Kanabis in kanabinoidi v medicini – zakonodajni vidik

The discovery of the endocannabinoid system has raised public interest in the medicinal use of cannabis, phytocannabinoids, and synthetic cannabinoids, which has always been closely regulated due to their psychotropic effects and potential abuse. The review takes a quick look at the current legal framework in the European Union, which regulates cannabis use and cultivation for medicinal purposes in line with the United Nations Conventions on the production, trade, and use of cannabis, phytocannabinoids, and synthetic cannabinoids. And while the EU legislation precisely defines requirements and marketing authorisation procedures for medicinal products for all EU member states, there is no common regulatory framework for magistral and officinal preparations containing cannabinoids, as they are exempt from marketing authorisation. Instead, their regulation is left to each member state, and it is quite uneven at this point, mainly due to cultural and historical differences between the countries, leading to different access to non-authorised medicinal products. Therefore, to meet great public interest, harmonised approaches on cannabinoid-containing products without marketing authorisation would be welcome to level the playing field in the EU.Odkritje endokanabinoidnega sistema je vzbudilo zanimanje javnosti za medicinsko uporabo konoplje, fitokanabinoidov in sintetičnih kanabinoidov, ki je bila zaradi psihotropnih učinkov in morebitne zlorabe že od nekdaj natančno regulirana. V prispevku je predstavljen pravni okvir Evropske unije, ki ureja uporabo in gojenje konoplje v medicinske namene, v skladu s konvencijami Združenih narodov o proizvodnji, trgovini in uporabi konoplje, fitokanabinoidov in sintetičnih kanabinoidov. Medtem ko zakonodaja Evropske unije natančno določa zahteve in postopke izdaje dovoljenja za promet za avtorizirana zdravila, ni skupnega regulatornega okvira za magistralne in oficinalne pripravke, ki so izvzeti iz avtorizacijskih postopkov. Njihova ureditev je prepuščena vsaki državi članici in se zaradi tega razlikuje, predvsem zaradi kulturnih in zgodovinskih razlik med državami, to pa vodi do različne dostopnosti do tovrstnih zdravil. Zaradi tega bi bili dobrodošli nekateri usklajeni pristopi držav članic EU, s katerimi bi zmanjšali razlike na trgu neavtoriziranih zdravil s kanabinoidi

Primerjava toksičnosti etanola in acetaldehida za podganje astrocite v primarni kulturi

This study compared the effects of toxicity of ethanol and its first metabolite acetaldehyde in rat astrocytes through cell viability and cell proliferation. The cells were treated with different concentrations of ethanol in the presence or absence of a catalase inhibitor 2-amino-1,2,4 triazole (AMT) or with different concentrations of acetaldehyde. Cell viability was assessed using the trypan blue test. Cell proliferation was assessed after 24 hours and after seven days of exposure to either ethanol or acetaldehyde. We showed that both ethanol and acetaldehyde decreased cell viability in a dose-dependent manner. In proliferation studies, after seven days of exposure to either ethanol or acetaldehyde, we observed a significant dose-dependent decrease in cell number. The protein content study showed biphasic dose-response curves, after 24 hours and seven days of exposure to either ethanol or acetaldehyde. Co-incubation in the presence of AMT significantly reduced the inhibitory effect of ethanol on cell proliferation. We concluded that long-term exposure of astrocytes to ethanol is more toxic than acute exposure. Acetaldehyde is a much more potent toxin than ethanol, and at least a part of ethanol toxicity is due to ethanol’s first metabolite acetaldehyde.V študiji smo primerjali toksičnost etanola in njegovega prvega metabolita acetaldehida za podganje astrocite z določitvijo celične viabilnosti in proliferacije. Celične kulture smo tretirali z različnimi koncentracijami etanola, etanola v prisotnosti inhibitorja katalaze 2-amino-1,2,4 triazol-a (AMT) ali z različnimi koncentracijami acetaldehida. Celično viabilnost smo vrednotili s pomočjo testa s tripanskim modrilom, celično proliferacijo pa s štetjem celic in določitvijo koncentracije proteinov po 24-urni, kot tudi 7-dnevni izpostavljenosti. S študijo smo pokazali, da tako etanol kot tudi acetaldehid v odvisnosti od njune koncentracije zmanjšata celično viabilnost. V študiji proliferacije sta etanol in acetaldehid, v odvisnosti od njunih koncentracij, značilno zmanjšala število celic po 7-dnevni izpostavljenosti. Pri ugotavljanju vsebnosti proteinov smo dobili bifazno krivuljo tako po 24-urni, kot tudi po 7-dnevni izpostavljenosti različnim koncentracijam etanola oziroma acetaldehida. Prisotnost AMT je signifi kantno zmanjšala učinek etanola na celično proliferacijo. Zaključimo lahko, da je dolgotrajna izpostavljenost astrocitov etanolu bolj toksična kot akutna. Acetaldehid je močnejši toksin kot etanol in vsaj del toksičnosti etanola je posledica delovanja njegovega prvega metabolita, acetaldehida

Chronic Pain Treatment: The Influence of Tricyclic Antidepressants on Serotonin Release and Uptake in Mast Cells

