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Conflicting ontologies of dronabinol and THC: impact on international control. C61 I: Schedule I of the 1961 Single Convention; C61 III: Schedule III of the 1961 Single Convention; C61 IV: Schedule IV of the 1961 Single Convention; C71 I: Schedule I of the 1971 Convention; C71 II: Schedule II of the 1971 Convention; THC: tetrahydrocannabinol. a Only when 'from synthetic origin' (INCB, 2019: 8); b Only when obtained from C. sativa (INCB, 2019: 8); c Only for some preparations for medical use (ECDD, 2019: 55).
Objective: Identify a coherent nomenclature of products containing cannabinoids (whether derived from Cannabis sativa L. or not). 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 to...
... Indeed, the concentration of phytocannabinoids varies during the reproductive phase [37,58], and there may be a relationship between the chemotype and the sensitivity of the genotype to the photoperiod . In agreement, Yang et al. (2020)  found that the maximum concentration of CBG in three photoperiod-sensitive genotypes was highest in the fourth week of flowering and subsequently decreased. ...
The main characteristic of Cannabis sativa L. is the production of compounds of medicinal interest known as phytocannabinoids. Environmental factors and crop management practices are directly related to the yield of these compounds. Knowing how these factors influence the production of phytocannabinoids is essential to promote greater metabolite yield and stability. In this review, we aim to examine current cannabis agronomic research topics to identify the available information and the main gaps that need to be filled in future research. This paper introduces the importance of C. sativa L., approaching state-of-the-art research and evaluating the influence of crop management and environment conditions on yield and phytocannabinoid production, including (i) pruning; (ii) light and plant density; (iii) ontogeny; (iv) temperature, altitude, and CO2 concentration; (v) fertilization and substrate; and (vi) water availability, and presents concluding remarks to shed light on future directions.
... Synthetic cannabinoid analogs (SCAs) are non-naturally occurring compounds (e.g., nabilone, HU-210, and dexanabinol) that bind CB1 and CB2. They are fully synthetic and should not be confused with semisynthetic phytocannabinoids (SPs), which are naturally occurring compounds obtained by a partial chemical synthetic process rather than the biosynthetic processes of phytocannabinoids (e.g., CBD converted into dronabinol) . Nabilone is a synthetic cannabinoid CB1 agonist that was previously investigated in a randomized, double-blind, active-controlled crossover study conducted in 30 MOH sufferers . ...
The endocannabinoid system (ECS) influences many biological functions, and hence, its pharmacological modulation may be useful for several disorders, such as migraine. Preclinical studies have demonstrated that the ECS is involved in the modulation of trigeminal excitability. Additionally, clinical data have suggested that an endocannabinoid deficiency is associated with migraine. Given these data, phytocannabinoids, as well as synthetic cannabinoids, have been tried as migraine treatments. In this narrative review, the current clinical evidence of potential ECS involvement in migraine pathogenesis is summarized. Furthermore, studies exploring the clinical effects of phytocannabinoids and synthetic cannabinoids on migraine patients are reviewed.
Le 2 décembre 2020, les Nations unies votaient la sortie du « cannabis » et de la « résine de cannabis » du Tableau IV annexé à la Convention unique sur les stupéfiants de 1961. Complexe et controversé, le vote et les recommandations de l’Organisation mondiale de la santé l’ayant motivé sont analysés et discutés. Après une revue et actualisation du contexte légal et de l’histoire de la classification internationale du cannabis et de ses médicaments dérivés, l’article revient sur l’impact, large mais mal compris, du changement de classification internationale des produits du cannabis, et les conséquences que celui-ci peut avoir pour les patientes et les patients, les professionnel.le.s de la santé, pour les États, mais aussi pour le système des Nations unies et pour le droit international plus largement. ––– On December 2, 2020, the United Nations voted for the withdrawal of “cannabis” and “cannabis resin” from Schedule IV of the Single Convention on Narcotic Drugs, 1961. Complex and controversial, the vote, and the World Health Organization’s recommendation that motivated it, are analyzed and discussed. After reviewing and updating the legal context and history of the international scheduling of cannabis and its derived medicines, the article addresses the impact, broad but often misunderstood, of the change in the international scheduling status of cannabis products, and the consequences it may have for patients, health- care professionals, states, but also for the United Nations system and for international law more broadly.
