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Cannabis tea revisited: A systematic evaluation of the cannabinoid composition of cannabis tea

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Abstract

Cannabis is one of the oldest known medicinal plants, and a large variety of biological activities have been described. The main constituents, the cannabinoids, are thought to be most important for these activities. Although smoking of cannabis is by far the most common way of consumption, a significant part of medicinal users consume it in the form of a tea. However, not much is known about the composition of cannabis tea, or the effect of different parameters during preparation, handling or storage. In this study we used the high-grade cannabis available in Dutch pharmacies to study the cannabinoid composition of tea under standardized and quantitative conditions. Experimental conditions were systematically varied in order to mimic the possible variations made by medicinal users. During analysis there was a specific focus on the cannabinoid tetrahydrocannabinol and its acidic precursor, tetrahydrocannabinolic acid. Also the role of non-psychoactive cannabinoids as components of cannabis tea are discussed. The results obtained in this study provide a clear quantitative insight in the phytochemistry of cannabis tea preparation and can contribute to a better appreciation of this mode of cannabis administration.

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... On the other hand, other components in the tea matrix may act as a solubilizer. Experimental data from Knezevic et al. and Hazekamp et al. showed that the THC content in tea infusions is subject to fluctuations influenced by the water temperature, water volumes, and steeping and boiling time during the preparation of the tea infusion [26,27]. Knezevic et al. showed a decrease in the THC content of about 49% in the plant material of fiber hemp after tea infusion at 43 • C. Whereas, at 97 • C, an increase in the THC content of about 53% in the plant material residue was determined [26]. ...
... However, they do not describe how much of the decarboxylated THCA was transferred to the tea infusion. Hazekamp et al. found that relatively more THCA was dissolved in boiling water than THC, probably due to the higher solubility of THCA compared to THC [27]. They also showed that even when the amount of THC content (about 174 mg, as the sum of THC and THCA) in 1 g of cannabis was potentially very high, the corresponding tea infusion contained only a fraction of THC (10 mg/L) [27]. ...
... Hazekamp et al. found that relatively more THCA was dissolved in boiling water than THC, probably due to the higher solubility of THCA compared to THC [27]. They also showed that even when the amount of THC content (about 174 mg, as the sum of THC and THCA) in 1 g of cannabis was potentially very high, the corresponding tea infusion contained only a fraction of THC (10 mg/L) [27]. According to them, the relatively low THC content is probably a result of the saturation of the water phase with THC [27]. ...
Article
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9-Tetrahydrocannabinol (THC) is known as the main psychotropic compound present in the hemp plant. It also occurs in commercially available hemp food products and may have adverse effects on consumers. This article provides an overview of the current situation of the THC content in hemp food products in Germany in recent years. The content of THC was evaluated in a data set of 5 different hemp food product groups (tea, seeds, seed oils, food supplements, and nonalcoholic beverages) comprising 511 samples. For the toxicological assessment, the THC intake was estimated and the exhaustion of acute reference dose (ARfD) and lowest observed adverse effect level (LOAEL) was calculated using average daily consumption scenarios. Data show that hemp beverages and seeds typically do not contain amounts of THC that can exceed toxicological thresholds. On the contrary, hemp food supplements, such as cannabidiol (CBD) products, can contain high levels of THC, since the THC content of 18% of the samples has the potential to exceed the LOAEL and 8% even exceed the minimum intoxication dose. However, a significant linear decrease in the THC content of hemp food supplements was observed between 2018 and 2021 (n = 111, R = -0.36, p < 0.0001). A problematic food group is also tea based on flowers, leading to an increase in overall THC levels in recent years. Regulation of low-THC products within the framework of controlled distribution of cannabis for recreational use appears to be advisable.
... The main psychoactive cannabis alkaloid THC combined with the non-psychotropic alkaloids CBD and CBN showed a higher activity than THC alone [8]. CBD and CBN have antibacterial and anti-inflammatory activity, and modulate immune responses [9]. CBD lacks psychoactive effects [10] but it may have more antipsychotic and anxiolytic characteristics [11,12] and it helps to increase some of THC's beneficial effects, reducing the psychoactivity of THC, enhancing its tolerability, and widening THC's therapeutic effects [13]. ...
... Moreover, CB2 appear to have an important neuroprotective role, revealing new therapeutic possibilities for treating neuropsychiatric and neurological diseases without the typical CB1-mediated side effects [17]. A major concern with the medicinal use of cannabis is the risk of THC overdosing, responsible for psychoactive effects [9]. THC is CB1 and CB2 receptor partial agonist. ...
... This preparation can be used as cannabis tea or decoction, according to standardized indications, or as inhalation of inflorescences vapors [26]. Indeed, the non- psychotropic cannabinoids can be potential candidates for medicinal claims attributed to the consumption of cannabis tea [9]. Furthermore, even if not included in the Decree, several Italian pharmacies started also to produce and sell different oily preparations, although no information on side effects and toxicity were yet available for these kind of products. ...
Article
Background & objective: Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. Conclusion: It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments.
... The cannabinoid composition is dependent on way the cannabis is processed. For example, due to the lipophilic character of some cannabinoids such as thc, the composition of cannabinoids in tea shifts to relatively lower concentrations of thc and higher concentrations of thc-acid (thca) (Hazekamp et al., 2007). Also, the temperature during processing is of relevance for cannabinoid composition due to conversion of cannabinoid acids (Hazekamp et al., 2007). ...
... For example, due to the lipophilic character of some cannabinoids such as thc, the composition of cannabinoids in tea shifts to relatively lower concentrations of thc and higher concentrations of thc-acid (thca) (Hazekamp et al., 2007). Also, the temperature during processing is of relevance for cannabinoid composition due to conversion of cannabinoid acids (Hazekamp et al., 2007). ...
... This lack of controlled dosing may reduce clinical efficacy or induce side effects and may also occur after vaporisation of cannabis or thc. With regards to oral administration of thc using cannabis tea, a previous study found tea to have a different cannabinoid composition compared to non-decocted cannabis (Hazekamp et al., 2007), affecting the clinical effects. To bypass these problems, methods have been developed to purify thc from cannabis and to formulate it in a stable dosage form. ...
... On the other hand, because of its psychotropic properties, Δ 9 -THC also limits the medicinal use of cannabis, even for actions conducted by other non-psychotropic bioactive constituents, including its own precursor, Δ 9 -THCA, which has a biological profile significantly distinct from Δ 9 -THC. Δ 9 -THCA is the most abundant cannabinoid from Bedrocan®, a cannabis variety authorized for medical use in several countries (Hazekamp et al., 2007). Cannabis tea preparations are very popular in some countries including The Netherlands and Jamaica, where decoctions are used by non-smokers and even by children and elderly people for non-recreational uses that include fever, cold, and stress (Boekhout van Solinge, 1996;Janse et al., 2004). ...
... Cannabis tea preparations are very popular in some countries including The Netherlands and Jamaica, where decoctions are used by non-smokers and even by children and elderly people for non-recreational uses that include fever, cold, and stress (Boekhout van Solinge, 1996;Janse et al., 2004). Heating associated to the preparation of cannabis tea and decoction is insufficient to decarboxylate acidic cannabinoids that, because of a much better water solubility, are selectively extracted (Hazekamp et al., 2007). Cannabis teas from dried plant material are therefore complementary to smoking or vaporizing in terms of cannabinoid profile, being enriched in acidic cannabinoids (Hazekamp et al., 2007). ...
... Heating associated to the preparation of cannabis tea and decoction is insufficient to decarboxylate acidic cannabinoids that, because of a much better water solubility, are selectively extracted (Hazekamp et al., 2007). Cannabis teas from dried plant material are therefore complementary to smoking or vaporizing in terms of cannabinoid profile, being enriched in acidic cannabinoids (Hazekamp et al., 2007). Given these considerations, it is surprising that, despite their early discovery in 1955 (Krejci et Santavy, 1955), acidic cannabinoids have not yet significantly benefited from the renaissance of studies on cannabis and cannabinoids. ...
