Schedule

Refractory epilepsies, resistant to regular antiepileptic drugs (AEDs) in paediatric population continue to be a challenge worldwide. Despite an increasing number of new AEDs approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one ofmany constituentsof the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. Cannabis has being used as treatment of seizure disorders nearly 5000 years ago in Asia and during 18^th  and 19^th centuries also in Europe and United States and was also found in pharmacopeas. However it has been moved into Schedule I class after Marijuana Act in 1937.

After nearly 80 years of prohibition today highly purified CBD has already got Food and Drug Administration (FDA) approval, while still waiting for EMA approval in Europe, and was moved as a substance to Schedule V class. On the other hand artisanal formulations of CBDare readily available and are seeing increased use in our patient population as well. We are presenting our own data of treatment of resistant epilepsies/encephalopathies with pure CBD, where we got excellent results: in a group of retrospectively studied children with severe forms of epilepsy, treated by cannabidiol alone there was 77 % reduction of seizures and 21% of children were even seizure free. Later studies, especially some systematic reviews, reported similar data from other retrospective, non-randomized studies using cannabidiol alone, but including also some studies using cannabis plant extracts with similar outcome. When studying retrospectively those children whose parents admitted that they were using different artisanal products of cannabis for their children epilepsy is posing additional problems: potential benefits of artisanal cannabis preparations in the treatment of epilepsy are difficult to quantify due to the lack of controlled trials, variability in artisanal cannabis preparations which represents a key challenge and concern for the use of artisanal products for medical treatment of epilepsy, given the lack of both regulation and verification of such products. However the comparisson between those studies using purified/isolated cannabis products and those using artisanal product has many challenges. As shown by Sulak et al. response to artisanal cannabis is promising: uncontrolled observational data of 272 patients, have shown some degree of seizure reduction in 86% of cases and 10% had complete cessation of seizures. Our own data on small group of children useing atisanal cannabis are aslo promising.After half a year the parents were given the questionnaire and the Caregiver Global Impression of Change Scale (CGIC) to fulfill. The responses were low – 59% of all questionnaires sent, posing another possible bias, that those parents where artisanal cannabis was not effective did not want to report this as was the case also in some other studies. However we were surprised with the findings on the  CGIC, which showed excellent results of 93% improvement. In a recent study of cannabidiol use in Lennox-Gastaut syndrome patients the results of CGIC scores were 57% in the 20 mg/kg/d group and 66% in the 10 mg/kg/d group, compared with 44% in the placebo group, reporting overall improvement. Further studies comparing eficiency of isolated cannabinoids and products made form the whole plant are in process and the results will be available shortly.

Discuss strategies US government has employed to systematically impede cannabis efficacy research & challenges trying to push natural cannabis flower through the entire FDA drug development process.

• What are the past & remaining US regulatory obstacles to conducting scientific EFFICACY studies on whole plant cannabis flower?
• Who are the ultra wealthy / powerbrokers besides Big Pharma etc hand cuffing scientists from enabling natural cannabis flower to complete FDA drug development process?
• What is preventing US researchers from developing medical cannabis flowerinto FDA approved medicine? Why is NIDA Flower not allowed to be used as Rx?
• What is the current state of research globally? What do we know so far ...and what else needs to be examined?
• Why is there no meaningful government dollars to study efficacy of cannabis but only safety?

A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer and specifically of gliomas. The mechanism of cannabinoid anticancer action relies, at least largely, on the ability of these agents to stimulate autophagy-mediated cancer cell death. Moreover, the combined administration of cannabinoids and temozolomide produces a strong anticancer effect, which correlates with an intense activation of the signalling route that triggers the activation of cytotoxic autophagy. Research conducted in our group has also led to the identification of mechanisms of resistance to cannabinoid anticancer action. For example, up-regulation of the growth factor Midlkine (MK) promotes resistance to cannabinoid anticancer action in gliomas via stimulation of the Anaplastic Lymphoma Kinase tyrosine kinase receptor (ALK); and could be a factor of bad prognosis in GBM patients. All these preclinical findings have facilitated the promotion of a clinical study to investigate the safety and efficacy of the combined administration of the cannabis-based medicine Sativex and temozolomide in recurrent GBM. In this presentation I will discuss these issues and also other possible future studies that may help to clarify whether cannabinoids may be useful as anticancer agents in patients with gliomas or other cancers.

