Journal articles: 'Synthetic and natural cannabinoids'

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Akram, Hina, Claire Mokrysz, and H. Valerie Curran. "What are the psychological effects of using synthetic cannabinoids? A systematic review." Journal of Psychopharmacology 33, no. 3 (February 21, 2019): 271–83. http://dx.doi.org/10.1177/0269881119826592.

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Background: Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects. Despite government sanctions against their production they continue to be available in ever-increasing varieties over the Internet. The psychological consequences of synthetic cannabinoid use are relatively unknown. Aim: The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use. Method: A literature search of three databases was conducted in February 2018, including the following keywords: Spice, synthetic cannabis, cognition, affect, behaviour, psychosis, depression and anxiety. Results: Seventeen studies involving a variety of participants were eligible for inclusion: one controlled administration study, seven cross-sectional studies, five Internet surveys and four qualitative studies. The controlled administration study showed that, compared to placebo, synthetic cannabinoids acutely affected some aspects of cognitive functioning and subjective psychological ratings. Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users. Methodological limitations were noted across different study designs. There is limited research on how doses, frequency or type of synthetic cannabinoid influence outcomes. Conclusions: Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains. As synthetic cannabinoid use is increasing in at-risk populations there is an urgent need for more and better research to inform users, professionals and policymakers.

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An, Dongchen, Steve Peigneur, Louise Antonia Hendrickx, and Jan Tytgat. "Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products." International Journal of Molecular Sciences 21, no. 14 (July 17, 2020): 5064. http://dx.doi.org/10.3390/ijms21145064.

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Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used. Recently, more detailed structural information for cannabinoid receptors was revealed thanks to the powerfulness of cryo-electron microscopy, which now can accelerate structure-based drug discovery. At the same time, novel peptide-type cannabinoids from animal sources have arrived at the scene, with their potential in vivo therapeutic effects in relation to cannabinoid receptors. From a natural products perspective, it is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, including voltage- and ligand-gated ion channels, G protein-coupled receptors such as CB1 and CB2, with astonishing affinity and selectivity. Therefore, it is believed that discovering novel cannabinoids starting from studying the biodiversity of the species living on planet earth is an uncharted territory.

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Sun, Yan, and Andy Bennett. "Cannabinoids: A New Group of Agonists of PPARs." PPAR Research 2007 (2007): 1–7. http://dx.doi.org/10.1155/2007/23513.

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Cannabinoids have been used medicinally and recreationally for thousands of years and their effects were proposed to occur mainly via activation of the G-protein-coupled receptorCB1/CB2(cannabinoid receptor 1/2). Discovery of potent synthetic analogs of the natural cannabinoids as clinically useful drugs is the sustained aim of cannabinoid research. This demands that these new compounds be free of the psychotropic effects that connected with the recreational use of cannabinoids. In preclinical studies cannabinoids displayed many of the characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) and it seems to be free of unwanted side effects. An increasing number of therapeutic actions of cannabinoid are being reported that do not appear to be mediated by eitherCB1orCB2, and recently nuclear receptor superfamily PPARs (peroxisome-proliferator-activated receptors) have been suggested as the target of certain cannabinoids. This review summarizes the evidence for cannabinoid activation on PPARs and possible associated remedial potentials.

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Thomas, Brian F. "Interactions of Cannabinoids With Biochemical Substrates." Substance Abuse: Research and Treatment 11 (January 1, 2017): 117822181771141. http://dx.doi.org/10.1177/1178221817711418.

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Recent decades have seen much progress in the identification and characterization of cannabinoid receptors and the elucidation of the mechanisms by which derivatives of the Cannabis sativa plant bind to receptors and produce their physiological and psychological effects. The information generated in this process has enabled better understanding of the fundamental physiological and psychological processes controlled by the central and peripheral nervous systems and has fostered the development of natural and synthetic cannabinoids as therapeutic agents. A negative aspect of this decades-long effort is the proliferation of clandestinely synthesized analogs as recreational street drugs with dangerous effects. Currently, the interactions of cannabinoids with their biochemical substrates are extensively but inadequately understood, and the clinical application of derived and synthetic receptor ligands remains quite limited. The wide anatomical distribution and functional complexity of the cannabinoid system continue to indicate potential for both therapeutic and side effects, which offers challenges and opportunities for medicinal chemists involved in drug discovery and development.

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Palamar, Joseph J., and Monica J. Barratt. "Synthetic cannabinoids: undesirable alternatives to natural marijuana." American Journal of Drug and Alcohol Abuse 42, no. 4 (April 11, 2016): 371–73. http://dx.doi.org/10.3109/00952990.2016.1139584.

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Lim, Kevin J. H., Yan Ping Lim, Yossa D. Hartono, Maybelle K. Go, Hao Fan, and Wen Shan Yew. "Biosynthesis of Nature-Inspired Unnatural Cannabinoids." Molecules 26, no. 10 (May 14, 2021): 2914. http://dx.doi.org/10.3390/molecules26102914.

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Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.

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Zádor, Ferenc, Sâmia Joca, Gábor Nagy-Grócz, Szabolcs Dvorácskó, Edina Szűcs, Csaba Tömböly, Sándor Benyhe, and László Vécsei. "Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression." International Journal of Molecular Sciences 22, no. 11 (May 31, 2021): 5903. http://dx.doi.org/10.3390/ijms22115903.