Article
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Medicinal cannabis and some neutral cannabinoids have been suggested as a potential therapy for liver diseases. Hypothesis: Δ9-tetrahydrocannabinolic acid (Δ9-THCA), the non-psychotropic precursor of Δ9-THC, is one of the most abundant cannabinoids presents in Cannabis Sativa. However, its biological activities have been poorly investigated. Herein, we studied the antifibrotic and antiinflammatory activities of Δ9-THCA in two different animal models of liver injury, providing a rationale for additional studies on the medicinal use of this cannabinoid in the treatment of liver fibrosis and the management of NAFLD. Study design: The antifibrotic activity of Δ9-THCA in vitro was investigated in the cell lines LX-2 and NIH-3T3-Col1A2-luc. Non-alcoholic liver fibrosis was induced in mice by CCl4 treatment or, alternatively, by 23-week high fat diet (HFD) feeding. Δ9-THCA was administered daily intraperitoneally during the CCl4 treatment or during the last 3 weeks in HFD-fed mice. Methods: TGFβ-induced profibrotic gene expression was analyzed by luciferase and qPCR assays. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose, insulin, leptin and triglyceride levels were measured in HFD mice. Results: Δ9-THCA inhibited the expression of Tenascin C (TNC) and Col3A1 induced by TGFβ in LX-2 cells and the transcriptional activity of the Col1A2 promoter in fibroblasts. Δ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration. Conclusions: Δ9-THCA prevents TGFβ-induced fibrotic markers in vitro and liver inflammation and fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, for the treatment of liver fibrosis and the management of NAFLD.
... In The Netherlands, the Office for Medicinal Cannabis (OMC) is in charge of the cultivation of high-grade pharmaceutical cannabis for medicinal purposes. 21 It is available at specialized pharmacies, and patients are advised through information brochures about the different strains of cannabis available and the methods of consumption. For instance, the OMC advises to either use a vaporizer or to prepare tea to avoid damage to the lungs. ...
... 22 However, only very small amounts of THC are soluble in boiling water. 21 Currently, the OMC offers different strains of medicinal cannabis, which are cultured according to stringent pharmaceutical standards. Each strain differs in their THC content and only 1 variant contains a noteworthy level of CBD, and with this strain, the OMC advises inhalation as the only administration route because CBD is insoluble in boiling water. ...
... So far, only a few limited studies have been conducted on pharmaceutical-grade cultivated cannabis as medicinal therapy and have marginally described patient groups that use it. 21,23,24 This study describes more than 100 patients reporting about the therapeutic satisfaction with their pharmaceutical-grade cannabis product. Furthermore, differences in subjective effects among the available strains are investigated. ...
Article
In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.
... Following the indications given by Hazekamp et al. [48] and authorized by the Italian Ministry of Health [44], cannabis inflorescences should be immersed in a container containing cold water at a 0.1% concentration; it is recommended not to use less than 100 mL of water. The preparation should be heated to boiling point and simmered on a low heat for 15 min, while covered; it is recommended not to exceed 30 min in the heating of the decoction and to stir it at regular intervals. ...
... Moreover, even when refrigerated at 4 • C, THC concentration in the decoction significantly decreased to less than 65% 3 days after preparation, while that of THCA-A and CBD decreased to less than 70% and 40%, respectively, after 7 days [34]. For this reason, extemporaneous preparation is recommended [48]. ...
... On one hand, it is preferred by the patients because it is easy to prepare and presents a good safety profile, avoiding the psychotropic effect of accidental THC overdosing. On the other hand, since the extraction recovery is poor, a large volume of decoction is required to produce analgesic effects [48,49]. Therefore, a growing demand for oily preparations has risen, to make available a preparation that is easier to administer. ...
Article
Full-text available
Cannabis has been used for centuries for therapeutic purposes. In the last century, the plant was demonized due to its high abuse liability and supposedly insufficient health benefits. However, recent decriminalization policies and new scientific evidence have increased the interest in cannabis therapeutic potential of cannabis and paved the way for the release of marketing authorizations for cannabis-based products. Although several synthetic and standardized products are currently available on the market, patients’ preferences lean towards herbal preparations, because they are easy to handle and self-administer. A literature search was conducted on multidisciplinary research databases and international agencies or institutional websites. Despite the growing popularity of medical cannabis, little data is available on the chemical composition and preparation methods of medical cannabis extracts. The authors hereby report the most common cannabis preparations, presenting their medical indications, routes of administration and recommended dosages. A practical and helpful guide for prescribing doctors is provided, including suggested posology, titration strategies and cannabinoid amounts in herbal preparations obtained from different sources of medical cannabis.
... In current opinion, these two components inten sify the effects of Δ 9 THC, although they themselves do not show intoxicant activity [3,4]. As results from de tailed investigations [2,[5][6][7], Δ 9 THC is formed in can nabis from THCA. This conversion occurs also in the cut plant. ...
... This conversion occurs also in the cut plant. During its thermal and/or light exposition THCA undergoes decarboxylation, transforming itself into psy choactive Δ 9 THC [2,[7][8][9][10]. For this reason the con sumption of cannabis products is usually preceded by their thermal treatment (smoking, vaporizing, boiling of extracts, cooking of cakes with cannabis addition, etc.). ...
... The final product of THCA and Δ 9 THC transforma tion is CBN [9,11,12]. Longer storage and drying of cannabis also result in the transformation of Δ 9 THC in to CBN [7][8][9][10]. ...
Article
Full-text available
The presented study discusses the difference in the results of estimation of Δ9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA) and cannabinol (CBN) amount in Cannabis sativa L., using long-lasting liquid extraction in the Soxhlet apparatus and pressurized liquid extraction (PLE) as sample preparation methods in the analytical procedure. THC amounts extracted in the PLE process using nhexane or methanol are very similar. THCA amounts extracted in the PLE process using n-hexane are generally greater than those extracted in the Soxhlet apparatus but smaller when methanol is applied in the PLE process. The obtained results evidently show that the mutual transformations of THCA, THC and CBN occur not only during Soxhlet extraction but also during short-lasting PLE. In the last case, however, they are small. The intensity of the transformation depends on the applied extractant type.
... Losses still occurred at freezer temperature (À18°C). 8 Hazekamp et al. 10 demonstrated short-term stability in ''cannabis tea.'' They added quantified amounts of THCA-A and THC to boiled water. ...
... Although there is growing interest in THCA-A among clinicians, 3,4 decarboxylation studies suggest that contamination with THC is nearly unavoidable. [5][6][7][8][9][10][11][15][16][17][18][19][20] The instability of THCA-A also hampers its pharmacological exploration. 21 ''How can anybody do an experiment if the compound likes to convert into something else just by sitting around, and the 'something else' has all kinds of activities?'' ...
... Our results with THC (K i = 50 nM at hCB 1 ) indicate that THC did not fall out of solution. Because THCA-A is more water soluble than THC, 10 we concluded that our results with THCA-A were not due to solubility issues. ...
Article
Full-text available
Introduction: Cannabis biosynthesizes Δ⁹-tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ⁹-tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB1). Materials and Methods: Purity of certified reference standards were tested with high performance liquid chromatography (HPLC). Binding affinity of THCA-A and THC at human (h) CB1 and hCB2 was measured in competition binding assays, using transfected HEK cells and [³H]CP55,940. Efficacy at hCB1 and hCB2 was measured in a cyclic adenosine monophosphase (cAMP) assay, using a Bioluminescence Resonance Energy Transfer (BRET) biosensor. Results: The THCA-A reagent contained 2% THC. THCA-A displayed small but measurable binding at both hCB1 and hCB2, equating to approximate Ki values of 3.1μM and 12.5μM, respectively. THC showed 62-fold greater affinity at hCB1 and 125-fold greater affinity at hCB2. In efficacy tests, THCA-A (10μM) slightly inhibited forskolin-stimulated cAMP at hCB1, suggestive of weak agonist activity, and no measurable efficacy at hCB2. Discussion: The presence of THC in our THCA-A certified standard agrees with decarboxylation kinetics (literature reviewed herein), which indicate contamination with THC is nearly unavoidable. THCA-A binding at 10μM approximated THC binding at 200nM. We therefore suspect some of our THCA-A binding curve was artifact—from its inevitable decarboxylation into THC—and the binding affinity of THCA-A is even weaker than our estimated values. We conclude that THCA-A has little affinity or efficacy at CB1 or CB2.
... The medicinal cannabis program of the Netherlands offers pharmaceutical-grade cannabis on prescription to chronically ill patients (OMC 2013). Although patients are advised to administer the product by using a vaporizer or by preparing it as a tea ( Hazekamp et al. , 2007, they are essentially free to choose their own preferred method of intake. Presently, most Dutch health insurance companies reimburse medicinal cannabis to some extent, and some now even cover the Volcano Medic vaporizer for medical use (NCSM 2012). ...
... Herbal cannabis can be consumed in the form of a decoction, also referred to as "cannabis tea. " Only a few standardized studies have been performed with tea preparations of cannabis (De Jong et al. 2005;Hazekamp et al. 2007;Steinagle and Upfal 1999). Nevertheless, cannabis tea was found to be a relatively popular method of intake among patients who reported to have experience with the oral use of cannabis medicine ( ). ...
