Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease

This is a proof-of-principle investigation of the safety and potential effectiveness of
inhaled vaporized cannabis when added to a stable analgesic regimen in sickle cell disease
(SCD) patients with chronic pain. The study will be comprised of two 5-day intervention
periods in the inpatient setting (the Clinical Research Center at SFGH), with completion of a
5-day daily pain diary prior to admission to establish an outpatient baseline. Participants
will be randomly assigned, in double-blind fashion, to treatment with (A) vaporized cannabis
with an approximately 1:1 ration of delta-9-tetrahydrocannabinol:cannabidiol or (B) vaporized
placebo. Those who receive treatment A during the first admission will receive treatment B in
the second, and those who receive treatment B during the first admission will receive
treatment A in the second. The two admissions will be spaced at least 14 days apart.

On Day 1 of each admission, subjects will provide blood samples for baseline markers of
inflammation and SCD disease progression. They will undergo assessments of pain, mood, and
quality of life. At 12 pm on Day 1, they will inhale vaporized study agent (equivalent to 1
cannabis/placebo cigarette) using the Volcano® vaporizer; on Days 2-4 they will inhale study
agent at 8 am, 2 pm, and 8 pm, and they will inhale their final dose on Day 5 at 8 am.
Subjects will continue their pre-study analgesic regimen while in the study. If additional
analgesia is required, supplemental therapy will be administered and the dose recorded. Pain
measurements by visual analogue scale will be obtained every 2 hours while subjects are
awake. On Day 5 a second set of blood samples for inflammation markers and disease
progression will be obtained, and subjects will again complete pain, mood, and quality of
life assessments.

Inclusion Criteria:

- Sickle cell disease, including sickle cell anemia (SS), sickle-hemoglobin C disease
(SC), and sickle beta thalassemia disease (Sb).

- Ongoing opioid analgesic therapy for chronic sickle cell disease-associated pain.

- Subjects must be on a stable dose of analgesic medication (opioid or other) for at
least 2 weeks before enrollment.

- All men and women in this study must agree to use adequate birth control during this
study. Acceptable barrier birth control methods are a male condom, female condom,
diaphragm, or intra-uterine (IUD).

- All women of reproductive potential (who have not reached menopause or undergone
hysterectomy, oophorectomy, or tubal ligation) must have a negative urine b-HCG
pregnancy test performed before initiating the protocol-specified medication.

- Prior history of use of cannabis. Subjects must have smoked cannabis on at least 6
occasions in their lifetime prior to enrollment.

- Subjects will self-report abstaining from smoking or ingesting cannabis for one week
prior to their enrollment into the study.

- Able to understand and follow the instructions of the investigator, including
completing the pain intensity rating scales.

- Karnofsky Performance Scale >60.

- Able and willing to provide informed consent.

- Able and willing to spend two separate periods of 5 days and 4 nights in the Clinical
Research Center at SFGH.

Exclusion Criteria:

- Severe coronary artery disease, uncontrolled hypertension, cardiac ventricular
conduction abnormalities, orthostatic mean blood pressure drop greater than 24 mmHg,
severe chronic obstructive pulmonary disease.

- Evidence of clinically significant hepatic or renal dysfunction based on judgment of
physician.

- Positive serum THC level on Day 1 of study.

- Active substance abuse (e.g., alcohol or injection drugs) as determined by urine
toxicity screening.

- Neurologic dysfunction or psychiatric disorder severe enough to interfere with
assessment of pain or sensory systems.

- Current use of smoked tobacco products.

- Women who are pregnant or breast-feeding may not take part in this study.

- Unable to read or speak English.