Study: cannabis a double-edged sword

October 23, 2007

A new neurobiological study has found that a synthetic form of THC, the active ingredient in cannabis, is an effective anti-depressant at low doses. However, at higher doses, the effect reverses itself and can actually worsen depression and other psychiatric conditions like psychosis.

The study, published in the October 24 issue of The Journal of Neuroscience, was led by Dr. Gabriella Gobbi of McGill University and Le Centre de Recherche Fernand Seguin of Hôpital Louis-H. Lafontaine, affiliated with l'Université de Montréal. First author is Dr. Gobbi's McGill PhD student Francis Bambico, along with Noam Katz and the late Dr. Guy Debonnel of McGill's Department of Psychiatry.

It has been known for many years that depletion of the neurotransmitter serotonin in the brain leads to depression, so SSRI-class anti-depressants like Prozac and Celexa work by enhancing the available concentration of serotonin in the brain. However, this study offers the first evidence that cannabis can also increase serotonin, at least at lower doses.

Laboratory animals were injected with the synthetic cannabinoid WIN55,212-2 and then tested with the Forced Swim test – a test to measure “depression” in animals; the researchers observed an antidepressant effect of cannabinoids paralleled by an increased activity in the neurons that produce serotonin. However, increasing the cannabinoid dose beyond a set point completely undid the benefits, said Dr. Gobbi.

"Low doses had a potent anti-depressant effect, but when we increased the dose, the serotonin in the rats' brains actually dropped below the level of those in the control group. So we actually demonstrated a double effect: At low doses it increases serotonin, but at higher doses the effect is devastating, completely reversed."

The anti-depressant and intoxicating 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 high stress or pain, explained Dr. Gobbi. They interact with the brain through structures called cannabinoid CB1 receptors. This study demonstrates for the first time that these receptors have a direct effect on the cells producing serotonin, which is a neurotransmitter that regulates the mood.

Dr. Gobbi and her colleagues were prompted to explore cannabis' potential as an anti-depressant through anecdotal clinical evidence, she said. "As a psychiatrist, I noticed that several of my patients suffering from depression used to smoke cannabis. 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. But there were no laboratory studies demonstrating the anti-depressant mechanism of action of cannabis."

Because controlling the dosage of natural cannabis is difficult – particularly when it is smoked in the form of marijuana joints – there are perils associated with using it directly as an anti-depressant.

"Excessive cannabis use in people with depression poses high risk of psychosis," said Dr. Gobbi. 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.

"We know that it's entirely possible to produce drugs which will enhance endo-cannabinoids for the treatment of pain, depression and anxiety," she said.

Source: McGill University

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3.7 / 5 (3) Nov 05, 2007
Oh I do love reading about the perils of Cannabis from people who have no idea what they're talking about. Such behaviour is easily the most prevalent form of Cannabis Psychosis.

This particular passage was the first to jar me awake:

"Because controlling the dosage of natural cannabis is difficult %u2013 particularly when it is smoked in the form of marijuana joints"

One of the main advantages - quoted by numerous medical studies (look up "self titration" and cannabis) [eg ] - of smoking is that the user can fine tune their doses much more easily; so where did that claim come from?

Then, of course, we go on to rabbit the party line:
"Excessive cannabis use in people with depression poses high risk of psychosis"

If true, where's the evidence? The pharmaceutical psychosis risk that we know about has two risk factors - COMT gene variants and excessive adolescent use.

There is no correlation that I'm aware of which links depression to cannabis psychosis. And if there were, then the prevalence of cannabis psychosis would be vastly greater than it is.

Moreover, experienced cannabis consumers know that the weed often amplifies your current emotional state. If you're up, it can take you higher. If you're down it can take you lower - so most have the sense not to use it when they're down.

As things stand, the risk of psychosis induced by the use of cannabis is roughly on a par with the risk of psychosis induced by being born left handed. Though you may have noticed there's a lot less fuss made about that risk.

"The study leader, Dr Clyde Francks, said: People really should not be concerned by this result. There are many factors which make individuals more likely to develop schizophrenia and the vast majority of left-handers will never develop a problem"

That statement is equally valid for cannabis users but much more difficult to find...
not rated yet Feb 13, 2008
>Laboratory animals were injected with the synthetic cannabinoid WIN55,212-2 and then tested with the Forced Swim test %u2013 a test to measure %u201Cdepression%u201D in animals;

Lol, funny how they project it from rats to people. And btw If i were really high on MJ and someone dumped me into a pool and forced to swim i would be pretty depressed also OTOH left to my own devices i would be pretty euforic. So bottom line is its most likely not the drug that makes one depressed its the forced activity which is not compatible with drug induced mindset.

Besides that simple test of rats "depression" is more then likely irrelevant when animal is high.
not rated yet Sep 08, 2008
I have been extremely suicidal for a few years now - I have tried all the conventional anti-depressants and none of them work for me however I have found very low dose cannabis to be completely and immediately effective.
My dose is less than one lungful of smoke - I think that one of the problems with modern cannabis use is that it stems from a tradition of large quantity usage because of traditionally low strength herb - now the artificial sansemilla herb is much more potent but people have not adapted their usage. It is like having a tradition of drinking beer by the pint - then moving onto scotch but still drinking it by the pint.
I also suspect melatonin levels would be significantly effected.
not rated yet Feb 21, 2009
sooo ummmmmm ,eat a small part of a cookie...
not rated yet Feb 21, 2009
djama, marijuana is used to help combat sleeping disorders. I can't say for sure, but marijuana makes the brain more sensitive to stimuli and so malatonin production would get stimulated a lot more and faster when you close your eyes when "high". I don't think it would affect the general level. Maybe if your serotonin level is higher from the joint, more of it will get converted. It would be interesting too find out.
not rated yet Feb 21, 2009
Marijuana is not higher potency today than it was was back then genetically. However, a lot of growers use hydroponics and give the plant chemical nutrients and mixtures to enhace the bud size and strength.

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