Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients with Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship

Manuela Contin, Luca Mancinelli, Alessandro Perrone, Loredana Sabattini, Susan Mohamed, Cinzia Scandellari, Matteo Foschi, Veria Vacchiano, Alessandra Lugaresi, Roberto Riva

Research output: Contribution to journalArticle

Abstract

Objectives We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS). Methods The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter. Results Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests. Conclusions Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalClinical Neuropharmacology
Volume41
Issue number5
DOIs
Publication statusPublished - Sep 1 2018

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Cannabidiol
Dronabinol
Multiple Sclerosis
Cannabinoids

Keywords

  • 9-tetrahydrocannabinol
  • cannabidiol
  • multiple sclerosis
  • oromucosal spray
  • pharmacokinetics-pharmacodynamics

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

Cite this

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title = "Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients with Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship",
abstract = "Objectives We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS). Methods The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter. Results Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests. Conclusions Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.",
keywords = "9-tetrahydrocannabinol, cannabidiol, multiple sclerosis, oromucosal spray, pharmacokinetics-pharmacodynamics",
author = "Manuela Contin and Luca Mancinelli and Alessandro Perrone and Loredana Sabattini and Susan Mohamed and Cinzia Scandellari and Matteo Foschi and Veria Vacchiano and Alessandra Lugaresi and Roberto Riva",
note = "Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Universit{\`a} di Bologna (Contin Manuela, Lugaresi Alessandra, Riva Roberto). La Prof.ssa A. Lugaresi viene da altro Istituto e lavori con affiliazioni diverse usciranno ancora nei prossimi anni.",
year = "2018",
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TY - JOUR

T1 - Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients with Multiple Sclerosis

T2 - A Pilot Study on the Plasma Concentration-Effect Relationship

AU - Contin, Manuela

AU - Mancinelli, Luca

AU - Perrone, Alessandro

AU - Sabattini, Loredana

AU - Mohamed, Susan

AU - Scandellari, Cinzia

AU - Foschi, Matteo

AU - Vacchiano, Veria

AU - Lugaresi, Alessandra

AU - Riva, Roberto

N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Contin Manuela, Lugaresi Alessandra, Riva Roberto). La Prof.ssa A. Lugaresi viene da altro Istituto e lavori con affiliazioni diverse usciranno ancora nei prossimi anni.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Objectives We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS). Methods The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter. Results Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests. Conclusions Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.

AB - Objectives We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS). Methods The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter. Results Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests. Conclusions Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.

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KW - oromucosal spray

KW - pharmacokinetics-pharmacodynamics

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