Nutrition and Alzheimer's Disease - Dangers of Insulin Resistance and Low Cholesterol

A paper by MIT's own engineer Stephanie Seneff and (as near as I can tell) a couple of medical research-reading renegades was published in the European Journal of Internal Medicine earlier this year.  It is remarkable to see (one presumes) a major European biomedical journal publish something from outsiders.  More amazing still is the easily understandable, well-referenced and cogent understanding of lipoproteins, metabolism, and brain chemistry.  In our specialty journals we often get shallow papers that peck at a single organ system, without a holistic understanding of physiology.

So with no further ado - let's dive in.  I'm going to summarize the best bits of the paper, but I strongly encourage you to read the paper for yourself - the link above is to a full-text version available at Seneff's own website at MIT.  Alzheimer's dementia is a disease I've blogged about before extensively, a degenerative disease characterized by nerve cell death, plaques and tangles, and linked with insulin resistance, diabetes, and… low cholesterol.

Millions of dollars and several decades have been spent chasing down the most obvious pathology - those plaques and tangles.  We innovative humans have invented all sorts of marvelously clever treatments - including vaccines against plaque, and drugs that interfere with plaque synthesis.  The problems is the vaccines did no good, and the trials for the plaque-busting drug was halted early due to an obvious "accelerated deterioration in cognition in the treatment group compared to placebo-based controls."

It seems the typical response to such failures is to think - oh, we aren't acting early enough or we aren't busting up enough plaques - which might be the case.  Or, as Seneff and crew suggest quite astutely,  the amyloid beta proteins that form the plaques might just be there for a good reason, a protective reason, and that's why they cover the Alzheimer's brain with such ferocity.

We know that there is a strong correlation between insulin resistance and early Alzheimer's, and also there is an association between mitochondrial dysfunction (particularly in complex 1) and Alzheimer's.  As I discussed in Basic Science: Energy is Everything and Brain Efficiency, when the mitochondria aren't happy, your brain isn't happy.  Mitochondrial dysfunction is also implicated in Parkinson's Disease and ALS, both long-term and ultimately fatal degenerative conditions.

And now, a point I've made before (in Low Cholesterol and Suicide)- the brain is relatively small, but has 25% of the body's cholesterol.  Cholesterol insulates neurons as part of the myelin sheath and provides the scaffold for the neural network, and is an important part of the membranes and all synapses.  While much of the cholesterol used in the brain is made in the brain, there is clear evidence that apolipoprotein E (ApoE) is a big player in the game of shuttling cholesterol, fat, and antioxidants to the central nervous system from the body's main cholesterol factory, the liver.  ApoE is made in nerve cells called astrocytes (who tend to and feed neurons), and ApoE allows the astrocytes to suck lipids, antioxidants, and cholesterol arriving in LDL and IDL particles from the bloodstream. Yes, astrocytes can transport LDL across the blood brain barrier.

The biggest genetic risk for Alzheimer's is being a carrier of a certain type of ApoE gene called ApoE4.  Research has shown that ApoE4 is associated with reduced cholesterol uptake by the astrocytes.  What has been confusing for the lipophobic medical establishment is that ApoE4 is associated with high LDL cholesterol… so it must be that nasty horrible LDL killing the brain!  But the key bit to understand is that LDL cholesterol in longitudinal studies tends to drop before the development of Alzheimer's disease.  Hmmm.  We can't ignore the following tantalizing clue either:

…high cholesterol level is positively correlated with longevity in people over 85 years old, and in some cases has been shown to be associated with better memory function and reduced dementia… the cerebrospinal fluid of [Alzheimer's Disease] patients is substantially depleted in lipoproteins, cholesterol, triglycerides, and free fatty acids compared to matched controls.