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Substance use/abuse is one of the main causes of depressive symptoms. Cannabis and synthetic cannabinoids in particular gained significant popularity in the past years. There is an increasing amount of clinical data associating such compounds with the inflammatory component of depression, indicated by the up-regulation of pro-inflammatory cytokines. Pro-inflammatory cytokines are also well-known to regulate the enzymes of the kynurenine pathway (KP), which is responsible for metabolizing tryptophan, a precursor in serotonin synthesis. Enhanced pro-inflammatory cytokine levels may over-activate the KP, leading to tryptophan depletion and reduced serotonin levels, which can subsequently precipitate depressive symptoms. Therefore, such mechanism might represent a possible link between the endocannabinoid system (ECS) and the KP in depression, via the inflammatory and dysregulated serotonergic component of the disorder. This review will summarize the data regarding those natural and synthetic cannabinoids that increase pro-inflammatory cytokines. Furthermore, the data on such cytokines associated with KP activation will be further reviewed accordingly. The interaction of the ECS and the KP has been postulated and demonstrated in some studies previously. This review will further contribute to this yet less explored connection and propose the KP to be the missing link between cannabinoid-induced inflammation and depressive symptoms.

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Gonçalves, Elaine C. D., Gabriela M. Baldasso, Maíra A. Bicca, Rodrigo S. Paes, Raffaele Capasso, and Rafael C. Dutra. "Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant." Molecules 25, no. 7 (March 29, 2020): 1567. http://dx.doi.org/10.3390/molecules25071567.

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Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound—Δ9-tetrahydrocannabinol (Δ9-THC)—as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

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Paulsen, Paul, Carsten Carstensen, and Julia Juliansen. "The title of this test article." Journal of Benefit-Cost Analysis 1, no. 1 (January 1, 2013): 1–10. http://dx.doi.org/10.1515/jbca-2013-1233.

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Geryk, R., M. Švidrnoch, A. Přibylka, K. Kalíková, V. Maier, and E. Tesařová. "A supercritical fluid chromatography method for the systematic toxicology analysis of cannabinoids and their metabolites." Analytical Methods 7, no. 15 (2015): 6056–59. http://dx.doi.org/10.1039/c5ay01107h.

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Duggan, Peter J. "The Chemistry of Cannabis and Cannabinoids." Australian Journal of Chemistry 74, no. 6 (2021): 369. http://dx.doi.org/10.1071/ch21006.

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The science of cannabis and cannabinoids encompasses a wide variety of scientific disciplines and can appear daunting to newcomers to the field. The encroachment of folklore and ‘cannabis culture’ into scientific discussions can cloud the situation further. This Primer Review is designed to give a succinct overview of the chemistry of cannabis and cannabinoids. It is hoped that it will provide a useful resource for chemistry undergraduates, postgraduates and their instructors, and experienced chemists who require a comprehensive and up to date summary of the field. The Review begins with a brief overview of the history and botany of cannabis, then goes on to detail important aspects of the chemistry of phytocannabinoids, endocannabinoids and synthetic cannabinomimetics. Other natural constituents of the cannabis plant are then described including terpenes and terpenoids, polyphenolics, alkaloids, waxes and triglycerides, and important toxic contaminants. A discussion of key aspects of the pharmacology associated with cannabinoids and the endocannabinoid system then follows, with a focus on the cannabinoid receptors, CB1 and CB2. The medicinal chemistry of cannabis and cannabinoids is covered, highlighting the range of diseases targeted with cannabis and phytocannabinoids, as well as key aspects of phytocannabinoid metabolism, distribution, and delivery. The modulation of endocannabinoid levels through the inhibition of key endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) is then discussed. The Review concludes with an assessment of the much touted ‘entourage effect’. References to primary literature and more specialised reviews are provided throughout.

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Newman, M., G. Denton, T. Walker, and J. Grewal. "The experience of using synthetic cannabinoids: A qualitative analysis of online user self-reports." European Psychiatry 33, S1 (March 2016): S309—S310. http://dx.doi.org/10.1016/j.eurpsy.2016.01.1059.

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IntroductionThe number of novel psychoactive substances (NPS) available is increasing. Synthetic cannabinoids (SC) are one of many NPS sold. SC aim to emulate the effects of natural cannabis by acting on cannabinoid receptors. Despite much research into pharmacology, there is limited data on the user experience of SC.AimIt is useful for psychiatrists, to understand what experiences people have whilst on illicit substances. The aim of this qualitative study is to gain an initial understanding of what characterizes the experiences of those who use SC.MethodFourty anonymously written online reports were collected from the “Erowid experience vaults” and analysed using the Empirical Phenomenological Psychological Method.ResultsThe analysis yielded 488 meaning units (MU). These were grouped into 36 categories revealing 5 broad themes: (1) physical affects; (2) sensory distortions and distortions of perception; (3) emotional and psychological effects; (4) re-dosing, addiction and comedown effects; (5) similarities to other substances.ConclusionSynthetic cannabinoids have a mixed effect on users with a myriad of experiences reported. Some experienced positive results from their usage such as euphoria and relaxation, however these were counter balanced by those who experienced some serious negative emotional and physical side effects such as anxiety, paranoia, palpitations and convulsions. SC appear to often emulate that of their natural counterpart, yet there is an unpredictability to them which can end with serious consequences. Online forum content gives us a strong base understanding of users experiences of SC. Further research is required to elucidate a more nuanced understanding.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Skriabin, Valentin, and Maria Vinnikova. "T195. PSYCHOTIC DISORDERS IN PATIENTS WHO USE SYNTHETIC CANNABINOIDS: CLINICAL CHARACTERISTICS AND PATIENT PROFILE." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S305—S306. http://dx.doi.org/10.1093/schbul/sbaa029.755.

