Safety and Effects on Responses to Stress and Pain of Natural Medical Marijuana Products
Condition: Pain
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 1

Summary: 
      This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic
      profile and the physiologic, neuroendocrine and behavioral stress and pain responses to acute
      single doses and repeated dosing of oral tablet formulation of natural Cannabidiol (CBD)
      alone and in combination with Tetrahydrocannabinol and matched Placebo (PLA).
    

Detailed description: 
      This proposal aims to systematically examine the safety and pharmacokinetic/pharmacodynamic
      (PK/PD) profile and the physiologic, neuroendocrine and behavioral stress and pain responses
      to acute single doses and repeated dosing of oral tablet formulation of natural Cannabidiol
      (CBD) at 40 mg and 100 mg alone and in combination with Tetrahydrocannabinol (THC) at 10, 20
      and 30 mg, and matched Placebo (PLA) under the following specific aims:

      Aim 1: To assess the safety and PK/PD profile of acute single doses of natural oral tablet of
      CBD (40 mg, 100 mg), and the CBD/THC combination (40/10, 40/20 and 100/30 mg) and matching
      placebo (PLA) over six separate sessions one week apart in healthy adult men and women who
      are current recreational cannabis users (STUDY 1).

      Aim 2: To examine the effects of separate CBD, THC, CBD/THC combination vs. PLA on
      subjective, physiological, neuroendocrine, cognitive and behavioral measures of stress, pain
      and anxiety at baseline and under acute pain provocation using an adapted Cold Pressor Test
      (CPT) in STUDY 1.

      Aim 3: To examine the safety and tolerability of the two specific doses of CBD/THC, selected
      on the basis of best PK/PD and tolerability profile from Study 1 vs. PLA on baseline and CPT
      provoked pain in individuals with chronic pain over a 7-day repeated dosing (STUDY 2).

      Study 1:

      Eight 21-45-year-old men and women , who are recreational marijuana users but do not meet
      criteria for moderate-severe cannabis use disorder will be recruited to complete six separate
      inpatient laboratory sessions one week apart during which they will be assigned to receive an
      acute dose of either 40 mg CBD or 100 mg CBD alone, a CBD/THC combination of 40/10, 40/20 or
      100/30 or PLA, in a random, counter-balanced, double-blind, cross-over design over a 6-week
      period. Sessions will be completed one -week apart to allow for an adequate washout period
      between sessions.

      Study 2:

      Adult men and women ages 21-60 (N=24) with chronic pain (not fully controlled by opioid pain
      medication), will be recruited and randomly assigned to receive the two most tolerable
      CBD/THC doses (two active doses of n=8 in each) or PLA (n=8) repeated dosing for 7 days. On
      day 1 and day 6/7 of the 7-day dosing, subjects will complete laboratory sessions. For 14
      days after the 7-day dosing, subjects will complete daily ratings of pain and other
      patient-related outcomes. Subjects cannot meet criteria for moderate to severe levels of
      cannabis use disorder or other substance use disorders.

      This registration will focus on Study 2.
    

Intervention name(s): Active CBD/THC Dose 1; Active CBD/THC Dose 2; matched placebo comparator
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.; Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.; Subjects will self-administer the assigned study medication daily at home after pickup and will be tested using medication compliance procedures. Subjects will visit the center 2 times in the 7-day period on days 1 and 7 for blood draws to assess medication compliance.
Other intervention name(s): Medical marijuana medicine; Medical marijuana medicine; Placebo
Intervention MeSH terms: Dronabinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment