Editorial: Medicinal Cannabis: Evolution of therapeutic use, future approaches and other implications

TYPE Editorial PUBLISHED 25 August 2022 DOI 10.3389/fphar.2022.999068 Editorial: Medicinal Cannabis: OPEN ACCESS Evolution of therapeutic use, EDITED AND REVIEWED BY Heike Wulff, University of California, Davis, future approaches and other United States *CORRESPONDENCE implications Francesca Baratta, [email protected] Paola Brusa 1, Francesca Baratta 1*, Massimo Collino 2 and SPECIALTY SECTION This article was submitted to Shimon Ben -Shabat 3 Experimental Pharmacology and Drug 1 Department of Drug Science and Technology, University of Turin, Torino, Italy, 2Department of Discovery, Neurosciences Rita Levi Montalcini, University of Turin, Turin, Piedmont, Italy, 3Department of Clinical a section of the journal Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, Southern, Israel Frontiers in Pharmacology RECEIVED 20 July 2022 ACCEPTED 25 July 2022 KEYWORDS PUBLISHED 25 August 2022 Cannabis, formulations, effectiveness, medical use, clinical trials CITATION Brusa P, Baratta F, Collino M and Ben -Shabat S (2022), Editorial: Medicinal Cannabis: Evolution of therapeutic use, future approaches and other implications. Editorial on the Research Topic Front. Pharmacol. 13:999068. Medicinal Cannabis: Evolution of Therapeutic Use, Future Approaches doi: 10.3389/fphar.2022.999068 and Other Implications COPYRIGHT © 2022 Brusa, Baratta, Collino and Ben -Shabat. This is an open-access article distributed under the terms of the Creative Commons Attribution License Cannabis has been used in even the oldest traditional medicines available. In the last (CC BY). The use, distribution or century, negative attention has prevailed regarding the psychotropic and abuse potential. reproduction in other forums is permitted, provided the original For this reason, Cannabis has been banned and declared illegal in many countries. In author(s) and the copyright owner(s) are recent years, however, there has been a more in-depth evaluation of the legalization of credited and that the original cannabinoids for medical use in several countries following heightened media attention publication in this journal is cited, in accordance with accepted academic and reports of effectiveness, although not always thoroughly backed up by scientific practice. No use, distribution or evidence. The official introduction of pharmaceutical-grade Cannabis inflorescences for reproduction is permitted which does medicinal purposes has allowed physicians and pharmacists, to prescribe and prepare not comply with these terms. several Cannabis preparations legally. Such products are currently being administered to patients without their efficacy being evaluated in controlled studies: for each patient the composition and route of administration may differ. In addition, many advanced administration systems have been developed or are still under development, but few clinical trials have been completed. In this context, this Research Topic focused on the in-depth analysis of the legal, technological and pharmacological aspects related to the medical use of Cannabis-based formulations. Anil et al. have directed their research specifically on the activity of Cannabis for medical use in the context of inflammatory processes. Although activities in this area are plausible, the high number of active molecules produced by Cannabis and simultaneously administered through the extractive products normally used in therapy, has not yet made it possible to identify their specific mechanisms of action. Once the modalities of action of Frontiers in Pharmacology 01 frontiersin.org Brusa et al. 10.3389/fphar.2022.999068 the active molecules have been clarified, it might be of interest to therapy may be limited by possible behavioural side effects. These use purified mixtures to obtain a more significant activity researchers then successfully worked on experimental animals to potentially (Anil et al.). identify a panel of blood metabolites predicting behavioural Specific literature reviews were then done for some effects (Maayah et al.). pathologies such as when Xin et al. investigated the potential Pennypacker et al. have evaluated whether the products therapeutic effect of CBD in bone diseases. Even in this case, available on the market in the United States of America are further studies are needed to evaluate the benefits and risks of consistent in the concentration of cannabinoids, with the cannabinoids’ use (Xin et al.). literature indications for use in therapy. Overall, the results of A large part of the clinical research relating to Cannabis for this study have been defined by the authors as alarming as medical use concerns its use in the context of diseases of the current product offerings do not reflect scientific evidence central nervous system. Ortiz et al. examined evidence (Pennypacker et al.). supporting the therapeutic utility of cannabinoids for treating In the regulatory context MacPhail et al. have analysed the trend neurodegenerative diseases, pain, mood disorders, and substance of prescriptions in Australia over the last 5 years, noting a substantial use disorders. Important considerations were also made on the increase in prescriptions over time that does not actually reflect a methods of formulation and the routes of administration (Ortiz worsening of the pathological conditions of the population but et al.). Lacroix et al. Also considered Cannabis in neurological rather a greater prescription linked to greater knowledge and disorders stressing that currently most of the scientific data acceptance of this type of therapy (MacPhail et al.). supports the potential therapeutic use of Cannabis but, as As regards the use in therapy of medical Cannabis, the current much as patients request it, the knowledge is still too little in- regulations have been analysed by Baratta et al. in those countries depth. It is therefore certainly urgent to manage clinical trials to where clinical studies have recently been conducted. The results of provide stronger and safer evidence (Lacroix et al.). the trials have been crossed with the pathologies for which the Procaccia et al. discussed how phytocannabinoid profiles current legislation provides that it is possible to prescribe Cannabis differed between plants according to chemovar types and allowing relevant considerations (Baratta et al.). examined the main factors influencing the accumulation of From all the publications collected, it is clear that there is a secondary metabolites in the plant, including genotype, growing great interest in the enormous potential of Cannabis in the conditions, processing, storage and the delivery route; the authors medical field but also a widespread awareness of the extreme highlighted how these factors make the use of Cannabis in therapy need to conduct in-depth research that clarifies the mechanisms highly complex (Procaccia et al.). of action of the quantity of components present in the In addition to the more well-known compounds such as THC phytocomplex of this plant species. and CBD, Cannabis produces over 120 other phytocannabinoids. The use of THC is associated with acute psychotropic effects that could potentially be avoided considering that minor cannabinoids Author contributions and their chemical counterparts could offer the same potential benefits without the same adverse effects. In this regard, Walsh All authors listed have made a substantial, direct, and et al. reviewed the literature to provide an overview of the intellectual contribution to the work and approved it for endocannabinoid system, phytocannabinoid biosynthesis and a publication. discussion on molecular pharmacology. Potential therapeutic uses of minor cannabinoids underlining that future studies will have to rigorously evaluate these compounds’ risk/benefit ratio (Walsh et al.). Conflict of interest The interest in molecules other than cannabinoids such as terpenes is certainly relevant. This interest has grown even The authors declare that the research was conducted in the greater since the possibility of an “entourage” effect between absence of any commercial or financial relationships that could the active molecules of Cannabis has been postulated. be construed as a potential conflict of interest. Accordingly, Finlay et al. in their study examined whether some terpenes acted directly on cannabinoid receptors. From the results obtained, it was not possible to exclude the existence of Publisher’s note an entourage effect. Still, this cannot be linked to a direct action of the terpenes on the cannabinoid receptors. However, the All claims expressed in this article are solely those of the pharmacological mechanism underlying this substances authors and do not necessarily represent those of their affiliated activity remains to be thoroughly investigated (Finlay et al.). organizations, or those of the publisher, the editors and the Maayah et al. pointed out that full-spectrum Cannabis reviewers. Any product that may be evaluated in this article, or extracts have been used in clinical trials to treat various claim that may be made by its manufacturer, is not guaranteed or diseases. However, despite their efficacy, their potential use in endorsed by the publisher. Frontiers in Pharmacology 02 frontiersin.org