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Re: Zoloft & Marijuana

Posted by Robin on May 11, 1999, at 0:51:20

In reply to Zoloft & Marijuana, posted by Joel on July 29, 1998, at 17:45:18

> I am a 27 year old male who is on 50mg of Zoloft per day. I also smoke
> >marijuana daily (once a day, small amounts). I am scared to ask my current
> >Dr. the effects this could have for insurance reasons. The only info I have found
> >said interaction was highly variable. Can anyone take a moment and elaborate
> >further on this? I have noticed no effect from the combination, and the
> >Zoloft seems to be working for the anxiety, or at least reduced it. Any
> >info would be greatly appreciated.
> >
> >A sincere thanks for your valuable time,
> >
> >Joel (North Carolina)

Dear Joel:

I read with great interest your query regarding the possible interactions between marijuana and the anti- depressant medication "Zoloft" which you are currently taking. Like all comments which you will read in this forum, those which I have outlined below should not be construed as being scientifically conclusive. Therefore I would urge you to check out what follows, with a competent medical authority.

Some years ago, I was prescribed an anti- depressant medication (an MAO compound) . Since I had failed to obtain any symptomatic relief from this drug after being on it for several months, I decided to experiment with marijuana in order to see if this would enhance the efficacy of the antidepressant.

Significantly, after smoking quite a bit of pot, I discovered that I could obtain complete remission from my depression, albeit for short periods of time (3-4 hours). Unfortunately, as I soon learned, I could not sustain this result with any consistency. After some reflection, I concluded this could be due to any number of reasons: i.e.. varying levels of THC in the marijuana , the amount of pot which I ingested &/ or metabolized on each occasion, etc. Thus since I could not achieve a sustained result, and given the fact that I was taking unknown risks by combining two psychoactive agents, I eventually abandoned this therapeutic avenue.

However over the ensuing years, with each successive physician whom I consulted, I raised the question as to why the marijuana had had such a salutary effect with me. Not surprisingly, given the lack of scientific information available to the average practitioner on such matters, I received no satisfactory explainations. In point of fact, most physicians to whom I talked about this matter, simply indicated that the remedial effect which I had experienced with pot, was most likely due to a psychological reaction ( i.e. it made me feel more relaxed which inturn induced symptomatic relief from the depression ). Needless to say I found this explaination somewhat wanting.

Last December, I stumbled upon an article on depression which provided an apparent explaination of this phenomena. You can find this article on the internet at (I will return to this article in a moment.)

To understand the significance of what I came across, you have to know a bit neurobiology & neurobiochemistry. You may very well be up to speed on this but on the off chance that you are not, let me briefly outline a bit of the scientific background on depression that you will need to be familiar with . What follows is taken from an article in the magazine Scientific American which you can read in full on the internet at

Building upon investigations done in the late 60's and early 70's, researchers have shown that unmedicated depressed patients have a dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis - the system in the brain that manages the body's response to stress. "When a threat to physical or psychological well being is detected, the hypothalamus amplifies the production of corticotrophin-releasing factor (CRF), which induces the pituitary to secrete ACTH . ACTH then instructs the adrenal gland atop each kidney to release cortisol... Together all of these changes .... (serve to produce a) chronic activation of the HPA axis (and) ... lay the ground for ...depression. (In particuliar) ...aberrations in CRF-producing neurons of the hypothalamus... bear most of the responsibility for HPA axis hyperactivity and the emergence of depressive symptoms... This magnification of CRF levels is reduced by treatment with antidepressants ..."

These findings have recently prompted drug companies to begin looking for agents that will effectively block the action of CRF. Diminishing CRF activity in the HPA axis will therefore (theoretically) produce an antidepressant effect.

The first article which I mentioned above ( at ) , contains the following citation. " Experiments with stoned rats suggest ( that marijuana) reduces the amount of corticotrophin-releasing factor in the brain area known as the amygdala. " Since the amygdala lies in close proximity to the hypothalamus , it stands to reason that marijuana might also produce an antidepressant effect by similiarly blocking the production of CRF in this area of the brain as well.

This might explain why you feel better when you smoke pot.

However even if this is substantiated by further research in humans, there are two problems with using marijuana as an antidepressant.

First and perhaps most obviously, it is difficult to function coherently when one is "stoned "

Secondly, there is a rebound surge of CRF production upon ceasing the use of cannabis. This may be associated with increased vulnerability to stress and a withdrawal-reaction.

Where does this leave you Joel ?

If you do benefit from taking pot in conjunction with the particuliar antidepressant that you are on, you may wish to try the new CRF antagonist agents that are now under development. These will probably come to trial in another year or so and if successful , will be available over the counter in another 3-5 years .

In the meantime, if you don't wish to inhale, you might want to investigate the cannabis analog Nabalone that was developed several years ago by the Eli Lilly Co. It is commonly prescribed to cancer patients to alleviate symptoms of nausea and evidently does not produce the euphoria that is common to marijuana. However I would strongly urge you seek the counsel of your attending physician in assessing whether or not this is a viable option for you . I honestly cannot advise you about this one way or the other since I completely lack any medical knowledge.

Hope the preceding has been of some help to you.




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