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An Overview of Galenic Preparation Methods for Medicinal Cannabis

Authors:
  • Hazekamp Herbal Consulting

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In recent years, the Cannabis plant (Cannabis sativa L.) has been rediscovered as a source of new medicines around the world. Despite the fact that a number of registered medicines have been developed on the basis of purified cannabis components, there is a rapid increasing acceptance and use of cannabis in its herbal form. Licensed producers of high quality cannabis plants now operate in various countries including The Netherlands, Canada, Israel, and Australia, and in many US states. The legal availability of cannabis flowers allows to prescribe and prepare different cannabis galenic preparations by pharmacists. It is believed that synergy between cannabis components, known as “entourage effect”, may be responsible for the superior effects of using herbal cannabis versus isolated compounds. So far, only a few cannabis components have been properly characterized for their therapeutic potential, making it unclear which of the isolated compounds should be further developed into registered medicines. Until such products become available, simple and accessible galenic preparations from the cannabis plant could play an important role. In cannabis, phytochemical and pharmacological attention has been attributed mainly to four major cannabinoids (Δ9- tetrahydrocannabinol, cannabidiol, cannabigerol and cannabichromene) and to terpene components. This means a basic knowledge of these compounds and their bioavailability in different administration forms is useful for producers as well as prescribers of galenic preparations. This work will outline the most important aspects of cannabinoids and terpenes, and their behaviors during preparation and use of various administration forms including vaporizing, cannabis oils and extracts, tea, and skin creams.
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... In recent years, the official introduction of pharmaceutical grade cannabis inflorescences for medicinal use has offered medical doctors the opportunity to prescribe, and for pharmacists to prepare, cannabis-based formulas [44]. ...
... In order to provide patients legal access to medical cannabis, an ever increasing number of countries have introduced specific regulations on this topic [45]. In Europe, for example, the United Kingdom (UK), Netherlands, Italy, Germany, the Czech Republic, Croatia and Finland have introduced specific regulations and guidelines regarding medicinal cannabis [44]. The same is true globally in Canada, the USA, Israel and Australia, for example [45]. ...
... The same is true globally in Canada, the USA, Israel and Australia, for example [45]. The regulatory framework for cannabis as a pharmaceutical product varies widely across the world, but in general, the laws in force in the different contexts specify the medical conditions, including pain, for which cannabis can be prescribed and which forms of administration are allowed [44]. ...
Article
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The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.
... With the turn of the century hemp has regained a role as drug thanks to the legal availability of pharmaceutical grade cannabis "flos", the scientific word for the dried, whole flowers from which different galenic formulations can be prepared. 1 Cannabis and synthetic cannabinoid-based medicaments are both used in the management of a variety of cancer-associated symptoms, such as pain, nausea and vomiting, 2 and in the treatment of spasticity, 3 epilepsy, 4 and mood disorders, such as anxiety and depression. 5 Their therapeutic potential is considered to be due at least in part to their capability of interacting with the endocannabinoid system (ECS), which has a homeostatic function of and is dysregulated in several pathological disorders. ...
... Yield 95% as yellow oil. 1 ...
... Yield 84% as transparent oil. 1 (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) A solution of the appropriate methyl ester-(1.0 eq., 7-12, 37-40 and 42) in methanol (6 mL) and 3 M acqueous NaOH (2 mL, 3.0 eq.) was refluxed for 3-4 h, checking the disappearance of the starting material by TLC. ...
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Focusing on the importance of the free phenolic hydroxyl moiety, a family of 23 alkylresorcinol-based compounds were developed and evaluated for their cannabinoid receptor binding properties. The non-symmetrical hexylresorcinol derivative 29 turned out to be a CB2-selective competitive antagonist/inverse agonist endowed with good potency. Both the olivetol- and 5-(1,1’-dimethylepthyl)resorcinol-based derivatives 23 and 24 exhibited a significant antinociceptive activity. Interestingly, compound 24 proved to be able to activate both cannabinoid and TRPV1 receptors. Even if cannabinoid receptor sub-type selectivity remained a goal only partially achieved, results confirm the validity of the alkylresorcinol nucleus as skeleton for the identification of potent cannabinoid receptor modulators.
... The plant came to the attention of Western scientists in 1839 when William O'Shaughnessy, a British medical doctor and surgeon working in India, discovered its potential. In the 20th century, the situation mutated, and Cannabis was stigmatised for the abuse of its psychotropic effects, and this led to it being banned from commerce and made illegal in many countries [1,2]. ...
... The molecules of greatest pharmaceutical interest are, however, those in the decarboxylated form, as these are most easily absorbed in the intestine [9]. The inflorescences, which may be sold in the raw state or prior to grinding, can be vaporised in specifically designed devices, or can undergo extraction to obtain compounds suitable for oral administration [2,5,10]. ...