The legal status of Cannabis is changing, fueling an increasing diversity of Cannabis -derived products. Because Cannabis contains dozens of chemical compounds with potential psychoactive or medicinal effects, understanding this phytochemical diversity is crucial. The legal Cannabis industry heavily markets products to consumers based on widely used labeling systems purported to predict the effects of different “strains.” We analyzed the cannabinoid and terpene content of commercial Cannabis samples across six US states, finding distinct chemical phenotypes (chemotypes) which are reliably present. By comparing the observed phytochemical diversity to the commercial labels commonly attached to Cannabis -derived product samples, we show that commercial labels do not consistently align with the observed chemical diversity. However, certain labels do show a biased association with specific chemotypes. These results have implications for the classification of commercial Cannabis , design of animal and human research, and regulation of consumer marketing—areas which today are often divorced from the chemical reality of the Cannabis -derived material they wish to represent.
Background: In 2016-2019, the WHO Expert Committee on Drug Dependence scientifically reviewed cannabis products. In that context, multiple references to a previous and similar assessment dating back to 1935 were made; but the content, outcome, and stakeholders involved in the 1935 review were unclear. Method: Transnational historiography of the international conversation on cannabis control in and around 1935, based on previously-unavailable primary material from international organisations, archives, and literature searches. Results: Two evaluations were undertaken in 1935 and 1938 by the “Comité des Experts Pharmacologistes” convened under the “Office International d’Hygiène Publique” (OIHP), predecessor of the WHO. Five specific medicines marketed by Parke-Davis were briefly reviewed, based on which the Experts recommended placing under international control all cannabis medicines –prior to that, only pure extracts were under control. The measure was confusing; few State Parties to the 1925 Convention implemented it; the second World War precipitated its oblivion. The international community resumed work on cannabis under the WHO in 1952; that same year, the OIHP was definitely closing its doors. No trace of the 1935 events appeared in any post-war proceeding. Conclusion: Political biasses and numerous methodological and ethical issues surround the 1935 episode: it cannot legitimately be called a “scientific assessment.” The role of stakeholders like Egypt and the OIHP in norm entrepreneurship and advocacy for multilateral controls over cannabis have been largely forgotten; that of the USA somewhat exaggerated. There might be other forgotten pieces of History: predecessor of WHO, the under-documented OIHP had mandates on other important fields, be it drug or epidemics control. Much knowledge on the History of humankind lays in unexplored archival records; errors made and lessons learnt from the past could inform our management of the conflict between public health and politics today.
To read the accepted manuscript, go to: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4055389 ––– Background: “Cannabis” and “cannabis resin” are derived from the Cannabis plant, used as herbal medications, in traditional medicine and as active pharmaceutical ingredients. Since 1961, they have been listed in Schedule IV, the most restrictive category of the single convention on narcotic drugs. The process to scientifically review and reschedule them was launched by the World Health Organisation (WHO) on 2 December 2016; it survived a number of hindrances until finally being submitted to a delayed and sui generis vote by the UN Commission on Narcotic Drugs on 2 December 2020, withdrawing “cannabis” and “cannabis resin” from Schedule IV. | Design/methodology/approach: To evaluate WHO’s scheduling recommendations, the process leading to the Commission vote and subsequent implications at global, national and patient/clinician levels. Narrative account of the four-year proceedings; review of the practical implications of both rejected and accepted recommendations. | Findings: The process was historically unprecedented, of political relevance to both medical Cannabis and evidence-based scheduling generally. Procedural barriers hampered the appropriate involvement of civil society stakeholders. The landscape resulting from accepted and rejected recommendations allow countries to continue creating decentralised, non-uniform systems for access to and availability of “cannabis” and “cannabis resin” for medical purposes. | Originality/value: Perspective of accredited observers; highlight of institutional issues and the lay of the land; contrast of stakeholders’ interpretations and engagement.
The cis-stereoisomers of Δ⁹-THC [(−)-3 and (+)-3] were identified and quantified in a series of low-THC-containing varieties of Cannabis sativa registered in Europe as fiber hemp and in research accessions of cannabis. While Δ⁹-cis-THC (3) occurs in cannabis fiber hemp in the concentration range of (−)-Δ⁹-trans-THC [(−)-1], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ⁹-cis-THC (3) is scalemic (ca. 80–90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR [(−)-3] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (−)-Δ⁹-cis-THC [(−)-3], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of “Δ⁹-THC and isomers” and needs therefore revision, or at least a more specific wording, to account for the presence of Δ⁹-cis-THCs [(+)-3 and (−)-3] in cannabis fiber hemp varieties.