Huperzine for Cognitive and Functional Impairment in Schizophrenia

Inclusion Criteria:

1. Psychiatric diagnosis of schizophrenia according to SCID-IV.

2. Currently treated with an antipsychotic medication.

3. Has tolerated current antipsychotic treatment adequately.

4. Has received an adequate trial of antipsychotic (a least 3 months of at least 300 mg/d
CPZ equivalent).

5. Has been receiving current psychotropic medication (s) for at least 8 weeks.

6. Has been receiving current doses of psychotropic medication (s) for at least 4 weeks.

7. Has been clinically stable for at least 12 weeks.

8. No more than moderate severity (4 on the 1-7 scale) on any PANSS positive item.

9. No more than 15 on the total of PANSS negative symptom items.

10. Simpson-Angus Scale total score <7.

11. Calgary Depression Scale for Schizophrenia total score <11.

12. Submaximal performance on at least one of the following MATRICS components
(letter-number span <20 OR HVLT total <31 OR CPT d-prime < 3.47).

13. Score > 1 SD below age-, gender-, and education-adjusted normal control mean on
MATRICS composite

14. Good general health with no additional diseases expected to interfere with the
studies.

15. Fluent in English.

16. Age 18-55.

17. Adequate visual and auditory acuity to allow neuropsychological testing.

18. Able to ingest oral medication.

19. Not pregnant or lactating (women of childbearing potential must use a medically
accepted method of birth control).

20. Onset of schizophrenia prior to age 45.

21. Available informant knowledgeable about subject's current functioning.

22. Informed consent obtained from the subject prior to entry into the study.

Exclusion Criteria:

1. Poor reading skills (raw score on MATRICS Wechsler Test of Adult Reading < 6).

2. History of systemic cancer within 5 years.

3. Use of any investigational drugs within 30 days prior to the screening visit.

4. Use of cholinesterase inhibitors (galantamine, rivastigmine, donepezil, or tacrine)
within 4 weeks of screening.

5. Any clinically significant laboratory test abnormality on screening tests (hematology,
chemistry, urinalysis, EKG). Clinically significant LFT elevations will be defined as
>2x the upper limit of normal.

6. Any significant neurologic disease including Alzheimer's disease, parkinson's disease,
stroke, huntington's disease, normal pressure hydrocephalus, brain tumor, progressive
supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history
of head injury with loss of consciousness for greater than one day within the past 5
years, or with residual deficits.

7. Use of antihypertensive agents with frequent CNS side effects (e.g. clonidine,
propranolol) within 4 weeks prior to the screening visit.

8. Use of medications known to alter drug absorption or metabolism (e.g. probenecid,
cimetidine, anti-fungal agents, erythromycin, rifampin, and anticonvulsants) within 4
weeks prior to the screening visit.

9. History of peptic ulcer disease within 2 years.

10. History of myocardial infarction, significant cardiovascular disease, or congestive
heart failure within 6 months, history of hepatic or renal insufficiency,
insulin-requiring diabetes or uncontrolled diabetes mellitus.

11. Clinically significant cardiac arrhythmia, resting pulse less than 50.

12. Present use or use in the 4 weeks prior to screening of anti-parkinsonian or
anticholinergic medications (e.g. Sinemet, amantadine, bromocriptine, pergolide,
selegiline, atropine, scopolamine, benztropine, trihexyphenidyl, hydroxyzine,
diphenhydramine).

13. Use of narcotic analgesics within 4 weeks prior to the screening visit.

14. History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV
criteria).

15. Receiving CYP 1A2 inhibitors such as certain SSRIs (all excluded in #4) cimetidine,
methoxsalen, quinolones, furafylline, or moclobemide.