The Pharmacokinetics and Pharmacodynamics of Oral and Vaporized Cannabidiol

The proposed study will be conducted at the Johns Hopkins Behavioral Pharmacology Research
Unit (BPRU) and the Johns Hopkins Bayview Clinical Research Unit (CRU). Participants will
complete 4 acute drug administration periods, each consisting of a single drug exposure
followed by a 5-day observation period (3-days (58-hours) inpatient and 2-days outpatient).
Biological specimens will be obtained to characterize the pharmacokinetics of THC, CBD, and
their metabolites in whole blood, oral fluid, urine, and hair during this period. Each
participant will receive all 4 dose conditions in a counterbalanced order using a placebo
controlled within-subject crossover design. The 4 drug conditions are as follows:

- Condition 1: Inhalation of cannabis vapor containing approximately a 20:1 ratio of
CBD:THC and will be measured to deliver a target dose of 100mg CBD and 5mg THC.

- Condition 2: Inhalation of 100mg CBD vapor.

- Condition 3: Ingestion of 100mg CBD.

- Condition 4: Placebo

Drug administration will be double blind and double dummy; both inhalation and oral ingestion
of study drugs will occur during all 4 sessions. The order of drug administration will be
counterbalanced across participants.

Research volunteers will be recruited until up to 18 participants have completed each of the
four study sessions (received Conditions 1-4). Immediately before (baseline) and following
each exposure, a battery of assessments including biological fluid collection and testing,
subjective questionnaire administration, and performance testing will be conducted for all
study participants. Post-exposure testing will be conducted in two phases: a 3-day (58 hour)
residential stay, and a 2-day outpatient period, for a total of 5 days. Participants who drop
out of the study prior to completion of all 4 drug conditions will be considered "incomplete"
and replaced. Approximately one week (minimum of 6 days) will separate the administration of
each dose.

The target demographic for study participation are healthy adults who: 1) have a history of
intentionally inhaling cannabis/CBD, 2) have not used cannabis in the past month (desire is
to have participants free of cannabinoids in biological matrices at the time of initial drug
administration), and 3) who are not currently dependent on or seeking treatment for use of
cannabis or other psychoactive drugs.

Study outcome variables include quantitative levels of CBD and its primary metabolites, THC
and its primary metabolites, results of drug testing procedures conducted in accordance with
current federal Mandatory Guidelines for workplace drug testing, subjective drug effect
ratings, and performance on behavioral assessments. Biological specimens will be analyzed by
an independent laboratory with validated analytical procedures that are specific and accurate
for measurement of marijuana constituents and related metabolites. Subjective, cardiovascular
and behavioral outcomes will be assessed using multiple regression analyses appropriate for
repeated measures testing based on the final characteristics of the data set (e.g. normal
distribution, skewness, kurtosis), and correlated with biomarker results of interest.

Inclusion Criteria

1. Have provided written informed consent

2. Be between the ages of 18 and 45

3. Be in good general health based on a physical examination, medical history, vital
signs, and screening urine and blood tests

4. Test negative for recent cannabis use in urine at the screening visit (confirmed by
GC/MS laboratory test) and again upon admission for each experimental session

5. Test negative for other drugs of abuse, including alcohol at the screening visit and
upon arrival for each experimental session

6. Demonstrate ability to expectorate 3-5 mL of "native" oral fluid over a 5-minute
period

7. Not be pregnant or nursing (if female). All females must have a negative serum
pregnancy test at the screening visit and a negative urine pregnancy test at clinic
admission.

8. Have a body mass index (BMI) in the range of 19 to 36 kg/m2

9. Have head hair that is at least 4 cm (approximately one and a half inches) in length
on the back of the head.

10. Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of
150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg

11. Have no allergies to any of the ingredients used to prepare cannabis brownies
(chocolate, eggs, wheat, etc.).

12. Report prior experience inhaling cannabis (either via smoking or vaporization).

Exclusion Criteria

1. Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine in
the month prior to the Screening Visit;

2. History of or current evidence of significant medical or psychiatric illness judged by
the investigator to put the participant at greater risk of experiencing an adverse
event due to exposure or completion of other study procedures.

3. Use of an OTC, systemic or topical drug(s), herbal supplement(s), or vitamin(s) within
14 days of experimental sessions; which, in the opinion of the investigator or
sponsor, will interfere with the study result or the safety of the subject.

4. Use of a prescription medication (with the exception of birth control prescriptions)
within 14 days of experimental sessions; which, in the opinion of the investigator or
sponsor, will interfere with the study result or the safety of the subject.

5. Use of hemp seeds or hemp oil in any form in the past 3 months.

6. Use of dronabinol (Marinol) within the past 6 months.

7. History of xerostomia (dry mouth), or the presence of mucositis, gum infection or
bleeding, or other significant oral cavity disease or disorder that in the
investigator's opinion may affect the collection of oral fluid samples.

8. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g.,
Prinzmetal's angina).