... In the Netherlands, patients are advised to prepare cannabis tea by adding 1.0 g of cannabis to 1 L of boiling water, letting it simmer for 15 min, and finally filtering out solid parts by using a common tea-strainer (OMC 2013). Despite the fact that cannabinoids are notoriously insoluble in water (Hazekamp and Verpoorte 2006) it was found that cannabis tea prepared in this way yielded significant amounts of cannabinoids in a reproducible manner (Hazekamp et al. 2007). Considerably more THCA than Δ 9 -THC (ratio about 5:1) was detected, which may be explained by the relatively higher water solubility of THCA compared to Δ 9 -THC, combined with a relatively slow decarboxylation rate of acidic cannabinoids in boiling water ( Hazekamp et al. 2007). ...
Chapter
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Book chapter published in the famous Handbook of Cannabis (2016) by Roger Pertwee. This was chapter 18 and it focused on self-medication of patients with cannabis: their motivations, obstacles, preferences and what we can learn from that.
... The use of Δ9-tetrahydrocannabinol (THC) deriving from Cannabis sativa L. started around 5000 years ago in Northeast and Central Asia and is currently spreading worldwide. Besides providing a source of fiber, food, oil, and inebriant, the psychoactive effects are utilized in various cultures, among others, western societies, the Caribbean (ganja), the Maghrib (kif), or India (bhang) (Bhatia et al., 2014;Hazekamp et al., 2007;Merzouki and Mesa, 2002). THC is traditionally used against fever, cold, and stress (Hazekamp et al., 2007) and indigestion and inflammation (Ijaz et al., 2016) and used to improve night vision of C. sativa L. smokers in northern Morocco (Russo et al., 2004). ...
... Besides providing a source of fiber, food, oil, and inebriant, the psychoactive effects are utilized in various cultures, among others, western societies, the Caribbean (ganja), the Maghrib (kif), or India (bhang) (Bhatia et al., 2014;Hazekamp et al., 2007;Merzouki and Mesa, 2002). THC is traditionally used against fever, cold, and stress (Hazekamp et al., 2007) and indigestion and inflammation (Ijaz et al., 2016) and used to improve night vision of C. sativa L. smokers in northern Morocco (Russo et al., 2004). C. sativa L has also been used as medicine agent in western societies for many health problems such as vomiting, nausea, pain, diarrhea, and others (Elsohly and Slade, 2005;Malik et al., 2015). ...
Article
Aging-related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. ?9-Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate-induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48?h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase-3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate-induced neurotoxicity. Moreover, THC significantly counteracted the glutamate-induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration-dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti-apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright
... This was especially observed in case of the pharmacologically active THC, THC-A A, CBD and CBDA. These results on the first standardized cannabis flowering tops produced in Italy were in agreement with those obtained by Hazekamp et al. in 2007 and by Romano and Hazekamp in 2013 with respect to tea and oil preparations [22,25] and are clearly explained by the lipophilic nature of cannabinoids. ...
... This was especially observed in case of the pharmacologically active THC, THC-A A, CBD and CBDA. These results on the first standardized cannabis flowering tops produced in Italy were in agreement with those obtained by Hazekamp et al. in 2007 and by Romano and Hazekamp in 2013 with respect to tea and oil preparations [22,25] and are clearly explained by the lipophilic nature of cannabinoids. ...
... This was especially observed in case of the pharmacologically active THC, THC-A A, CBD and CBDA. These results on the first standardized cannabis flowering tops produced in Italy were in agreement with those obtained by Hazekamp et al. in 2007 and by Romano and Hazekamp in 2013 with respect to tea and oil preparations [22,25] and are clearly explained by the lipophilic nature of cannabinoids. ...
... This was especially observed in case of the pharmacologically active THC, THC-A A, CBD and CBDA. These results on the first standardized cannabis flowering tops produced in Italy were in agreement with those obtained by Hazekamp et al. in 2007 and by Romano and Hazekamp in 2013 with respect to tea and oil preparations [22,25] and are clearly explained by the lipophilic nature of cannabinoids. ...
Article
Background: Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting. The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone. The Italian National Institute of Health sought to establish conditions and indications on how to correctly use nationally produced cannabis to guarantee therapeutic continuity in individuals treated with medical cannabis. Methods: The evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil was conducted using an easy and fast ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Results: Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids. This was especially observed in the case of the pharmacologically active THC, CBD and their acidic precursors. Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions. At ambient temperature, a significant THC and CBD decrease to 50% or less of the initial concentration was observed over 3 and 7 days, respectively. When refrigerated at 4 °C, similar decreasing profiles were observed for the two compounds. The cannabinoids profile in cannabis oil obtained after pre-heating the flowering tops at 145 °C for 30 min in a static oven resulted in a complete decarboxylation of cannabinoid acids CBDA and THCA-A. Nevertheless, it was apparent that heat not only decarboxylated acidic compounds, but also significantly increased the final concentrations of cannabinoids in oil. The stability of cannabinoids in oil samples was higher than that in tea samples since the maximum decrease (72% of initial concentration) was observed in THC coming from unheated flowering tops at ambient temperature. In the case of the other cannabinoids, at ambient and refrigerated temperatures, 80%-85% of the initial concentrations were measured up to 14 days after oil preparation. Conclusions: As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.
... On the European drugs market the two distinct products ''marijuana'' (herbal cannabis) and ''hashish'' (cannabis resin) are mainly traded. According to the European Drug Report 2014, 73.6 million (21.7%) adults (15-64) used cannabis in their lifetime, while 18.1 million (5.3%) adults (15-64) and 14.6 million (11.2%) young adults (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) consumed cannabis in the last year. The prevalence of the misuse of these herbal products is pronounced due to the fact that over 80% of the seizures in Europe are cannabis [3]. ...
... In Hazekamp's group reported on an evaluation of the cannabinoid composition of cannabis tea. In their study preparation parameters, effects of solubilizers as well as the storage and the stability of tea samples were described [25]. ...
... Wykazano jednak, że w procesie parzenia herbaty do roztworu przedostaje się ok. 15% THC oraz kwas tetrahydrokanabinolowy (o właściwościach immunomodulacyjnych, pozbawiony działania psychoaktywnego) i inne kwasy kanabinoidowe [14,15]. Wchłanianie THC z przewodu pokarmowego jest zmienne i powolne, mniejsza jest biodostępność -ok. ...
... W innym badaniu z randomizacją porównano skuteczność dodania nabiksymoli do terapii opioidami u chorych z nowotworem w zależności od zastosowanej dawki. Chorych podzielono na 4 grupy: przyjmujących placebo, przyjmujących nabiksymole w małych dawkach (1-4 podań sprayu na dobę), średnich (6-10), i dużych (11)(12)(13)(14)(15)(16). Wykazano skuteczność podawania małych i średnich dawek nabiksymoli. ...
Article
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W ostatnich latach wzrosło zainteresowanie kanabinoidami w leczeniu objawowym w opiece paliatywnej. Wielokierunkowe ich działanie, pomimo ograniczonej skuteczności, czyni je atrakcyjną alternatywą, szczególnie u chorych z wieloma objawami współistniejącymi. Do wskazań o udowodnionej skuteczności kanabinoidów należą ból, spastyczność, drgawki, zaburzenia snu, nudności i wymioty, zespół Tourette’a. Mimo iż skuteczność w leczeniu bólu jest ograniczona, to potwierdzono ją w bólu neuropatycznym oraz w leczeniu adiuwantowym w połączeniu z opioidami. Korzystny profil działań niepożądanych, w tym brak depresyjnego działania na układ oddechowy, sprawia, że kanabinoidy mogą uzupełnić stosunkowo wąski zestaw leków, jakie pozostają do dyspozycji lekarza medycyny paliatywnej.
... While most common extraction and delivery methods of cannabis employ heat sufficient to convert most cannabinoids into their neutral form [45], decarboxylation is often incomplete and trace amounts of acidic cannabinoids can be found in the bodily fluids of cannabis consumers [46]. Certain delivery methods that have a long history of therapeutic use, such as cannabis tea, maintain the predominantly acidic state of cannabinoids [47]. Most research into the clinical effects of cannabinoids to date have focused on the neutral forms, but new interest is emerging to investigate the distinct physiologic effects of acidic cannabinoids [25]. ...
... The Cannabis plant yields inactive acidic forms of thc and cbd, namely thc-a and cbd-a. The process of decarboxylation, which occurs through thermal treatment (heating or combustion), generates the pharmacologically active formats 15,16 . Although dried botanical cannabis from licensed producers for medical use is not thermally treated, medical cannabis oils contain cannabinoids that have undergone decarboxylation (Tweed Inc. ...
Article
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"Cannabinoid" is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously. Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors. Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options. Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities. Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants. The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia. Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy. The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy.
... Detailed description of the five different protocols used for preparation of Cannabis oils.Effects of preheatingPreheating of cannabis samples has been recommended as a way to potentiate the final extract, i.e. to decarboxylate the acidic cannabinoids naturally present in cannabis plant material, such as THCA and CBDA, and turn them into their more potent counterparts such as THC and CBD[18,19]. Therefore, we tested two decarboxylation methods by heating cannabis plant material (1 g in an open glass vial) under two conditions: I) in a water bath at a low boil (temp. ...
