your perspective). Smoking marijuana only does not have the same effect as smoking cigarettes, no cancer, no emphysema links whatsoever. Look it up.


steve
said

I smoke pot daily and I can function better than most people who are sober. I can smoke a bowl and go for a 30 min jog, do some push ups, lift weights and I can read, write and work at my computer. I understand Pot effects people differently, but I can stop smoking it at anytime without withdrawal. I have been diagnosed with seasonal depression and have never taken antidepressents; and refuse to. When I am depressed pot helps me to take my mind off what is causing my depression, but if I am high and continue to think about the depression I am still depressed! I don't believe that pot helps the depression, it diverts your attention away from it. You still need to deal with life and have to be aware of that fact! Pot needs to be respected and explored further for its positive attributes. If I didn't have pot I don't think I would alive today!

Pot isn't an addiction, its a life style for many. Say what you will but its true! Thanks


AL
said

Injecting WIN55,212-2 intracerebrally ensures that it actually gets to the brain in accurate doses. Scientists are trying to find ways to get lab animals to 'smoke up', but you can imagine how difficult it would be to make a dose-response curve based on this heh.. but yes synthetic THC is a good representation of the real stuff, just in a more consistent and measurable way. Make sense?


IAN
said

I agree with Tessa that there is strong evidence to show pot does not effects the lungs as cigarettes do. The problem with it is it will inhibit the ability to learn and absorb knowledge and therfore should not be used by the young who need to learn.


jd
said

Pot is also a great sleep-aid and helps reduce anxiety. Frequent users are very adept at controlling their dosage to get exactly what they need (through trial and error). The illegality of pot remains one of the great hypocrisies of our culture. Additionally, it's none of anyone elses business what I put into my body. Not the governments and certainly not the pious scolds among us.


KW
said

Re Medical Marihuana. We have a senior neighbour who has been smoking medical marihuana for years due to Parkinson's Disease. This lady has developed serious respiratory problems but refuses to give up smoking the medical marihuana for prescription pain medication. This lady gets taken to hospital by ambulance approx three times a month for respiratory distress. I can't help but wonder if it isn't the 'marihuana high' that is the attraction and not the pain relief?


Michelle
said

John - K was not implying that most marijuana users bake their weed. She was merely wondering about the uses of vapourizers and baking/cooking with it.

To K - there are vapourizers available to limit the effect on the lungs. I also know some people that prefer to bake with it because they enjoy it more and find it more effective. I would expect the results vary for everyone.

I have experience smoking for back pain (I am under 30) and I found it much more beneficial than the pain killers and muscle relaxants that my Dr preferred I use. I've also seen older friends with more severe injuries both on heavier drugs and self medicating and frankly, from the results I've seen I'd rather smoke.

And another point to make is that after a period of time I did not have to smoke as much because I was improving! How many drugs can accomplish that? And on the flip side, how many drugs do people develop a higher tolerance to and then have to move up to stronger drugs?

After some discussion with my Dr about my alternative methods she prescribed me the pill version (Cesamet). I took it once. I took it before bed, and woke up the next morning feeling like I was walking in a cloud (The effect lasted for approx. 12 hrs!) I will never take the pill form again. Although, I'm sure it works much better for others.

There are a lot of different benefits to smoking marijuana and it is a mistake for non-users to assume that it is a gateway drug (was definitely not the case with myself, or many others that I know.) Also, the negative image attached to marijuana use prevents the full positive effects of the drug to be further studied. As far as I'm concerned smoking a "joint" is far less dangerous than taking Oxycotin.




G
said

I agree with K. This is a report on synthetic THC, not naturally cannabis grown in the sun or hydroponically. Perhaps this is another failure at synthesis - like the synthetics that were prescribed for treatment a little more than 5 years ago. Those synthetics did nothing but cause headaches and provide false hope for treatment.

A study on synthetic THC cannot prove that natural THC is a trigger that worsens depression. Had the study stated that the "smoked up/filled a chamber with THC vapours, as K pointed out (which incidentally doesn't "burn" the plant and therefore doesn't fill the user's lungs with smoke and tar), and then expose a bunch of rats to it, perhaps the results would be the same, but the study didn't do that. Everyone knows that heresay is just that - heresay; and is not "evidence" of any kind.

This approach is too similar to comparing apples and geese for any results to be taken seriously.


Bee Row
said

Synthetic THC is not fake. It just means it was clinically produced rather than extracted from a plant. It is simply a pure form of THC, not another chemical designed to mimic THC.


sk
said

My experience with it is similar to the study - I smoked it for years as an antidepressant and it was effective until I started using it heavily. At that point my depression realy got noticably worse, so I quit and the depression has lessened to previous levels.


Venon
said

Tessa,
I am interested to learn the source of this recent information you write about. Perhaps you have a link or reference to share? I haven't researched the topic for studies but while in university I did have the pleasure of hearing a guest lecturer who works with people who have had mouth and neck surgery for cancer. She said that more than 95% of patients were smokers, presumably tobacco (although some people are both marijuana and tobacco smokers). And yet there are people that try to claim that tobacco and oral/neck cancer are not related! She ALSO said she was seeing more and more oral/neck cancer in marijuana-only smokers--some in their twenties. Your statement that "chronic users of marijuana display no signs" make me wonder about the sample size, subjects, age, period of use and how signs of illness were measured. Who/What is your source?


screaming monk
said

It is self evident that a psychotropic drug will have an effect on mood.

