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 language | English |
|---|---|
| Pages (from-to) | 171-176 |
| Number of pages | 6 |
| Journal | Clinical Neuropharmacology |
| Volume | 41 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
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Keywords
- 9-tetrahydrocannabinol
- cannabidiol
- multiple sclerosis
- oromucosal spray
- pharmacokinetics-pharmacodynamics
ASJC Scopus subject areas
- Pharmacology
- Clinical Neurology
- Pharmacology (medical)
Cite this
Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients with Multiple Sclerosis : A Pilot Study on the Plasma Concentration-Effect Relationship. / Contin, Manuela; Mancinelli, Luca; Perrone, Alessandro; Sabattini, Loredana; Mohamed, Susan; Scandellari, Cinzia; Foschi, Matteo; Vacchiano, Veria; Lugaresi, Alessandra; Riva, Roberto.
In: Clinical Neuropharmacology, Vol. 41, No. 5, 01.09.2018, p. 171-176.Research output: Contribution to journal › Article
}
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.
KW - 9-tetrahydrocannabinol
KW - cannabidiol
KW - multiple sclerosis
KW - oromucosal spray
KW - pharmacokinetics-pharmacodynamics
UR - http://www.scopus.com/inward/record.url?scp=85054302013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054302013&partnerID=8YFLogxK
U2 - 10.1097/WNF.0000000000000294
DO - 10.1097/WNF.0000000000000294
M3 - Article
C2 - 30024443
AN - SCOPUS:85054302013
VL - 41
SP - 171
EP - 176
JO - Clinical Neuropharmacology
JF - Clinical Neuropharmacology
SN - 0362-5664
IS - 5
ER -