... For example, a large number of patients claim medical benefits from consuming Cannabis tea, in which THCA-A is usually the most abundant cannabinoid present. 48 Even when smoked, THCA-A is only partially transformed to THC. The conversion rates during smoking range from a maximum of 70% under optimized analytical conditions (temperatures higher than 140°C) to simulated smoking processes, Although the ability of THCA-A to bind to cannabinoid CB1 and CB2 receptors in vitro remains controversial, other molecules involved in lipid metabolism have been identified as potential targets. ...
Article
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Δ(9)-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ(9)-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term "THCA" to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.
... Besides smoking and vapourization, cannabis is known to be consumed in baked goods such as cookies or brownies, or drunk as teas or infusions. However, absorption of these products by the oral route is slow and erratic, and the onset of effects is delayed with the effects lasting much longer compared to smoking (see section 2.2); furthermore, dosages for orally administered products are even less well established than for smoking/vapourization (111,286,289,343). Other forms of preparation reported in the lay literature include cannabis-based butters, oils, compresses, creams, ointments, and tinctures (64,344,345,346,347) but again, no dosing information exists here and much of the information is anecdotal in nature. ...
Research
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This research monograph is a peer-reviewed summary of the scientific evidence on the uses and harms of cannabis and cannabinoids for medical purposes.
... Dena den, uraren irakite-puntua ez da nahikoa eta ondorioz dekarboxilazioa ez da guztiz ematen. Horrela izanik, gorputzeratzen diren kannabinoideak forma azidoan daude batez ere [175]. Bestalde, teknika honen eraginkortasuna kanabinoideen disolbagarritasun baxuak baldintzatzen du (THC 1-2 µg/mL % 0.9 den NaCl disoluzioan) [176]. ...
Thesis
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Tesi hau bi zutabe nagusitan banatzen da. Lehenengoan ardo hondakinen balioa handitzeko metodologia bat garatu da. Lehenik, ardo hondakinetatik polifenolak eta gantz azidoak bakoitza bere aldetik erauzteko jariakin gainkritiko bidezko erauzketa (SFE) optimizatu da. Polifenolak ez dira oso egonkorrak ordea eta gorputzean bioeskuragarritasun baxua dute. Arazo hauek konpontzeko polifenolak zurrusta-bibrazio bidezko mikrokapsularatzearen (VNM) bidez enkapsulatu dira. Bigarren zutabean etorkizun hurbilean kannabisa sendagai bezala erabili ahal izateko 3 urrats eman dira. Alde batetik, landare ezberdinak efektu ezberdinekin lotzea ahalbidetu dezakeen landareen kannabinoideen hatz-marka osatzeko fragmentazio bikoitzeko masa-espektometriari akoplaturiko eraginkortasun handiko likido kromatografia (HPLC-MS/MS) bidezko metodo bat garatu da. Bestalde, gernuan eta plasman kannabinoideak eta euren metabolitoak kuantifikatzeko metodo bat ere garatu da, hidrolisi entzimatiko-alkalino bikoitza eta HPLC-MS/MS analisi teknika erabiliz. Azkenik, konposatu puruen eta landare mota jakinen produkzioa optimizatzeko, kemotipo ezberdineko landareen hazkuntzan zeharreko kannabinoideen eta terpenoen garapena aztertu da
... urtera arte ez zen ikerketa estandarizaturik gauzatu teari buruz. Ikerketa honetan ordea teknika sendoa eta errepikakorra dela ikusi da, eta kannabinoideen kontzentrazio altu samarrak erdiesten dira, batez ere kannabidoide azidoen kasuan [13]. ...
Chapter
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[en] Abstract: In this section, we will talk about the Cannabis plant, about the molecules which compose it, those molecules with a meaningful odor and psicotropic effect. Their molecular structure will be studied and the already known effects will also be explained. Moreover, the different consumption ways will be describe together with their special features. Finally, different analysis techniques will be expalined in order to analyze the previously explained molecules. [eus] Laburpena: Atal honetan, Kannabis landareari buruz arituko gara, landarea osatzen duten molekula bereziei buruz hain zuzen ere. Euren molekula-egitura eta ezagutzen diren ezaugarriak azalduz, usain eta eragin psikotropikoaren erantzule diren molekulak aztertuko dira. Bestalde, landarea kontsumitzeko modu anitz egon daitezke, eta haien deskribapena eta bakoitzaren berezitasunak emango dira. Amaitzeko, hasiera batean azaldutako molekulen analisi-teknikak adieraziko dira.
... The daily dose reported seemed to be slightly higher among those who used edibles (mean 3.4 g/day -median 1.5 g/day) compared to those using cannabis as tea (mean 2.4 g/daymedian 1.5 g/day). This may be remarkable given the fact that cannabinoids are only sparingly soluble in cannabis tea (Hazekamp 2007). Vaporizing and smoking both required similar amounts of cannabis, with mean values of 3.0 grams daily each (median 2.0 and 1.5 g/day, respectively). ...
Article
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Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.
... The product is cultivated by contracted company Bedrocan BV, and dispensed through pharmacies in the form of dried female flowers (Cannabis Flos) packaged in 5 g containers. Patients are advised to administer medicinal cannabis by using a cannabis vaporizer or by preparing it as a tea [10, 11]. In a growing number of cases, costs are reimbursed by health insurance companies [12]. ...
Article
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Background: A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor's prescription. This study describes a retrospective database study of The Netherlands. Methods: Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003-2010. Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties. Results: Five thousand five hundred forty patients were identified. After an initial incidence of about 6/100,000 inhabitants/year in 2003 and 2004, the incidence remained stable at 3/100,000/year in 2005-2010. The prevalence rate ranged from 5 to 8 per 100,000 inhabitants. Virtually all patients used some form of prescription medication in the 6 months preceding start of cannabis use, most particularly psycholeptics (45.5 %), analgesics (44.3 %), anti-ulcer agents (35.9 %) and NSAIDs (30.7 %). We found no significant association between use of medication of common indications for cannabis (pain, HIV/AIDS, cancer, nausea, glaucoma) and variety of cannabis used. Conclusions: This is the first nationwide study into the extent of prescription of medicinal cannabis. Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol (THC) and cannabidiol (CBD), no differences in choice of variety was found associated with indication.
... This lack of controlled dosing may reduce clinical efficacy or induce side effects and may also occur after vaporization of cannabis or THC. With regards to oral administration of THC using cannabis tea, a previous study found tea to have a different cannabinoid composition compared with nondecocted cannabis [17], affecting the clinical effects. To bypass these problems, methods have been developed to purify THC from cannabis and to formulate it in a stable dosage form. ...
Article
What is already known about this subject: • Cannabis based medicines are registered as a treatment for various indications, such as pain and spasms in multiple sclerosis (MS) patients, and anorexia and nausea in patients with HIV or receiving cancer treatment. • the pharmacokinetics of the various administration routes of cannabis and cannabis based medicines are variable and dosing is hard to regulate. What this study adds: • Namisol is a new tablet containing pure THC (>98%) that has a beneficial pharmacokinetic profile after oral administration. • Namisol gives a quick onset of pharmacodynamic effects in healthy volunteers, which implies a rapid initiation of therapeutic effects in patients. Aims: Among the main disadvantages of currently available Δ(9) -tetrahydrocannabinol (THC) formulations are dosing difficulties due to poor pharmacokinetic characteristics. Namisol® is a novel THC formulation, designed to improve THC absorption. The study objectives were to investigate the optimal administration route, pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of Namisol®. Methods: This first in human study consisted of two parts. Panel I included healthy males and females (n = 6/6) in a double-blind, double-dummy, randomized, crossover study with sublingual (crushed tablet) and oral administration of Namisol® (5 mg THC). Based on these results, male and female (n = 4/5) participants from panel I received oral THC 6.5 and 8.0 mg or matching placebo in a randomized, crossover, rising dose study during panel II. PD measurements were body sway; visual analogue scales (VAS) mood, psychedelic and heart rate. THC and 11-OH-THC population PK analysis was performed. Results: Sublingual administration showed a flat concentration profile compared with oral administration. Oral THC apparent t(1/2) was 72-80 min, t(max) was 39-56 min and C(max) 2.92-4.69 ng ml(-1) . THC affected body sway (60.8%, 95% CI 29.5, 99.8), external perception (0.078 log mm, 95% CI 0.019, 0.137), alertness (-2.7 mm, 95% CI -4.5, -0.9) feeling high (0.256 log mm, 95% CI 0.093, 0.418) and heart rate (5.6 beats min(-1) , 95% CI 2.7, 6.5). Namisol® was well tolerated. Conclusions: Oral Namisol® showed promising PK and PD characteristics. Variability and t(max) of THC plasma concentrations were smaller for Namisol® than reported for studies using oral dronabinol and nabilone. This study was performed in a limited number of healthy volunteers. Therefore, future research on Namisol® should study clinical effects in patient populations.
