Tag Archives: Dunedin study

Should your teen use marihuana?

Is marihuana bad for teen brain development?  The short answer is no one knows.  The long answer can be found here — https://www.pnas.org/content/117/1/7.  It’s probably the best thing out there on the question [ Proc. Natl. Acad. Sci. vol. 117 pp. 7 – 11 ’20 ].  The article basically says we don’t know, but lays out the cons (of which there are many) and the pros (of which there are equally many).

If you’re not a doc, reading the article with its conflicting arguments harmful vs. nonharmful, and then deciding what to tell your kid is very close to what practicing medicine is like.  Important decisions are to be made, based on very conflicting data, and yet the decisions can’t be put off.  Rote memory is of no use and it’s time to think and think hard.

Assuming you don’t have a PNAS subscription, or you can’t follow the link here are a few points the article makes.

It starts off with work on rats. “Tseng, based at the University of Illinois in Chicago, investigates how rats respond to THC (tetrahydrocannabinol), the main psychoactive ingredient in cannabis. He’s found that exposure to THC or similar molecules during a specific window of adolescence delays maturation of the prefrontal cortex (PFC), a region involved in complex behaviors and decision making”

Pretty impressive, but not if you’ve spent decades watching various treatments for stroke which worked in rodents crash and burn when applied to people (there are at least 50 such studies).  What separates us from rodents physically (if not morally) is our brains.  Animal studies, with all their defects of applicability to man is one of the two approaches we have — no one is going to randomize a bunch of 13 year olds to receive marihuana or not and watch what happens.

== Addendum 9 Jan ’20 — too good to pass up — Science vol. 367 pp. 83 – 87  ’20 shows just how different we are from rodents.  In addition to our cerebral cortex being 3 times thicker, human cortical neurons show something not found in any other mammal — These are graded action potentials in apical dendrites, important because they allow single neurons to calculate XORs (either a or b but not both and not none), something previously only thought possible for neuron ensembles.  XORs are important in Boolean algebra, hence in computation. ==

The other approach is observational studies on people which have led us down the garden path many times– see the disaster the women’s health study avoided here — https://luysii.wordpress.com/2016/08/23/the-plural-of-anecdote-is-not-data-in-medicine-at-least/.

45,000 Swedish military conscripts examined at conscription (age 19) and 15 years later.  Those who had used cannabis over 50 times before conscription were 6 times as likely to be diagnosed with schizophrenia.

Against that, is the fact that cannabis use has exploded since the 60s but schizophrenia has not (remaining at a very unfortunate 1% of the population).

In the Dunedin study, cannabis use by 15 was associated with a fourfold risk of schizophrenia at 26 (but not if they started using cannabis after 16 years of age. — https://en.wikipedia.org/wiki/Dunedin_Multidisciplinary_Health_and_Development_Study.

You can take the position that all drugs we use to alter mental state (coffee, cigarettes, booze, marihuana, cocaine, heroin) are medicating underly conditions which we don’t like.  Perhaps marihuana use is just a marker for people susceptible to schizophrenia.  Mol. Psychiat. vol. 19 pp. 1201 – 1204 ’14 — 2,000 healthy adults were studied looking a genome variants known to increase the risk of schizophrenia.  Those with high risk variants were ‘more likely’ to use marihuana — not having read the actual paper i don’t know how much more.

There is a lot more in the article about the effects of cannabis on cognition and cognitive development — the authors note that ‘they have not replicated well’.  You’ll have to read the text (which you can get by following the link) for this.

One hope for the future is the ABCD study (Adolescent Brain Cognitive Development Study) — aka the ABCD study.  By 2018 it reached its goal of  accumulating 10,000 kids between the ages of 9 and 10.  They will be followed for a decade (probably longer if the results are interesting).  It’s the hope for the future — but that doesn’t tell you what to say to your kid now.  Read the article, use your best judgement and welcome to the world of the physician.

What is sad, is how little the field has advanced, since I wrote the (rather technical) post on marihuana in 2014.

