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Medicina
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Use of Medicinal Cannabis and Synthetic Cannabinoids
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Use of Medicinal Cannabis and Synthetic Cannabinoids

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Intensive Care/ Anesthesiology".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 64159

Special Issue Editors

Prof. Dr. Francesco Paolo Busardò

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Guest Editor
Faculty of Medicine and Surgery, University “Politecnica delle Marche” of Ancona, Via Tronto 71, 60124 Ancona, Italy
Interests: forensic toxicology; analytical toxicology; drugs; pharmacology; chromatography/mass Spectrometry
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Pichini

E-Mail Website
Co-Guest Editor
National Centre on Addiction and Doping, National Institute of Health, 00161 Rome, Italy
Interests: clinical pharmacotoxicology; forensic pharmacotoxicology; psychoactive substances; doping agents
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Raffaele Giorgetti

E-Mail Website
Co-Guest Editor
Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60121 Ancona, Italy
Interests: legal medicine; clinical and forensic toxicology; insurance medicine; bioethics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to launch a “Special Issue” focusing on cannabis, clinical applications and synthetic cannabinoids.

Cannabis remains the most consumed drug of abuse worldwide. At the same time, its medical use in several diseases is growing in importance. Many chronic pathologies, including neurogenic pain that has not found success with standard medical treatments, are benefiting from medical cannabis.

At the same time, in countries where cannabis legalization has not taken place, some manufacturers have started producing and selling "light cannabis": dried flowering tops containing the psychoactive principle Δ-9-tetrahydrocannabinol (THC) at concentrations lower than 0.2% together with a variable concentration of cannabidiol (CBD). The consumption of this peculiar product is spreading within the European Union.

In this Special Issue, attention will be paid to different aspects and uses not only of phytocannabinoids from cannabis plant, but also synthetic cannabinoids, with particular attention being paid to their diffusion and the serious health threat for consumers.

Prof. Francesco Paolo Busardò
Prof. Raffaele Giorgetti
Dr. Simona Pichini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cannabis
  • medical cannabis
  • light cannabis
  • synthetic cannabinoids
  • pharmacology
  • toxicology

Published Papers (9 papers)

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Editorial

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3 pages, 246 KiB  
Editorial
Medicinal Cannabis and Synthetic Cannabinoid Use
by Simona Pichini, Alfredo Fabrizio Lo Faro, Francesco Paolo Busardò and Raffaele Giorgetti
Medicina 2020, 56(9), 453; https://doi.org/10.3390/medicina56090453 - 07 Sep 2020
Cited by 4 | Viewed by 2244
Abstract
Cannabis products have been used for centuries by humans for recreational and medical purposes. Resent research, proposed the promising therapeutic potential of cannabis and related cannabinoids for a wide range of medical conditions, including psychiatric and neurological diseases. This Special Issue presents the [...] Read more.
Cannabis products have been used for centuries by humans for recreational and medical purposes. Resent research, proposed the promising therapeutic potential of cannabis and related cannabinoids for a wide range of medical conditions, including psychiatric and neurological diseases. This Special Issue presents the latest updates on medicinal cannabis and synthetic cannabinoids pharmacology, toxicology and new analytical methods to identify and quantify these compounds in conventional and non-conventional biological matrices. Moreover, it provides current data regarding their adverse effects, safety, application for medical purposes and their harmful effects. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)

