Patients experiencing a first episode of schizophrenia who also use
marijuana or other cannabis products appear to have greater loss of brain
volume over five years, along with other significant brain changes, compared
with nonusing patients and healthy comparison subjects.
Moreover, the cannabis-using patients showed a less-pronounced improvement
in positive and negative symptoms compared with nonusing patients, according
to Dutch researchers. Their report was posted on AJP in Advance on
February 15 and will appear in the April print edition of the journal.
The results suggest a neuroanatomical explanation for previous studies that
have found a poorer outcome among cannabis-using patients.
"Cannabis use has been reported in up to 50 percent of the patients
with schizophrenia, and cannabis-using patients, including those with a recent
onset, seem to be clinically different from those not using cannabis,"
lead investigator Monica Rais, M.D., told Psychiatric News."
They are reported to have more positive symptoms but fewer negative
symptoms, an earlier onset, and an increased number of psychotic relapses or
"We hypothesized that the reported outcome differences between these
two patient populations could be reflected in peculiar patterns of brain
volume changes over time," Rais said.
She is with the Department of Psychiatry at the University Medical Center
Utrecht in the Netherlands.
Though the cannabis-using patients did experience less-pronounced
improvement in symptoms, in this study the researchers did not find
statistically significant differences in global functioning outcome measures
or in the number of days hospitalized; this may be due to the relatively small
number of subjects in the study, Rais and colleagues wrote.
However, the longitudinal study advances the understanding of cannabis and
its relationship to brain changes and underscores the importance of drug
counseling for patients with schizophrenia. Previous links between brain
volume and cannabis use in schizophrenia patients either have been indirect or
have relied on measurements at only one point.
"Our results underline the importance of making a maximal effort to
persuade patients with schizophrenia to stop using cannabis and warn young
people in general for the possible risks associated with its use," Rais
In the study, 51 patients with first-episode schizophrenia and 31
comparison subjects without schizophrenia were recruited from the
First-Episode Schizophrenia Research Program at the University Medical Center
Utrecht. The comparison subjects did not use any illicit substances before or
during the study.
The cohort was followed for five years to examine the relationship between
brain morphology, the use of cannabis, and outcome. Patients with a lifetime
diagnosis of abuse or dependence of a substance other than cannabis or
nicotine were excluded.
At baseline, severity of illness was measured with the Positive and
Negative Syndrome Scale. Drug use was assessed with the Composite
International Diagnostic Interview, and the information provided by the
patient was confirmed by a relative. Random urine toxicology tests were
performed throughout the study.
The researchers also assessed the number of days spent in the hospital over
the five-year period for all patients, and every patient was monitored
carefully for the amount and type of medication prescribed.
During the study, 19 patients used only cannabis and no other illicit
drugs, and 32 patients did not use any illicit drugs.
At the end of the five years, schizophrenia patients showed a larger
decrease in gray matter volume over time than healthy subjects, and this
decrement in gray matter volume was significantly more pronounced in the
patients who continued to use cannabis. Moreover, the differences could not be
attributed to outcome or baseline characteristics, the researchers wrote.
The cannabis-using group also showed less improvement in positive and
negative symptoms over the five-year period, though this slower improvement
did not translate into a statistically significant difference in functional
The cannabis-using group also showed more pronounced increases in lateral
and third ventricle volumes than healthy subjects and patients who did not use
Among all patients in the study—whether they used cannabis or
not—the increase in lateral and third ventricle volumes was related to a
higher score on the Camberwell Assessment of Needs (CAN), and an increase in
lateral ventricle volume was related to a lower Global Assessment of
Functioning score. (The CAN is a measure of the help patients need in daily
However, no significant correlations between increase in ventricular size
and the clinical variables could be found between the cannabis-using and
nonusing groups. So it would appear that brain volume loss may not wholly
account for poorer functional outcome, the researchers concluded.
Similarly, the precise nature of the relationship between cannabis and
brain volume loss remains to be elucidated. Excessive neuronal damage in
drug-using patients with schizophrenia could either be a direct consequence of
cannabis intake or occur as a consequence of psychotic symptoms in
schizophrenia associated with cannabis use. Or it could be related to the
possibility that cannabis-using patients may be more likely to be noncompliant
with antipsychotic medication, which is believed to attenuate the progressive
brain changes in schizophrenia.
"Although further studies need to be conducted to confirm whether the
brain volume loss is a direct or an indirect effect of cannabis in
schizophrenia, this study suggests that some of the detrimental effects of
cannabis on the course of illness may be explained by its effect on the
progression of brain changes in schizophrenia," Rais and colleagues
"Excessive Brain Volume Loss Over Time in Cannabis-Using
First-Episode Schizophrenia Patients" is posted at<http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2007.07071110v1>.▪