Chirality in Cannabinoid Research.

Mankind has long utilized Cannabis for diverse purposes. However, it has only been since the late 19th century that its individual cannabinoids began to be isolated, analyzed, and synthesized. By the mid-20th century it was discovered that many cannabinoids were asymmetric, with chirality often controlling their pharmacology. Increasingly accurate measurement and understanding of cannabinoid chirality will facilitate their synthesis and accelerate their medicinal applications.

The Cannabis Spread throughout the Continents and its Therapeutic Use in History.

BACKGROUND: Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East's human societies. Cannabis has been used not only for recreational purposes but as food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders. AIM: This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) The empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians' ii.) The current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system. METHODS: This study was performed through a detailed analysis of the studies on the historical significance and medical applications of Cannabis sativa by using international scientific databases, historical and medical books, ancient Greek and Chinese manuscripts translations, library and statistical data from government reports and texts from the National Library of Greece (Stavros Niarchos Foundation), from the School of Health Sciences of the National and Kapodistrian University of Athens (Greece). We selected papers and texts focusing on a historical point of view about the medical importance of the plant and its applications for a therapeutic purpose in the past. RESULTS AND CONCLUSION: Through a detailed analysis of the available resources about the origins of C. sativa, we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21st centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays, they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.

Historical and Current Perspectives of Synthetic Marijuana: Critical Review.

Synthetic marijuana use has increased significantly since 2008 among young adults in the United States, as have adverse reactions to it, leading to a dramatic increase in emergency department visits. However, much of the research conducted on it has been case studies, which report detrimental symptoms on an individual basis. Only a limited number of studies aim to better understand the larger parameters of this epidemic to assist health care providers and policy makers, including early detection, intervention, and adequate treatment. In addition, there has been limited critical review of this substance to help health care professionals educate the public about the negative health effects of using this drug. This article explores the critical reviews of synthetic marijuana, also commonly known as "K2" and "Spice," synthesizing information from literature reviews, case studies, media information, and government websites. Findings were organized by synthetic marijuana's history, description, adverse reactions including withdrawal symptoms and death incidents, detection screening, treatment, and legislative issues. Health care providers need to understand the detrimental effects of this illicit and harmful substance to both the body and mind and sometimes irreversible damage caused to individuals who consume it. Policy makers, the public, and affected individuals and their family members need to be educated as well.

Application of Cannabinoids in Neurosciences: Considerations and Implications.

Medicinal cannabinoid use continues to evolve across the United States, although legitimate federal recognition for medicinal purpose is lacking. Variability exists across states within the United States with respect to legislation, and health care institutions encounter challenges when patients present with a history of medicinal cannabinoid use. Emerging evidence in the field of neurosciences suggests a role of cannabinoids for neurologic medical conditions such as Parkinson disease, multiple sclerosis, and epilepsy. We aim to provide an overview of cannabinoids including a historical perspective, pharmacology, applications in neurosciences, and challenges in health care and academia. Knowledge of the appropriate role of cannabinoids in the clinical setting is essential for all health care practitioners including nursing.

[A brief history of marijuana in the western world]. / Breve historia sobre la marihuana en Occidente.

Marijuana is a substance with a long and controversial history. At different times in its history, which goes back over 5,000 years, this plant has been used for different purposes, ranging from recreational and leisure to its use in the treatment of several diseases or to offer relief in processes that entail a certain type of malaise, and including its consideration as a means of relaxation and meditation. Although it was supposed that the roots of marijuana lay in Central America, it is now known that this is but an urban legend with little credibility and that its origins can be found recorded in Chinese medical references dating back to the year 2737 BC. Although this plant was not originally from Central America, it has aroused interest around the world, and above all in Mexico. It is in this country where the use of cannabis has gone from applications in textiles and medicine to its free sale, the bans on its use due to political and social pressures, its tolerance and, recently, its decriminalisation for recreational and medicinal use. Unfortunately there are few references on the history of this plant in Mexico, and thus we have considered it interesting to present some data about the generalities of marijuana, a brief history in the world, the development of decriminalisation in North America, its medicinal uses and its course through Mexico to the present day.

TITLE: Breve historia sobre la marihuana en Occidente.La marihuana es una sustancia con una extensa y controvertida historia. A lo largo del tiempo, esta planta, y desde hace mas de 5.000 años, ha sido utilizada para diferentes fines, que van desde el uso ludico y recreativo, pasando por un medio de relajacion y meditacion, hasta su uso en el tratamiento de varias enfermedades o el alivio de procesos vinculados a cierto tipo de malestares. Aunque se supuso que la marihuana tenia su origen en Mesoamerica, ahora se sabe que es solo una leyenda urbana de poca credibilidad y que sus origenes los podemos registrar en referencias medicas chinas datadas alrededor del año 2737 a. de C. Si bien esta planta no tiene un origen mesoamericano, si ha generado interes en el mundo, y sobre todo en Mexico. Es en este pais donde el uso del cannabis ha ido desde intereses textiles y medicinales hasta el consumo ludico, pasando por su venta libre, la prohibicion por presiones politicas y sociales, su tolerancia y, recientemente, su despenalizacion para uso ludico y medicinal. Desgraciadamente existen pocas referencias de la historia de esta planta en Mexico, por lo que ha sido de nuestro interes presentar algunos datos sobre las generalidades de la marihuana, una breve historia en el mundo, el desarrollo de la despenalizacion en Norteamerica, sus usos medicinales y su paso por Mexico hasta nuestros dias.