All of us, but especially readers of a since-removed blog post that was part of the Venus-gate paleo disruption of a few weeks ago about the supposed dangers of densely packed saturated fat should have an understanding of how lipoproteins work.  Lipoproteins (such as HDL, LDL, chylomicrons, and VLDL) basically look like this:

Image from Wikipedia

Lipoproteins carry fats and other delicacies through the blood.  The blood is dangerous and filled with nasty things like oxygen and iron that can break down our gentle fats.  We don't want our fats oxidized - so the lipoproteins tuck the fats into the inside to keep them safe and snuggly.  Again, a MAJOR REASON for the particular structure of lipoproteins is to keep those fats safe and not exposed to the blood.  Once fats are delivered to cell membranes, we still want to keep them safe - and cholesterol is like a bit of plate armor - it helps the fats stack more tightly, protecting them from oxidative damage and invading microbial pathogens. 

Seneff et al continue to stack the evidence in their paper - dietary avoidance of fat (replaced by carbohydrate) and the increasingly zealous prescriptions for cholesterol-lowering medication has coincided with the rise in Alzheimer's Dementia and diabetes and obesity.  These are only correlations, but one might consider that to be some evidence in favor of the plausible hypothesis that stripping the brain of cholesterol especially in an oxidative, hyperglycemic environment could lead to very sick neurons.  

These sick neurons do their darndest to go forward despite the growing burden of oxidative damage and smokey, spewing mitochondria - until the end, when they are so damaged the only thing to do is to call in the immune system to send self-destruct signals.  And here is where those amyloid beta proteins come in - they are hypothesized to try to stand in for cholesterol and to help shift the cell from using the damaged mitochondria to utilizing different sources in the cell cytoplasm to make energy (for the biochem nerds - specifically glucose is redirected to the pentose shunt, an anaerobic pathway generating NADPH which also can protect the cell from oxidation).  Their purpose, then, is to reduce the ongoing damage as a last stand prior to self-destruction of the neurons.  When the cells ultimately give up the ghost, the defensive forces are left in place, crystallize, and form the famous plaques.  As Seneff so elegantly puts it:  "A legacy of complex protein debris is left in place."

Back to insulin resistance and hyperglycemia, the legacy in turn of our processed carbohydrate, inflammatory, fructose-intensive Western diets - turns out the same apolipoproteins that are critical to the functioning of our cholesterol machinery are also particularly vulnerable to damage called glycation in a high-glucose environment.  Glycation is known to disturb the uptake of ApoE by the astrocytes (that first step in processing cholesterol used by the brain).  Diabetics with Apo-E4 are at higher risk for Alzheimer's, and it is thought that the less efficient ApoE4 combined with the detrimental effects of glycation could be the reason.

Enter the ketogenic diet, which in a pilot study has been found to be therapuetic for Alzheimers.  It involves an extremely high fat diet, supplying plenty for the brain, and results in the brain being able to use alternative energy sources (ketones) that skip the damaged mitochondrial complex 1.  It will also tend to lower insulin resistance and eliminate glycation, as blood sugar will be low.

And then enter the  pathogens - with excess glucose and advanced glycolation end-products floating around in the blood, diabetics are more vulnerable to bacterial infection than the average person. Alzheimer's Dementia is also associated with infection with certain chronic pathogens, including H. pylori and Chlamydia pneumoniae.  There are plausible mechanisms by which these infections increase inflammation and oxidative damage, hastening the onset of dementia.

What have we learned?  Don't eat processed carbs, ketones and fat are our friends, avoid inflammation and foster your immune system's resistance to infection to protect your brain.

What is the scariest scenario?  Well, all the diabetics.  They are at higher risk for heart disease, and in the US at least they are very aggressively statinized, especially in the last 10 years.  It would be considered malpractice for a primary care doc or cardiologist not to encourage statin use in a diabetic with a whiff of high cholesterol.  But it seems quite plausible that drastically reducing cholesterol in combination with the hyperglycemia of diabetes is the perfect storm for developing Alzheimer's.

Dr. Steve Parker noted a study that showed no increase in Alzheimer's in autopsies of diabetics.  The study was done in Japan between 1998 and 2003, and is strong evidence against the fact that plain old type II diabetes would cause Alzheimer's.  In Japan there is, in general, lower cholesterol levels, and in Japanese low cholesterol is known to coincide with stroke risk.  In addition, this study was done mostly before the mainstream statin explosion in the United States, anyway.  I don't know how aggressively the Japanese diabetics  are "treated" for  high cholesterol.  I wonder if the differences in the processed food burden along with cholesterol-lowering drugs explain the difference between the strong epidemiological evidence linking insulin resistance and diabetes to Alzheimer's in the Western world and the lack of relationship between diabetes and Alzheimer's in the Japanese study.

Well, we better figure it out soon.  Dementia is growing, expected to triple in the next 40 years - if we don't figure it out.  I'm gonna go eat some coconut oil.

A Grand Unified Theory of Psychiatry?

It is no secret that on this blog, I am a reductionist.  All psychiatric illness (shoot, all of chronic Western disease) has the same pathology (inflammation) and starts with the same treatment (an anti-inflammatory lifestyle, including diet, healthy coping and stress amelioration, and good sleep).

At an individual level, of course, it is not so simple.  I can't be an effective doctor for you without knowing your experience, and spending enough time with you to figure out how you tick.  That way I can modulate my advice to meet you where you are.  And that in a nutshell is the failing of modern medicine.  It tries to replace a personal relationship with testing and algorithms in the name of science, efficiency, and expediency.  Problem is, for a doctor (especially a primary care doctor), such a practice is soul-killing (who wants to be responsible, in a litigious society especially, for the health of 5000 patients you barely know?).  For the nation, the algorithm is expensive, careless, and dangerous.  It works for the protoypical patient and in some obvious areas, such as safety checklists and counts in the operating room, but once anyone comes in with human quirks and complications, the data goes out the window.  Not to mention the ridiculous attention to relatively meaningless numbers (cholesterol panels, for example) in lieu of a rational human-friendly evolutionary model for health.

I live in Massachusetts, where managed care has a prominent role.  In psychiatry, several insurance companies have attempted to gather data based on various scales and standardize treatment to some extent.  I've participated (somewhat unwillingly - as it was clear from the outset the data gathering would simply use valuable time and resources better directed towards other things) in these endeavors, and also in research.  In the "real world" the use of scales to try to gather data for what works for the insurance company has proven each time to be a complicated disaster, and has been abandoned.  People in my waiting room aren't particularly interested in filling out the scales the insurance company wants them to, and thus the results are conflicting and meaningless.  In research or in the symptom scale measures I might choose for my patients based on our relationship and my knowledge of their history, there is a different sort of vibe.  It's a collaboration.  It's personalized medicine.  In research, the patients are pre-selected not to have certain comorbidities (so in general they are less complicated than the patients who show up at the actual doctor's office), and they are volunteers, even paid volunteers!

With enough data points and a big enough computer, I'm sure more rational models of algorithm care could be produced.  But for now, nothing replaces simply knowing your patient and spending time learning who they are.  Nothing replaces the art of medicine, particularly, I think, the art of personalized psychiatry.   And, perhaps counter-intuitively, we all suffer when medicine becomes increasingly compartmentalized and specialized.  All doctors should be generalists and have a robust clinical knowledge of all fields.  Recently, my consultations have been instrumental in diagnosing two cases of hyperparathyroidism - the only reason it came down to me is that I am the only one in a managed care model who has more than about 5 minutes at a time to spend with patients.  I'm expensive (being extensively, expertly trained over many, many years), but I like to think I'm worth it.  That said, your psychiatrist should not be diagnosing your hyperparathyroidism.  That's a travesty and a failure of modern medicine.

But - we stand to learn a great deal and develop confidence and wisdom if we dial down on the specific pathophysiology and genetics of psychiatric disorders.  And what we find, more and more (which is what one would suspect, from the Grand Unified Inflammation Theory), is that the pathologies and genetics overlap.  Another Nature paper came out recently, sent to me by Jamie Scott, that brings together the disparate diseases of schizophrenia and anxiety.  And that's kinda cool.  Let's break it down.

Convergent functional genomics of anxiety disorder: translational identification of genes, biomarkers, pathways, and mechanisms

A bit about anxiety.  It is the most prevalent psychiatric disorder, affecting 18.1% of Americans annually, but remarkably enough, less studied in a rigorous sense than the much more rare schizophrenia or autism spectrum disorders.  Some anxiety disorders seem to be based on an anxious temperament (generalized anxiety disorder, panic disorder) whereas others are based on obvious stressors (phobias, PTSD).  Others are mixed, like obsessive compulsive disorder.  Anxiety is typically along for the ride in depression (at least in the patients I see), and makes for a more complex patient more resistant to typical treatment.  In general, anxiety can be defined as a pathologic increased reactivity to the environment, driven by fear and uncertainty in light of perceived threats.

Anxiety disorders are the protoypical disorder of the modern world, where our hunter-gatherer brains are trying to manage remembering 50 passwords, the threat of H1N1 and terrorism, kidnapping and car accidents.

In the Nature paper, the authors used human and animal genetic data (emphasizing the gene expression studies rather than the specific gene studies) plus some controlled animal trials to dig up the most likely genes that might give you a predisposition to be more anxious than usual.  Not surprisingly, they found a lot of genes that were active in the hippocampus, related to stress hormone response and GABA transmission.  Other genes, such as polymorphisms in the dopamine system, are also obvious, and the "grand unified theory" supporting evidence is that many of these genes are also suspected to be awry in bipolar disorder, schizophrenia, and depressive disorders.  One suspect gene (QKI) has a central role in myelination, is a biomarker for anxiety, and there is evidence of changes in the expression in humans of QK1 in response to stress.

One of the top genetic pathways suspected in anxiety is also the pathway associated with signaling in Huntington's disease - a disease that is (speculatively) perhaps strongly associated with wheat consumption.  Gene expression, again, has been emphasized, which accounts for genetics, epigenetics, and environmental regulation.  "Genes that change together act together" - "the co-expression data sets… generted in various brain regions offer testable hypothesis for transcriptional co-regulation, and for epistatic interactions among the corresponding loci."

In English?  Our genes code our vulnerability to environmental insult.  Some of the same genes that make you vulnerable to schizophrenia also make you vulnerable to anxiety and depression.  The environmental insult is typically modulated through the stress response system, which is also modulated through diet and experience and movement and sleep.

Live and move and work and think like a human, and you will be more resilient.  Stray from our evolutionary programming, and you are going out on a limb.

New Studies: Nutritional and Pathologic Clues in Autism

I've devoted quite a few entires to autism (more properly called the autism spectrum disorders).  Perhaps because the illness can be so devastating, attacks so young, and is so mysterious in its origin.  I've migrated many of the autism entries over to Psychology Today, and the specifically nutritionally-related ones can be found here:

Diet and Autism
Diet and Autism - Newer Studies and Intriguing Links
Autism, Inflammation, Speculation, and Nutrition

The first new paper I want to present today is a Letter in Nature:  Transcriptomic analysis of autistic brain reveals convergent molecular pathology.  Like most Nature papers, the prose is dense with advanced molecular biology and neuroscience, but I think I can glean the meaning of it.  In this study, the researchers examined post-mortem brains from 19 autism cases and 17 controls.  They focused on three areas previously shown to be different in the autistic brain (specifically areas of the cerebral cortex and cerebellum), finding the most differences between autistic brains and controls in the cortex.

What is interesting about these sorts of studies is that they look at gene expression rather than just genetics, meaning they find out which genes are activated differently between cases and controls.  They found that many different genes were affected (consistent with the findings in autism in general - there is no single "autism gene" causing all cases, though 1% of cases have a 15q duplication, for example).  The interesting part is that the gene expression that was different between cases and controls clustered around specific areas, and were highly related to what is called "cortical patterning." These are some of the same gene areas that were already suspected to be causative for autism spectrum disorders,  and are also suspected to be causative in schizophrenia.  Other genes that were upregulated were functioning as part of the immune and inflammatory response.

