Effects of Cannabis Administration Routes on Human Performance and Pharmacokinetics
Condition: Cannabis Use
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Marijuana (cannabis) is an illegal drug. Researchers want to study people s reactions,
      attention, and behavior after they take marijuana in different ways. They want to learn
      better ways to detect drugs in a person s body They also want to know how long marijuana can
      be found in blood, urine, saliva, and breath.

      Objectives:

      - To learn how people respond to delta-9-tetrahydrocannabinol (THC, a marijuana component)
      and how their bodies handle it after it is given in different ways.

      Eligibility:

      - Adults age 18 50 who use marijuana.

      Design:

        -  Participants are screened under another NIDA protocol.

        -  This study involves up to 6 visits to NIDA.

        -  At the first visit, participants will practice the tasks and tests they will do at their
           dosing sessions. They will learn how to give breath and saliva samples.

        -  Dosing sessions 1 4 will last 3 5 days each. All participants will be admitted to a
           research clinic the night before these sessions. Some participants can stay at the
           clinic and some must go home between sessions.

        -  At each session, participants will eat a brownie with placebo or marijuana. Then they
           will smoke a placebo or marijuana cigarette. Some will inhale placebo or marijuana after
           it is vaporized.

        -  Throughout the sessions:

        -  Participants will give urine, saliva, and breath samples. Their blood will be taken with
           a tube in a vein and finger pricks. Their vital signs will be checked.

        -  Participants will answer questionnaires and take thinking tests. They will also take
           tests that assess eye movement, balance, and time estimation.

        -  Participants may have a 5th dosing session. They will eat a marijuana brownie and have
           the above tests and samples.
    

Detailed description: 
      Objectives

      Cannabinoids are most commonly administered via smoking. Oral consumption in medications,
      teas, oils, or food also is widely utilized. Additionally, cannabis vaporization followed by
      inhalation for medical and illicit administration is common. Differences in cannabis
      pharmacodynamics and pharmacokinetics between these three administration routes and in
      occasional and frequent cannabis smokers are not thoroughly characterized. This study
      evaluates cannabis pharmacodynamics and pharmacokinetics in occasional and frequent smokers
      after smoked, vaporized, and oral cannabis administration.

      <TAB>

      Study Population

      Up to 80 healthy cannabis smokers, aged 18-50, without a history of adverse reactions to
      cannabis will be recruited. For dosing sessions 1-4, ten occasional smokers (smoking
      frequency greater than or equal to 2 times/month but <3 times/week) and ten frequent smokers
      (smoking frequency generally greater than or equal to 5times/week) are required. For the
      optional 5th session, 8-20 participants (regardless of smoking history) are required.

      <TAB>

      Study Design

      Occasional and frequent cannabis smokers are recruited to participate. Prior to dosing
      sessions, there is a training visit for all study procedures. Sessions 1-4 are 3 and 4 days
      each for occasional and frequent cannabis smokers, respectively, and the study design is
      double blind, double dummy, randomized, crossover, and placebo-controlled. In each session,
      participants will consume a placebo or active oral (baked in a brownie) cannabis (6.9%
      9-tetrahydrocannabinol [THC]) dose followed by either placebo or active smoked or vaporized
      cannabis. Only one active dose will be administered in each dosing session. Whole blood, oral
      fluid, urine, dried blood spots, and breath are collected throughout all sessions. Due to the
      large THC body burden stored in the tissues, we will collect biological specimens for a
      longer period in frequent cannabis smokers than for occasional cannabis smokers. An optional
      5th dosing session will be offered in which participants receive a single oral cannabis dose
      for pharmacokinetic monitoring. The placebo cannabis plant material has a low THC
      concentration. As we are expecting that the active brownie dose might result in low THC oral
      fluid contamination, it is necessary to have an active brownie THC dose that is not followed
      by placebo vaporizer or smoked cannabis. Occasional smokers may stay or be discharged between
      sessions, including between the 4th and optional 5th dosing session, but dosing must not
      exceed self-reported intake frequency. Frequent smokers must be discharged for at least 72 h
      between dosing sessions 1-4, and must stay on the unit at the end of session 4 for session 5
      if they choose to participate. The difference between requirements for occasional and
      frequent smokers to participate in the optional 5th dose is due to the potential confound of
      low THC concentrations in frequent smokers that might not permit the detection of low THC
      concentrations after consumption of a low oral THC dose. Occasional cannabis smokers will
      reside on the closed research unit for approximately 72 h for dosing sessions 1-4, and for
      approximately 66 h for dosing session 5. Frequent cannabis smokers will reside on the closed
      research unit for approximately 90 h for dosing sessions 1-3 (and 4 if not participating in
      optional session 5). If a frequent smoker chooses to participate in dosing session 5, they
      will remain on the unit for approximately 162 h for sessions 4 and 5. Participants will
      complete a battery of subjective, objective, and neurocognitive tests before and after
      dosing. Subjective effects are assessed with visual analog scales. Objective measurements
      include physiological measurements, expired carbon monoxide, reddening of the conjunctivae
      and tests measuring psychomotor skills and cognitive functions.

      <TAB>

      Outcome Parameters

      Primary outcome measures include subjective and objective assessments, performance on
      neurocognitive tasks, and cannabinoid concentrations in whole blood, oral fluid, urine, dried
      blood spots, and breath. Correlations between cannabinoid concentrations in whole blood,
      dried blood spots, oral fluid, and breath will be investigated, the Oral Fluid Working Group
      for the Partnership for Clean Competition oral fluid screening algorithm will be evaluated,
      and the pharmacokinetic profiles of alternative cannabinoids will be characterized. Secondary
      investigations include comparing cannabinoid stability in dried blood spots and whole blood,
      evaluating the World Anti-Doping Agency urine 11-nor-9-carboxy-THC decision limit,
      characterizing the performance of the Alere DDS2 on-site oral fluid screening device, and
      evaluating effects of acute cannabis administration on leptin and other appetitive
      peptides.<TAB>
    

Intervention name(s): Placebo + Placebo; Oral Cannabis + Placebo; Placebo + Inhaled Cannabis; Placebo + Smoked Cannabis; 6.9% cannabis oral
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Participants will consume a brownie containing the equivalent of one placebo (0.001% THC) cigarette followed by smoking or inhaling (after vaporization) the equivalent of one placebo (0.001% THC) cigarette.; Participants will consume a brownie containing the equivalent of one active (6.9% THC) cannabis cigarette followed by either smoking or inhaling (after vaporization) the equivalent of one placebo (0.001% THC) cigarette.; Participants will consume a brownie containing the equivalent of one placebo (0.001% THC) cigarette; Participants will consume a brownie containing the equivalent of one placebo (0.001% THC) cigarette followed by smoking the equivalent of one active (6.9% THC) cigarette.; Participants will consume a brownie containing the equivalent of one active (6.91% THC) cannabis cigarette.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Cannabis; Pharmacodynamics; Marijuana; Cannabinoids; Vaporized