... Cannabis is considered as the most controversial plant worldwide, next to the important medical use, and it is also the most frequently consumed drug of abuse in European countries [1]. Cannabis products can be consumed in a variety of ways, such as smoking, vaporizing, preparing cannabis tea and using it in baked products [2]. ...
Article
Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes.
... -Efectos directos Se observaron efectos psicoactivos dosis-dependientes del Delta-9-trans-Tetrahidrocannabinol (9-THC) en los sujetos después de usar las vías de administración intravenosa, oral e inhalada (Tabla 2). También se han reportado otras vías de administración como la vaporización (Zuurman et al., 2008) y beber té de cannabis (Hazekamp, Bastola, Rashidi, Bender, y Verpoorte, 2007). ...
Article
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Objective This systematic review aims to summarize current evidence on which naturally present cannabinoids contribute to cannabis psychoactivity, considering their reported concentrations and pharmacodynamics in humans. Design Following PRISMA guidelines, papers published before March 2016 in Medline, Scopus-Elsevier, Scopus, ISI-Web of Knowledge and COCHRANE, and fulfilling established a-priori selection criteria have been included. Results In 40 original papers, three naturally present cannabinoids (∆-9-Tetrahydrocannabinol, ∆-8-Tetrahydrocannabinol and Cannabinol) and one human metabolite (11-OH-THC) had clinical relevance. Of these, the metabolite produces the greatest psychoactive effects. Cannabidiol (CBD) is not psychoactive but plays a modulating role on cannabis psychoactive effects. The proportion of 9-THC in plant material is higher (up to 40%) than in other cannabinoids (up to 9%). Pharmacodynamic reports vary due to differences in methodological aspects (doses, administration route and volunteers’ previous experience with cannabis). Conclusions Findings reveal that 9-THC contributes the most to cannabis psychoactivity. Due to lower psychoactive potency and smaller proportions in plant material, other psychoactive cannabinoids have a weak influence on cannabis final effects. Current lack of standard methodology hinders homogenized research on cannabis health effects. Working on a standard cannabis unit considering 9-THC is recommended.
... In addition, THC inhalation using a Volcano Ò vapouriser (http://www.storz-bickel.com), which, through the use of hot air, allows for conversion of THC (isolated from Cannabis Sativa L. from the OMC) into volatile THC, thus preventing THC loss due to first-pass effects and also avoiding formation of toxic combustion by-products formed during smoking or insufficient conversion of THC acid into THC upon the preparation of medicinal cannabis tea, 24 is also under clinical evaluation. 25 Specific oncology-orientated research conducted with the crude cannabis variants, that is, Bedrocan Ò , Bedrobinol Ò , and Bediol Ò , is limited. ...
Article
In The Netherlands, since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids, is available for clinical research, drug development strategies, and on prescription for patients. To date, this policy, initiated by the Dutch Government, has not yet led to the desired outcome; the amount of initiated clinical research is less than expected and only a minority of patients resorts to the legal product. This review aims to discuss the background for the introduction of legal medicinal cannabis in The Netherlands, the past years of Dutch clinical experience in oncology practice, possible reasons underlying the current outcome, and future perspectives.
... Despite being a popular historical method of consuming cannabis, tea preparations are not very popular or recommended for several reasons (27). First, cannabinoid extraction during steeping will be very low due to the low water solubility of cannabinoids. ...
Article
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Understanding the cultural and medical history of cannabis use is an important component to the successful integration of cannabis in modern clinical practices. This review chronicles over six thousand years of documented cannabis use in cultural practices, medical applications, breeding practices to enhance the pharmacological properties, and the various methods by which people have consumed the plant.
... Δ 9 -THC and CBD are present in the plant as THCA and CBDA, respectively [12,13]. Decarboxylation is temperature-dependent [14,15], and preheating of cannabis samples has been recommended to potentiate the final cannabis oil extract [16,17]. ...
Article
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The medicinal use of cannabis oil is increasing all over the world. Few analytical methods for the quantification of cannabinoids have been validated using internationally accredited guidelines. This work describes the development and validation of a selective and sensitive gas chromatography-mass spectrometry method for the qualitative analysis of the main cannabinoids, namely cannabidiolic acid, tetrahydrocannabinolic acid, cannabigerol, and cannabichromene as well as quantitative determination of cannabidiol, Δ⁹-tetrahydrocannabinol, and cannabinol, present in cannabis oils. The method was fully validated according to Food and Drug Administration and International Conference on Harmonization guidelines. A linear range of 0.1–30 μg/mL was obtained for CBD and Δ⁹-THC and 0.034–11.7 μg/mL for CBN, presenting determination coefficients above 0.99. The lower limits of quantification ranged from 0.034 to 0.1 μg/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 3.9–13.8 and 4.7–14.1%, respectively. Extraction efficiency at lower limits of quantification was 95–103%. Verification of method validity was performed with authentic cannabis oil samples. To our knowledge, this is the first method available in Argentina, validated according to international guidelines, for quantification of CBD, Δ⁹-THC, and CBN in cannabis oil. The primary application of this method is to differentiate between cannabis oils with high or low content of Δ⁹-THC, CBD, or mixed Δ⁹-THC/CBD. This is of fundamental importance for the patient and so that the physicians can carry out a suitable therapy.
... Extraction in aqueous or organic solvents is a way to obtain a highly concentrated content of cannabinoids and other beneficial components. By using water, an herbal tea can be obtained, whose composition was investigated by Hazekamp et al. [15]. The results indicated that cannabis tea has only limited potency, as it is probably a saturated solution of THC. ...
Article
Recently, an increasing number of pharmacists had to supply medicinal products based on Cannabis sativa L. (Cannabaceae), prescribed by physicians to individual patients. Cannabis olive oil preparation is the first choice as a concentrated extract of cannabinoids, even though standardized operative conditions for obtaining it are still not available. In this work, the impact of temperature and extraction time on the concentration of active principles was studied to harmonize the different compounding methods, optimize the extraction process, and reduce the variability among preparations. Moreover, starting from the cannabis inflorescence, the effect of temperature on tetrahydrocannabinolic acid decarboxylation was evaluated. For the analysis, a GC/MS method, as suggested by the Italian Ministry of Health, and a GC/flame ionization detection method were developed, validated, and compared.
... About 44% of patients assumed a cannabis decoction containing less than 1 mg of THC, and 33% of the decoction-taking patients reached blood concentrations of THC lower than 1 ng/ml, which is considered the minimum effective blood concentration. Among the main reasons, the low temperatures used in the heating process originated a conversion into decarboxylated analogs unpredictable and incomplete, with the presence of THCA-A and CBDA in decoction preparations [16,24]. Moreover, the conversion of THCA-A into THC is limited in boiling water, also due to the result of saturation of the water phase with THC, whilst THCA-A is more hydrophilic and soluble [25]. ...
Article
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Purpose: The recent release of a medical cannabis strain has given a new impulse for the study of cannabis in Italy. The National Health Service advises to consume medical cannabis by vaporizing, in decoction or oil form. This is the first study that explores the pharmacokinetics and tolerability of a single oral dose of cannabis as decoction (200 ml) or in olive oil (1 ml), as a first step to improve the prescriptive recommendations. Methods: This is a single-center, open-label, two-period crossover study designed to assess the pharmacokinetics and tolerability of oral cannabis administered to 13 patients with medication overuse headache (MOH). A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was conducted for the quantification of THC, CBD, 11-OH-THC, THC-COOH, THC-COOH-glucuronide, THCA-A, and CBDA. Blood pressure, heart rate, and a short list of symptoms by numerical rating scale (NRS) were assessed. Results: Decoctions of cannabis showed high variability in cannabinoids content, compared to cannabis oil. For both preparations, THCA-A and CBDA were the most widely absorbed cannabinoids, while THC and CBD were less absorbed. The most important differences concern the bioavailability of THC, higher in oil (AUC0-24 7.44, 95% CI 5.19, 9.68) than in decoction (AUC0-24 3.34, 95% CI 2.07, 4.60), and the bioavailability of CBDA. No serious adverse events were reported. Conclusions: Cannabis decoction and cannabis oil showed different pharmacokinetic properties, as well as distinct consequences on patients. This study was performed in a limited number of patients; future studies should be performed to investigate the clinical efficacy in larger populations.
