The Pharmacokinetics of Single Dose Oral Tetrahydrocannabinol and Cannabidiol

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cannabis, Chronic Kidney Diseases, Dialysis

Intervention / Treatment
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* Drug: Tetrahydrocannabinol-Cannabidiol Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult age>25 years 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 agree to take the medication as directed in the study provides informed consent Exclusion Criteria: body mass index <20 or >35kg/m2 physical dependence on any drug other than caffeine or nicotine history of clinically significant adverse event associated with cannabis intoxication history of psychosis or mania or any active major psychiatric disorder recent (within 30 days) use of any cannabinoid (natural or synthetic) identified by self-report or urine drug screen for cannabinoids 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) evidence of liver dysfunction (ALT less than 3 times upper limit of normal, bilirubin below upper limit of normal, international normalized ratio<1.5) pregnant or breastfeeding women change in ideal body weight or dry weight in the last 4 weeks intradialytic hypotension (systolic blood pressure<90mmHg) requiring an intervention in the previous 4 weeks

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THC/CBD<br>Oral THC 0.1mg/kg and CBD 2.5mg/kg | Drug: Tetrahydrocannabinol-Cannabidiol Combination<br>* Oral THC 0.1mg/kg and CBD 2.5mg/kg<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics