Novel Δ⁹‐tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects

Abstract

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 Δ9‐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 t1/2 was 72–80 min, tmax was 39–56 min and Cmax 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 tmax 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.

Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial

“…Each block contained two drug periods: THC for three consecutive days, followed by placebo (or vice versa) and separated by a fourday-washout period. As the pharmacodynamic effects of oral THC occurred within 1-2 hours after administration in a previous phase I study (17), a study period of three days was expected to be sufficient to evaluate the acute effects of THC on behavior. The duration of the washout period of four days was determined based on the terminal half lives of THC (mean 71.9 min) and its active metabolite 11-OH-THC (mean 196 min) after oral administration of 5mg THC in the same study (17).…”

Population Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short- and Long-term Pharmacokinetics

“…The first dataset contains 13 subjects and a total of 243 THC plasma concentrations from trial 0828 at the CHDR, as described by Klumpers et al [27]. There were six healthy male subjects and seven healthy female subjects included in the trial, all were mild cannabis users for at least 1 year (cannabis use no more than once a week) who were given an oral formulation of 5, 6.5, or 8 mg THC called Namisol Ò .…”

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects

“…Earlier reports of sublingual administration have indicated that THC is effectively absorbed by this route (26 -28). For example, sublingual administration of a crushed Namisol w tablet (oral formulation containing 5 mg of THC) to 13 subjects resulted in a maximum plasma concentration (C max ) of 2.3 ng/mL of THC with a peak time of 74.5 min (T max ) (29).…”