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Current Italian legislation provides that medical Cannabis can be administered orally as an extract if it has been titrated to determine the concentration of active molecules. In this context, there is a need to provide known and adequate quantities of active ingredients in order to guarantee uniform therapies that lead to the optimization of risks/benefits. This is fundamental considering that the limited availability on the market of registered Cannabis-based products for medical use means that prescribed therapies are usually prepared as galenic preparations. Consequently, the preparation procedures must be consistent with the instrumentation usually present in the laboratories of community pharmacies. In this context, the purpose of this work was to standardize the preparation procedure for oil-in-water (O/W) emulsions to exploit advantages in terms of ease of administration and dosage adjustment, but also to ensure the palatable organoleptic characteristics of the finished product. For the formulations being studied, in addition to the quality according to the directives set out in the European Pharmacopoeia, the stability was evaluated to assure adequate validity for therapeutic uses.
... In the West, the plant started to attract scientific interest only in the 20th century. However, in the last century, the cultivation, sale, and use of Cannabis was made illegal in the majority of countries (Lafaye, et al., 2017;Pisanti and Bifulco, 2019;Romano and Hazekamp, 2019;Arias, et al., 2021). ...
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Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of industrial origin and the introduction onto the market of inflorescences for medical use mean that medical doctors can now prescribe Cannabis-based medicines in those countries which allow it. Nevertheless, there is still considerable controversy on this topic in the scientific community. In particular, this controversy concerns: the plant species to be used; the pathologies that can be treated and consequently the efficacy and safety of use; the routes of administration; the methods of preparation; the type and dosage of cannabinoids to be used; and, the active molecules of interest. As such, although medical Cannabis has been historically used, the results of currently completed and internationally published studies are inconclusive and often discordant. In light of these considerations, the aim of this work is to analyse the current legislation in countries that allow the use of medical Cannabis, in relation to the impact that this legislation has had on clinical trials. First of all, a literature search has been performed (PubMed and SciFinder) on clinical trials which involved the administration of Cannabis for medical use over the last 3 years. Of the numerous studies extrapolated from the literature, only about 43 reported data on clinical trials on medical Cannabis, with these mainly being performed in Australia, Brazil, Canada, Denmark, Germany, Israel, Netherlands, Switzerland, the United Kingdom and the United States of America. Once the reference countries were identified, an evaluation of the legislation in relation to Cannabis for medical use in each was carried out via the consultation of the pertinent scientific literature, but also of official government documentation and that of local regulatory authorities. This analysis provided us with an overview of the different legislation in these countries and, consequently, allowed us to analyse, with greater awareness, the results of the clinical trials published in the last 3 years in order to obtain general interest indications in the prosecution of scientific research in this area.
... Smoking results, however, in adverse effects on the respiratory system via the production of potentially toxic substances [14]. Alternative delivery methods such as oral administration under edible or spray forms and transdermal delivery of topical forms all require some method of extraction of the cannabinoids from the raw biomass [15,16]. ...
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Full-text available
Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most extensively studied cannabinoids. They have been associated with the therapeutic and medicinal properties of the cannabis plant and also with its popularity as a recreational drug. In this paper, an industrial method for cannabis extraction using 915 MHz microwaves coupled with continuous flow operation is presented. The main advantages of the microwave-assisted extraction (MAE) are associated to the continuous-flow operation at atmospheric pressure which allows for higher volumes of biomass to be processed in less time than existing extraction methods, with improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation or winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency, i.e., up to 95% of the active compounds from cannabis biomass can be recovered at industrial scale.
... Smoking results, however, in adverse effects on the respiratory system via the production of potentially toxic substances [14]. Alternative delivery methods such as oral administration under edible or spray forms and transdermal delivery of topical forms all require some method of extraction of the cannabinoids from the raw biomass [15,16]. ...
Preprint
Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids and have been associated with the therapeutic and medicinal properties of the cannabis plant. In this paper, continuous flow microwave assisted extraction (MAE) is presented and compared with other methods for commercial cannabis extraction. The practical issues of each extraction method are discussed. The main advantages of MAE are: continuous-flow method which allows for higher volumes of biomass to be processed in less time than existing extraction methods, improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation, winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency even at the industrial scale. Whereas the typical recovery of active compounds using supercritical CO¬2 remains around 70-80%, via MAE up to 95% of the active compounds from cannabis biomass can be recovered at the industrial scale.
... 12 On the other hand, vaporization technique encompass the usage of vaporizers that steadily heat up cannabis herbs to temperatures high enough to extract THC, CBD and other cannabinoids but too low to expedite the release of harmful toxins such as benzene and toluene as well as odor, which are emitted thereby presumably, lowering the associated health risks throughout marijuana smoking duration. 13 This technique is widely used and differs from traditional smoking given that it does not involve combustion. For this reason therefore, vaporization method is considered safer in that it minimizes exposure to the potentially harmful marijuana smoke effluents that could be carcinogenic and toxic to the health of both active and passive smokers. ...
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