TY - JOUR
T1 - Safety and pharmacokinetics of oral Cannabidiol when administered concomitantly with intravenous Fentanyl in humans
AU - Manini, Alex F.
AU - Yiannoulos, Georgia
AU - Bergamaschi, Mateus M.
AU - Hernandez, Stephanie
AU - Olmedo, Ruben
AU - Barnes, Allan J.
AU - Winkel, Gary
AU - Sinha, Rajita
AU - Jutras-Aswad, Didier
AU - Huestis, Marilyn A.
AU - Hurd, Yasmin L.
N1 - Publisher Copyright:
Copyright © 2015 American Society of Addiction Medicine.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods: This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center inNewYork City. Participantswere healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg ofCBDpretreatment, followed by a single 0.5 (session 1) or 1.0μg/kg (session 2) of intravenous fentanyl dose. The primary outcomewas the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results: SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.
AB - Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods: This double-blind, placebo-controlled cross-over study of CBD, coadministered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center inNewYork City. Participantswere healthy volunteers aged 21 to 65 years with prior opioid exposure, regardless of the route. Blood samples were obtained before and after 400 or 800 mg ofCBDpretreatment, followed by a single 0.5 (session 1) or 1.0μg/kg (session 2) of intravenous fentanyl dose. The primary outcomewas the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results: SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. After low-dose CBD, tmax occurred at 3 and 1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC P = NS) between sessions. Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.
KW - cannabidiol
KW - cannabis
KW - opioid dependence
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=84942804432&partnerID=8YFLogxK
U2 - 10.1097/ADM.0000000000000118
DO - 10.1097/ADM.0000000000000118
M3 - Article
C2 - 25748562
AN - SCOPUS:84942804432
SN - 1932-0620
VL - 9
SP - 204
EP - 210
JO - Journal of Addiction Medicine
JF - Journal of Addiction Medicine
IS - 3
ER -