Cannabinoids and hallucinogens for headache.

Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or "marijuana" once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success. The legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy.

High-performance sport, marijuana, and cannabimimetics.

The prohibition on use of cannabinoids in sporting competitions has been widely debated and continues to be a contentious issue. Information continues to accumulate on the adverse health effects of smoked marijuana and the decrement of performance caused by the use of cannabinoids. The objective of this article is to provide an overview of cannabinoids and cannabimimetics that directly or indirectly impact sport, the rules of sport, and performance of the athlete. This article reviews some of the history of marijuana in Olympic and Collegiate sport, summarizes the guidelines by which a substance is added to the World Anti-Doping Agency Prohibited List, and updates information on the pharmacologic effects of cannabinoids and their mechanism of action. The recently marketed cannabimimetics Spice and K2 are included in the discussion as they activate the same receptors as are activated by THC. The article also provides a view as to why the World Anti-Doping Agency prohibits cannabinoid or cannabimimetic use incompetition and should continue to do so.

Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions.

Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded. Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development. The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms. This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.

Cannabinoids in health and disease.

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.

Cannabinoid pharmacology: the first 66 years.

Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB(1) and CB(2) receptors and of endogenous ligands for these receptors, to the development of CB(1)- and CB(2)-selective agonists and antagonists and to the realization that the endogenous cannabinoid system has significant roles in both health and disease, and that drugs which mimic, augment or block the actions of endogenously released cannabinoids must have important therapeutic applications. Some goals for future research are identified.

Cannabinoid pharmacotherapy: past, present and future.

Cannabinoids are medically interesting, but the available data are still weak scientifically and overwhelming anecdotally. In the management of pain, cannabinoids have been shown to have antinociceptive properties in animal models of pain, with non-opiate mechanisms appearing to predominate. A widely cited meta-analysis suggested that cannabinoids offer moderate pain relief, similar to codeine, and limited by side effects. Further research, particularly into modes of delivery, to assess their therapeutic potential are needed. Any successful future clinical development of cannabinoid pharmacotherapy depends upon a dosage form that is reliable, rapidly titratable to effect, non-smoked, and preferably parenteral to avoid hepatic first pass metabolism.

Medicinal use of cannabis: history and current status.

OBJECTIVE: To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids. METHODS: The literature on therapeutic uses of cannabis and cannabinoids was assessed with respect to type of study design, quality and variability of data, independent replications by the same or other investigators, magnitude of effects, comparison with other available treatments and reported adverse effects. The results of this review were also compared with those of major international reviews of this topic in the past five years. CONCLUSIONS: Pure tetrahydrocannabinol and several analogues have shown significant therapeutic benefits in the relief of nausea and vomiting, and stimulation of appetite in patients with wasting syndrome. Recent evidence clearly demonstrates analgesic and anti-spasticity effects that will probably prove to be clinically useful. Reduction of intraocular pressure in glaucoma and bronchodilation in asthma are not sufficiently strong, long lasting or reliable to provide a valid basis for therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently promising to warrant further properly designed clinical trials. There is still a major lack of long term pharmacokinetic data and information on drug interactions. For all the present and probable future uses, pure cannabinoids, administered orally, rectally or parenterally, have been shown to be effective, and they are free of the risks of chronic inflammatory disease of the airways and upper respiratory cancer that are associated with the smoking of crude cannabis. Smoking might be justified on compassionate grounds in terminally ill patients who are already accustomed to using cannabis in this manner. Future research will probably yield new synthetic analogues with better separation of therapeutic effects from undesired psychoactivity and other side effects, and with solubility properties that may permit topical administration in the eye, or aerosol inhalation for rapid systemic effect without the risks associated with smoke inhalation.

Looking back at Cannabis research.

Research leading to the isolation of the plant cannabinoids during the 1960 s and to the endogenous cannabinoids, during the 1990 s is described. Investigations on two non-psychotropic, synthetic cannabinoids, HU-211, a neuroprotective agent and HU-308, a specific CB2 agonist are presented.

Drugs in prehistory: chemical analysis of ancient human hair.

Concern about drug abuse in modern populations has led to the development of specific methods for identification of cocaine, opiates and cannabis in human hair. Drug use in prehistory can provide indirect evidence of interpopulational contact and social stratification. This paper reports drug evaluation in nineteen ancient hair samples from archaeological sites in northern Chile. Each sample was tested for the presence of traces of cocaine, opiates and cannabis, in order to establish a standard methodology for studies of drug use among prehistoric groups. Although results are negative, this absence of evidence could be due to two main causes: (1) the individuals evaluated did not use any drugs, which does not mean that other members of their cultural group did, or (2) the wide range of known drugs studied did not consider some group specific drugs, derived from local or imported plants, thus meaning that a greater drug range must be tested. In any case, our study confirms that drug testing in prehistoric samples is viable. However, in order to determine what kind of substances were used in prehistoric times new patterns that incorporate all drugs which are not part of the western pharmacopeia must be created. Finally, a methodology for the study of drug use among prehistoric groups using ancient hair samples is described.