Monkeys with no memories and the marijuana munchies

Endocannabinoids are chemicals we make that are important in many functions, including cognitive thought, and memory. When our internal endocannabinoid levels are low, we also start to crave sugar. (THC, the active ingredient in marijuana, is also a cannabinoid, and using it messes with our cannabinoid system, giving us the munchies).

In this study, endocannabinoid levels were evaluated in the prefrontal cortex area of 23 pairs of brain cadavers of people with schizophrenia and normal age and gender matched comparisons. Messenger RNA levels for endocannabinoid production were lower in the schizophrenic brains.

Eighteen brains of macaque monkeys who had been exposed long-term to one of two antipsychotics, haloperidol (Haldol) or olanzapine (Zyprexa), were compared to brains that had never been exposed to these medications. There was no significant difference in their endocannabinoid levels. So even though the medication was helping some aspect of the schizophrenia, it was not correcting the endocannabinoid imbalance.

That might provide one reason why it might be hard for schizophrenics to stay compliant with their medication--they're not being given a medication that helps their brains remember to take it.

As a nutritionist, I also see an important "next study". Knowing that omega-3 fatty acids DO improve cognition and memory, I wonder what would happen if that supplementation was added to the protocol?

It also explains why these clients have such an appetite for sweets, and the kind of foods that further degrade the brain. It's coming from a pretty entrenched biological mechanism.

Eggan SM, Hashimoto T, Lewis DA. Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry. 2008 Jul;65(7):772-84.

OK, I managed to keep a straight face until now, which I wanted to do since schizophrenia is an entirely serious topic and people with the disease deserve my respect. Completely. But do you know how hard it was to word this study without using the distracting phrase "monkey brain"? I figured this guy must have been a subject, given his predilection for popsicles.

When you play with antipsychotics, you play with fire.

Antipsychotic medications have worked wonders to enhance the lives of many people. However, in recent years, antipsychotics have also been used for an increasing number of off-label uses and in progressively younger populations than they ever were before. Before handing these medications out like they are candy, it's important to evaluate the risks associated with using these medications. A recent study suggested that we should be much more careful about choosing our treatment populations than we have been to date.

Before I get to the meat of the study, I'd like to preface this post with an explanation of the study design. The authors of this study are concerned about safety risks in young children and pregnant women when they are given antipsychotic medications. However, they had to develop a research model that did not place young children and pregnant women at risk in the process of looking into this issue. So...rather than give antipsychotics to these two populations, they chose to administer a battery of antipsychotics to a group of roundworms. Roundworms were chosen because they are an accepted research model for investigating matters related to brain and nervous system development. That is definitely a limitation of the study, as most people I know would not say they have much in common with this guy...but that's one of the tough things about studying medications and their risks...how to investigate those risks without causing more damage.

Anyway...when the roundworms were given three of these medications, clozapine (Clozaril), fluphenazine (Prolixin), and haloperidol (Haldol), there was less development of neurons in general and axons (a specific anatomical feature of a neuron) in neurons devoted to mechanosensory function (that's touching and registering what you're touching). Neurons that were produced also tended to not migrate to the location where they would be expected to migrate, meaning there might have been neurons there, but they were, so to speak, all dressed up with no place to go.

In some neurons, axons grew past their functional anatomical size. And some had abnormal anatomical features.

Other antipsychotics produced similar results, although not to as significant a degree. The drugs mentioned included: risperidone (Risperdal), aripiprazole (Abilify), quetiapine (Seroquel), trifluoperazine (Stelazine) and olanzapine (Zyprexa).

I'm not going to pontificate about the ethical dilemma encountered when treating a pregnant woman with schizophrenia. The choices made in those situations involve complex risk/benefit considerations that are the responsibility of the patient and her physician.

However, I will say that responsible use of these medications in women of childbearing age is imperative. Forty-nine percent of all pregnancies ending in childbirth in 1994 were unintended, and 48% of all women aged 15-44 in 1994 had had at least one unintended pregnancy at some point in their life. It happens, and it happens a lot.

So if you're a physician and you're handing out prescriptions for antipsychotics for off-label uses to women of childbearing age...no matter how much judgment, education, evaluation, etc. you think you're providing, you really are playing with fire.




Donohoe DR, Weeks K, Aamodt EJ, Dwyer DS. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans. Int J Dev Neurosci. 2008 May-Jun;26(3-4):371-80.

http://www.guttmacher.org/pubs/journals/3002498.html

Potential nutritional help for antipsychotic side effects

One of the most distressing side effects of antipsychotics is a syndrome called "tardive dyskinesia," in which a person develops involuntary movements and tics throughout the face and body.

Researchers in India report that rutin, an antioxidant, may actually help lessen the degree of these involuntary movements. In this particular study, the effect of rutin on vacuous chewing movements, tongue protrusions and facial jerking was studied in a population of rats who developed these behaviors after being given the drug Haldol. Rutin significantly inhibited all of these movements.

The researchers hypothesize that in the process of doing the work that it is supposed to do to help the schizophrenia, oxidative damage occurs which degrades the nervous system and induces involuntary movements. Rutin is a powerful antioxidant which appears to directly reduce this particular type of oxidation.

What is rutin? It is a flavonoid that is primarily found in buckwheat, citrus fruits, noni, black tea and apple peel. It is also available as a supplement, though until researchers pursue this relationship more thoroughly, it is probably best to include more of these listed foods in the diet. Sometimes adding too much of a "good thing" can disrupt the therapeutic potential of medications.

An additional note, rutin is also used in some cultures as an emergency contraceptive. So if you are of child bearing age and are on Haldol, it is important to use this information with caution.


Bishnoi M, Chopra K, Kulkarni SK. Protective effect of rutin, a polyphenolic flavonoid against haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes. Fundam Clin Pharmacol. 2007 Oct;21(5):521-9.
http://www.phytochemicals.info/phytochemicals/rutin.php