Thursday, August 2, 2012


For all that I have a jabbery twitter account and like putting filters over my crap pictures for posting on instagram, I'm not exactly the kind of person that when you meet me for the first time, I'll say, "HEY, HAVE YOU SEEN MY BLOG??"

In fact, many of my friends and patients don't even know I have a blog.  It's sort of a niche audience.  But as the years go by and the archives build, more and more I will talk to a colleague or therapist who might refer to me, or even someone at the gym, and they will say, "Oh, by the way, I saw your blog…"  

The colleagues are especially exciting.  In the past few months I've been invited to a few more journal clubs and Grand Rounds to speak to more psychiatrists, neurologists, and other head-interested professionals.  Some of these folks might even have a research budget.  I really love these opportunities, because when it comes down to it, Evolutionary Psychiatry is not about the paleo diet.  It's about the pathology of mental illness and conceiving our brains as connected to our bodies and guts and environment.  It's about how physical and mental health are derived from our genes and the protoplasm of the world around us.  It's about simple interventions and the complex ways in which they influence our nerves and hormones and flesh.

It's a niche audience, but I feel Evolutionary Psychiatry deserves to be mainstream medicine.  It's about asking questions in a common sense fashion, and approaching disease with multi-pronged, inflammation-reducing and neurotransmitter-savvy and sensible solutions.  It's about acknowledging the wisdom of the past generations and translating the therapies and traditions into real results.  Mostly it is about asking the questions in a way that will generate the answers we need for the science to be useful.

My daughter asked me if the iPhone knew everything.  I said, a vast amount, no doubt, if you ask the question just the right way.  She will never remember an early life without Siri.

I didn't plan on blogging today, but in my mailbox arrived the brand spanking new fresh edition of the Green Journal, and two of the articles just SING evolutionary psychiatry.  So here I am again.

A Silent Film: Danny Dakota and the Wishing Well (reminds me of those angsty John Hughes movies from the 80s, before he started doing movies about John Travolta and babies)

The first article is a double-blind placebo controlled trial of NAC in cannabis-dependent adolescents (1).  I know there is a bit of a link between paleophiles, libertarians, real food hippies, and weed, but I've never been a big fan.  Mostly because I'm often confronted with parents and older adolescents who struggle with psychosis and/or lack of motivation and crippling anxiety who smoke pot ALL THE TIME.  Not to mention the older folks who come in after decades of daily heavy use and can barely finish a sentence.  I've covered it before here and here.  Weed has some interesting properties, no doubt, but I've seen it to be more the fountain of rotten brain, agoraphobia, and dementia than the fountain of creativity and youth.  My sample is not randomized, and I have no doubt of that.  But roll the dice and take your chances, as they say.

ERGO, I think finding ways to get adolescents to smoke less pot might be a good thing.  And in the linked paper, it is noted that 25% of high school students use pot, 7% on a daily basis.  Besides standard psychosocial therapies, there's not much out there to help adolescents quit the dependency.  Could a pill help?

NAC, as we know, is particularly exciting in psychiatric disorders because it targets glutamate and antioxidants in a novel way.  There's no prescription pharmaceudical with the research data or similar mechanism.  In animal models, self-administering addictive drugs down-regulates the cysteine-glutamate exchanger in the nucleus accumbens.  NAC upregulates this exchanger, reducing the reinforcement of drug-seeking.

The authors of the study did a promising open-label pilot trial and then organized a larger randomized controlled trial.  Cannabid-dependent adolescents (13-21) who desired some help and met other exclusionary criteria were randomized to placebo or 1200mg NAC daily for 8 weeks.  All participants received cessation counseling at every research visit.  Cannabis use was determined by urine sample (which will be positive for about a month with moderate cannabis use, depending on body habitus).