What is intriguing about this study is that the researchers felt it showed convergence of the many different genetic causes in the area of transcription and splicing of certain genes as the underlying mechanism of the disorder.  They were also able to show that the inflammation was secondary rather than primary.

All right, we made it through the tough part.  Now on to the second paper, which is far more nutritionally related (possibly - it's just an observational study, but it is interesting).  Prenatal Vitamins, One-carbon Metabolism Gene Variants and Risk for Autism.

So, the intro - Prevalence in the US is about 1 in 110 children and may be rising (a recent Yale study in South Korea study suggests autism affects 1 in 38 children there).  It is widely accepted that genetic risk underlies the disorder, but there are also definitely interactions with environmental factors.  The recent study showing increased risk of autism in short intervals between pregnancies could implicate nutritional factors.  Valproic Acid (depakote) which disrupts folate metabolism is a known cause of autism and neural tube defects.

Other literature suggest that some children with autism have altered B vitamin metabolism and a reduced ability to methylate things.   So in this brand new study, the researchers specifically looked at vitamin supplement intake.  Children with autism in California were identified as part of large, population-based, case-control CHARGE study.  Their mothers were asked in telephone interviews whether they consumed prenatal vitamins, multivitamins, fortified cereals, and other supplements in the period 3 months before conception, and then during pregnancy and breastfeeding.  If they answered yes, they were asked specifically what vitamins and brands were consumed.

Interesting results ensued - 97% of mothers of the normal controls and 96% of mothers of the children with autism reported taking prenatal vitamins.  However, mothers who took the vitamins in the 3 months before conception and in the first month of pregnancy were significantly less likely to have autistic children than those who didn't.  There was no difference between vitamin and non-vitamin takers in months 2-9 of pregnancy or later.  The findings were controlled for various confounders, such as mom's education, race, whether conception was intentional or not, year of birth, etc.

Even more interesting - use of regular multivitamins in lieu of the prenatals was not associated with decreased risk of autism compared to taking no vitamins.  The major difference between most prenatal vitamins and regular multis is a doubling of folic acid.  The government says the synthetic folic acid is the same as the folate in food - Chris Kresser notes here that conversion from synthetic folic acid to the active tetrahydrofolate is poor in humans, and while synthetic folic acid pretty definitely reduces risk of neural tube defects, it also likely increases the risk of cancer - these kinds of population risks are a tough call.  If you are trying to get pregnant and you aren't always sure you are getting a lot of folate from foods, it may well be worth the risk to take synthetic folic acid for the periconception period.  Well, that's something to chew on.

The researchers in this study also checked genetics, finding that children with methylation issues (related to the folate cycle) were also more likely to have autism.  Maternal periconceptual folic acid seems to increase methylation in specific gene regions in the child (1), which can have epigenetic effects that can affect a child throughout life.

Get nutrients from food whenever possible, but there are certain circumstances in which wise supplementation may be very important.   And for public health recommendations (assuming the SAD) - supplementation for women trying to become pregnant seems wise, and when one reviews IOM and other reports, one often sees a fair accounting of the risks involved.  In fact, that is often why IOM or other recommendations seem quite conservative.   The questions continue!

More Exciting News

Yesterday I received an email from Brent Pottenger offering up an open spot as a presenter at the Ancestral Health Symposium in a couple of months.  Since I'm already going and I've already booked the accommodations, seems like a no-brainer to accept the invitation  - also, I get to present with Jamie Scott, so double bonus!  We will do something along the lines of evolutionary medicine as a model for resiliency of body and mind, or maybe Forging Superhumans with Coconut Butter.  We'll have to see what unfolds.

