Effects of Cannabis Administration Routes on Human Performance and Pharmacokinetics

NCT02177513 | Completed Phase 1

• 2 other identifiers: 99991413514-DA-N135
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cannabis Use

Keywords

Cannabis; Pharmacodynamics; Marijuana; Cannabinoids; Vaporized

Outcome Measures

Primary Outcomes (4)

• Cannabis' pharmacodynamic effects

  Multiple times daily

• Cannabis' pharmacokinetic profiles

  Multiple times daily

• Pharmacokinetic/Dynamic Modelling

  Once

• Cannabis oral fluid cutoff evaluation

  Once

Secondary Outcomes (6)

• Cannabinoid stability in dried blood

  Multiple times

• Pharmacokinetic/Dynamic Modelling

  Multiple times

• Cannabinoid stability in oral fluid

  Multiple times

• Cannabis' effects on appetitive peptides

  Multiple times daily

• Cannabis urine cutoff evaluation

  Once

Study Arms (5)

1

ACTIVE COMPARATOR

Drug: Placebo + Smoked Cannabis

2

ACTIVE COMPARATOR

Drug: Placebo + Inhaled Cannabis

3

ACTIVE COMPARATOR

Drug: Oral Cannabis + Placebo

4

PLACEBO COMPARATOR

Drug: Placebo + Placebo

5

ACTIVE COMPARATOR

Drug: 6.9% cannabis oral

Interventions

Placebo + Placebo DRUG

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.

4

Oral Cannabis + Placebo DRUG

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.

3

Placebo + Inhaled Cannabis DRUG

Participants will consume a brownie containing the equivalent of one placebo (0.001% THC) cigarette

2

Placebo + Smoked Cannabis DRUG

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.

1

6.9% cannabis oral DRUG

Participants will consume a brownie containing the equivalent of one active (6.91% THC) cannabis cigarette.

5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 50 years of age;
• Cannabis consumption with a minimum frequency of at least twice per month during the three months prior to the study and average frequency of cannabis smoking of less than three times per week (occasional cannabis smoker) in the past 3 months or at least an average of five times per week (frequent cannabis smoker) in the past 3 months;
• A positive urine cannabinoid screen if in the frequent cannabis smoker group;
• Peripheral veins suitable for repeated venipuncture and/or placement of an intravenous catheter, as assessed by a physician s assistant, nurse, or physician;
• Blood pressure (BP) and heart rate (HR) at or below the following values while sitting after five min rest: systolic BP (SBP) 140 mm Hg, diastolic BP (DBP) 90 mm Hg, heart rate (HR) 100 bpm;
• ECG and three-minute rhythm strip without clinically relevant abnormalities;
• Women with reproductive potential must use a medically acceptable form of contraception for the duration of the study. Medically acceptable forms of contraception include: oral contraceptive, intrauterine device (IUD), depot hormonal preparation (ring, injection implant), or a barrier method of contraception such as a diaphragm, sponge with spermicide, or a condom. Abstinence is an alternative lifestyle and subjects practicing abstinence may be included in the study.
• Must be able to safely suspend use of CNS depressant, anticholinergic, and/or sympathomimetic medications before study dosing. Length of medication suspension will be equal to 3 half-lives of the medication in use.

You may not qualify if:

• Current physical dependence on any drug other than cannabis, caffeine, or nicotine;
• Currently using cannabis for medical purposes under the explicit recommendation of a physician providing medical care;
• History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests , that might put the subject at increased risk of adverse events such as history of psychotic disorder, clinically significant mood and/or anxiety disorder, diabetes, liver, renal or cardiovascular disease;
• Liver enzymes greater than or equal to 2 times upper normal limit and/or clinical signs/symptoms consistent with liver disease including but not limited to nausea, vomiting, jaundice, itching, abdominal pain, and swelling;
• History of clinically significant adverse events associated with cannabis intoxication such as severe anxiety and panic, paranoia and psychosis, sustained tachycardia, or severe hypotension;
• Donation of more than 450 mL blood within 8 weeks of study treatment phase;
• Hemoglobin less than 12.0 g/dL and/or clinical signs/symptoms consistent with anemia including but not limited to fatigue, tachycardia, shortness of breath, and dizziness;
• If female, pregnant or nursing;
• Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 90 days preceding study enrollment;
• History of food allergy or sensitivity to gluten, dairy, egg, soy, and/or chocolate.
• Any form of color blindness

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (6)

• Vega WA, Aguilar-Gaxiola S, Andrade L, Bijl R, Borges G, Caraveo-Anduaga JJ, DeWit DJ, Heeringa SG, Kessler RC, Kolody B, Merikangas KR, Molnar BE, Walters EE, Warner LA, Wittchen HU. Prevalence and age of onset for drug use in seven international sites: results from the international consortium of psychiatric epidemiology. Drug Alcohol Depend. 2002 Dec 1;68(3):285-97. doi: 10.1016/s0376-8716(02)00224-7.

  PMID: 12393223 BACKGROUND

• Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;(168):657-90. doi: 10.1007/3-540-26573-2_23.

  PMID: 16596792 BACKGROUND

• Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-60. doi: 10.2165/00003088-200342040-00003.

  PMID: 12648025 BACKGROUND

• Newmeyer MN, Swortwood MJ, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabis Edibles: Blood and Oral Fluid Cannabinoid Pharmacokinetics and Evaluation of Oral Fluid Screening Devices for Predicting Delta9-Tetrahydrocannabinol in Blood and Oral Fluid following Cannabis Brownie Administration. Clin Chem. 2017 Mar;63(3):647-662. doi: 10.1373/clinchem.2016.265371. Epub 2017 Feb 10.

  PMID: 28188235 DERIVED

• Newmeyer MN, Swortwood MJ, Taylor ME, Abulseoud OA, Woodward TH, Huestis MA. Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration. J Appl Toxicol. 2017 Aug;37(8):922-932. doi: 10.1002/jat.3440. Epub 2017 Jan 31.

  PMID: 28138971 DERIVED

• Newmeyer MN, Swortwood MJ, Barnes AJ, Abulseoud OA, Scheidweiler KB, Huestis MA. Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake. Clin Chem. 2016 Dec;62(12):1579-1592. doi: 10.1373/clinchem.2016.263475. Epub 2016 Oct 10.

  PMID: 27899456 DERIVED

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Marilyn Huestis, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 27, 2014
• Study Start: June 14, 2014
• Primary Completion: April 27, 2016
• Study Completion: April 27, 2016
• Last Updated: December 16, 2019

Record last verified: 2016-04-27

Locations

US (1)