7. Project Summary:
The prevalence of cannabis use disorder (CUD) in people with
schizophrenia is estimated to be 25-50%, and CUD in these patients is
associated with poorer functional outcomes, early onset of psychosis and
symptoms exacerbation, and higher rates of psychiatric hospitalization. There
are few, if any, validated treatments for CUD in this population. Patients with
schizophrenia also have wide-ranging deficits in neurocognitive function, which
may be altered by cannabis use in a negative manner. However, brain
stimulation techniques such as repetitive transcranial magnetic stimulation
(rTMS) may hold promise for reducing cannabis use and improving
neurocognition (e.g., working memory, attention) in patients with schizophrenia.
Preliminary experience from our laboratory and elsewhere have shown that
schizophrenia patients with co-morbid CUD tolerate rTMS procedures with
minimal adverse events, that they can be retained in short-term intervention
trials, and that working memory deficits, drug use, withdrawal and craving may
be reduced by high-frequency (20 Hz) rTMS procedures. The proposed R21
study would test the effects of active (n=20) versus sham (n=20) high frequency
rTMS (20 Hz) delivered by a standard Figure-8 TMS coil on cannabis use and
cognitive outcomes in a total of N=48 patients with schizophrenia and co-morbid
CUD, in a 6-week, double-blind, randomized, parallel groups controlled trial. All
subjects would receive contingency management and drug counseling
interventions to encourage trial endpoint cannabis abstinence, which we have
shown to be effective in the schizophrenia CUD population. The primary outcome
measure would be trial endpoint self-reported cannabis use assessed by timeline
follow-back confirmed by cannabis urine toxicology. Secondary outcome
measures include neurocognitive outcomes (e.g., verbal memory and learning,
working memory), cannabis craving and withdrawal and psychosis symptom
ratings (Positive and Negative Symptoms Scale, Calgary Depression Scale for
Schizophrenia). We predict that active versus sham rTMS would significantly
reduce cannabis use and increase trial endpoint negative cannabis urine
frequency, and improve neurocognitive outcomes such as verbal learning and
memory and working memory, as well as reductions in withdrawal and craving,
positive and negative symptoms of psychosis in schizophrenia. The significance
of this study is that a novel neuroscience-based treatment for co-morbid CUD
and schizophrenia may be developed for use in the clinic, and reduce the burden
of this important co-morbidity which is associated with serious functional
impairment in schizophrenia.