The Pharmacokinetics of Single Dose Oral Tetrahydrocannabinol and Cannabidiol (POT-GFR-PK)

The Pharmacokinetics of Oral Tetrahydrocannabinol and Cannabidiol Across the Spectrum of Glomerular Filtration Rate: a PharmacoKinetic Study

POT-GFR-PK is a single dose pharmacokinetic study oral tetrahydrocannabinol (THC) and cannabidiol (CBD) in healthy adult controls and individuals with chronic kidney disease including those treated with in-center hemodialysis.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Diseases; Cannabis; Dialysis
• Intervention / Treatment: Drug: Tetrahydrocannabinol-Cannabidiol Combination

Detailed Description

Adults aged greater than 25 years including 6 with eGFR>60ml/min/1.73m2, 6 eGFR 30-59ml/min/1.73m2, 6 eGFR <30ml/min/1.73m2 (CKD Epidemiology Collaboration equation) and 6 receiving in-center hemodialysis at least 2x weekly via a tunnelled catheter will receive THC 0.1mg/kg and CBD 2mg/kg by mouth in the form of MediPharm Labs-001 (MPL-001) (50mg CBD/2mg THC per 1mL). In healthy controls and participants with chronic kidney disease, blood samples will be collected at t=0, 1, 2, 3, 3.5 and 4 hours post THC/CBD administration. In participants receiving in-center hemodialysis, blood samples will be collected at t=0, 1, 2, 3, 3.5 and 4 hours post THC/CBD administration and during hemodialysis at t=0, 60, 120, 180 minutes and 15 minutes prior to the end of hemodialysis (at a reduced pump speed with blood flow 50-100ml/min) and 60 minutes post-hemodialysis. A 24 hour urine will be collected in all participants except those receiving hemodialysis without any residual urine output. Dialysate samples will be collected at 1,2,3 hours during hemodialysis and at the end of hemodialysis. Blood samples will also be collected at 24 and 48 hours. Plasma, urine and dialysis cannabinoids (THC, CBD and their metabolites) will be quantified using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4A6
      • St. Joseph's Healthcare Hamilton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. adult age>25 years
2. estimated glomerular filtration rate (eGFR)>60ml/min/1.73m2 or eGFR<60ml/min/1.73m2 by the CKD Epidemiology Collaboration equation including in-center hemodialysis at least 2x weekly for a minimum of 3 hours per treatment via a tunnelled catheter treated >90 days
3. agree to take the medication as directed in the study
4. provides informed consent

Exclusion Criteria:

1. body mass index <20 or >35kg/m2
2. physical dependence on any drug other than caffeine or nicotine
3. history of clinically significant adverse event associated with cannabis intoxication
4. history of psychosis or mania or any active major psychiatric disorder
5. recent (within 30 days) use of any cannabinoid (natural or synthetic) identified by self-report or urine drug screen for cannabinoids
6. taking any medication with known interactions with THC or CBD via cytochrome P450 (CYP) CYP2C9, CYP2C19 and CYP4A6 or CYP2D4 (e.g. anti-epileptic drugs, calcineurin inhibitors, anti-fungal)
7. evidence of liver dysfunction (ALT less than 3 times upper limit of normal, bilirubin below upper limit of normal, international normalized ratio<1.5)
8. pregnant or breastfeeding women
9. change in ideal body weight or dry weight in the last 4 weeks
10. intradialytic hypotension (systolic blood pressure<90mmHg) requiring an intervention in the previous 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: THC/CBD; Oral THC 0.1mg/kg and CBD 2.5mg/kg	Drug: Tetrahydrocannabinol-Cannabidiol Combination; Oral THC 0.1mg/kg and CBD 2.5mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tetrahydrocannabinol and its metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Tetrahydrocannabinol and its metabolites time to Cmax	Time to Cmax	48 hours
Tetrahydrocannabinol and its metabolites last detection time	Last detection time	48 hours
Tetrahydrocannabinol and its metabolites area under the curve	Area under the curve	48 hours
Tetrahydrocannabinol and its metabolites renal clearance	Renal clearance	48 hours
Tetrahydrocannabinol and its metabolites dialytic clearance	Dialytic clearance	48 hours
Cannabidiol and its metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Cannabidiol and its metabolites time to Cmax	Time to Cmax	48 hours
Cannabidiol and its metabolites last detection time	Last detection time	48 hours
Cannabidiol and its metabolites area under the curve	Area under the curve	48 hours
Cannabidiol and its metabolites renal clearance	Renal clearance	48 hours
Cannabidiol and its metabolites dialytic clearance	Dialytic clearance	48 hours
Other cannabinoids and their metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Other cannabinoids and their metabolites time to Cmax	Time to Cmax	48 hours
Other cannabinoids and their metabolites last detection time	Last detection time	48 hours
Other cannabinoids and their metabolites area under the curve	Area under the curve	48 hours
Other cannabinoids and their metabolites renal clearance	Renal clearance	48 hours
Other cannabinoids and their metabolites dialytic clearance	Dialytic clearance	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Weakness, fatigue, pain, falls, abnormal coordination, numbness or tingling, sedation, sleepiness, tremor, confusion, disorientation, dissociation, abnormal speech, muscle spasms, nausea, vomiting, diarrhea, altered mood, depression, euphoric mood, hallucinations, blurred vision, dizziness, imbalance, palpitations, hypotension, syncope, urinary tract infection, allergic reactions, shortness of breath, lung infection, fever, sweatiness, headache	48 hours
Blood pressure	Systolic and diastolic blood pressure in mmHg	48 hours
Heart rate	Heart rate in beats per minute	48 hours

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Center for Medicinal Cannabis Research
• Investigators: Principal Investigator: Michael Walsh, MD, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Actual): February 16, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Cannabidiol; Dronabinol; Nabiximols
• Other Study ID Numbers: POT_GFR_PK_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No