Novel Δ(9) -tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects.
BACKGROUND
• Cannabis based medicines are registered as a treatment for various indications, such as pain and spasms in multiple sclerosis (MS) patients, and anorexia and nausea in patients with HIV or receiving cancer treatment. • the pharmacokinetics of the various administration routes of cannabis and cannabis based medicines are variable and dosing is hard to regulate.


CONCLUSIONS
• Namisol is a new tablet containing pure THC (>98%) that has a beneficial pharmacokinetic profile after oral administration. • Namisol gives a quick onset of pharmacodynamic effects in healthy volunteers, which implies a rapid initiation of therapeutic effects in patients.


OBJECTIVE
Among the main disadvantages of currently available Δ(9) -tetrahydrocannabinol (THC) formulations are dosing difficulties due to poor pharmacokinetic characteristics. Namisol® is a novel THC formulation, designed to improve THC absorption. The study objectives were to investigate the optimal administration route, pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of Namisol®.


METHODS
This first in human study consisted of two parts. Panel I included healthy males and females (n = 6/6) in a double-blind, double-dummy, randomized, crossover study with sublingual (crushed tablet) and oral administration of Namisol® (5 mg THC). Based on these results, male and female (n = 4/5) participants from panel I received oral THC 6.5 and 8.0 mg or matching placebo in a randomized, crossover, rising dose study during panel II. PD measurements were body sway; visual analogue scales (VAS) mood, psychedelic and heart rate. THC and 11-OH-THC population PK analysis was performed.


RESULTS
Sublingual administration showed a flat concentration profile compared with oral administration. Oral THC apparent t(1/2) was 72-80 min, t(max) was 39-56 min and C(max) 2.92-4.69 ng ml(-1) . THC affected body sway (60.8%, 95% CI 29.5, 99.8), external perception (0.078 log mm, 95% CI 0.019, 0.137), alertness (-2.7 mm, 95% CI -4.5, -0.9) feeling high (0.256 log mm, 95% CI 0.093, 0.418) and heart rate (5.6 beats min(-1) , 95% CI 2.7, 6.5). Namisol® was well tolerated.


CONCLUSIONS
Oral Namisol® showed promising PK and PD characteristics. Variability and t(max) of THC plasma concentrations were smaller for Namisol® than reported for studies using oral dronabinol and nabilone. This study was performed in a limited number of healthy volunteers. Therefore, future research on Namisol® should study clinical effects in patient populations.
Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden Echo Pharmaceuticals, 14thFloor Unit A1, Jonkerbosplein 52, 6534 AB Nijmegen, the Netherlands. linda.ek@gmail.com
Linda E
LE
Klumpers
Tim L
TL
Beumer
Johan G C
JG
van Hasselt
Astrid
A
Lipplaa
Lennard B
LB
Karger
H Daniël
HD
Kleinloog
Jan I
JI
Freijer
Marieke L
ML
de Kam
Joop M A
JM
van Gerven
D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D004856:Postural Balance / Q000187:drug effects*; D055815:Young Adult
D018712:Analgesics, Non-Narcotic; D013759:Dronabinol