A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery
Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twel...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2022-01-01
|
| Series: | Medical Cannabis and Cannabinoids |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/521352 |
| _version_ | 1818297131892473856 |
|---|---|
| author | Stefan Lorenzl Franz Gottwald Angelika Nistler Laura Brehm Renate Grötsch Georg Haber Christian Bremm Christiane Weck Carina Trummer Werner Brand |
| author_facet | Stefan Lorenzl Franz Gottwald Angelika Nistler Laura Brehm Renate Grötsch Georg Haber Christian Bremm Christiane Weck Carina Trummer Werner Brand |
| author_sort | Stefan Lorenzl |
| collection | DOAJ |
| description | Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50–2.68) and AUC0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile. |
| first_indexed | 2024-12-13T04:14:34Z |
| format | Article |
| id | doaj.art-caa1eb492bc74f3dafd7d9c17e0f638c |
| institution | Directory Open Access Journal |
| issn | 2504-3889 |
| language | English |
| last_indexed | 2024-12-13T04:14:34Z |
| publishDate | 2022-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Medical Cannabis and Cannabinoids |
| spelling | doaj.art-caa1eb492bc74f3dafd7d9c17e0f638c2022-12-21T23:59:55ZengKarger PublishersMedical Cannabis and Cannabinoids2504-38892022-01-015191910.1159/000521352521352A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal DeliveryStefan Lorenzl0Franz Gottwald1Angelika Nistler2Laura Brehm3Renate Grötsch4Georg Haber5Christian Bremm6Christiane Weck7Carina Trummer8Werner Brand9Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, AustriaCannaXan GmbH, Warngau, GermanyApurano Pharmaceuticals GmbH, Warngau, GermanyApurano Pharmaceuticals GmbH, Warngau, GermanyGemeinschaftspraxis Dr. Grötsch & Dr. Heimer, Holzkirchen, GermanyDepartment of Neurology, University Hospital Agatharied, Hausham, GermanyDürnbachstrasse 54a, Schliersee, GermanyInstitute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, AustriaCannaXan GmbH, Warngau, GermanyCannaXan GmbH, Warngau, GermanyIntroduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50–2.68) and AUC0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.https://www.karger.com/Article/FullText/521352pharmacokineticssafetycannabinoidsoromucosal spraynanoparticles |
| spellingShingle | Stefan Lorenzl Franz Gottwald Angelika Nistler Laura Brehm Renate Grötsch Georg Haber Christian Bremm Christiane Weck Carina Trummer Werner Brand A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery Medical Cannabis and Cannabinoids pharmacokinetics safety cannabinoids oromucosal spray nanoparticles |
| title | A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery |
| title_full | A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery |
| title_fullStr | A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery |
| title_full_unstemmed | A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery |
| title_short | A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery |
| title_sort | phase i trial to determine the pharmacokinetics psychotropic effects and safety profile of a novel nanoparticle based cannabinoid spray for oromucosal delivery |
| topic | pharmacokinetics safety cannabinoids oromucosal spray nanoparticles |
| url | https://www.karger.com/Article/FullText/521352 |
| work_keys_str_mv | AT stefanlorenzl aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT franzgottwald aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT angelikanistler aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT laurabrehm aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT renategrotsch aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT georghaber aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT christianbremm aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT christianeweck aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT carinatrummer aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT wernerbrand aphaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT stefanlorenzl phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT franzgottwald phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT angelikanistler phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT laurabrehm phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT renategrotsch phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT georghaber phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT christianbremm phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT christianeweck phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT carinatrummer phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery AT wernerbrand phaseitrialtodeterminethepharmacokineticspsychotropiceffectsandsafetyprofileofanovelnanoparticlebasedcannabinoidsprayfororomucosaldelivery |