Cannabidiol and Autonomic Function at Rest
Condition: Healthy
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Cannabidiol (CBD) is one of 700 chemicals derived from the Cannabis sativa plant and is both
      legal and widespread for distribution in the state of Vermont. The central hypothesis of this
      proposal is that in apparently healthy adults, acute CBD favorably affects the autonomic
      nervous system and that this will be evident by an increase in heart rate variability. The
      overall goal is to understand how CBD affects the autonomic and cardiovascular systems at
      rest, and when perturbed. The investigators will study a narrow age range of adults,
      administer varying acute doses of CBD, characterize baseline cardiovascular variables, and
      record responses to autonomic challenge maneuvers. This will provide the framework to assess
      potential therapies and/or risk factors of CBD, particularly as it relates to healthy
      individuals. More information that is so widely taken, especially one that targets receptors
      known to be involved in cardiovascular signaling pathways is imperative.
    

Detailed description: 
      The study will be conducted in the Exercise Physiology Laboratory in the Jeffords Science
      Building at Castleton University. Participants will be asked to fast overnight, avoid
      beverages or food containing caffeine, alcohol, or CBD for at least 12h, and to not perform
      physical effort for 6h prior to each session.

      During the initial session, individuals will: have their height and body mass measured,
      complete a health history questionnaire, and sign a consent form approved by Castleton
      University's Institutional Review Board. Prior to data collection, individuals will be
      advised of the possible risks, methods, and potential benefits of this study. They will also
      be familiarized with the noninvasive cardiovascular monitoring equipment, which they will be
      putting on themselves. These include an automated blood pressure (BP) cuff and a heart rate
      (HR) chest strap monitor.

      On the day of each experiment, participants will be given a standardized meal and asked to
      put on the BP cuff and HR monitor. Individuals will remain seated for the length of the
      experiment (doing nothing or reading). Baseline measurements will be taken remotely following
      15 minutes of rest. Under supervision, participants will be asked to consume oral CBD oil
      (0mg, 25 mg, 50 mg, or 200mg), infused in non-CBD containing MCT (medium-chain triglycerides)
      oil to standardize dose volume of 3ml. Assessments will be measured remotely at intervals up
      to 2.5 hours after ingestion. The study will be double-blind, thus neither the participant
      nor researcher will be aware of the CBD dose for a particular session. Participants will be
      asked to return for 3 additional consecutive weeks, each session will be a different dose of
      CBD.

      In the final experimental session (to be completed after initial analyses of dose responses),
      participants will be given a standardized meal and asked to put on the blood pressure cuff
      and HR monitors. Individuals will remain seated for the length of the experiment. Following
      15 minutes of rest, participants will be asked to perform two autonomic stress tests: the
      isometric hand grip test, and the cold face test. First, the maximum voluntary contraction
      (MVC) for the isometric hand grip test will be assessed. Participants will be asked to press
      a handgrip dynamometer with full strength. To perform the isometric handgrip test,
      participants will again use the dynamometer and maintain handgrip at 30 percent MVC for 2
      min. A recovery period of 10 minutes between each test will be observed. For the cold face
      test, a cold compress (1-2 degrees Celcius) will be applied to the forehead and maxillary
      region of the subjections face for 2 min. Following these baseline tests, participants will
      be asked to consume a dose of CBD (determined following analyses of the initial 4 sessions)
      and perform the two autonomic stress tests again 2h post ingestion.
    

Intervention name(s): cannabidiol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Cannabidiol oral product formulated in MCT (medium chain triglyceride) oil; Placebo oral product formulated in MCT (medium chain triglyceride) oil
Other intervention name(s): CBD
Intervention MeSH terms: Cannabidiol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each participant will receive a different dose in consecutive weeks (4 doses total, one of which is a placebo), thus serving as their own control.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science