... Dann interagieren die Endocannabinoide auch mit "Ligand-gated-Ionenkanälen" (5HT 3 -, nikotinischen Acetylcholin-, Glycin-, i onotropen Glutamat-NMDA-Rezeptoren) sowie "Voltage-gated-Ionenkanälen". Grotenhermen et al. 2015;Hazekamp et al. 2007;Hollister et al. 1981;Kathmann et al. 2006;Marcu 2016;Pertwee 2006;Verhoeckx et al. 2006). ...
... THC is highly lipophilic, which accounts for its significantly large distribution volume, cumulation in fat-rich tissues (brain, lungs, kidneys), and slow elimination [25]. This high lipophilicity and poor solubility in water limits use in infusions, although 15% of THC and tetrahydrocannabinol acid (a derivative with some immune-modulating properties and bereft of psychoactivity) comes to the solution during infusion preparation [26,27]. ...
Article
Full-text available
There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional.
... CME are derived from Cannabis botanical raw material and contain the active pharmaceutical ingredient (cannabinoids) at various levels of purification and refinement (Fig. 2). Enrichment of active ingredients for manufacture of Cannabis-based drugs can be achieved using aque-ous (decoction) [39], organic (e.g., ethanolic) [40], supercritical fluid [41,42] and edible plant oil-based extraction [43] (Fig. 2), with aqueous being the least appropriate given the low solubility of cannabinoids in water [44,45]. Purification of the botanical drug substance may involve repeated extraction, chromatographic separation, distillation, as well as winterisation, whereby non-target lipidsoluble materials, such as waxes, are removed by filtration at -20 ° C [46]. ...
Article
Full-text available
The plant genus Cannabis is a prolific producer of unique pharmaceutically relevant metabolites, commonly referred to as cannabinoids. Robust and standardised methods for the quantification of cannabinoids within botanical and drug forms is a critical step forward for an emerging Cannabis-based pharmaceutical industry, which is poised for rapid expansion. Despite a growing body of analytical methods for the quantification of cannabinoids, few have been validated using internationally accredited guidelines. Moreover, standardised methods have yet to be developed for application at various stages of manufacture as well as for different levels of processing and refinement. Validation parameters for establishing robust standardised methods for cannabinoid quantification within Cannabis-based drug forms are critically discussed. Determining an appropriate level of specificity (discrimination) among heterogeneous botanical matrices as well as evaluating accuracy (recovery) and inter-laboratory precision (reproducibility) within strict and volatile regulatory environments are potential obstacles to the establishment of robust analytical procedures. We argue that while some of these challenges remain unique to Cannabis, others are common to botanical-based drug development and manufacture. In order to address potential barriers to analytical method standardisation, a collaborative research initiative inclusive of academic and commercial stakeholders is proposed.
... For administration, the decoction was administered orally after preparation by boiling the contents of a sachet containing minced MC in 200 mL water and 30 mL of milk for 15-20 min (Hazekamp et al. 2007). Alternatively, the cannabis was administered by vaporization using a cannabis vaporizer at a temperature of 210°C (Gieringer et al. 2008). ...
Article
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Background The use of cannabis for treating fibromyalgia syndrome (FMS) has not been comprehensively investigated. Thus, we have assessed the efficacy and adverse events (AEs) of short- and long-term medical cannabis (MC) treatment for FMS. Methods Data were obtained from medical reports archived in the pain clinic of Ponderano (Italy; retrospective study). FMS patients, who were resistant to conventional therapy, received licensed MC with various Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content, as powdered whole flowers (decoction or vaporization) or oil extracts. Demographic and clinical parameters, including Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), Hospital Anxiety and Depression Scale, Widespread Pain Index (WPI), Severity Score (SyS), and side effects, were obtained after 1, 3, and 12 months. Data were analyzed with Wilcoxon signed-rank tests for paired data. Results Thirty-eight patients were included. Thirty, 18, and 12 patients continued therapy for 1, 3, and 12 months, respectively. Significant improvements ( p < 0.01) were observed in NRS, ODI, WPI, and SyS at 1 month; in NRS, ODI, and WPI at 3 months; and in NRS, ODI, and SyS at 12 months. Therapy was interrupted by 17 patients (48.6%) owing to nonserious AEs according to the FDA. The most common side effects were mental confusion (37%), dizziness (14%), nausea/vomiting (14%), and restlessness/irritation (14%). The median daily dose of milled flowers administered as THC-dominant MC and hybrid MC (with similar THC/CBD ratio) was 200 mg/day and 400 mg/day, respectively. After 3 months of titration, the median content of THC administered with THC-dominant MC cultivars was 46.2 mg, and of THC + CBD administered as a hybrid MC cultivar, was 23.6 mg + 38 mg. At 3 months, median THC content administered in the oil extract of the THC-dominant MC cultivars was 9.7 mg, while that of THC + CBD administered in the oil extract of the hybrid MC cultivars was 1.8 mg + 2 mg. Conclusions MC may represent an alternative treatment for patients with FMS who are unresponsive to conventional therapy. However, its application may be limited by the incidence of nonserious AEs.
... Prescribing a cannabis-based decoction, considering the low recovery rates of THC and CBD and, consequently, the high volume of preparation that the patient would have to ingest, should not be the first choice for cannabis-based therapies. More important, only the soluble cannabinoids acids can be extracted in water, and these will not significantly decarboxylated successively [67]. Furthermore, the high raw material costs necessary to obtain the desired doses of active molecules should be seriously taken into account [46]. ...
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.
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An interesting and valuable discussion has arisen from our recent article (Lachenmeier et al., 2020) and we are pleased to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Kruse and Beitzke (2020) on behalf of the European Industrial Hemp Association (EIHA) that possibly contributed to their concerns about the validity of our data, toxicological assessment and conclusions regarding regulatory status of cannabidiol (CBD) products. First and foremost, our study did only assess the risk of psychotropic Δ ⁹ -tetrahydrocannabinol (THC) without inclusion of non-psychotropic Δ ⁹ -tetrahydrocannabinolic acid (THCA). Secondly, as this article will discuss in more detail, there is ample evidence for adverse effects of CBD products, not only in paediatric patients, but also in adult users of over-the-counter CBD products (including inadvertent “high” effects). Thirdly, the exposure and risk assessment was conducted using up-to-date guidelines according to the European Food Safety Authority (EFSA) and the German Federal Institute for Risk Assessment (BfR). And finally, the current legal situation in the European Union, without approval of any hemp extract-containing product according to the Novel Food regulation, actually allows blanket statements that all such products are illegal on the market, and this indeed would imply a general ban on the use and marketing of such products as food or food ingredients until such an approval has been granted. We hope that this reassures the F1000Research readership regarding the validity of our results and conclusions. We are pleased, though, that the EIHA has acknowledged the fact that there are non-compliant CBD products available, but according to our data these are a substantial fraction of the market.
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Herbal teas of fiber-type hemp varieties (Cannabis sativa L.) rich in cannabidiolic acid (CBDA) and cannabidiol (CBD) and poor in Δ9-tetrahydrocannabinol acid (THCA) and Δ9-tetrahydrocannabinol (THC) are very popular today. The conditions for preparing herbal infusions are not well standardized and analysis of the lipophilic cannabinoids in infusions is difficult. Therefore, we analyzed the hemp leaf residues after tea preparation by using a response surface modelling approach to estimate the effects of variations in temperature, water volume and extraction time on the residual content of five cannabinoids (CBDA, CBD, THCA, THC, cannabinol (CBN)) in the hemp leaves after extraction. The quantity of remaining cannabinoids was mainly influenced by temperature in the first order. Volume and extraction time were only exerting minor influences under usual tea preparation processes. At elevated water temperatures CBD and THC values were even higher than in the original drug material presumably due to decarboxylation of CBDA and THCA. Rising temperatures increased extraction of CBDA and CBD, as opposed to THCA and THC. The degradation of THC to CBN was not significant at the conditions of infusion preparation. Analyzing herbal residues after tea brewing is just an approximation to the true values of valuable or unfavorable compounds in tea, overestimating the true values. However, that approach offers a good control for further improvements of herbal tea analysis and gives reliable indications for risk assessment.
Chapter
The Cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Based on the number of publications, it is one of the best-studied plants in the world. The relatively recent discovery of cannabinoid receptors and the human endocannabinoid system has opened up a new and exciting field of research. But despite the pharmaceutical potential of Cannabis, its classification as a narcotic drug has prevented its successful development into modern medicine. Fortunately, the chemistry of Cannabis has been studied in much detail. In particular the psychoactive cannabinoid tetrahydrocannabinol (THC) has received great scientific attention, and much is known about its biological effects and mechanisms of action. Besides an extensive description of the chemistry of the cannabinoids, this chapter also introduces the lesser-known terpenoids, flavonoids, and other constituents of the Cannabis plant. Comprehensive information on a variety of subjects is presented, including chromatographic analytical methods, pharmacokinetics, and structure-activity relationships. The known biological effects of Cannabis constituents are discussed in relationship to the development of modern cannabinoid-based medications. Finally, some practical aspects of working with Cannabis are discussed.
