Program conference 2019

8:30      Press conference

9:00      Introductory word

9:20      Current state of cannabinoid research                                      and what is next?

Doc. RNDr. Lumír Ondřej Hanuš, DrSc., Dr.h.c.mult.                                                                            (Asana Bio Group Ltd. Tel Aviv; Hebrew University, Jerusalem, Israel)

The cannabis plant has been used since the dawn of time (whether we talk about the industrial, medical or recreational use). However, it was not until the discovery of delta-9-tetrahydrocannabinol by Šantavý, Gaoni and Mechoulam, that we were finally able to study its effects. And when the discovery of the cannabinoid receptors by Devane and the identification of endocannabinoids by Hanuš, Devane and Ben Shabat followed, we could start to examine the full medical potential of cannabis. The use of this plant and its products by the patients without a medical assistance became the cornerstone of the cannabis treatment. Cannabis used to be used as a medicine in the Czechoslovakia, today it helps the patients primarily in Israel, thus this presentation will also focus on the progress of cannabis treatment in Israel.

10:00          New approaches towards cannabinoid            production in vitro

Prof. PharmDr. Petr Babula, Ph.D.                                                                                                          (Physiology Department, Faculty of Medicine, Masaryk University)

Cannabis sativa L. is a plant with very complex and rich phytochemical profile. Cannabis contains, among other things, the well-known cannabinoids, i.e. C21 terpenophenolic specialized metabolites, which have been the biggest cannabis scientific concern for quite some time. The plant also comprises of other substances, such as terpenes (starting from mono- to triterpenes), flavonoids (especially apigenin, luteolin, quercetin and kaempferol C-/O- and O-glycosides), phenolic glycosides, and nitrogenous bases (alkaloids included). The production of cannabinoids in vitro is not easy and hindered by many problems, which have not yet been overcome. Nonetheless, the hairy root cultures represent the first success. Ultimately, modern biotechnological ways to produce cannabinoids is the great challenge for the future.

10:25      Cannabinoid pharmacology

 Cannabinoid pharmacodynamics                                                                                                                                             Prof. MUDr. Alexandra Šulcová, CSc. .                                                                                             (International Cannabis and Cannabinoids Institute, Czech Republic)                                                    Cannabinoid pharmacokinetics                                                                                                                                                PharmDr. Ondřej Zendulka, Ph.D.                                                                                                           (Pharmacology Department, Faculty of Medicine, Masaryk University)
 

Prof. MUDr. Alexandra Šulcová, CSc.; Cannabinoid pharmacodynamics

It was not before the discovery of plant THC in 1964 and determination of its chemical structure in 1967 that we were able to study pharmacodynamics of cannabinoids. Later it was proven that THC binds with specific structures of cell membranes, also known as cannabinoid receptors (CB1; CB2; TRPV1; GPR 18; GPR 55; GPR 119; PPAR nuclear receptors). Gradually, the ligands of mentioned receptors were isolated in bodies of vertebrates (including humans) and are now called endocannabinoids (anandamide, 2-AG, NADA, Noladin, and virodhamine). This functional endogenous receptor system, also known as endocannabinoid system for its ligands, is very interesting for its biochemistry and metabolism (which is also called endocannabinoidom). More and more selective or non-selective synthetic cannabinoid ligands are also being discovered among other known phytocannabinoids and endocannabinoids (coming from various pharmacological classes: agonists, antagonists, and inverse agonists). The endocannabinoid system is quite ubiquitous in the bodies of vertebrates, therefore the physiology and pathophysiology of endocannabinoid activities and the medical alternatives are thoroughly examined. When it comes to medical applications of phytocannabinoids, the "entourage effect" is being described. There are three entourage effect mechanisms to consider: a) pharmacokinetic - the interaction stimulates the absorption and distribution of active principles or suppresses their biodegradation and excretion; b) direct pharmacodynamics- the substances with the same effect bind to the same receptor; c) indirect pharmacodynamics- the substances with the same effect but they use a different molecular (receptor) mechanism.

