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      Medicinal Cannabis: In Vitro Validation of Vaporizers for the Smoke-Free Inhalation of Cannabis

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          Abstract

          Inhalation by vaporization is a promising application mode for cannabis in medicine. An in vitro validation of 5 commercial vaporizers was performed with THC-type and CBD-type cannabis. Gas chromatography/mass spectrometry was used to determine recoveries of total THC (THC tot) and total CBD (CBD tot) in the vapor. High-performance liquid chromatography with photodiode array detection was used for the quantitation of acidic cannabinoids in the residue and to calculate decarboxylation efficiencies. Recoveries of THC tot and CBD tot in the vapor of 4 electrically-driven vaporizers were 58.4 and 51.4%, 66.8 and 56.1%, 82.7 and 70.0% and 54.6 and 56.7% for Volcano Medic ®, Plenty Vaporizer ®, Arizer Solo ® and DaVinci Vaporizer ®, respectively. Decarboxylation efficiency was excellent for THC (≥ 97.3%) and CBD (≥ 94.6%). The gas-powered Vape-or-Smoke showed recoveries of THC tot and CBD tot in the vapor of 55.9 and 45.9%, respectively, and a decarboxylation efficiency of ≥ 87.7 for both cannabinoids. However, combustion of cannabis was observed with this device. Temperature-controlled, electrically-driven vaporizers efficiently decarboxylate inactive acidic cannabinoids and reliably release their corresponding neutral, active cannabinoids. Thus, they offer a promising application mode for the safe and efficient administration of medicinal cannabis.

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          Most cited references 24

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          Molecular characterization of a peripheral receptor for cannabinoids.

          The major active ingredient of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and delta 9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of delta 9-THC, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the nonpsychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.
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            Structure of a cannabinoid receptor and functional expression of the cloned cDNA.

            Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.
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              Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

               Ethan Russo (2011)
              Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL(-1) . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. http://dx.doi.org/10.1111/bph.2011.163.issue-7. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 January 2016
                2016
                : 11
                : 1
                Affiliations
                [1 ]Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern, Switzerland
                [2 ]Center of Laboratory Medicine, University Institute of Clinical Chemistry, Inselspital, University Hospital Bern, Bern, Switzerland
                Martin Luther University, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist. Competing Interest Statement regarding AiFame/AiLab: Company was not a sponsor. Company was not involved in initiating, designing, and performing the study nor in preparing the manuscript. Coauthor US joined the company after having finished the experiments. As company is not a vaporizer manufacturer and supplier it does not benefit from the present study. As company is a producer and supplier of cannabis extracts and cannabinoids (CBD), it benefits only from medicinal cannabis research in general. Ownership of stocks or shares: only coauthor US. Paid employment or consultancy: only coauthor US. Patent applications (pending or actual, vaporizers): no. Research grants: no. Travel grants and honoraria for speaking or participation at meetings: no.

                Conceived and designed the experiments: CL JM RB. Performed the experiments: CL JM US. Analyzed the data: CL JM US RB. Wrote the paper: CL RB.

                [¤a]

                Current address: Apotheke Dr. Lanz, Langenthal, Switzerland

                [¤b]

                Current address: AiFame/AiLab, Wald-Schönengrund, Switzerland

                Article
                PONE-D-15-32701
                10.1371/journal.pone.0147286
                4718604
                26784441
                © 2016 Lanz et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 2, Pages: 18
                Product
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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