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Abstract Background Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are the two principal ingredients of natural cannabis with counteracting functions. Synthetic cannabinoids (SCs) are much more potent than natural cannabis, since they act as a more potent full agonist at the cannabinoid subtype 1 receptor than THC, and they also lack cannabinoids such as CBD that may otherwise counteract psychoactive properties of THC. Therefore, SCs may induce a more severe clinical presentation than natural cannabis does: the use of SCs may be associated with agitation, anxiety, tachycardia, hallucinations, irritability, memory and cognitive impairment, violent behavior, unresponsiveness, and psychosis. Clinical characteristics, specificity of the disease course and patient profile of the SC-induced psychoses are still poorly characterized in the scientific literature. The present study was therefore designed to evaluate the psychotic disorders in patients with synthetic cannabinoid use disorder in terms of patient profile and clinical characteristics with reference to their follow-up. Methods A total of 60 male patients (n=60; mean (standard deviation [SD]) age: 23.6 (3.5) years) diagnosed with psychotic disorder induced by the SC use who were hospitalized at the intensive care unit or emergency department of the Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare were included in this single-centre, longitudinal, observational cohort study. The catamnestic follow-up period was up to 2 years. Results We evaluated different clinical cases of SC-induced psychoses and identified four clinical types of them on the ground of leading psychopathological syndrome during the patient’s entire length of hospitalization: Then we performed a catamnestic follow-up of patients to reveal the possible schizophrenic process manifestation in patients who use SC. Catamnestic follow-up revealed that manifestation of the schizophrenic process was present in 8 patients (13% of cases). Discussion Our results revealed that SC-induced psychoses affect young adults primarily. Consistent with the statement that the majority of first-time SC users are experienced marijuana smokers, SC was used following other transitional substances rather than as the first substance in the majority of our patients, with cannabis being the most popular antecedent substance. SC was not the first substance used in the majority of our patients, and it had been preceded by use of other transitional substances, such as cannabis in most cases. Despite the exogenous nature, structurally such psychoses are often endoformic. For instance, even the delirium is atypical and includes the elements of Kandinsky-Clerambault’s syndrome. Psychopathologically hallucinations and delusions dominate in the clinical presentation of the psychoses (with predominant hallucinatory symptoms or affective paranoid symptoms). Development of substance-induced psychoses is often associated with the manifestation of the schizophrenic process (in our study it was revealed in 13% of cases). It is extremely difficult to create a differential diagnosis between such psychotic disorders and a primary endogenous psychotic episode. In such cases the appearance of deficit symptoms specific for schizophrenia becomes crucial.

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Yazici, Ahmet Bulent, Esra Yazici, and Atila Erol. "Delirium and High Creatine Kinase and Myoglobin Levels Related to Synthetic Cannabinoid Withdrawal." Case Reports in Medicine 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/3894749.

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Synthetic cannabinoids (SCs) are included in a group of drugs called new psychoactive substances. Effects of SCs on the central nervous system are similar to other cannabinoids, but 2–100 times more potent than marijuana. Thus, addiction and withdrawal symptoms are more severe than natural cannabinoids. Withdrawal symptoms of SCs were reported in the literature previously. But there is no report about SC withdrawal delirium and its treatment. Several studies reported that agonists of CB1 receptors play a role in GABA and glutamatergic neurotransmission, which is similar to the effects of alcohol on GABA and glutamatergic receptors. Previous studies on alcohol delirium cases suggested that elevated creatine kinase (CK) can be a marker of progress. This study reports delirium and high serum CK levels related to SC withdrawal and offers a treatment with benzodiazepine for them. We described two cases treated in our inpatient clinic about SC withdrawal with increase of serum CK level and other laboratory parameters. One of them demonstrated delirium symptoms and the other did not with early rapid treatment.

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Riboulet-Zemouli, Kenzi. "‘Cannabis’ ontologies I: Conceptual issues with Cannabis and cannabinoids terminology." Drug Science, Policy and Law 6 (January 2020): 205032452094579. http://dx.doi.org/10.1177/2050324520945797.

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Objective Identify a coherent nomenclature for Cannabis sativa L. derived products and their analogues. Design Research undertaken in parallel to the three-year assessment of Cannabis derivatives by the World Health Organisation. The scope is limited to Cannabis products intended for human incorporation (internal and topical consumption). Primarily embedded in pharmacognosy, the study incorporates a wide range of scholarly and grey literature, folk knowledge, archives, pharmacopœias, international law, field pharmacy, clinical and herbal medicine data, under a philosophical scrutiny. Generic and Cannabis-specific nomenclatural frames are compared to determine the extent to which they coincide or conflict. Results All lexica reviewed use weak, ambiguous, or inconsistent terms. There is insufficient scientific basis for terms and concepts related to Cannabis at all levels. No sound classification exists: current models conflict by adopting idiosyncratic, partial, outdated, or utilitarian schemes to arrange the extraordinarily numerous and diverse derivatives of the C. sativa plant. In law and policy, no clear or unequivocal boundary between herbal and non-herbal drugs, nor natural and synthetic cannabinoids was found; current nomenclatures need updates. In science, the botanical Cannabis lexicon overlooks parthenocarpy, and wide disagreement remains as to the taxonomy and systematics of the plant; chemical research should address differences in kinds between synthetic cannabinoids; pharmacopœias include little information related to Cannabis, and disagree on broader classes of herbal medicines, virtually failing to embrace many known Cannabis medicines. Since existing products and compounds fail to be categorised in an evidence-based manner, confusions will likely increase as novel cannabinoid compounds, genetic and biotechnological modifications surge. Conclusions The lack of clarity is comprehensive: for patients, physicians, and regulators. This study proposes an update of terms at several levels. It points at gaps in morphological descriptions in botany and pharmacognosy and a need for a metaphysical address of cannabinoids. Methods of obtention are identified as a common criterion to distinguish products; the way forward suggests a mutually exclusive nomenclatural pattern based on the smallest common denominator of obtention methods. In the context of a swelling number of Cannabis products being consumed (be it via medical prescription, adult-use, ‘hemp’ foodstuff and cosmetics, or other purposes), this study can assist research, contribute to transparent labelling of products, consumer safety and awareness, pharmacovigilance, medical standards of care, and an update of prevention and harm reduction approaches. It can also better inform regulatory policies surrounding C. sativa, its derivatives, and other cannabinoid-containing products.

