Pharmacokinetics and Side Effects of Δ9-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

Marie Bach Sønderskov; Dinah Sherzad Khatir; Krista Dybtved Kjærgaard; Jørgen Bo Hasselstrøm; Lambert Kristiansen Sørensen; Eva Aggerholm Sædder; Charlotte Uggerhøj Andersen

doi:10.1016/j.ekir.2024.12.030

Pharmacokinetics and Side Effects of Δ⁹-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

Marie Bach Sønderskov^*, Dinah Sherzad Khatir, Krista Dybtved Kjærgaard, Jørgen Bo Hasselstrøm, Lambert Kristiansen Sørensen, Eva Aggerholm Sædder, Charlotte Uggerhøj Andersen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

Introduction: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. Methods: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ⁹-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. Results: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77–3.48), 4.16 (3.35–5.28), and 4.31 (3.16–5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (C_max) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). Conclusion: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.

Originalsprog	Engelsk
Tidsskrift	Kidney International Reports
Vol/bind	10
Nummer	3
Sider (fra-til)	707-719
Antal sider	13
ISSN	2468-0249
DOI	https://doi.org/10.1016/j.ekir.2024.12.030
Status	Udgivet - mar. 2025

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10.1016/j.ekir.2024.12.030

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Citationsformater

@article{ba708991c36f4354bf3eac43b7d78bf0,

title = "Pharmacokinetics and Side Effects of Δ9-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD",

abstract = "Introduction: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. Methods: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ9-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. Results: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77–3.48), 4.16 (3.35–5.28), and 4.31 (3.16–5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (Cmax) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). Conclusion: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.",

keywords = "cannabidiol, chronic kidney disease, medicinal cannabis, pharmacokinetics, Δ-tetrahydrocannabinol",

author = "S{\o}nderskov, {Marie Bach} and Khatir, {Dinah Sherzad} and Kj{\ae}rgaard, {Krista Dybtved} and Hasselstr{\o}m, {J{\o}rgen Bo} and S{\o}rensen, {Lambert Kristiansen} and S{\ae}dder, {Eva Aggerholm} and Andersen, {Charlotte Uggerh{\o}j}",

note = "Publisher Copyright: {\textcopyright} 2024 International Society of Nephrology",

year = "2025",

month = mar,

doi = "10.1016/j.ekir.2024.12.030",

language = "English",

volume = "10",

pages = "707--719",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "3",

}

Pharmacokinetics and Side Effects of Δ⁹-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD. / Sønderskov, Marie Bach ; Khatir, Dinah Sherzad; Kjærgaard, Krista Dybtved et al.
I: Kidney International Reports, Bind 10, Nr. 3, 03.2025, s. 707-719.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Pharmacokinetics and Side Effects of Δ9-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

AU - Sønderskov, Marie Bach

AU - Khatir, Dinah Sherzad

AU - Kjærgaard, Krista Dybtved

AU - Hasselstrøm, Jørgen Bo

AU - Sørensen, Lambert Kristiansen

AU - Sædder, Eva Aggerholm

AU - Andersen, Charlotte Uggerhøj

PY - 2025/3

Y1 - 2025/3

N2 - Introduction: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. Methods: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ9-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. Results: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77–3.48), 4.16 (3.35–5.28), and 4.31 (3.16–5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (Cmax) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). Conclusion: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.

AB - Introduction: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. Methods: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ9-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. Results: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77–3.48), 4.16 (3.35–5.28), and 4.31 (3.16–5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (Cmax) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). Conclusion: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.

KW - cannabidiol

KW - chronic kidney disease

KW - medicinal cannabis

KW - pharmacokinetics

KW - Δ-tetrahydrocannabinol

UR - http://www.scopus.com/inward/record.url?scp=85216473252&partnerID=8YFLogxK

U2 - 10.1016/j.ekir.2024.12.030

DO - 10.1016/j.ekir.2024.12.030

M3 - Journal article

AN - SCOPUS:85216473252

SN - 2468-0249

VL - 10

SP - 707

EP - 719

JO - Kidney International Reports

JF - Kidney International Reports

IS - 3