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Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it. Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs). Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects. PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation. The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis.
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An interesting and valuable discussion has arisen from our recent article (Lachenmeier et al., 2020) and we are pleased to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Kruse and Beitzke (2020) on behalf of the European Industrial Hemp Association (EIHA) that possibly contributed to their concerns about the validity of our data, toxicological assessment and conclusions regarding regulatory status of cannabidiol (CBD) products. First and foremost, our study did only assess the risk of psychotropic Δ ⁹ -tetrahydrocannabinol (THC) without inclusion of non-psychotropic Δ ⁹ -tetrahydrocannabinolic acid (THCA). Secondly, as this article will discuss in more detail, there is ample evidence for side effects of CBD products, not only in paediatric patients, but also in adult users of over-the-counter CBD products (including inadvertent “high” effects). Thirdly, the exposure and risk assessment was conducted using up-to-date guidelines according to the European Food Safety Authority (EFSA) and the German Federal Institute for Risk Assessment (BfR). And finally, the current legal situation in the European Union, without approval of any hemp extract-containing product according to the Novel Food regulation, actually allows blanket statements that all such products are illegal on the market, and this indeed would imply a general ban on the use and marketing of such products as food or food ingredients until such an approval has been granted. We hope that this reassures the F1000Research readership regarding the validity of our results and conclusions. We are pleased, though, that the EIHA has acknowledged the fact that there are non-compliant CBD products available, but according to our data these are a substantial fraction of the market.
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From the pharmaceutical and medicinal point of view Cannabis saliva L. is an interesting and perspective material. It contains biologically active cannabinoids whose isolation and identification in the 1960's enabled a rapid research that has been bringing interesting results to this day. Especially revealing the human endocannabinoid system and the pharmacological effects of cannabinoids or derived synthetic compounds are the most interesting areas. The research in this field continues also toward pharmaceutical dosage forms with convenient route of administration and pharmacokinetics parameters to be used in clinical practice. Cannabinoids open completely new approaches in the treatment of many relevant human diseases and can become perspective and potential remedies. This review article deals with the effects of cannabinoids on human endocannabinoid system, their use in pharmacotherapy, their adverse effects, their interactions with other drugs and the convenient pharmaceutical dosage forms. Additional information concerning laws valid in the Czech Republic and used analytical forensic methods of cannabinoids are reviewed here as well.
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This Correspondence article is a counterstatement to a Brief Report published by Lachenmeier and co-workers on 17th February 2020 in F1000Research: “Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?”. This counterstatement proposes that the authors of that article neither present proof or evidence for the alleged side effects of CBD products (no case reports presented with utilisable data), nor do they show that side effects are due to the presence of THC. Primarily, there is no clear definition of THC because the authors do not explain whether they mean Delta9-THC only (without its precursor tetrahydrocannabinolic acid (THCA)) or total-THC (the sum of Delta9-THC and its precursor THCA, normalised to THC); indeed EU Recommendation 2016/2115 on the monitoring of cannabinoids in food requires the measurement and documentation of the precursor acids complementary to the decarboxylated cannabinoids. The key part of the authors’ work – Table 2 with the assessment of the CBD products – leaves the reader in the dark about the nature of “THC”. This is all the more concerning because acid-free Delta9-THC is psychotropic but THCA is not. Additionally, the classification of the CBD products (“toxicity assessment”) presented is based on the assignment of the quantitative relation to the LOAEL (lowest observed adverse effect level) of THC (2.5 mg of acid-free Delta9-THC per adult and day as assigned by EFSA, 2015). However, many assumptions by Lachenmeier et al. on daily intake of CBD products are questionable, in particular food supplements, where the recommended daily consumption was missing on the label. Finally, the authors of the paper also compare their findings with the German recommendations on maximum levels of total-THC in food, ignoring that those limits refer to total-THC and the ready-to-eat products, and not to the food ingredient itself – in particular hemp tea products.
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A novel plate‐like nano‐sorbent based on copper/cobalt/chromium layered double hydroxide was synthesized by a simple coprecipitation method. The synthesized nanoparticels were introduced into a stainless steel cartridge using a dry packing method. Then, the packed cartridge was introduced as a novel on‐line “packed in‐tube” configuration and followed by high performance liquid chromatography for the determination of trace amounts of ∆9‐tetrahydrocannabinol from biological samples and cannabis leaves. The as‐prepared sorbent exhibited long lifetime, good chemical stability, and high anion‐exchange capacity. Several important factors affecting the extraction efficiency, such as extraction and desorption times, pH of the sample solution and flow rates of the sample and eluent solutions, were investigated and optimized. Under optimized conditions, this method showed good linearity for ∆9‐tetrahydrocannabinol in the ranges of 0.09‐500 μg L−1, 0.3‐500 μg L−1 and 0.4‐500 μg L−1 with coefficients of determination of 0.9999, 0.9991 and 0.9994 in water, serum and plasma samples, respectively. The inter‐ and intra‐assay precisions (n = 3) were respectively in the ranges of 1.8‐4.6% and 1.9‐4.0% at three concentration levels of 10, 50 and 100 μg L−1. The limits of detection were also in the range of 0.02‐0.1 μg L−1. This article is protected by copyright. All rights reserved
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Quality control is imperative for Cannabis since the primary cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), elicit very different pharmacological effects. THC/CBD ratios are currently determined by techniques not readily accessible by consumers or dispensaries and which are impractical for use in the field by law-enforcement agencies. CuPc- and F16-CuPc-based organic thin-film transistors have been combined with a cannabinoid-sensitive chromophore for the detection and differentiation of THC and CBD. The combined use of these well-characterized and inexpensive p- and n-type materials afforded the determination of the CBD/THC ratio from rapid plant extracts, with results indistinguishable from high-pressure liquid chromatography. Analysis of the prepyrolyzed sample accurately predicted postpyrolysis THC/CBD, which ultimately influences the psychotropic and medicinal effects of the specific plant. The devices were also capable of vapor-phase sensing, producing a unique electrical output for THC and CBD relative to other potentially interfering vaporized organic products. The analysis of complex medicinal plant extracts and vapors, normally reserved for advanced analytical infrastructure, can be achieved with ease, at low cost, and on the spot, using organic thin-film transistors.
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Background The medicinal properties of cannabis are now recognized. Indeed, in many countries, lawmakers have introduced specific laws and programmes to allow patients to use cannabis preparations in various forms; nevertheless, controversial situations can still be found. In Europe, medicinal- grade cannabis is mainly available as standardized dried flower tops of the cannabis plant used in magistral formulas. These are pharmaceutical preparations compounded in a pharmacy – following Good Compounding Practices - in accordance with a physician’s prescription for an individual patient. Aim of this work is to discuss the available Cannabis based preparations and regulation for prescription and distribution, with reference to Italy. Methods We undertook a structured search of Italian laws, ministerial decree and circulars related to therapeutic use of Cannabis, interpreted in light of Italian Society of Compounding Pharmacists’ (SIFAP) position. Results Seven documents were analysed. Cannabis can be orally administered to patients - as a dried drug dosed in filter or capsules for infusion or as an extract in olive oil prepared in a pharmacy - or inhaled with a specific vaporizer. Considering the costs and limited availability of Dutch medicinal-grade cannabis, the Italian Government, with the latest Decree of November 9th, 2015, has authorized the production of cannabis in the Military Pharmaceutical Chemical Institute on Florence, describing also the therapeutic use of cannabis and the requirements to be adhered to by physicians and pharmacists. Conclusion A well-established national regulation guarantees the proper therapeutic use of Cannabis. Description of preparation method in monograph Pharmacopoeia will be the way to assure quality and therefore the efficacy of these products.
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Motor and mental performance was tested after smoking a placebo cigarette and after smoking a marihuana cigarette calibrated to deliver 5 mg. of delta -9-tetrahydrocannabinol. A significant decrement in all motor performance tests and in five of nine mental performance tests was observed after the marihuana cigarette. We were not able to detect any cannabinols in the blood or urine of subjects who smoked the marihuana.
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The isolation and elucidation of the structures of Δ1-tetrahydrocannabinol (Δ1-THC), cannabigerol, cannabichromene, and cannabicyclol are described. A facile conversion of cannabidiol into Δ1-THC takes place on treatment with boron trifluoride etherate. The absolute configuration of the chiral centers at C-3 and C-4 of Δ1-THC is established as R.
