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Novel Δ 9 ‐tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects
Author(s) -
Klumpers Linda E.,
Beumer Tim L.,
van Hasselt Johan G. C.,
Lipplaa Astrid,
Karger Lennard B.,
Kleinloog H. Daniël,
Freijer Jan I.,
de Kam Marieke L.,
van Gerven Joop M. A.
Publication year - 2012
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2012.04164.x
Subject(s) - pharmacokinetics , crossover study , medicine , dronabinol , pharmacology , pharmacodynamics , tolerability , dosing , placebo , oral administration , population , nausea , cannabis , anesthesia , cannabinoid , adverse effect , receptor , environmental health , pathology , psychiatry , alternative medicine
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • 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. WHAT THIS STUDY ADDS • 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. AIMS 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.