Any drug that is used everyday, will result in physiological changes, some perhaps permanent.

Though abusing pot will result in an undesirable 'state of mind', low daily doses given to people with some forms of depression, might in fact be medicinal, and ultimately beneficial.

I am sure some have intuitively recognized this for quite some time.

If one is mentally healthy, it is foolhardy to damage a good thing with any substance abuse.

Living without drugs is always the preferred course, unless of course, no other known remedy exists for a malady, be it mental or physical.




Paul
said

Couldn't this study equally show that THC just impairs the rat's learning abilities? A smart rat knows that it'll get out sooner if it doesn't bother to swim around.


Kimberlee
said

Several doctors prescribed anti-depressants for me over the years. I declined because I wasn't depressed. Its just that really hard things have happened and they just prescribed it to help me through it - but I didn't trust it. However, my husband and I have smoked MJ for 20 years together (since we were 18). We've done ok too. We own our own home on acreage, two nice cars, are parents to two great teenagers, my husband works for the fed. govt. for 17 years and I have a nice p/t job close to home. And YA we smoke POT. Maybe we're onto something here. We have great fun together and are successful. It really makes me ANGRY that we have to sneak around to buy it. Infuriating actually...because its better than any lab-made prescription drug. And yes I'm stoned now - could you tell?


Natasha
said

I have emailed the prof that did this study and I'm sure that my suspicions will be confirmed with reguards to "high" and "low" doses of THC.
Even chronic users of marijuana are only subjected to a low dose of THC. Literally, you would have to be hittin the bong all day for several days for the levels of THC in your body to reach this "high" dose level.
Studies on the effects of pot are too quickly jammed into the headlines, it is important to think critically for yourself when you read "news" (pot can make depressed people feel better, clearly) like this.


KW
said

Smoking marihuana damages the lung tissue as does smoking tobacco. Today's marihuana is 5-10 times more potent than marihuana in the 60's and is capable of damaging the lungs 5-10 times faster. New research shows significant mental health issues (personality disorders, bi-polar,schizorphernia to name a few). A marihuana sidebar for those who think marihuana is harmless. Was researching plants that were not hazardous to the family cat. Guess what popped up! Marihuana leaves are poisonous to cats.


sam tallman
said

Dear Teresa Knight,
I would suggest you consult science and solid western medical research: chronic users of marijuana do indeed show signs of cancer and damage to the lungs.

There is no way that inhaling a tar-like substance, plus smoke, does not damage lungs; tars and smoke DO damage lungs; it is not a matter of debate.


Des Emery
said

Tessa Knight - you can't defend the use of MJ in smoke. Nothing, set on fire and then inhaled, does the lungs any good, no matter how it makes you feel. It is not anti-cancer medication, but, like tobacco, slowly shuts down the lungs, smothering the chronic user to death. And like any drug, repeat drug, the body can get somewhat used to it, but it is never a 'good' thing.

And you totally mis-read the effects of the rat experiments. The drugged rats lose the memory of their previous rescue, and re-act in the same manner as they did the first time, instead of using their native intelligence to calmly wait for rescue.

Personally, as a cripple with the extra burden of a stroke, I do not find life so dis-heartening that I want to waste my time fogged out of touch with reality.


Karen
said

When our son was diagnosed with Crohnes Disease he started using pot to help with the pain. He was using it so much that he started to experience psychotic incidents and was diagnosed as schizophrenic. We didn't believe he was and after much deliberation he stopped using pot and has been able to get back his life and works full time in a very demanding job. It took almost four years before he was able to do this - in his case pot almost ruined his life.


Christian
said

K - How can it be fake THC? what do you think they just magically create it. They extract it from the plant as far as I know..
Anyone disagree?


Tessa Knight
said

John
You need to update your information on Marijuana. Information available as early as two years ago, possibly sooner, shows even chronic users of marijuana display no signs or cancer, emphysema, or damage to the bronchial tubes, etc.

On topic, If I was the rat and it was a second go in the tank, I'd quit sooner as well - whether I was on anti-depressants/depressants or not.


elizabeth
said

I do not know about MJ in pill form -- my doctor told me he had some, but they were $65 a pill!


John
said

K - please do not suggest that the majority of Marijuana users, even medicinal ones, are baking it into their brownies. Most smoke it, plain and simple and this will have the unfortunate effect of damaging respiratory function.


Allan M
said

I can see this making sense. I myself have taken anti-depressants for just over 5 years, and know from a bit of research that if you take too much of any anti-depressant, depression and anxiety can get a lot worse. If marijuana is an anti-depressant it would be no surprise that too much would just make things worse, as with other anti-depressants.

It was only after using anti-depressants that I began using marijuana from time to time, and I can vouch that it did not contribute to my depression. I was depressed before I tried weed, not of it. Ironically I can stop weed in a snap without any issues, but it will take months for me to get weened off of anti-depressants now that I no longer need them.

K
said

How about vaporizing it? Cooking with it? Try not to confuse marijuana with tobacco.


Jesse Otteman
said

But smoking marijuana, or anything similar for that matter, is not good for the lungs, even at small amounts. For medicinal purposes it would be better if marijuana were introduced in a pill form, maybe even in a syrup form. Inhaling it, even on a semi-regular basis, damages the lung tissue.



K
said

Just wondering how creditable a marijuana study is using synthetic THC? Are you not just performing a study on the synthetic. How close is this to real THC? Why not just use THC? I cannot imagine them creating false results with fake THC. Curious.


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