Should pregnant women smoke pot?

Well, maybe this is why college board scores have declined so much in recent decades that they’ve been normed upwards. Given sequential MRI studies on brain changes throughout adolescence (with more to come), we know that it is a time of synapse elimination. (this will be the subject of another post). We also know that endocannabinoids, the stuff in the brain that marihuana is mimicking, are retrograde messengers there, setting synaptic tone for information transmission between neurons.

But there’s something far scarier in a paper that just came out [ Proc. Natl. Acad. Sci. vol. 112 pp. 3415 – 3420 ’15 ]. Hedgehog is a protein so named because its absence in fruitflies (Drosophila) causes excessive bristles to form, making them look like hedgehogs. This gives you a clue that Hedgehog signaling is crucial in embryonic development. A huge amount is known about it with more being discovered all the time — for far more details than I can provide see http://en.wikipedia.org/wiki/Hedgehog_signaling_pathway.

Unsurprisingly, embryonic development of the brain involves hedgehog, e,g, [ Neuron vol. 39 pp. 937 – 950 ’03 ] Hedgehog (Shh) signaling is essential for the establishment of the ventral pattern along the whole neuraxis (including the telencephalon). It plays a mitogenic role in the expansion of granule cell precursors during CNS development. This work shows that absence of Shh decreases the number of neural progenitors in the postnatal subventricular zone and hippocampus. Similarly conditional inactivation of smoothened results in the formation of fewer neurospheres from progenitors in the subventricular zone. Stimulation of the hedgehog pathway in the mature brain results in elevated proliferation in telencephalic progenitors. It’s a lot of unfamiliar jargon, but you get the idea.

Of interest is the fact that the protein is extensively covalently modified by lipids (cholesterol at the carboxy terminal end and palmitic acid at the amino terminal end. These allow hedgehog to bind to its receptor (smoothened). It stands to reason that other lipids might block this interaction. The PNAS work shows this is exactly the case (in Drosophila at least). One or more lipids present in Drosophila lipoprotein particles are needed in vivo to keep Hedgehog signaling turned off in wing discs (when hedgehog ligand isn’t around). The lipids destabilize Smoothtened. This work identifies endocannabinoids as the inhibitory lipids from extracts of human very low density lipoprotein (VLDL).

It certainly is a valid reason for women not to smoke pot while pregnant. The other problem with the endocannabinoids and exocannabinoids (e.g. delta 9 tetrahydrocannabinol), is that they are so lipid soluble they stick around for a long time — see https://luysii.wordpress.com/2014/05/13/why-marihuana-scares-me/

It is amusing to see regulatory agencies wrestling with ‘medical marihuana’ when it never would have gotten through the FDA given the few solid studies we have in man.

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Comments

  • M Simon  On March 25, 2015 at 9:32 pm

    OTOH we have lots of mice studies and copious anecdotes about the anti-cancer properties of cannabis. Not to mention CBDs and certain types of epilepsy. And the effects on diabetes type II. And whole rafts of other diseases. Alzheimer’s and MS just to name two.

    You might want to look up “dr. william courtney brain tumor”. A very interesting anecdote.

    If you really cared about human health and pregnant women a ban on alcohol would make more sense. FAS is well known. By most people.

    And the brain study on the bad effects of cannabis on adolescents? When it was corrected for alcohol the effect went away. We are going after the wrong dangerous drug.

    But as you well know a second attempt to ban alcohol would get laughed away. The same will be true one day of cannabis.

    BTW Raphael Mechoulam is a great proponent of cannabis as medicine. He rather dislikes the fact that proper assays are not being done for the medical aspects. But that is in part due to the black market nature of the current situation.

  • luysii  On March 26, 2015 at 3:42 am

    The plural of anecdote is not data. While the endocannabinoid work is purely theoretical on an organism far removed from us, cyclopamine is worth your attention http://en.wikipedia.org/wiki/Cyclopamine, as the mechanism is well worked out (interference with Hedgehog signaling) and the result isn’t pretty.

    Thanks for commenting

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