The bummer part is that it looks like we will be presenting at the same time as Stephan Guyenet, and I was really looking forward to his talk!  Oh well - the 16 of you who stay in our room for our presentation are hopefully in for some fun times.

In other news, I updated my Fructose Malabsorption and Depression post for Psychology Today (now called Could Soda and Sugar Be Causing Your Depression?) including some extra studies.  That one could be important - and it would be nice if you clicked over there, stumbleupon and retweet so that maybe someone with a nose and budget for research will really look into it. 

New posts later this week!

A Testimonial

Posted over at Robb Wolf's site with a commentary by Mat Lalonde - a child with significant improvement in autism symptoms mere days initiating a casein free, gluten-free paleo diet:

Scarlet's turnaround




- Posted using BlogPress from my iPhone

More About the Mysteries of Cannabis

In my last post on cannabis, I reviewed some observational evidence that smoking marijuana could be seriously bad news if you have psychosis or relatives who do, putting you at higher risk for psychosis yourself.  Ultimately there will be no gold standard randomized controlled trial - the design for that would be: randomize one group of teenagers at high risk for psychosis to smoking pot (hey, make it multi-arm - some will smoke LOTS of pot, and others less), and have another group not smoke pot, follow them through young adulthood, and see what happens.

Yeah, that's not going to happen.  But what we do have as evidence in several epidemiologic studies and some prospective cohort trials is that the more pot and the earlier a teenager starts smoking pot, the higher the risk of developing psychosis.  We also have some plausible biologic mechanisms (this study, for example, seems to show that folks with cannabis dependence and folks with schizophrenia have similar brain metabolism in key areas, which were significantly different than non-schizophrenic non-cannabis dependent folks).  And in animal studies, where randomized controlled trials can be done,  heavy doses of THC seemed to damage the brain.

I feel like music.  How about Austin's own Spoon, with Don't You Evah (right click to open in new tab).

Is the news all bad for funny cigarettes?  Any time one badmouths marijuana or questions its benefits one will find that a bunch of people pop up with all sorts of miraculous properties of cannabis.  And, in truth, cannabis is not just about THC, and is an exceedingly interesting plant with all sorts of intriguing cannabinoids in it.  As commenter Erik noted, cannabidiol seems to be neuroprotective and balance some of the more toxic effects of THC, suggesting that "vintage pot" with a better ratio between the two might be much healthier.  

I have used cannabinoids clinically (never in psychiatry, however) - there is an FDA-approved synthetic THC called marinol that we used to give out on the cancer ward in medical school, in Texas, to cachectic patients who had no appetite.  Back then before the proliferation of a ton of antiretrovirals we saw a lot more advanced AIDS - those patients also seemed to benefit from marinol to increase appetite.  I must say I did a number of consults on hospitalized cancer patients in Massachusetts, but never saw marinol prescribed up here.   If you look at the link to marinol you will find the DEA page describing that the purified synthetic THC is much safer than cannabis smoked au naturale.

Some of the DEA's points are valid  - lord knows what is in the cannabis you might buy from your friendly neighborhood dealer - and certainly in the case of immunosuppressed cancer and advanced AIDS patients, smoked joints could easily be adulterated with natural fungi that grow into big nasty (and deadly) fungus balls in the lung.  I saw a case of this fungus ball in medical school in a patient immunosuppresed with HIV who also happened to smoke a lot of pot.  It could have been from other sources, of course, but my attendings assured me they had seen it several times in AIDS patients who were heavy pot users.  It's not a pleasant way to go, and the treatments are horrible.

(Over time, you see enough cognitively bereft heavy pot users and psychotic heavy pot users and top that off with deadly fungus balls, and you can see why I'm none too fond of the stuff.  These types of experiences are anecdotal, but influential to any doctor in practice.  Part of being human, I suppose.)