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Gurm, Harmeet, Jeremy A. Hirota, and Sandeep Raha. "Cannabinoid Signalling in Immune–Reproductive Crosstalk during Human Pregnancy." Biomedicines 9, no. 3 (March 7, 2021): 267. http://dx.doi.org/10.3390/biomedicines9030267.

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Despite the intricate involvement of the endocannabinoid system in various physiological processes, it remains one of the most under-studied biological systems of the human body. The scope of endocannabinoid signalling is widespread, ranging from modulation of immune responses in innate and adaptive immunity to gestational processes in female physiology. Cannabinoid receptors are ubiquitously distributed in reproductive tissues and are thought to play a role in regulating the immune–reproductive interactions required for successful pregnancy, specifically among uterine natural killer cells and placental extravillous trophoblasts. The use of cannabis during pregnancy, however, can perturb endocannabinoid homeostasis through effects mediated by its major constituents, Δ-9-tetrahydrocannabinol and cannabidiol. Decidualization of the endometrium, invasion, and angiogenesis may be impaired as a consequence, leading to clinical complications such as miscarriage and preeclampsia. In this review, the crosstalk between endocannabinoid signalling in uterine natural killer cells and placental extravillous trophoblasts will be examined in healthy and complicated pregnancies. This lays a foundation for discussing the potential of targeting the endocannabinoid system for therapeutic benefit, particularly with regard to the emerging field of synthetic cannabinoids.

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Scheau, Cristian, Constantin Caruntu, Ioana Anca Badarau, Andreea-Elena Scheau, Anca Oana Docea, Daniela Calina, and Ana Caruntu. "Cannabinoids and Inflammations of the Gut-Lung-Skin Barrier." Journal of Personalized Medicine 11, no. 6 (May 31, 2021): 494. http://dx.doi.org/10.3390/jpm11060494.

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Recent studies have identified great similarities and interferences between the epithelial layers of the digestive tract, the airways and the cutaneous layer. The relationship between these structures seems to implicate signaling pathways, cellular components and metabolic features, and has led to the definition of a gut-lung-skin barrier. Inflammation seems to involve common features in these tissues; therefore, analyzing the similarities and differences in the modulation of its biomarkers can yield significant data promoting a better understanding of the particularities of specific signaling pathways and cellular effects. Cannabinoids are well known for a wide array of beneficial effects, including anti-inflammatory properties. This paper aims to explore the effects of natural and synthetic cannabinoids, including the components of the endocannabinoid system, in relation to the inflammation of the gut-lung-skin barrier epithelia. Recent advancements in the use of cannabinoids as anti-inflammatory substances in various disorders of the gut, lungs and skin are detailed. Some studies have reported mixed or controversial results, and these have also been addressed in our paper.

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Calina, Daniela, Ana Maria Buga, Mihaela Mitroi, Aleksandra Buha, Constantin Caruntu, Cristian Scheau, Abdelhakim Bouyahya, Nasreddine El Omari, Naoual El Menyiy, and Anca Oana Docea. "The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation—Evidence from In Vivo Studies." Journal of Clinical Medicine 9, no. 8 (July 27, 2020): 2395. http://dx.doi.org/10.3390/jcm9082395.

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Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies. In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments. The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood–brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins. In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.

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Protti, Michele, James Rudge, Angelo Eliseo Sberna, Gilberto Gerra, and Laura Mercolini. "Dried haematic microsamples and LC–MS/MS for the analysis of natural and synthetic cannabinoids." Journal of Chromatography B 1044-1045 (February 2017): 77–86. http://dx.doi.org/10.1016/j.jchromb.2016.12.038.

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Chicca, A., M. A. Schafroth, I. Reynoso-Moreno, R. Erni, V. Petrucci, E. M. Carreira, and J. Gertsch. "Uncovering the psychoactivity of a cannabinoid from liverworts associated with a legal high." Science Advances 4, no. 10 (October 2018): eaat2166. http://dx.doi.org/10.1126/sciadv.aat2166.

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Phytochemical studies on the liverwort Radula genus have previously identified the bibenzyl (−)-cis-perrottetinene (cis-PET), which structurally resembles (−)-Δ9-trans-tetrahydrocannabinol (Δ9-trans-THC) from Cannabis sativa L. Radula preparations are sold as cannabinoid-like legal high on the internet, even though pharmacological data are lacking. Herein, we describe a versatile total synthesis of (−)-cis-PET and its (−)-trans diastereoisomer and demonstrate that both molecules readily penetrate the brain and induce hypothermia, catalepsy, hypolocomotion, and analgesia in a CB1 receptor–dependent manner in mice. The natural product (−)-cis-PET was profiled on major brain receptors, showing a selective cannabinoid pharmacology. This study also uncovers pharmacological differences between Δ9-THC and PET diastereoisomers. Most notably, (−)-cis-PET and (−)-trans-PET significantly reduced basal brain prostaglandin levels associated with Δ9-trans-THC side effects in a CB1 receptor–dependent manner, thus mimicking the action of the endocannabinoid 2-arachidonoyl glycerol. Therefore, the natural product (−)-cis-PET is a psychoactive cannabinoid from bryophytes, illustrating the existence of convergent evolution of bioactive cannabinoids in the plant kingdom. Our findings may have implications for bioprospecting and drug discovery and provide a molecular rationale for the reported effects upon consumption of certain Radula preparations as moderately active legal highs.

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Frisoni, Paolo, Erica Bacchio, Sabrine Bilel, Anna Talarico, Rosa Gaudio, Mario Barbieri, Margherita Neri, and Matteo Marti. "Novel Synthetic Opioids: The Pathologist’s Point of View." Brain Sciences 8, no. 9 (September 2, 2018): 170. http://dx.doi.org/10.3390/brainsci8090170.

