University of Alabama at Birmingham (UAB) Adult CBD Program

The specific goals of this phase 1 dose finding study conducted in consecutively enrolled
patients 15 years and older are to prospectively and longitudinally assess the safety and
tolerability, including cognitive effects, of CBD at various doses between 5 mg/kg/day and 25
mg/kg/day with additional titration in some cases up to 50 mg/kg/day. In order to participate
in the study, participants will need to fulfill the inclusion and exclusion criteria.

Inclusion Criteria:

- Any patient with disabling epilepsy with diagnosis confirmed by video/EEG monitoring
and

- Patient should have history of a trial of at least four AEDs including one trial
of a combination of two concomitant AEDs, without successful seizure control.
Vagus nerve stimulation (VNS), RNS deep brain stimulation, or the ketogenic diet
can be considered an equivalent to a drug trial,

- Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4
weeks prior to submitting records for review by the CBD Treatment Approval
Committee.

- VNS or RNS must be on stable settings for a minimum of 3 months,

- If on ketogenic diet, must be on stable ratio for a minimum of 3 months.

- The referring provider needs to make available for review all of the following:

- Most recent Brain MRI report,

- Most recent ECG report,

- Video/EEG monitoring report confirming the diagnosis of epilepsy,

- Evidence that the patient has failed 4 AEDs as indicated above,

- Current Medication List

- Patient must have at least 4 clinically countable seizures per month. Seizure history
to include a documented history of generalized seizures (drop attacks, atonic,
tonic-clonic and/or myoclonic), focal seizures without loss of consciousness with a
motor component, focal seizures with loss of consciousness, or focal seizures with
secondary generalization,

- Results of routine testing including blood work (CBC,CMP liver function tests (LFTs),
renal panel, Urinary Analysis, and levels of all AEDs) and digital copy of a routine
EEG along with the formal written report performed within 3 months prior to submitting
records for CBD Treatment Approval review. If any AED dose was adjusted within three
months prior to submitting records for CBD Treatment Approval Committee review, level
on the new dose will need to be provided. If applicable, results of any metabolic or
genetic testing performed should be included in submitted records for review:.

- If applicable, documentation (including date of surgery) of prior VNS, RNS, Corpus
Callosotomy, or other epilepsy surgery the patient has received.

- Age 15 years and older,

- Patients are able to keep and provide seizure calendar for at least 3 months prior to
submitting records for CBD Treatment Approval Committee review. The patient will need
to provide an updated calendar at the time of enrollment,

- Acceptable method of contraception (or abstinence) for women of childbearing potential
and for male patients with partners of childbearing potential; female patients must
have_a negative urine pregnancy test on the day of initiating CBD,

- For patients who agree to participate in the optional neuroimaging substudy, an MRI
screen will be obtained to show that the patient does not have contraindication to
receiving MRI/fMRI at 3 Tesla (e.g., metallic artifact).

- Approval for inclusion by the CBD Treatment Approval Committee.

- Current State of Alabama Resident

- Acceptable documentation of Alabama residency includes the following:

- a state issued ID, such as a driver's license, from patient or patient's parent/
legally authorized representative (LAR).

- documents showing the patient or patient's parent/LAR rents/owns property in the
state,

- state voter registration from patient or patient's parent/LAR, or

- a recent state tax return from patient or patient's parent/LAR.

Exclusion Criteria:

- Active psychogenic non-epileptic seizures (PNES); Patients with more than 1 year
freedom from PNES will not be excluded,

- Patients who are pregnant, breastfeeding, or not using acceptable methods of
contraception during the course of the study and for three months thereafter,

- Male patient's partner is of child bearing potential; unless willing to ensure that
they (male patients) or their partner(s) are using acceptable methods of contraception
during the course of the study and for three months thereafter

- History of substance abuse/addiction,

- Use of medical marijuana or CBD based product in the past 30 days,

- Initiation of felbamate within last 12 months,

- Allergy to CBD or any marijuana-type products,

- ALT >5 x ULN or AST >5 x ULN, as seen in participant's laboratory results submitted to
the CBD Treatment Approval Committee for review.

- Hemoglobin <1 0 or Hematocrit <30 or WBC < 2000, as seen in participant's laboratory
results submitted to the CBD Treatment Approval Committee for review.

- In investigator's judgment, active medical condition/treatment that impacts study
activities.

- Unable to provide consent (and no LAR),

- Unable/Failure to comply with study visits/requirements and/or instructions,

- Confirmed diagnosis for Dravet Syndrome or Lennox Gastaut Syndrome that qualifies the
patient for a GW Dravet Syndrome or Lennox Gastaut Syndrome randomized controlled
clinical trial for which the patient is eligible pursuant to the GW clinical trial
enrollment criteria unless

(a) there is no study that is either actively open for enrollment of patients at UAB
or that is expected to actively begin enrolling patients at The University of Alabama
at Birmingham within two (2) months of the date on which the patient is screened for
the UAB Pediatric CBD Program or UAB Adult CBD Program,

- Subjects with contraindications to MRI/fMRI at 3 Tesla (e.g., metallic artifact) will
not be offered participation in the optional substudy.

- Primary residence in a State different than Alabama.