In the NAC group, 40.9% of the cannabis tests were negative (assuming all missed urine tests were positive).  In the placebo group, 27.2% were negative, a statistically signficant difference.   Participants who had made the decision to quit and were negative at baseline were six times more likely to be abstinent through the rest of the study, those with fewer years of use were more likely to be negative, and those with major depressive disorder were more likely to continue using.  There were no significant differences in adverse events between NAC and placebo users (like most studies, NAC users had fewer side effects than placebo, 38 in the NAC group and 46 in the placebo group).

These results should be repeated and consolidated at multi-treatment center groups, but all in all it adds to the NAC family of interesting psychiatric results.

The Ting Tings Hit Me Down Sonny

The second interesting article is about poor nutrition at age 3 and schizotypal personality at age 23.  Studies of populations in China and the Netherlands have shown that periods of famine during pregnancy results in the birth of children who are twice as likely to have schizophrenia or schizoid personality, and the risks can be worse when malnutrition extends to the postnatal period.  Thinness in childhood from malnutrition is associated with later schizophrenia as well.

Is it the malnutrition or some other variable that increases the risk?  Malnutrition is associated with low IQ, and low IQ is also associated with the development of schizophrenia.  Iron deficiency is associated with malnutriton, stunting, and schizophrenia.  Let's try to sort it all out…

In Mauritius, all children (1795) from two towns born in 1969 to 1970 were followed from the age of three.  Height (in developing countries, a measure of nutitional status) and hemoglobin (which is an indirect measure of iron) were collected and normalized for the different ethnic groups.  An "adversity index" was also measured from a home visit for each child, counting points for uneducated parents, semiskilled parents, single parents, separation from parents, large family size, poor health of mother, teenage mother, or overcrowded home.  IQ was measured at age 11.  Schizotypal personality was measured with a questionnaire at age 23.

The researchers found that poor nutrition in early childhood resulted in poor cognitive performance (IQ at age 11) and a higher risk of schizotypal personality at age 23.  The adversity index at age 3 was also significantly related to IQ at age 11.  Individuals with higher performance (vs. verbal) IQs were less likey to have schizotypal features.  It is thought that malnutrition leads to hippocampal and frontal brain impairments, leading to difficulty with emotional regulation, maintaining relationships, and the all important executive function.

How do these finding play in the first world?  I suppose it depends on how many pregnant young women live off of vending machine food.  Still, more evidence that nutrition is important.  As if we didn't know.


  1. I've been noticing the phenomenon from the first study in my own life. As you might know I write about how to make drinking alcohol less unhealthy, and one of the main strategies for doing this is to radically increase glutathione levels in the body, sometimes using NAC (it really is quite good on the day of consumption). But I and other people tend to notice that it's just not as addictive a drug now. People increase their glutathione levels and end up decreasing their alcohol intake.

    Good health can sometimes be a buzzkill...

  2. Ultimately are buzzes should come from be holding our newborns, and enjoying our friends, and sunsets and mountains and all those things drowned out by substance use.

  3. By accident deleted this one from Stabby:

    Stabby has left a new comment on your post "Mainstreaming":

    Truth. :D

  4. I could be wrong, but my observation of people who use marijuana is surprisingly opposite of yours. I have an academic career, and most of the highly motivated, brilliant, and successful scientists and engineers I know use marijuana to relax in the evenings, and reduce stress and anxiety.

    I have a totally different sample than you, most of the people I interact with that don't have PhDs are working on getting one… and I am seen as very unusual/eccentric for not using marijuana. I know many brilliant people still at the top of their respective field(s) in their 60s, who are still very sharp after a lifetime of using marijuana.

    Is it possible that your causation be the opposite from what it seems? What if people that smoke marijuana didn't develop anxiety or other symptoms from it, but use it because it successfully medicates their symptoms or makes them feel better?

    1. check out my previous links where MJ use correlates linearly and positively in prospecive studies with psychosis and other nastiness.