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Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.

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McParland, Aidan, Kapustin Daniel, Anuj Bhatia, Hance Clarke, Trivedi Aditya, Richard Brull, and Mandeep Singh. "695 Cannabinoids and Sleep Health in Patients with Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis." Sleep 44, Supplement_2 (May 1, 2021): A271—A272. http://dx.doi.org/10.1093/sleep/zsab072.693.

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Abstract Introduction Neuropathic pain (NP) syndromes are debilitating conditions which can impact sleep health and overall quality of life significantly. Pharmacological treatment with cannabinoids has not been evaluated for its impact on sleep health. The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain control, and patient impression of treatment efficacy. Methods We reviewed randomized controlled trials comparing synthetic and natural cannabinoids (CB) to placebo in patients with central and peripheral neuropathic pain syndromes. A systematic search of the standard literature databases was conducted, including randomized controlled trials evaluating the pharmacological treatment of NP syndromes using cannabinoids. Data on NRS pain scales, sleep quality, daytime somnolence, nausea, dizziness, and patient global impression of change (PGIC) scores were recorded. Meta-analysis using the random effects model was conducted where appropriate. Results Of the 3536 studies screened, a total of 8 randomized controlled trials including 1051 patients (placebo: 478 patients; CB: 573 patients) with neuropathic pain were included. Cannabinoids included in the studies were Sativex (GW-1000–02), Nabilone, and medical cannabis preparations with THC dose ranging from 1mg to 130mg per day. Pain scores were significantly reduced in the CB group (standardized difference in means (SDM) = -0.236, 95% CI=-0.375 to -0.100, p-value = 0.001) compared to placebo (Figure 1). Significant improvement in sleep quality (Figure 2) was also observed in the CB group (SMD 0.389, 95% CI, 0.233 to 0.546, p<0.013). Additionally, patients in the CB group were more likely to report improvement in PGIC scores (OR=2.3, 95% CI 1.37 to 3.9, p=0.002) compared to patients treated with placebo (Figure 3). Notably, CB-treated patients were more likely to experience daytime somnolence (OR=2.2, 95% CI 1.3 to 3.9, p=0.004), nausea (OR=1.7, 95% CI 1.1 to 2.5, p=0.02), and dizziness (OR=3.8, 95% CI 2.6 to 5.7, p<0.001). Conclusion Cannabinoids are useful agents for NP as evidenced by significant improvement in pain, sleep quality, and PGIC. With the advent of new agents and more refined cannabis derivatives, further research is needed to comprehensively explore treatment effectiveness. Future work should incorporate clinically validated measures of sleep health to better evaluate this outcome. Support (if any):

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Mattoteia, Daiana, Aniello Schiano Moriello, Orazio Taglialatela-Scafati, Pietro Amodeo, Luciano De Petrocellis, Giovanni Appendino, Rosa Maria Vitale, and Diego Caprioglio. "The Combined Effect of Branching and Elongation on the Bioactivity Profile of Phytocannabinoids. Part I: Thermo-TRPs." Biomedicines 9, no. 8 (August 23, 2021): 1070. http://dx.doi.org/10.3390/biomedicines9081070.

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The affinity of cannabinoids for their CB1 and CB2 metabotropic receptors is dramatically affected by a combination of α-branching and elongation of their alkyl substituent, a maneuver exemplified by the n-pentyl -> α,α-dimethylheptyl (DMH) swap. The effect of this change on other cannabinoid end-points is still unknown, an observation surprising since thermo-TRPs are targeted by phytocannabinoids with often sub-micromolar affinity. To fill this gap, the α,α-dimethylheptyl analogues of the five major phytocannabinoids [CBD (1a), Δ8-THC (6a), CBG (7a), CBC (8a) and CBN (9a)] were prepared by total synthesis, and their activity on thermo-TRPs (TRPV1-4, TRPM8, and TRPA1) was compared with that of one of their natural analogues. Surprisingly, the DMH chain promoted a shift in the selectivity toward TRPA1, a target involved in pain and inflammatory diseases, in all investigated compounds. A comparative study of the putative binding modes at TRPA1 between DMH-CBC (8b), the most active compound within the series, and CBC (8a) was carried out by molecular docking, allowing the rationalization of their activity in terms of structure–activity relationships. Taken together, these observations qualify DMH-CBC (8b) as a non-covalent TRPA1-selective cannabinoid lead that is worthy of additional investigation as an analgesic and anti-inflammatory agent.

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Antonella, Brizzi, and Pessina Federica. "Old Strategies and New Perspectives in Modulating the Endocannabinoid System." Current Bioactive Compounds 15, no. 2 (March 12, 2019): 159–73. http://dx.doi.org/10.2174/1573407214666180627144214.

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Endocannabinoid System (ES) has gained over the years a leading position in scientific research thanks to its involvement in numerous patho/physiological conditions. Accordingly, its main components, such as receptors, enzymes and mediators, have become important drug targets for the management of diseases where it is dysregulated. Within the manuscript, several classes of cannabinergic ligands are examined, emphasizing molecules coming from the natural world, unique source of active compounds. Firstly, the endogenous lipid ES modulators are described, starting from the major endocannabinoids to the plethora of endocannabinoid congeners. Afterwards, Cannabis-derived cannabinoids, namely well-known phytocannabinoids and new constituents from different varieties of Cannabis, are reviewed also mentioning the huge effort of pharmaceutical research in obtaining synthetic analogues. Finally, an overview of peptides and miscellaneous natural products points out new opportunities to modulate ES, offering an enormous chemical heterogeneity. Accordingly, hemopressin and related peptides, plant-derived alkylamides, terpenoid derivatives, neolignans and examples from the marine world can provide interesting hints and original ideas to develop new cannabinergic compounds.