Research

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9 pages, 1102 KiB  
Communication
UHPLC-HRMS and GC-MS Screening of a Selection of Synthetic Cannabinoids and Metabolites in Urine of Consumers
by Manuela Pellegrini, Emilia Marchei, Esther Papaseit, Magí Farré and Simona Zaami
Medicina 2020, 56(8), 408; https://doi.org/10.3390/medicina56080408 - 13 Aug 2020
Cited by 14 | Viewed by 3207
Abstract
Background and Objectives: The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas [...] Read more.
Background and Objectives: The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas chromatography-mass spectrometry (GC-MS) were used for the determination of three synthetic cannabinoids JWH-122, JWH 210, UR-144 and their metabolites in urine of consumers. Materials and Methods: Sample preparation included an initial hydrolysis with β-glucuronidase and liquid-liquid extraction. The UHPLC-HRMS method included a Kinetex 2.6 u Biphenyl 100A (100 × 2.1 mm, 2.6 μm) (Phenomenex, Italy) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode was used (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m × 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Results: Both methods have been successfully used for screening of parent synthetic cannabinoids and their metabolites in urine samples of consumers. Conclusions: The screening method applied JWH-122, JWH-210, UR-144 and their metabolites in urine of consumers can be applied to other compounds of the JWH family. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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14 pages, 3344 KiB  
Article
Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol
by Santa Mammana, Eugenio Cavalli, Agnese Gugliandolo, Serena Silvestro, Federica Pollastro, Placido Bramanti and Emanuela Mazzon
Medicina 2019, 55(11), 747; https://doi.org/10.3390/medicina55110747 - 18 Nov 2019
Cited by 56 | Viewed by 8858
Abstract
Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line [...] Read more.
Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG–CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG–CBD combination for further preclinical studies. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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14 pages, 907 KiB  
Article
Alcohol and Cannabis Intake in Nursing Students
by Carlos Tejedor-Cabrera and Omar Cauli
Medicina 2019, 55(10), 628; https://doi.org/10.3390/medicina55100628 - 24 Sep 2019
Cited by 15 | Viewed by 3808
Abstract
Background and objectives: Drug misuse among young people has become a major worldwide health concern. The present study analyzes substance misuse and its social and personal consequences in young university students. Materials and Methods: Screening of alcohol misuse was based on the Alcohol [...] Read more.
Background and objectives: Drug misuse among young people has become a major worldwide health concern. The present study analyzes substance misuse and its social and personal consequences in young university students. Materials and Methods: Screening of alcohol misuse was based on the Alcohol Use Disorder Identification Test (AUDIT), while screening of substance-related risks and problems was performed with the Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) score. Results: The population was composed of nursing students at the University of Valencia (Valencia, Spain) (n = 185). More than 50% of the surveyed students reported alcohol intake based on the CRAFFT scale; 31.4% were classified as having “risky alcohol use”, and 19.5% met the criterion for hazardous drinking based on the AUDIT score. In turn, 34.1% of the sample reported marijuana/hashish intake based on the CRAFFT scale. A gender effect was only observed for marijuana/hashish use, which was significantly (p < 0.001) higher in male students. No other gender differences were observed. In the logistic regression analysis, only age was identified as a protective factor for obtaining a reduced risk score with both the AUDIT and the CRAFFT. Among the social and personal consequences of drug misuse, the inability to “stop drinking once you have started” or the inability to “remember what happened while consuming” was significantly associated with an increased frequency of alcohol consumption (OR 20.93, p < 0.0001 and OR 13.68, p < 0.05, respectively). Conclusions: Our findings are consistent with emerging social concerns about drug misuse in the university population, including nursing students as future healthcare professionals. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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Review

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26 pages, 894 KiB  
Review
Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review
by Lourdes Poyatos, Ana Pilar Pérez-Acevedo, Esther Papaseit, Clara Pérez-Mañá, Soraya Martin, Olga Hladun, Adrià Siles, Marta Torrens, Francesco Paolo Busardo and Magí Farré
Medicina 2020, 56(6), 309; https://doi.org/10.3390/medicina56060309 - 23 Jun 2020
Cited by 39 | Viewed by 8912
Abstract
Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral [...] Read more.
Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. Materials and Methods: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. Results: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. Conclusions: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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15 pages, 394 KiB  
Review
Herbal Preparations of Medical Cannabis: A Vademecum for Prescribing Doctors
by Pietro Brunetti, Simona Pichini, Roberta Pacifici, Francesco Paolo Busardò and Alessandro del Rio
Medicina 2020, 56(5), 237; https://doi.org/10.3390/medicina56050237 - 15 May 2020
Cited by 56 | Viewed by 5933
Abstract
Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic [...] Read more.
Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic potential of cannabis and paved the way for the release of marketing authorizations for cannabis-based products. Although several synthetic and standardized products are currently available on the market, patients’ preferences lean towards herbal preparations, because they are easy to handle and self-administer. A literature search was conducted on multidisciplinary research databases and international agencies or institutional websites. Despite the growing popularity of medical cannabis, little data is available on the chemical composition and preparation methods of medical cannabis extracts. The authors hereby report the most common cannabis preparations, presenting their medical indications, routes of administration and recommended dosages. A practical and helpful guide for prescribing doctors is provided, including suggested posology, titration strategies and cannabinoid amounts in herbal preparations obtained from different sources of medical cannabis. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
22 pages, 415 KiB  
Review
Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy
by Bogdan Ionel Tamba, Gabriela Dumitrita Stanciu, Cristina Mariana Urîtu, Elena Rezus, Raluca Stefanescu, Cosmin Teodor Mihai, Andrei Luca, Gabriela Rusu-Zota, Maria-Magdalena Leon-Constantin, Elena Cojocaru, Bogdan Gafton and Teodora Alexa-Stratulat
Medicina 2020, 56(1), 24; https://doi.org/10.3390/medicina56010024 - 09 Jan 2020
Cited by 21 | Viewed by 4247
Abstract
Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review [...] Read more.
Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography–mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
14 pages, 518 KiB  
Review
Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review
by Laura Orsolini, Stefania Chiappini, Umberto Volpe, Domenico De Berardis, Roberto Latini, Gabriele Duccio Papanti and John Martin Corkery
Medicina 2019, 55(9), 525; https://doi.org/10.3390/medicina55090525 - 23 Aug 2019
Cited by 85 | Viewed by 18568
Abstract
Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has [...] Read more.
Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients. Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics ‘Cannabis’, ‘Synthetic Cannabinoids’, ‘PTSD’, and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD. Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep. Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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Other