PharmDr. Ondřej Zendulka, PhD; Cannabinoid pharmacokinetics

Basically all natural cannabinoids (including THC and CBD) are lipophilic substances that pervade the biological membranes which separate the cellular compartments. This is the reason why cannabinoids are so easily absorbed by mucous membranes of oral cavity or respiratory tract when they are inhaled. In this case, cannabinoids take effect nearly as fast as if they were injected intravenously. On contrary, the transdermal application is followed with much slower absorption as cannabinoids penetrate the hypodermis quite tardily. The oral administration is connected with slower absorption and also with the issue of interindividual variability and insufficient bioavailability because of intensive hepatic metabolism. Thanks to its lipophilicity cannabinoids may be easily distributed into various tissues, and if they are used chronically, they usually accumulate in adipose tissue. THC and CBD are substrates of hepatic cytochromes P450, which are the main biotransformative mechanism in phytocannabinoid elimination. Resulting metabolites are then excreted via urine and bile. The transfer of THC through placenta to breast milk may be of clinical importance for pregnant women and nursing mothers.                                                                                                                    The involvement of the cytochrome P450 in cannabinoid metabolism is important in context of medical interactions. The combination of substrates of this enzymatic system with substances which are inductors or inhibitors of cytochromes may result in the need for adjustment of cannabinoid or other medicament dosage. It should also be mentioned that cannabinoids may change the cytochrome effects. Nonetheless, how the endocannabinoid system regulates the cytochrome P450 effects has also not been clarified yet.

11:05      Methods of cannabinoid profiling -                                           requirements, possibilities and limitations

Doc. RNDr. Petr Tarkowski, Ph.D.                                                                                                            (Faculty of Science, Palacký University in Olomouc)  

This lecture is about the methods of chemical analysis of cannabinoids. We will have a discussion on different analytical method requirements of various control and research labs. The talk will also focus on the strength of data acquired by individual methods and also on the limitations of the most popular methods.  

11:30       Standardization of secondary metabolites in the medical cannabis plant: challenges and potential solutions

Dr. Nirit Bernstein                                                                                                                                     (Institute of Soil, Water and Environmental Sciences, Volcani Research Center, Israel)

The diverse medical potential of cannabis (Cannabis sativa L.) is predicated on the complex chemical profile, comprising hundreds of secondary metabolites including cannabinoids, terpenes and flavonoids. Major challenges involved in the usage of cannabis for medicine sources from the lack of standardization of the therapeutic secondary metabolites in the products supplied to patients. Environmental and growing conditions such as light, temperature, mineral nutrients and water availability affect plant development and function, including the synthesis of secondary metabolites in cannabis. Understanding plant response to environmental and cultivation conditions is the focus of current research, and the information obtained will be of importance for technological improvement of production in cannabis industry. We tested the hypothesis that physical and chemical elicitors imposed during cultivation induce changes in the chemical profile of medical cannabis that can be used for standardization of the active secondary metabolites. We have identified physical and chemical conditions which affect the chemical profile, and some breakthroughs were made towards understanding the regulation of the chemical profile. Physical elicitors such as light intensity and quality, temperature and humidity; and chemical elicitors such as nutrients and methyl salicylate were found to affect cannabinoids and terpenes production. For example, NPK supplementation significantly increased CBG levels and lowered CBN levels, while humic acids significantly reduced the natural spatial variability of all of the cannabinoids studied. However, the increased uniformity came at the expense of the higher levels of cannabinoids naturally found in the upper parts of plants. Some elicitors affected the cannabinoid concentration in a specific manner. In the talk we will discuss regulatory effects of various elicitors on the cannabinoid and terpene profile in an organ and spatially dependent manner. 

11:55     The production of medical cannabis for the state according to the valid regulations and directives of GACP, GMP

Ing. Luděk Novák (Elkoplast Slušovice s.r.o.) 

The company Elkoplast Slušovice s.r.o. and their division of medical cannabis production aim to fulfil the needs of potential customers. This is why the policy of Good Manufacturing Practices of medical substance applies as well as the system of quality control of Good Agricultural Practices and Good Distribution Practices. The consistent application of such policies and systems helps improve the quality of products which in return helps the systems and policies to become also more effective. Every delivery of custom-made services (which is growing and production of medical products, in our case) has to maintain high-quality custom-made technical design adjusted in compliance with Good Manufacturing Practices policy with respect to technical production requirements of the customer and regulation requirements. The manufactured and dispatched products have to always be high-quality and the customer has to be informed by the distribution chain about the proper use of the product.