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Velayudhan, Latha, Katie McGoohan, and Sagnik Bhattacharyya. "Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis." PLOS Medicine 18, no. 3 (March 29, 2021): e1003524. http://dx.doi.org/10.1371/journal.pmed.1003524.

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Background Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years. Methods and findings A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those <50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes and heterogeneity in included studies. Conclusions This pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age.

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Radhika Tyagi, Sangrila Singh, Anjali Joshi, Vishali Chopra, Priyank Vyas, and Amit Gupta. "Overview of Salvia divinorum –Substance-induced psychosis." International Journal of Research in Pharmaceutical Sciences 11, SPL4 (December 21, 2020): 1714–18. http://dx.doi.org/10.26452/ijrps.v11ispl4.4360.

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As per the literature, humans ingest a comprehensive range of food materials including drugs along with dietary supplements which are mainly derived through medicinal plant products and modifying the purpose of the central nervous system (CNS). These psychoactive based properties are mainly attributable to the existence of plant-derived secondary metabolites. Most of the cases or studies showed the effects of these phytochemicals derived from secondary metabolites on the human CNS might be linked either to their ecological roles or molecular along with biochemical based properties are reported in case of plants along with higher animals. One of the mental health disorders, psychosis where person losses its capacity of critical thinking, they perceive things differently as compared to the people around. They see or hear things that other people cannot see or hear (hallucination) or even believe things that are not true (delusion). There are so many synthetic psychosis inducer synthetic cannabinoids (SCs) as well as semi-synthetic and natural. Psychosis is a disorder which shows the effect for long-term or sometimes for the short term on an individual. In this review we will mainly look for natural psychosis inducers like Salvia divinorum and this plant may produce some secondary metabolites. Still, many of these are found to show an effect on human health in some or the other way which may range from hallucination to organ failure. These secondary metabolites affect the hippocampus region of the human brain, which is linked with memory. It is interesting to note how one chemical is used for an organism for protection and that one chemical act as a mind-altering chemical for the higher class of organism – the humans.

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Sharp, Phoebe, Simon Hudson, Laura Hikin, Paul R. Smith, and Stephen R. Morley. "The changing pattern of synthetic cannabinoid use within England, April 2014 to March 2018." Medicine, Science and the Law 59, no. 3 (May 8, 2019): 180–86. http://dx.doi.org/10.1177/0025802419845796.

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IntroductionSynthetic cannabinoids (SC), designed to mimic delta-9-tetrahydrocannabinol, the natural component of cannabis, have seen a rapid increase in popularity since 2008. Nearly 200 SC have been detected to date. However, there are limited data available reporting the changing trend in their use. Here, we report the temporal changes in SC use, as well as the demographic profile of users.MethodIn this retrospective study, case background and toxicology findings were collected from forensic toxicology reports dated between 1 April 2014 and 31 March 2018 that included a positive result for the presence of one or more SC and/or metabolites.ResultsA total of 113 cases were positive for SC; 103 (91.2%) of the individuals were male, with a median age of 40 years (range 15–80 years). Over the four-year time period, a total of 12 different SC were detected; seven of these SC were detected in more than six cases each. The most commonly detected SC had a lifetime of one to two years before being replaced. Discussion and conclusion: Our data show that SC were being used for approximately one to two years before they were superseded by newer structures. It is therefore extremely difficult to predict future patterns of SC use and is consequently not advisable to offer limited screening.

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Anzillotti, Luca, Francesca Marezza, Luca Calò, Roberta Andreoli, Silvia Agazzi, Federica Bianchi, Maria Careri, and Rossana Cecchi. "Determination of synthetic and natural cannabinoids in oral fluid by solid-phase microextraction coupled to gas chromatography/mass spectrometry: A pilot study." Talanta 201 (August 2019): 335–41. http://dx.doi.org/10.1016/j.talanta.2019.04.029.

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Mensen, Vincent T., Annabel Vreeker, Johan Nordgren, Amanda Atkinson, Rafael de la Torre, Magi Farré, Johannes G. Ramaekers, and Tibor M. Brunt. "Psychopathological symptoms associated with synthetic cannabinoid use: a comparison with natural cannabis." Psychopharmacology 236, no. 9 (April 9, 2019): 2677–85. http://dx.doi.org/10.1007/s00213-019-05238-8.

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Scossa, Federico, Maria Benina, Saleh Alseekh, Youjun Zhang, and Alisdair Fernie. "The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants." Planta Medica 84, no. 12/13 (May 29, 2018): 855–73. http://dx.doi.org/10.1055/a-0630-1899.

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AbstractPlants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes in planta of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the “early” biochemical or the more recent integrative approaches–based on omics-analyses–have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.

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Geiger, Sarah, Kathrin Nickl, Erich H. Schneider, Roland Seifert, and Jörg Heilmann. "Establishment of recombinant cannabinoid receptor assays and characterization of several natural and synthetic ligands." Naunyn-Schmiedeberg's Archives of Pharmacology 382, no. 2 (July 9, 2010): 177–91. http://dx.doi.org/10.1007/s00210-010-0534-5.

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Kurdil, NV. "Natural opium products in the modern structure of drug poisoning (literature review and results of drug screening for 1990-2020)." One Health and Nutrition Problems of Ukraine 54, no. 1 (May 20, 2021): 5–12. http://dx.doi.org/10.33273/2663-9726-2021-54-1-5-12.