Here it is below

Why marihuana scares me

There’s an editorial in the current Science concerning how very little we know about the effects of marihuana on the developing adolescent brain [ Science vol. 344 p. 557 ’14 ]. We know all sorts of wonderful neuropharmacology and neurophysiology about delta-9 tetrahydrocannabinol (d9-THC) — http://en.wikipedia.org/wiki/Tetrahydrocannabinol The point of the authors (the current head of the Amnerican Psychiatric Association, and the first director of the National (US) Institute of Drug Abuse), is that there are no significant studies of what happens to adolescent humans (as opposed to rodents) taking the stuff.

Marihuana would the first mind-alteraing substance NOT to have serious side effects in a subpopulation of people using the drug — or just about any drug in medical use for that matter.

Any organic chemist looking at the structure of d9-THC (see the link) has to be impressed with what a lipid it is — 21 carbons, only 1 hydroxyl group, and an ether moiety. Everything else is hydrogen. Like most neuroactive drugs produced by plants, it is quite potent. A joint has only 9 milliGrams, and smoking undoubtedly destroys some of it. Consider alcohol, another lipid soluble drug. A 12 ounce beer with 3.2% alcohol content has 12 * 28.3 *.032 10.8 grams of alcohol — molecular mass 62 grams — so the dose is 11/62 moles. To get drunk you need more than one beer. Compare that to a dose of .009/300 moles of d9-THC.

As we’ve found out — d9-THC is so potent because it binds to receptors for it. Unlike ethanol which can be a product of intermediary metabolism, there aren’t enzymes specifically devoted to breaking down d9-THC. In contrast, fatty acid amide hydrolase (FAAH) is devoted to breaking down anandamide, one of the endogenous compounds d9-THC is mimicking.

What really concerns me about this class of drugs, is how long they must hang around. Teaching neuropharmacology in the 70s and 80s was great fun. Every year a new receptor for neurotransmitters seemed to be found. In some cases mind benders bound to them (e.g. LSD and a serotonin receptor). In other cases the endogenous transmitters being mimicked by a plant substance were found (the endogenous opiates and their receptors). Years passed, but the receptor for d9-thc wasn’t found. The reason it wasn’t is exactly why I’m scared of the drug.

How were the various receptors for mind benders found? You throw a radioactively labelled drug (say morphine) at a brain homogenate, and purify what it is binding to. That’s how the opiate receptors etc. etc. were found. Why did it take so long to find the cannabinoid receptors? Because they bind strongly to all the fats in the brain being so incredibly lipid soluble. So the vast majority of stuff bound wasn’t protein at all, but fat. The brain has the highest percentage of fat of any organ in the body — 60%, unless you considered dispersed fatty tissue an organ (which it actually is from an endocrine point of view).

This has to mean that the stuff hangs around for a long time, without any specific enzymes to clear it.

It’s obvious to all that cognitive capacity changes from childhood to adult life. All sorts of studies with large numbers of people have done serial MRIs children and adolescents as the develop and age. Here are a few references to get you started [ Neuron vol. 72 pp. 873 – 884, 11, Proc. Natl. Acad. Sci. vol. 107 pp. 16988 – 16993 ’10, vol. 111 pp. 6774 -= 6779 ’14 ]. If you don’t know the answer, think about the change thickness of the cerebral cortex from age 9 to 20. Surprisingly, it get thinner, not thicker. The effect happens later in the association areas thought to be important in higher cognitive function, than the primary motor or sensory areas. Paradoxical isn’t it? Based on animal work this is thought to be due pruning of synapses.

So throw a long-lasting retrograde neurotransmitter mimic like d9-THC at the dynamically changing adolescent brain and hope for the best. That’s what the cited editorialists are concerned about. We simply don’t know and we should.

Having been in Cambridge when Leary was just getting started in the early 60’s, I must say that the idea of tune in turn on and drop out never appealed to me. Most of the heavy marihuana users I’ve known (and treated for other things) were happy, but rather vague and frankly rather dull.

Unfortunately as a neurologist, I had to evaluate physician colleagues who got in trouble with drugs (mostly with alcohol). One very intelligent polydrug user MD, put it to me this way — “The problem is that you like reality, and I don’t”.