12:20    Current data of SÚKL regarding cannabis for medical use

Ing. Nikola Jantosová (State Institute for Drug Control - SÚKL)

At the end of 2018, the State Institute for Drug Control conducted a questionnaire survey aimed at finding out the current situation in clinical practice in the Czech Republic. Questions were related to indications, benefits of treatment, reasons for treatment termination, the amount of prescribed dose per patient per month, opinion on possibility to cover the treatment from public health insurance, and the sources of information. SUKL provides detailed data from a statistical survey concerning cannabis prescription and dispensing. SUKL updates and publishes this data on a monthly basis on its website and continues to fulfil the legal obligations associated with ensuring the availability of cannabis for medical use in the Czech Republic. In June 2018, SÚKL received 4.2 kilograms of cannabis for medical use and, in January 2019, another 1.05 kilograms of medical cannabis has been received. The distribution of cannabis from licensed grower to pharmacies is conducted exclusively via the distributor Alliance Heathcare a.s., selected by SÚKL in a public tender. SÚKL enters into a contract with pharmacy operators who want to dispense medical cannabis in their pharmacies.

12:45     Lunch


14:45      Medical cannabis around the world

Ing. Pavel Pachta, CSc.                                                                                                                (International Regulatory Affairs Director, International Cannabis and Cannabinoids Institute, Czech Republic)

The definitions of medical cannabis use terms differ. Many see medical cannabis as cannabis-based medicine which is not licensed by the usual approval proceeding and whose use is permitted by special regulations. Israel, California (USA), Canada a Netherlands were the first states to legalize medical cannabis. Today, there are more than 40 countries and the number is growing quickly. The countries, however, differ in their cannabis legislation, and thus the number of their medical cannabis users also varies. The global scope of medical cannabis use (which was affected by the international anti-narcotics and anti-psychoactive substances control conventions of the past) is also gradually changing.

15:10       Cannabis in the context of Czech and International drug policy. Unwanted consequences of war on drugs

Mgr. Jindřich Vobořil, Pg.Dip. (NGO Podané ruce)

The 1961 Convention prohibited the use of many substances and created the system of repressive policy mechanisms all over the world. The excessive oppression and committed rhetoric of the War on Drugs brought about unexpected side effects in the form of extreme crime rates. The opioids and cannabis have been the boogeymen in many countries for decades. The medical cannabis research stopped and some cannabis biases last even until today. However, time has shown that the War on Drugs has completely failed and the only way to cut down addiction rates is regulation. For some time, there has been debate (mostly politicized by the media) on the medical use of cannabis. Nowadays, the situation appears to result in the pendulum effect until everybody compromises on the right form of regulation of this plant.


15:35      Practical experiences with cannabis prescription and application for medical purposes in the Czech Republic

MUDr. Radovan Hřib (Center for pain treatment, University hospital St. Anna in Brno)

16:00       Processing cannabis in pharmacy with tips

Mgr. Monika Pecháčková (Hospital pharmacy, University hospital St. Anna in Brno) 

Možnosti individuální přípravy léčivého přípravku s obsahem konopí pro léčebné použití. Především příprava tobolek pro perorální cestu podání pacientovi. Okrajově cenotvorba takto připravených léčivých přípravků.

16:25       Cannabis in palliative care

MUDr. Ondřej Sláma, Ph.D.                                                                                                                      (Ambulation of supportive and palliative oncology, Masaryk Memorial Cancer Institute, director of Palliative Society of Czech Medical Association of J. E. Purkyně) 

16:50       Performing surgeries five weeks after elbow fracture

MUDr. Filip Hudeček (I. Orthopaedic clinic at St. Anne´s University Hospital and a patient ) and MUDr. Radovan Hřib (Center for pain treatment, University hospital St. Anna in Brno) 

17:15        Panel discussion

 Konopí a věda
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