The involvement of serotonin (5-HT) in chronic pain mechanisms is established. 5-HT inhibits central painful stimuli, but recent data suggests that 5-HT could also enhance pain stimulus from the periphery, where mast cells play an important role. We aimed in our study to clarify the influence of selected tricyclic antidepressants (TCAs) on mast cell function: secretion, uptake, and reuptake of 5-HT, that could interfere with 5-HT levels and in this way contribute to the generation of pain. As an experimental model, we used isolated rat peritoneal mast cells and incubated them with selected TCAs (clomipramine, amitriptyline, doxepin, and imipramine) under different experimental conditions. 5-HT release, uptake, and reuptake were determined spectrofluorometrically. We showed that TCAs were able to inhibit 5-HT secretion from mast cells, as well as uptake of exogenous 5-HT and reuptake of secreted 5-HT back into mast cells. The effects of TCAs were concentration dependent; higher concentrations of TCAs inhibited the secretion of 5-HT induced by compound 48/80, whereas lower concentrations of TCAs inhibited 5-HT uptake. The most effective TCA was halogenated clomipramine. As TCAs are well introduced in chronic pain treatment, the insight into mechanisms of action is important for an understanding of their effect in various pain conditions

A regulatory take on cannabis and cannabinoids for medicinal use in the European Union.

The discovery of the endocannabinoid system has raised public interest in the medicinal use of cannabis, phytocannabinoids, and synthetic cannabinoids, which has always been closely regulated due to their psychotropic effects and potential abuse. The review takes a quick look at the current legal framework in the European Union, which regulates cannabis use and cultivation for medicinal purposes in line with the United Nations Conventions on the production, trade, and use of cannabis, phytocannabinoids, and synthetic cannabinoids. And while the EU legislation precisely defines requirements and marketing authorisation procedures for medicinal products for all EU member states, there is no common regulatory framework for magistral and officinal preparations containing cannabinoids, as they are exempt from marketing authorisation. Instead, their regulation is left to each member state, and it is quite uneven at this point, mainly due to cultural and historical differences between the countries, leading to different access to non-authorised medicinal products. Therefore, to meet great public interest, harmonised approaches on cannabinoid-containing products without marketing authorisation would be welcome to level the playing field in the EU

Primerjava toksičnosti etanola in acetaldehida za podganje astrocite v primarni kulturi

This study compared the effects of toxicity of ethanol and its first metabolite acetaldehyde in rat astrocytes through cell viability and cell proliferation. The cells were treated with different concentrations of ethanol in the presence or absence of a catalase inhibitor 2-amino-1,2,4 triazole (AMT) or with different concentrations of acetaldehyde. Cell viability was assessed using the trypan blue test. Cell proliferation was assessed after 24 hours and after seven days of exposure to either ethanol or acetaldehyde. We showed that both ethanol and acetaldehyde decreased cell viability in a dose-dependent manner. In proliferation studies, after seven days of exposure to either ethanol or acetaldehyde, we observed a significant dose-dependent decrease in cell number. The protein content study showed biphasic dose-response curves, after 24 hours and seven days of exposure to either ethanol or acetaldehyde. Co-incubation in the presence of AMT significantly reduced the inhibitory effect of ethanol on cell proliferation. We concluded that long-term exposure of astrocytes to ethanol is more toxic than acute exposure. Acetaldehyde is a much more potent toxin than ethanol, and at least a part of ethanol toxicity is due to ethanol\u27s first metabolite acetaldehyde.V študiji smo primerjali toksičnost etanola in njegovega prvega metabolita acetaldehida za podganje astrocite z določitvijo celične viabilnosti in proliferacije. Celične kulture smo tretirali z različnimi koncentracijami etanola, etanola v prisotnosti inhibitorja katalaze 2-amino-1,2,4 triazol-a (AMT) ali z različnimi koncentracijami acetaldehida. Celično viabilnost smo vrednotili s pomočjo testa s tripanskim modrilom, celično proliferacijo pa s štetjem celic in določitvijo koncentracije proteinov po 24-urni, kot tudi 7-dnevni izpostavljenosti. S študijo smo pokazali, da tako etanol kot tudi acetaldehid v odvisnosti od njune koncentracije zmanjšata celično viabilnost. V študiji proliferacije sta etanol in acetaldehid, v odvisnosti od njunih koncentracij, značilno zmanjšala število celic po 7-dnevni izpostavljenosti. Pri ugotavljanju vsebnosti proteinov smo dobili bifazno krivuljo tako po 24-urni, kot tudi po 7-dnevni izpostavljenosti različnim koncentracijam etanola oziroma acetaldehida. Prisotnost AMT je signifikantno zmanjšala učinek etanola na celično proliferacijo. Zaključimo lahko, da je dolgotrajna izpostavljenost astrocitov etanolu bolj toksična kot akutna. Acetaldehid je močnejši toksin kot etanol in vsaj del toksičnosti etanola je posledica delovanja njegovega prvega metabolita, acetaldehida

Hormesis - an example of astrocyte response after ethanol exposure

Purpose: In the present work we describe hormesis and review documented hormetic responses in astroglial cells after exposure to different stressors. We present an example of the astrocyte response to acute and chronic ethanol exposure with hormetic characteristics. Methods: As an experimental model, newborn rat cortical astrocytes in culture were used. The cells were exposed to ethanol or the primary metabolite of ethanol (acetaldehyde) for 24 h or 7 days. After treatment, the protein content was determined, and the IL-6 levelsin the culture medium were measured using an enzymelinked immunoassay. Results: Treatment of astroglial cells with ethanol or acetaldehyde led to enhanced protein content and stimulated IL-6 production in the low concentration zone followed by diminished protein content and an inhibition ofIL-6 production at higher concentrations. Chronic exposure of astrocytes wasmore toxic than acute exposure for both compounds, and acetaldehyde was more toxic compared to ethanol. Conclusion: Ethanol and acetaldehyde representstressors for cultured astrocytes and evoke a typical hormetic response after acute and chronic exposure