More on Cannabinoids

Given recent discussions on this blog on the neuroscience of marijuana, I thought this brand new paper on stress and the cannabinoid receptor was extremely interesting. The Israeli scientists demonstrated that microinjecting an agonist of the CB1 receptor (a primary binding site of THC, the active ingredient in pot) significantly reduced the elevation of stress hormones in response to scary stressors. They researchers argue that their evidence "supports a wide therapeutic application for cannabinoids in the treatment of conditions associated with the inappropriate retention of aversive memories and stress-related disorders." Like I said before, pot just might be the next Prozac. Are you listening Eli Lilly?

On a side note, I'd love to see some further research into one of the main unintended side-effects of pot: paranoia. Why does a drug that ordinarily erases anxiety sometimes lead to the opposite mental state? This is part of larger pattern, of course, in which many psychoactive drugs tend to trigger the precise symptom that they're trying to cure. So Prozac increases the risk of suicide, anti-psychotics can cause psychosis, etc. Just another reminder that the brain is a profound mystery, dense with redundancies and feedback loops.

Thanks for the tip Tanya!

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There's a growing body of research that indicates that THC alone produces paranoia, but cannabidiol (another major constituent of marijuana) somehow blocks the anxiety. See Zuardi et al., 1982 or, perhaps more dramatically, this video of a BBC reporter first injected with THC + cannabidiol and later with THC alone. There's also some evidence that cannabidiol alone may be an effective antipsychotic.

Paranoia: perhaps a consequence of awareness of the fact that being high implies illegal possession of a controlled substance and therefore risk of imprisonment? Until this factor is removed I do not think it productive to spend time looking for neurological causes.

By Gray Gaffer (not verified) on 10 Sep 2009 #permalink

I'm with the Gray Gaffer. (Great name, by the way, Gaffer). Sipping Jack Daniels never makes me paranoid because I'm not expecting the cops to kick in the door.

I see the anxiolytic properties of cannabinoids as direct mechanistic explanation for amotivational syndrome, another significant effect marijuana use. Without anxiety to drive one towards action, pot-heads often lead lives with a complacency for how things are. I'm all for relieving pathological anxiety and people using marijuana recreationally, but I dare say it's immoral for someone to be a pot-head and to let that significantly interfere with their capacity to effect a positive change on the human condition.

Brandon: wow... so there is a moral imperative that everyone must effect a positive change on the human condition?

No thanks. The moral imperative (if there is one) is that one live in such a manner to not effect a negative in the lives that their life touches.

Gray, plenty of folks get paranoid trips up here in Canada, where possessing pot is treated as a misdemeanour or more often simply ignored. I doubt the possibility of police intrusion is a relevant confounder.

Jonah, as far as antipsychotics causing psychosis: WTF? I was with you right up to that statement.

By Epictetus (not verified) on 10 Sep 2009 #permalink

Paranoia question reference guilt / misdemeanor should be deciphered.

Interesting that many might have said I had a 'moral streak' yet I never felt any paranoia during my mj experiences. Perhaps it was my 'personal research' bias that alleviated any guilt. Incidentally, the data were exciting, reproducible, but apparently not transferable to others. How unfortunate!

By Elizabeth (not verified) on 11 Sep 2009 #permalink

I don't pretend to categorize this as a scientific explanation, but given my own experiences with pot, I find that the state of being high generally causes a large magnification in both the intensity and the perceived significance of whatever happens to be holding my attention at the moment. So doritos suddenly taste amazing, cool music is that much better, a crappy movie is actually pretty fun to watch, and so on.

The flip side of this is that a stray negative thought or something unexpected or potentially frightening can sort of take over. What might normally not be a big deal can get away from me and suddenly become a mini crisis. I've also observed, informally just among myself and other people I know who smoke or have smoked pot, that problems with paranoia tends to happen more often when people are relatively inexperienced with the drug and unaccustomed to feeling high or more worried about it's effects. On that same note, I've found that after realizing this I can control issues of paranoia pretty well by choosing to think something different or positive if I feel myself becoming paranoid or afraid. Same for avoiding environments that are antagonistic or stressful, which is why I generally don't like crowded public places while stoned. Also, perhaps this is obvious, but smoking less makes this effect less intense.

I'd be curious if this is related to the anti-anxiety properties somehow or a separate effect. Perhaps there is mechanism the brain somehow uses to regulate attention and significance of stimuli, that if it gets 'broken' somehow can cause things like anxiety and PTSD issues? Maybe one of the effects of pot is to help such a mechanism get unstuck on particular stressful or traumatic events.

