A Possible Explanation of Schizophrenia and How Cannabis Affects Schizophrenia

Copyright 2011, James Michael Howard, Fayetteville, Arkansas, U.S.A.

(I have come to the conclusion in 2016 that the actual natural ligand of the cannabinoid receptor is dehydroepiandrosterone (DHEA). This is directly pertinent to this explanation of DHEA and schizophrenia of 2011)

It is my hypothesis that schizophrenia is caused by low DHEA in utero. This results in poor brain development. Later in life, cortisol and testosterone act to reduce the effects of already low DHEA and adversely affect brain function as well as maintenance of anatomy. DHEA naturally begins to decline in the early twenties. This is why schizophrenia often occurs in the late teens / early twenties (puberty and loss of DHEA) and is often triggered by a stressful event (cortisol). Therefore, at this time, brain function and maintenance is inhibited and, in the case of cortisol, may be reduced. I suggest this reduces prefrontal function and increases lower brain function, the seat of hallucinations. It is known that DHEA is low in schizophrenia and that DHEA acts positively in neuron growth and function. (DHEA has also been found to be high in schizophrenia. I suggest low DHEA may account for "negative" symptoms and high DHEA may account for "positive" symptoms of schizophrenia.)

Derived from the foregoing, I have developed an explanation of how cannabis exerts its effects. I suggest that cannabis may affect binding of DHEA to androgen receptors. I think cannabis attaches to the androgen receptor and this has been supported (Endocrinology. 1980 Sep;107(3):848-50). Since DHEA uses the androgen receptor, cannabis will adversely affect the effects of DHEA. Part of my work includes an explanation that production of DHEA at morning triggers consciousness, so cannabis will reduce consciousness. By displacing DHEA from frontal receptors, DHEA availability increases for other parts of the brain. (I think all tissues, including various tissues of the brain, compete for available DHEA.) This produces the effects of cannabis. Consciousness is reduced with concomitant increase in lower brain function. This explains increased appetite, hearing, etc caused by cannabis.

I explain the positive symptoms of schizophrenia in the same way cannabis increases lower brain structures. As DHEA declines in frontal areas which stimulate consciousness in schizophrenia, lower brain structures are subsequently increased. Even in reduced DHEA conditions, the available DHEA is sequestered by these lower brain structures Hence, positive symptoms are increased as the frontal areas are reduced in function. That is lower brain activity (metabolism) is increased. It is known that cannabis increases positive symptoms in psychosis. Cannabis, in psychosis, further reduces the function of DHEA in the frontal areas and increase available DHEA for the lower brain. (DHEA stimulates metabolism and frontal metabolism is reduced in schizophrenia.)

As I suggested in my explanation of schizophrenia in the first paragraph, above, cortisol increases at the expense of DHEA and reduces the effects of DHEA. It is known that cortisol, in excess quantities over prolonged exposure, is a neurotoxin. I suggest this occurs because the effects of DHEA are reduced. DHEA is known to positively affect growth and maintenance of neurons.

I think the brains of schizophrenics are not as developed as normals in utero and, perhaps, early on in neonates. This is why they are vulnerable to the effects of cortisol and testosterone. Reducing DHEA by these hormones reduces maintenance of the frontal areas and they experience declines in function and anatomy. To finally respond to your findings, I suggest in these individuals whose brains did not form robustly in utero, the effects of cannabis on DHEA cause further decline and exacerbate the onset of psychosis.

Some research has indicated that cannabis use may improve negative symptoms of schizophrenia.  The increase in available DHEA, as a result of cannabis use, which I described above that increases positive symptoms should improve negative symptoms.  (See my explanation of schizophrenia in the first paragraph of this post.)