Effects of Huperzine A in Treatment of Moderate to Severe TBI

Inclusion Criteria:

- Males and females aged 18 to 65

- Moderate or severe TBI, based on admission Emergency Room GCS 3-12

- All subjects will be greater than 2 weeks, but no more than 1 year, after the
qualifying TBI, and will be symptomatic at enrollment (i.e. all subjects will exhibit
evidence of ongoing posttraumatic amnesia via the Galveston Orientation Amnesia test
(GOAT), or score at least 1.5 SD below the mean for completion time on Part B of the
Trail Making Test.

- Agreement to undergo no changes in concomitant medications (including dietary
supplements) or therapeutic interventions during the first 12 weeks of the study (that
is, the 12 weeks of dosing with study drug), except where medically indicated. Stable
concomitant drug regimen (greater than two weeks pre-enrollment without changes)

- Normal swallowing

- English-speaking (since not all of the outcome metrics are normed outside of the
English language)

- Patient can be on seizure medication.

Exclusion Criteria:

- Patients taking acetylcholinesterase inhibitors and other cholinergic and
anticholinergic drugs (e.g., tacrine, physostigmine, velnacrine, donepezil,
rivastigmine, metrifonate) and CYP1A inducing drugs.

- Evidence of more than 1 seizure in the past 4 weeks prior to enrollment: Patients may
not be enrolled if there is evidence of more than one seizure (clinical or
electrographic, but not including epileptiform or other irritative discharges) during
the 4 weeks prior to enrollment.

- Premorbid history of epilepsy with seizure frequency >1 per month: Patients with a
history of idiopathic epilepsy may not be enrolled if their seizure frequency was > 1
per month in the 3 months prior to injury. If pre-injury seizure frequency was < 1 per
month but there is documented evidence that post-injury seizure frequency is > 1 per
month or there is documented evidence of an increase in the severity or duration of a
single seizure relative to the premorbid history, the patient must be excluded.

- Evidence of premorbid major CNS disorder, developmental disorder, psychiatric disorder
or substance abuse: Prior to sustaining TBI, patient was diagnosed and/or treated for
a major neurologic condition, pervasive developmental disorder (e.g., mental
retardation, autism), psychiatric disorder or substance abuse that continued to
produce functional disability up to the time of injury.

- Individuals with disorders of consciousness, as defined at the time of screening of
having vegetative and/or minimally conscious state, will not be enrolled. However,
these patients may be followed until they:

- Meet eligibility criteria

- Are more than 12 weeks post injury

- Are discharged

- Pregnancy, as determined by urine hCG testing before randomization

- Breast feeding females

- Significant hematologic, renal or hepatic dysfunction [Hepatic/renal dysfunction is
generally identified as lab results > two times the upper limits of normal (ULN), and
hematologic dysfunction is determined by clinically significant abnormal lab results],
on baseline laboratory examination.

- Slow heart rate (bradycardia) or other heart conditions related to rate

- History of peptic ulcer disease

- History of asthma or emphysema

- History of GI/urinary tract blockages (i.e. ileus, IBS)

- History of glaucoma