Just my idle speculation as a non-neuroscientist. :)

@6: Even as a Misdemeanor Canada will refuse you entry, for life, even if the charges were dropped. All the Canadian border guards care about is "have you ever been arrested". If 'Yes" it's "Go Home, we don't want your kind here". Just the possibility of a confrontation with the cops, however mild or whether or not they may just ignore it, doesn't matter, you are still at their whim. They are not bound to ignore it, and a misdemeanor is still a court appearance, a black mark on your record, and many jobs and countries close their doors to you. So paranoia is still justified as a conscious concern (depending on situation). And when I was much younger, my home country (UK) was jailing folks for up to 25 years for possession of a single joint. One guy went to jail for 20 for a single microscopic bit of pollen.

It's the possible outcomes, not the likely outcomes, that matter.

By Gray Gaffer (not verified) on 11 Sep 2009 #permalink

My theory: Cannabis high is similar to mania -- euphoria and racing thoughts. Mania sometimes leads to psychosis.

By Eric Gisin (not verified) on 12 Sep 2009 #permalink

I'm not sure there is any contradiction. Paranoia is a maladaptive cognitive response to distorted perception; The anxiety is secondary. You can be paranoid without anxiety if you believe you can identify and control the perceived threat, or if you are a sociopath.

I always found it strange that pot is used to help people cope with chemo-induced nausea. When I was a teenager, I developed an aversion to it, because it induced seasickness in me. Different brains, different results.

Prohibition is unfortunate and misguided public policy, especially when dangerous substances like whisky are legal, and relatively benign ones like pot are not. I'm glad this discussion is going on.

As stated before we may be looking at the wrong parts of pot where THC may be the paranoia trigger.

Its also very important to understand human beings have different reactions to various chemicals, and to assume people will process things the same way is the first mistake. You see this now with diets and lifestyle related to autism.

I can attest to the use of cannabis as a treatment for a stress-related eating disorder in one case (mine, obviously). Yes, I know this sounds like the punchline of a joke, but I'm quite serious. In high school and college I'd fast and restrict calories, over-exercize, see "fat" where no one else could despite having a BMI under 21. Then I went abroad and started smoking hash on a semi-regular basis. I found that although it did sometimes, but not always, transiently increase my appetite, it had the effect of calming my weight/food obsessive thoughts and behaviours for several days after the high was a distant memory. Too much hash or bud from a water bong sometimes made me too stoned, or freaked out, but a mellow buzz at intervals for a period of two years was enough to help me turn the corner from very disordered eating to only occasional bouts of disordered eating (with known stress-related triggers). I know this is anecdotal evidence, but I would seriously advocate treating people suffering from anorexia, bulemia, and NOS EDs with small doses of cannabinoids.

It seems to me that the brain is hard-wired to teach us desirable behavior by positive and negative reinforcers. It reinforces desirable behavior (eating, drinking, exercising, sex) by releasing neurotransmitters that make us feel good when we participate on those behaviors. And we feel pain that doesn't stop until we desist, when we behave in an undesirable way, like putting our finger in a flame. And it seems to me that the brain is sending more subtle messages when we feel anxiety, depression and so on. Rather than investigating the behaviors that might be responsible, we take a pill to make the message go away. While pills may provide relief in the short term, they should not be a final solution. Recall that Mother Nature bats last.

THC vs CBN debate I think.
In pot there's THC ... the rebnowned active ingredient ... and it's at it's highest in hydropnically grown, harvested early ganja. The menace of 'skunk' as it's been described.

Now in Amsterdam, where it's all grown according to organic principles (I'm not a fan of organic, but it has some great by-products in this case) - in soil, and picked when perfectly ripe.

As piot ripens THC begins to break down into CBN ... (like starches turn to sugars in ripening fruit I guess).

THC = paranoia and upishness - flakeyness really.

CBN is the in-built antidote ... it calms, stops the THC working as well

I'm not a scientist by trade ... I'm an enthusiastic amateur ... and a long-term smoker and researcher of said hobby in my youth, but I think that a good quality product would reduce this spate of kids (also not a good idea - brain's still developing - in fact in teenagers at a vastly increased rate) going loopy and catatonic :)

Just a thouhgt ... who knows ... it's wacky and zany ;P but it might just work :)