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Invasive pulmonary aspergillosis (IPA) is often a lethal entity in transplant recipients (up to 90%). We report the successful treatment of a case of IPA in a renal transplant recipient whose only risk for exposure was habitual marijuana smoking. Although marijuana smoking has been linked to the development of IPA in patients immunosuppressed for a variety of reasons, this case is the first report involving a solid organ transplant recipient. The patient's clinical course and treatment are described and the literature is reviewed with respect to environmental and patient risk factors. In this case, IPA was associated with the patient's heavy usage of marijuana during the immediate posttransplant period. Treatment was successful and included the experimental amphotericin product amphotericin B colloidal dispersion. Contemporaneous exposure to a large amount of inocula of Aspergillus within 30 days of receiving high doses of steroids appeared to be the most important factor that predisposed this patient to IPA. Transplant recipients should be specifically proscribed from marijuana use during periods of high steroid administration.
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To determine whether ingestion of hemp seed tea could result in positive urine drug screens for cannabinoids, volunteers were recruited to donate urine after consuming hemp seed or placebo tea. Among the 22 participants, 10 ingested 12 ounces of hemp seed tea, 10 ingested 24 ounces, and 2 ingested 12 ounces of placebo tea. Urine cannabinoid specimens were obtained at baseline and at 4, 8, and 24 hours after ingestion. A total of 10 specimens had trace quantities of cannabinoids detected in 7 subjects on gas chromatography/mass spectrometry testing, all below the Department of Transportation cutoff level of 15 ng/mL. These results demonstrate that under the conditions of this study, hemp seed tea consumption can result in detectable urine cannabinoids but would not trigger a positive EMIT or gas chromatography/mass spectrometry urine drug test for cannabinoids.
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A solvent programmed reversed-phase HPLC method with UV detection for the determination of delta9-tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinolic acid A (THCA-A) in foods containing parts of hemp such as edible oil, herb-teas (infusion), herbal hemp or hempseed is presented. The THC peak is also detected by fluorescence. The detection limits with UV detection are 0.01 ng for THC and 0.05 ng for THCA-A and with fluorescence detection 0.1 ng for THC. The relative standard deviation under repeatability conditions of the chromatographic procedure is about 0.5% and that of the over-all analytical procedure for THC in vegetable oils 2% (concentration range of 10-100 mg/kg).
Article
The relationship between aflatoxins and liver cancer is well established. In addition the inhalation exposure to carcinogen aflatoxin B1 (AFB 1) is considerable. Genotoxic chemical is known to react with DNA either directly or after metabolic activation to form adducts, a step thought to be relevant with respect to chemical carcinogenesis. The presence and the amount of specific DNA adducts provide a good indication of chemical exposure and genetic damage resulting the exposure to carcinogens and account for same of factors affecting individual susceptibility to cancer. Analysis of DNA adducts requires that the sensitivity of the methods to be sufficient high to allow detection of about 1 adduct/109 normal nucleotides. Most suitable method is based in physiochemical technique such as HPLC. Because circumstantial epidemiological evidence suggests that AFB1 inhalation may cause primary lung cancer. We investigate AFB1 by HPLC in three different tobacco sources, and in 39 patients with compatible lung cancer or chronic bronchitis. The patients were divided by clinical manifestations in lung cancer (n: 25) and chronic bronchitis (n: 14). Twenty-three of 25 patients presented epidermoid lung cancer within smoking habit, and 2 of 25 presented adenocarcinoma without smoking habit. In chronic bronchitis group 12 of 14 cases presented smoking habit. The control PBS liquid was negative to AFB1; the different tobacco sources, a) Virginia of Jujuy, b) Brasilero and c) black of Salta presented AFB1 positive determinations respectively. The bronchial tissues obtained by lung biopsies presented positive AFB1 in lung epidermoid cancer at 0.68 +/- 0.82 mg/L. The adenocarcinoma presented AFB1 negative determinations. In chronic bronchitis patients with smoking habit (n: 12) presented AFB1 positive with a level less than the epidermoid lung cancer group, 0.21 +/- 0.109 mg/L, p < .025.
Article
Derivatives of the azoalkane 2,3-diazabicyclo[2,2,2]oct-2-ene (1a) with bridgehead 1,4-dialkyl (1b), 1,4-dichloro (1c), 1-hydroxymethyl (1d), 1-aminomethyl (1e), and 1-ammoniummethyl (1f) substituents form host-guest inclusion complexes with beta-cyclodextrin. They were employed as probes to assess substituent effects on the kinetics and thermodynamics of this complexation by using time-resolved and steady-state fluorimetry, UV spectrophotometry, induced circular dichroism (ICD) measurements, and (1)H NMR spectroscopy. The kinetic analysis based on quenching of the long-lived fluorescence of the azoalkanes by addition of host provided excited-state association rate constants between 2.6 x 10(8) and 7.0 x 10(8) M(-)(1) s(-)(1). The binding constants for 1a (1100 M(-1)), 1b (900 M(-1)), 1c (1900 M(-1)), 1d (180 M(-1)), 1e (250 M(-1)), and 1f (ca. 20 M(-1)) were obtained by UV, NMR, and ICD titrations. A positive ICD signal of the azo absorption around 370 nm was observed for the beta-cyclodextrin complexes of 1a, 1d, and 1f with the intensity order 1a > 1d approximately 1f, and a negative signal was measured for those of 1b, 1c, and 1e with the intensity order 1c < 1b approximately 1e. The ICD was employed for the assignment of the solution structures of the complexes, in particular the relative orientation of the guest in the host (co-conformation).
Article
A fully automated procedure using alkaline hydrolysis and headspace solid-phase microextraction (HS-SPME), followed by on-fiber derivatization and gas chromatographic–mass spectrometric (GC–MS) detection has been developed for determination of cannabinoids in hemp food samples. After addition of a deuterated internal standard, the sample was hydrolyzed with sodium hydroxide and submitted to direct HS-SPME. After absorption of analytes for on-fiber derivatization, the fiber was placed directly into the headspace of a second vial containing N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), before GC–MS analysis. Linearity was good for Δ 9-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; regression coefficients were greater than 0.99. Depending on the characteristics of the matrix the detection limits obtained ranged between 0.01 and 0.17 mg kg−1 and the precision between 0.4 and 11.8%. In comparison with conventional liquid–liquid extraction this automated HS-SPME–GC–MS procedure is substantially faster. It is easy to perform, solvent-free, and sample quantities are minimal, yet it maintains the same sensitivity and reproducibility. The applicability was demonstrated by analysis of 30 hemp food samples. Cannabinoids were detected in all of the samples and it was possible to differentiate between drug-type and fiber-type Cannabis sativa L. In comparison with other studies relatively low THC concentrations between 0.01 and 15.53 mg kg−1 were determined.
Article
There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.
Pharmo rapport: medicinal gebruik van cannabis. Pharmo Institute for Drug Outcome Research
  • A F C Janse
  • N S Breekveldt-Postma
  • J A Erkens
  • R M C Herings
Janse, A.F.C., Breekveldt-Postma, N.S., Erkens, J.A., Herings, R.M.C., 2004. Pharmo rapport: medicinal gebruik van cannabis. Pharmo Institute for Drug Outcome Research, Utrecht, The Netherlands.
Influence of medicinal cannabis (MC) on the pharmacokinetics (PK) of docetaxel (DOC) and irinotecan (CPT-11)
  • De Jong
  • F A Engels
  • F E Sparreboom
  • A Loos
  • W J De Bruijn
  • P Friberg
  • L E Mathot
  • R A Verweij
  • J Mathijssen
De Jong, F.A., Engels, F.E., Sparreboom, A., Loos, W.J., De Bruijn, P., Friberg, L.E., Mathot, R.A., Verweij, J., Mathijssen, R.H., 2005. Influence of medicinal cannabis (MC) on the pharmacokinetics (PK) of docetaxel (DOC) and irinotecan (CPT-11). In: AACR Meeting Abstracts, pp. 938c-939c.
Hemp tea versus hemp milk: subjective effects and elimination studies of THC and its main metabolite
  • C Giroud
  • M Augsburger
  • L Rivier
  • P Mangin
Giroud, C., Augsburger, M., Rivier, L., Mangin, P., 1997. Hemp tea versus hemp milk: subjective effects and elimination studies of THC and its main metabolite. In: Proceedings of the 35th TIAFT meeting, Padova, Italy, pp. 112-121.
Cannabis and Cannabinoids
  • F Grotenhermen
  • E Russo
Grotenhermen, F., Russo, E., 2002. Cannabis and Cannabinoids. Haworth Press, New York, pp. 67-72.
Official website: www.cannabisbureau.nl. Website visited
OMC, Office of Medicinal Cannabis, The Netherlands, 2006. Official website: www.cannabisbureau.nl. Website visited 20 August 2006.
Influence of medicinal cannabis (MC) on the pharmacokinetics (PK) of docetaxel (DOC) and irinotecan (CPT-11)
  • De Jong
Hemp tea versus hemp milk: subjective effects and elimination studies of THC and its main metabolite
  • Giroud