A remote history of cannabis use disorder appears to be associated with structural differences in brain areas related to working memory in both control subjects and patients with schizophrenia.
Within each group, the differences were significant between cannabis users and nonusers, Dr. Matthew J. Smith and colleagues reported Dec. 15 in Schizophrenia Bulletin. All of the regions involved are rich in cannabis type 1(CB1) receptors.
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A remote history of cannabis use disorder appears to be associated with structural differences in brain areas related to working memory in both control subjects and patients with schizophrenia.
It’s not clear, though, whether cannabis caused the differences or whether they were pre-existing – and possibly predisposed the subjects to become dependent on the drug, wrote Dr. Smith of Northwestern University, Chicago, and his coauthors. "One could hypothesize that the observed asymmetry represents the effects of cannabis, which induces a loss of normal variation in subcortical nuclei. However, the observed asymmetry could also represent a neurobiological vulnerability that predisposes individuals to substance abuse, which has been suggested in studies of cocaine addiction."
Whatever the true nature of the association, it raises questions about the wisdom of legalizing marijuana use, the authors said (Schizophr. Bull. 2013 Dec. 15 [doi:10.1093/schbul/sbt176]).
"These findings argue that efforts to legalize recreational and medicinal cannabis use should more carefully consider the potential impact of cannabis use on [working memory] and the underlying structures that support it in vulnerable populations," they wrote. "Of special concern is that cannabis use could begin long before an adolescent or young adult would know if they were in one of these vulnerable groups."
The research group consisted of 54 controls (10 with a history of cannabis use disorder) and 43 patients with schizophrenia (15 with a history of cannabis use disorder). The researchers compared working memory and calculated structural and volumetric measures in the striatum, thalamus, and globus pallidus, both between and within the groups.
The control subjects were an average of 25 years old; the patients were 26 years. Schizophrenia had been present for about 8 years in the patients. In all subjects, cannabis use disorder (CUD) had ceased 2-3 years before the study began. During use, however, 80% of controls and 92% of patients used cannabis daily; the remainder used it weekly. Nearly 90% of the patients began using the drug before schizophrenia onset.
In measures of working memory, clean control subjects scored higher than CUD controls, clean patients, and CUD patients, but working memory was not different between the clean and CUD patients, Dr. Smith and his associates reported.
When measuring the striatum, the researchers found that CUD controls exhibited differences within the structure relative to clean controls. These differences occurred in the dorsal regions of the nucleus accumbens. CUD patients not only showed inward differences of the nucleus accumbens but also of anterior stratum, extending dorsally to the tail.
In the globus pallidus, differences were found within each group but not between the groups. Both CUD groups showed inward shape differences in the anteriodorsal and ventral regions, compared with their clean comparators.
The thalamus showed the same pattern of within-group differences. Both CUD groups displayed inward shape differences in the anterior, mediodorsal, ventrolateral, pulvinar, and lateral geniculate regions. In the control group, these differences appeared to be greater in the left hemispheres. In the patient group, they appeared greater in the right hemisphere.
The cannabis-related shape differences were inversely correlated with working memory in both groups, the investigators said.
The investigators cited several limitations. For example, because the data were cross-sectional, it was not possible to infer causality. Also, quantitative measures of cannabis use were not accessed.
Nevertheless, the findings suggest that a resolved CUD "may have parallel effects in [controls and patients] in the striatum and globus pallidus, and that a comorbid CUD could augment the underlying disease process associated with schizophrenia in the mediodorsal thalamus," Dr. Smith and his coauthors remarked.
Dr. Smith had no financial disclosures. The study was funded by the National Institute of Mental Health.