    2. I doubt people who are that high achieving are sitting around smoking dope all day. Using a marijuana cigarette once in awhile, well after brain development has completed, is quite a different thing from sitting around smoking dope 24/7 in adolescence. It's like comparing a vinophile who enjoys alcohol as a side hobby, to a ghetto dwelling majorska addict. People who enjoy wine recreationally as part of an otherwise high functioning stress filled mentally challenging life have a working brain that hasn't been destroyed by alcohol. ON the other hand Mr Majorska doesn't bathe, sleeps in a gutter, and downs booze as soon as he opens his eyes to chase away the shakes. Brain is likely mush.

      But you know, it's not the substance. It's how it's used and how often its used and in what person.

  5. I just found your blog today in doing research in alternatives to Prescription SSRIs. I work in the front office of a holistic chiropractor's office and am studying homeopathy through a distance learning course. Homeopathy is my passion and I would love to specialize in homeopathy for mental disorders. My brother is on all kinds of psych drugs and I would love to get him off of them. Do you have any suggestions or opinions for weaning off of prescription meds and introducing natural supplementation? I realize that it may not always be possible.

  6. N=1
    first, I was that agorophobic pothead adolescent
    then, I was smoke-as-much-as-I-can adult for 20+ years
    then I took NAC (and a few other AOs) for Hep C
    then I stopped spending money on pot and spent it on supplements instead
    now I can take or leave both the pot and the supps.
    I haven't smoked in weeks and don't feel like it right now.
    I didn't know NAC had this rep. at the time.
    But I sure experienced it.

  7. Stabby, where do you write about alcohol and nutrition?
    I do some teaching around that very topic, and good info is hard to find.

  8. Hi. I enjoy your writings so I'm "following" you - hope you don't mind.

  9. Great post. My clinical experience with marijuana smokers is the same as yours. I also have some observational experience with "functional" marijuana smokers and like functional alcoholics. They generally do not do as well as they think, but I am not seeing them in a professional capacity. I think that the single most important question about it is whether or not the person is a daily smoker rather than trying to estimate amounts and I got that from an old study.

    The nutritional aspects of young children reminds me of a paper in the Lancet by Rene Spitz on psychosocial dwarfism from the 1940s. I was reading it as part of a study on the neuroendocrine aspects of malnutrition, childhood adversity (a great research concept) and brain development.

    Do you think that NAC is ready for prime time yet and by that I mean off label prescribing for any application?

    1. NAC has a better research record and more data for trichitillomania than any other agent, even the SSRIs, which are first line. I've used it for bipolar depression in someone who had disastrous side effects to all the standard meds (or treatment failure) and it seems to be working very well. We had a long discussion of course. I wish we had more long term data, though most of the psych studies are
      6 months, which is longer than most pharmaceutical trials by a long stretch.

  10. I came across pyroluria in Nora Gedgaudas' book, Primal Body, Primal Mind. Fascinated by the correlation to addiction and mood disorders. I answered yes to many of the questions posed and took a zinc tally with no resultant taste, indicating borderline zinc/B6 deficiencies. I've upped my supplementation on these, haven't noticed any huge changes, but it's only been a week. Wondering if you have any thoughts about pyroluria.

  11. The NAC study only measured use against abstinence. I bet you would have found that used was reduced overall in the NAC group still giving positive tests.
    From my experience the changes NAC produces in drug-seeking behaviour are gradual, and one has to process them and adjust one's overall life habits. There is a continual testing of the difference until it is undeniable.
    In this case (as with antabuse) relapse can be part of the cure.

  12. I haven´t had the time to read all of your excellent blog, but I tried to find if you had written anything about iron and iron supplements. I have bipolar disorder type II and have been really stable for 1,5 years without any medications - a little on the hypomanic side but almost no depression at all. Paleo and blue-blocking sun-glasses helped me. But now I´m down to a hemoglobin level at 8,7 g/dL (I´m female, 40 years old). I have a faster pulse, but no other symptoms - until I try to get some iron. I have tried four different iron supplements and eating more meat. Every time it sends me very quickly into a mixed episode. Any ideas why? The only clue I have is that my ASAT and ALAT started to go up when I tried Blutsaft (herbs and iron).


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