Friday, January 18, 2008

High and Low Highs

Turns out that there really may be a difference between the heavy pot smokers and casual use and between the effects of pot the drug warriors scare us with and the effects on most users. Here’s from the research abstract:

There is a general consensus that the effects of cannabinoid agonists on anxiety seem to be biphasic, with low doses being anxiolytic and high doses ineffective or possibly anxiogenic. Besides the behavioural effects of cannabinoids on anxiety, very few papers have dealt with the neuroanatomical sites of these effects. We investigated the effect on rat anxiety behavior of local administration of THC in the prefrontal cortex, basolateral amygdala and ventral hippocampus, brain regions belonging to the emotional circuit and containing high levels of CB1 receptors. THC microinjected at low doses in the prefrontal cortex (10 μg) and ventral hippocampus (5 μg) induced in rats an anxiolytic-like response tested in the elevated plus-maze, whilst higher doses lost the anxiolytic effect and even seemed to switch into an anxiogenic profile. Low THC doses (1 μg) in the basolateral amygdala produced an anxiogenic-like response whereas higher doses were ineffective. All these effects were CB1-dependent and closely linked to modulation of CREB activation. Specifically, THC anxiolytic activity in the prefrontal cortex and ventral hippocampus was paralleled by an increase in CREB activation, whilst THC anxiogenic response in the basolateral amygdala was paralleled by a decrease in CREB activation. Our results suggest that while a mild activation of CB1 receptors in the prefrontal cortex and ventral hippocampus attenuates anxiety, a slight CB1 receptor stimulation in the amygdala results in an anxiogenic-like response. The molecular underpinnings of these effects involve a direct stimulation of CB1 receptors ending in pCREB modulation and/or a possible alteration in the fine tuning of local neuromodulator release.

Uh . . . huh?

From Frontal Cortex:

In other words, a good high works in the prefrontal cortex and ventral hippocampus while a bad high turns on the amygdala. As most pot smokers eventually discover, there is a fine pharmacological line between comic relaxation and vague paranoia.

So, does this mean that “gateway” drug thing depends on the dosage? Shouldn’t people be told that? How is this different from the use of alcohol in moderation and in abuse and why doesn’t that get punished the same way pot users do? Enough questions? You think so? Can I go on with this forever???? . . . .

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