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Despite the rapid increase in synthetic drug use in the United States, the European Union, and many other parts of the world, narcotic and psychoactive substances of natural origin remain relevant to toxicologists. Aim. To analyze the results of drug screening of opium drugs in 1990-2020 and their impact on the formation of acute unintentional poisoning among the adult population of Kyiv. Materials and Мethods. A retrospective analysis of the reports of the toxicological laboratory of the Kyiv City Clinical Emergency Hospital for 1990-2020 on the results of chemical-toxicological screening for drug content in persons diagnosed with "Acute drug poisoning" (ICD-10: T40.0-T40.3). Methods used: Immuno-chromatographic analysis (ICA), thin layer chromatography (TLC) and gas-liquid chromatography with mass spectral detection (GC/MS). Results. According to official data in Ukraine in 2019, the substances that caused people to seek medical help are distributed as follows: opioids – 68.53%; cannabinoids – 6.84%; cocaine – 0.08%; hallucinogens – 0.04%; other drugs – 24.51%. Among those who died as a result of drug poisoning, the proportion of opiates T40.2 (codeine, morphine) was 16%; opium T40.0 – 4%; methadone T40.3 – 23%; other drugs T40.4 (pethidine) – 2%, which together is 45%. According to the results of chemical-toxicological screening for opiate content, it was found that the first step in the average annual growth rate is occupied by: buprenorphine (+7.95%), morphine (+7.6%) and heroin (+6.04%). The number of positive tests decreased in the group of opiates –"shirka" (–9.38%) and opium alkaloids (–2.55%). Over the last 10 years, there has been a progressive increase in the annual number of positive tests for methadone content (+39.3%) at R 2 =8904, which indicates a high stability of the growth rate. Conclusions. Opiates continue to occupy an important segment in the structure of drugs, where their positions for the period 1990-2020 strengthened buprenorphine, morphine and heroin against the weakening of the position of opium ("shirka") and opium alkaloids; at the same time there is a rapid increase in the proportion of semisynthetic and synthetic opioids. These changes necessitate continuous improvement of methods of chemical and toxicological studies of opium products, clinical diagnosis and prevention of related poisonings.

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Pereira, Lionel E., Nitin Toteja, Anbreen Khizar, and Cathryn A. Galanter. "6.96 EFFECT OF SYNTHETIC CANNABINOIDS AND NATURAL CANNABIS ON SEVERITY OF PSYCHOTIC SYMPTOMS AND AGGRESSION IN ADOLESCENTS AND YOUNG ADULTS WITH PSYCHOSIS IN AN INPATIENT SETTING." Journal of the American Academy of Child & Adolescent Psychiatry 55, no. 10 (October 2016): S235—S236. http://dx.doi.org/10.1016/j.jaac.2016.09.415.

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Berger, Geraint, Nipun Arora, Ian Burkovskiy, Yanfang Xia, Anu Chinnadurai, Robert Westhofen, Georg Hagn, et al. "Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice." Molecules 24, no. 23 (November 21, 2019): 4239. http://dx.doi.org/10.3390/molecules24234239.

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Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.

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Islam, Md Jahirul, Byeong Ryeol Ryu, Md Obyedul Kalam Azad, Md Hafizur Rahman, Eun Ju Cheong, Jung-Dae Lim, and Young-Seok Lim. "Cannabinoids Accumulation in Hemp (Cannabis sativa L.) Plants under LED Light Spectra and Their Discrete Role as a Stress Marker." Biology 10, no. 8 (July 24, 2021): 710. http://dx.doi.org/10.3390/biology10080710.

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Hemp adaptability through physiological and biochemical changes was studied under 10 LED light spectra and natural light in a controlled aeroponic system. Light treatments were imposed on 25 days aged seedlings for 16 h daily (300 µmol m−2 s−1) for 20 days. Plant accumulated highest Cannabidiol (CBD) in R7:B2:G1 light treatment, with relatively higher photosynthetic rate and lower reactive oxygen species, total phenol content, total flavonoid content, DPPH radical scavenging capacity, and antioxidant enzymatic activities. Tetrahydrocannabinol (THC) also accumulated at a higher level in white, R8:B2, and R7:B2:G1 light with less evidence of stress-modulated substances. These results indicated that CBD and THC have no or little relation with light-mediated abiotic stress in hemp plants. On the contrary, Tetrahydrocannabinolic acid (THCA) was accumulated higher in R6:B2:G1:FR1 and R5:B2:W2:FR1 light treatment along with lower photosynthetic rate and higher reactive oxygen species, total phenol content, total flavonoid content, DPPH radical scavenging capacity, and antioxidant enzymatic activities. However, Cannabidiolic acid (CBDA) was accumulated higher in R6:B2:G1:FR1 light treatment with higher stress-modulated substances and lower physiological traits. CBDA was also accumulated higher in R8:B2 and R7:B2:G1 light treatments with less evidence of stress-modulated substances. Besides, Greenlight influenced CBD and CBDA synthesis where FR and UV-A (along with green) play a positive and negative role in this process. Overall, the results indicated that the treatment R7:B2:G1 enhanced the medicinal cannabinoids most, and the role of THCA as a stress marker is more decisive in the hemp plant than in other cannabinoids under attributed light-mediated stress.

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Freund, Shaina A., and Adrian S. Banning. "Synthetic cannabinoids." Journal of the American Academy of Physician Assistants 30, no. 11 (November 2017): 1–4. http://dx.doi.org/10.1097/01.jaa.0000525914.28344.e2.

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Mills, Brooke, Andres Yepes, and Kenneth Nugent. "Synthetic Cannabinoids." American Journal of the Medical Sciences 350, no. 1 (July 2015): 59–62. http://dx.doi.org/10.1097/maj.0000000000000466.

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Antoniou, T., and D. N. Juurlink. "Synthetic cannabinoids." Canadian Medical Association Journal 186, no. 3 (October 7, 2013): 210. http://dx.doi.org/10.1503/cmaj.130510.