6 pages, 1402 KiB  
Brief Report
Rising Trends in Hospitalizations for Cardiovascular Events among Young Cannabis Users (18–39 Years) without Other Substance Abuse
by Rupak Desai, Hee Kong Fong, Kaushal Shah, Vikram Preet Kaur, Sejal Savani, Kishorbhai Gangani, Nanush Damarlapally and Hemant Goyal
Medicina 2019, 55(8), 438; https://doi.org/10.3390/medicina55080438 - 05 Aug 2019
Cited by 36 | Viewed by 7062
Abstract
Background and objectives: Modern-day epidemiologic data on the risk and shifting landscape of occurrence of cardiovascular events in cannabis users remain inadequate and rather conflicting, especially amongst the young adult population. Furthermore, the problem of polysubstance use among youth is challenging for healthcare [...] Read more.
Background and objectives: Modern-day epidemiologic data on the risk and shifting landscape of occurrence of cardiovascular events in cannabis users remain inadequate and rather conflicting, especially amongst the young adult population. Furthermore, the problem of polysubstance use among youth is challenging for healthcare professionals and policy-makers. Previous studies report higher risk of concomitant use of tobacco, alcohol, cocaine, and amphetamine in young cannabis users. However, most of these studies did not eliminate the confounding effects of concomitant other substance abuse while assessing the incidence and outcome of cardiovascular events in cannabis users. Materials and methods: Using weighted discharge records from the National Inpatient Sample (NIS) from 2007–2014, we assessed the national trends in hospitalizations for major cardiovascular events including acute myocardial infarction (AMI), arrhythmia, stroke, and venous thromboembolic events (VTE) among young cannabis users (18–39 years), excluding cases with concomitant substance abuse with alcohol, tobacco, cocaine, and amphetamine. Results: Of 52.3 million hospitalizations without other substance abuse, 0.7 million (1.3%) young adults were current/former cannabis users. Among young adults without concomitant substance abuse, the frequency of admissions for AMI (0.23% vs. 0.14%), arrhythmia (4.02% vs. 2.84%), and stroke (0.33% vs. 0.26%) was higher in cannabis users as compared to non-users (p < 0.001). However, the frequency of admissions for VTE (0.53% vs. 0.84%) was lower among cannabis users as compared non-users. Between 2007 and 2014, we observed 50%, 79%, 300%, and 75% relative increases in hospitalizations for AMI, arrhythmias, stroke, and VTE, respectively, among young cannabis users as compared to non-users, showing relatively inferior or no ascent in the rates (ptrend < 0.001). Conclusions: The rising trends in hospitalizations for acute cardiovascular events among young cannabis users without concomitant other substance abuse call for future prospective well-designed studies to assess cannabis-related short-and long-term cardiovascular implications while simultaneously developing focused interventions towards raising awareness among the young population regarding the potential deleterious effects of cannabis use. Full article
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
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