Research Summary

Background

Despite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia.
Aims To investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56).
Method Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter.
Results Patients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers.
Conclusions A defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.
Philip R. Szeszko, PhD, Delbert G. Robinson, MD and Serge Sevy, MD et al
Correspondence: Dr Philip R. Szeszko, Zucker Hillside Hospital, Psychiatry Research, 75–59 263rd Street, Glen Oaks, NY11004, USA. Tel: +1 718 470 8489; fax: +1 718 343 1659; email: szeszko@lij.edu

Source: The British Journal of Psychiatry (2007) 190: 230-236. doi: 10.1192/bjp.bp.106.024521
© 2007 The Royal College of Psychiatrists

James M. Howard,
Independent Biologist

It is my hypothesis that schizophrenia results from reduced fetal brain growth and development due to low maternal DHEA. This is exposed later in life by hormones that interfere with DHEA availability, that is, cortisol and testosterone, along with the natural decline of DHEA that begins around age twenty. Therefore, schizophrenia often occurs following a stressful event (cortisol) in the late teens or early twenties (testosterone and loss of DHEA) or later in life as DHEA reaches very low levels. Schizophrenia is characterized by low DHEA. Individuals with normal DHEA along with reduced fetal DHEA may not develop schizophrenia.
I suggest that the psychoactive chemicals of cannabis exert their effects by binding to androgen receptors. It has been found that THC and CBN inhibit binding of dihydrotestosterone to the androgen receptor (Endocrinology 1980; 107: 848-50). This binding to receptors in the advanced forebrain would reduce executive function and increase lower brain function by redistributing DHEA. That is, blocking access to upper brain receptors would increase lower brain function and increase lower brain functions such as appetite, etc.
DHEA binds to the androgen receptor. Cannabis use would reduce DHEA binding to the androgen receptor. It is this blocking of DHEA at its upper level receptors and subsequent redistribution of availability for lower brain activity that I think produces the effects of cannabis.
It is known that DHEA directly affects the anterior cingulate cortex (Psychopharmacology (Berl) 2006; 188: 541-51). Interference of DHEA binding in the anterior cingulate cortex of individuals with reduced growth and development in this area may reduce both function and maintenance of this area with the result being the symptoms of schizophrenia.