Other DEA points are the same old conventional wisdom and faulty reasoning that led T. Colin Campbell to conclude that animal protein causes cancer from some rodent studies using isolated casein and aflatoxin.  Natural cannabis contains a mixture of cannabinoids with different effects - one can't necessarily extrapolate the effects of just THC to marijuana in general (though it seems more reasonable to do so with the modern "skunk" high-THC marijuana).  And "purified synthetic THC" could be kinda like casein without the whey in aflatoxin-poisoned rodents - a bad idea for pretty much anyone if you aren't a step away from death via advanced disease + starvation.

So, the lengthy intro aside, let's examine some of the evidence for marijuana that shows positive effects in the human brain.  Fortunately we have the Rolls Royce of academic reviews available - a Cochrane Review - Cannabinoids for the treatment of dementia.  

So what's the good news for marijuana?  Well, cannabis receptor 1 and 2 (CB1 and CB2).  CB1 is primarily active in the central nervous system, and CB2 is found more in the periphery, particularly on the white blood cells.  Some studies of cannabinoids seem to find them to be, in the whole, neuroprotective.  They regulate glutamate transmission (reducing neurotoxicity) and may reduce neuroinflammation.  They might protect the brain from toxic injury.  THC may also be what is called a cholinesterase inhibitor, which is a class of drugs that are now used to treat Alzheimer's.

Small open label trials showed that marinol (synthetic THC) reduced agitation and helped weight gain in dementia patients.  Another small trial of cannabidiol showed it helped with sleep.  But, as Peter has been known to say, small, third-rate studies are small, third-rate studies, and do little more than give us a reason to design larger, better studies that might prove a point or two.  The great thing about a Cochrane review is those scientists comb MEDLINE and OVID and conference reports and ongoing research trials and PUBMED for the awesome studies.  Those that are randomized, controlled, and done with acceptable follow-up and inclusion criteria.   And when you comb the literature for that sort of study with respect to cannabis products and dementia, you find one study that wasn't even the greatest of studies (15 patients, using marinol), so the reviewers ultimately have to say there is no reliable evidence that cannabis should be used clinically in dementia patients.

And what about non-dementia, non-psychosis studies - neuroimaging studies, for example?  After all, I treat a particular population - one apt to be anxious, depressed, demented, or psychotic.  If you are none of the above, are not at high risk for psychosis (ie no family members with psychotic disorders and no personal history), and like to spend the days smoking out on your mom's basement couch - how risky is it to your brain?  Well, a neuroimaging review seems to indicate there are metabolic changes in the brain related to smoking pot, but no one is sure what it means.   Other kinds of studies of neuropsychologic testing also show mixed results.

What seems to be the consensus when one reads general articles meant for psychiatrists (in Psychiatric Times, for example), is that marijuana in the brain is perhaps best conceptualized as a potent nerve growth factor.  In a young, growing brain (a teenager), likely replete with plenty of nerve growth factor, extra nerve growth factor has the potential to be disastrous - lighter fluid on a briskly burning fire.  In an older, demented brain (a smoldering, dying fire), nerve growth factor may well be therapeutic, but there isn't enough good evidence to conclude that is the case.

Is marijuana "paleo?"  The anthropologists can answer that question far better than I can.  Is it healthy?  I can name circumstances which encompass the majority of my patients in which there is some reasonable evidence that it is most likely very unhealthy and risky.  I'm willing to withhold judgment about it's ultimate therapeutic value in other cases (like dementia) until more evidence is in.   And certainly there will, logically, be a difference between artisan variety vintage stuff than the "skunk" high-THC brands of today.

And let's not forget the underlying evolutionary principle - human babies born of natural eating and natural living mothers and fathers are strong and amazing and not broken.  We are not automobiles  - when left to an evolutionary diet and activities we are likely to thrive, as we always have.  And cannabis has the potential to be a potent long-term brain-altering substance.  There's an old adage in psychiatry:  Don't fix what ain't broken.

In the modern world, well, let's hope the science researchers design and implement some good studies that can answer our questions!

Dopamine Series at Psychology Today

Dopamine Primer

Dopamine, the Left Brain, Women, and Men

Genius and Madness