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Solages, Martine M. "Synthetic Cannabinoids∗." Child and Adolescent Psychopharmacology News 20, no. 5 (October 2015): 1–3. http://dx.doi.org/10.1521/capn.2015.20.5.1.

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Pintori, Nicholas, Barbara Loi, and Maddalena Mereu. "Synthetic cannabinoids." Behavioural Pharmacology 28, no. 6 (September 2017): 409–19. http://dx.doi.org/10.1097/fbp.0000000000000323.

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Camp, Nancy E. "Synthetic Cannabinoids." Journal of Emergency Nursing 37, no. 3 (May 2011): 292–93. http://dx.doi.org/10.1016/j.jen.2011.01.006.

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Tauchen, Jan. "Natural Products and their (Semi-)Synthetic Forms in the Treatment of Migraine: History and Current Status." Current Medicinal Chemistry 27, no. 23 (July 1, 2020): 3784–808. http://dx.doi.org/10.2174/0929867326666190125155947.

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Background: Migraine may be described as a headache with moderate to extreme pain that is often accompanied by incapacitating neurological symptoms. It is estimated that 12% of the world population suffers from migraine. Although a number of drugs have been used for treatment of migraine, most of these are not effective for every patient and may have undesirable side-effects. Thus, there is an enormous unmet need in current migraine therapy for discovering safer and more effective agents. Methods: The information summarized in this review was obtained through extensive literature review and search of relevant books and articles with the use of Web of Knowledge and SciVerse Scopus databases. Results: Greater understanding of the molecular mechanisms underlying the etiopathogenesis of migraine is helpful in identifying novel targets for antimigraine drugs such as cannabinoid, histamine, and melatonin receptors. In the past, natural product-derived constituents have served as an invaluable source of numerous medicinally useful antimigraine agents and it may be expected that further promising drug candidates from natural products will be discovered for antimigraine pharmacotherapy with better efficacy and fewer adverse-effects. Conclusion: The discovery of novel targets in migraine therapy has opened new horizons for compounds that have not been clinically tested or that previously failed in clinical trials as potential antimigraine drugs. Ginkgolide B, melatonin, histamine, oxytocin, various ribosomal peptide toxins, kavalactones, devil’s claw-derived compounds, salvinorin A and petasin are among those agents that show considerable promise as novel drugs in migraine prevention and treatment. It is necessary to conduct more research to better understand their antimigraine action, to confirm their effectiveness and safety, and to introduce them into clinical practice.

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Le Boisselier, R., J. Alexandre, V. Lelong-Boulouard, and D. Debruyne. "Focus on cannabinoids and synthetic cannabinoids." Clinical Pharmacology & Therapeutics 101, no. 2 (December 20, 2016): 220–29. http://dx.doi.org/10.1002/cpt.563.

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Pop, Emil. "Nonpsychotropic Synthetic Cannabinoids." Current Pharmaceutical Design 6, no. 13 (September 1, 2000): 1347–59. http://dx.doi.org/10.2174/1381612003399446.

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Kichloo, Asim, Michael Albosta, Michael Aljadah, Zain El-Amir, Ghazaleh Goldar, Muhammed Zatmar Khan, Dushyant Singh Dahiya, Srilakshmi Vallabhaneni, Farah Wani, and Jagmeet Singh. "Marijuana: A systems-based primer of adverse effects associated with use and an overview of its therapeutic utility." SAGE Open Medicine 9 (January 2021): 205031212110009. http://dx.doi.org/10.1177/20503121211000909.

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Marijuana use is on the rise in the United States. By the end of 2019, 33 states have legalized marijuana use and marijuana byproduct use for medical purposes. However, marijuana use does not come without side effects. This manuscript reviews the increasing usage of marijuana and the different forms (natural and synthetic) that patients may use when presenting to clinicians. It also addresses the biochemical and behavioral changes observed with marijuana use, including the location and changes associated with cannabinoid receptors (abbreviated CB1 and CB2). These two topics lead into an extensive review of the side effects of marijuana use. This manuscript discusses gastrointestinal side-effects, such as Cannabinoid Hyperemesis Syndrome, pancreatitis, and hepatotoxicity. It also briefly reviews cardiovascular, neurologic, and pulmonary side effects. This article provides an overview of therapeutic effects of marijuana including the antiemetic effect, its medical utility as an appetite stimulant, and usefulness in cancer patients post-chemotherapy. A thorough social history pertaining to marijuana use is an important consideration for clinicians in patients presenting with a variety of symptoms, including those effecting the gastrointestinal, cardiovascular, pulmonary, or neurologic systems.

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Karila, Laurent, Amine Benyamina, Lisa Blecha, Olivier Cottencin, and Joël Billieux. "The Synthetic Cannabinoids Phenomenon." Current Pharmaceutical Design 22, no. 42 (January 1, 2017): 6420–25. http://dx.doi.org/10.2174/1381612822666160919093450.

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Fellner, Avi, Felix Benninger, and Ruth Djaldetti. "Synthetic cannabinoids revealing adrenoleukodystrophy." Journal of Clinical Neuroscience 24 (February 2016): 155–56. http://dx.doi.org/10.1016/j.jocn.2015.07.020.

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Ashton, C. Heather, and P. Brian Moore. "Regulation of synthetic cannabinoids." Lancet 374, no. 9701 (November 2009): 1595. http://dx.doi.org/10.1016/s0140-6736(09)61949-8.

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Sumnall, Harry. "Regulation of synthetic cannabinoids." Lancet 374, no. 9701 (November 2009): 1595. http://dx.doi.org/10.1016/s0140-6736(09)61950-4.

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Underwood, E. "Alarm over synthetic cannabinoids." Science 347, no. 6221 (January 29, 2015): 473. http://dx.doi.org/10.1126/science.347.6221.473.

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Journal articles on the topic 'Synthetic and natural cannabinoids'

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