Vedno večje število kliničnih študij navaja, da imajo lahko pri nekaterih boleznih in v določenih pogojih konoplja ali kanabinoidi zdravilno vrednost. Raziskava o zdravilih na osnovi konoplje, ki so jo leta 2016 izvedli Mikael A. Kowal et al., je zajela nadzorovane klinične študije zdravil na osnovi konoplje, izvedene v letih od 2010 do 2014, ki so sledile raziskavam, ki so jih objavili Hazekamp in Grotenhermen (2010) ter Ben Amar (2006). Uporabili smo enako metodologijo kot te tri predhodne raziskave za obdobje, ki je sledilo – od 1. januarja 2015 do 31. decembra 2016. Izvedli smo sistematično iskanje v znanstveni podatkovni bazi PubMed, ki jo gosti ameriška Nacionalna medicinska knjižnica ZDA (U.S. National Library of Medicine). Ta podatkovna baza zajema okrog 20 milijonov znanstvenih publikacij s področja bioloških znanosti in biomedicinskih podatkov. Iskanje se je osredotočilo na klinične študije, ki so bile randomizirane, (dvojno) slepe in nadzorovane s placebom. Ključne besede, ki so bile uporabljene, so bile: konoplja, marihuana, hašiš, kanabinoid(i), tetrahidrokanabinol, kanabidiol, THC, CBD, dronabinol, marinol, nabilon, nabiksimoli in Sativex. Identificiranih je bilo 45 nadzorovanih študij, ki so vrednotile zdravilne učinke kanabinoidov. V končni izbor smo uvrstili le ustrezno nadzorovane klinične študije. Čisti THC in nekaj njegovih analogov je pokazalo pomembne terapevtske prednosti pri lajšanju kroničnih nevropatskih bolečin, pri slabosti in bruhanju ter pri spodbujanju teka pri bolnikih z rakom oziroma aidsom. Poleg THC se kot drug koristen kanabinoid v terapevtske namene kaže CBD (kanabidiol).
Ključne besede: kanabinoidi, konoplja, terapevtski potencial, nadzorovane klinične študije, učinkovitost, varnost, kanabidiol.

Hemp (Cannabis sativa subsp. sativa L.) was grow as an annual crop for food and fiber for many centuries around the world, and so is today. Hemp seed contains a wide range of vitamins in minerals and is a good source of essential unsaturated fatty acids and essential amino acids. In the second part of the lecture, the results of a research study on cannabinoid content in hemp in Slovenia from 2017 will be presented.

Cancer is multimodal disease that could not be targeted by a single therapy, as has been demonstrated in particular in brain tumors.  Among these, glioma in its most advanced stage, the glioblastoma, is highly aggressive and therapeutically non-responsive tumor in humans. The modern treatment modalities, surgical removal, irradiation and chemotherapy are supported or even replaced by adjuvant treatment strategies, including immunotherapy and more holistic approach by natural substances, e.g. flavonoids, phenols, terpenes and cannabinoids.

The evidences have accumulated that cannabinoids inhibit growth in invasiveness of tumor cells and continues to be solidified, based on cellular experiments in vitro and in animal studies, but unfortunately still not sufficiently from human clinical studies. In addition, due to large genetic micro-heterogeneity and further epigenetic transformation of recurrent glioblastoma, it is hard to predict how an individual patient will respond to cannabinoid treatment.  Here, we aimed to examine the individualized patients'tumor response to the two most active cannabinoids, i.e. THC ad CBSD in terms of their potential synergistic effects on cell viability and apoptosis. As glioblastoma are classified intothree subtypes that differ significantly in their genetic fingerprints, patients’ survival rate and chemo- and radio-resistance, we are correlating their in vitro response to the individual tumor subtype. In addition, the levels ofat leasttwo cannabinoids CB1 and CB2 differ significantlyamong the patients, so we also need to explore, weather these may determine the response to the tumors in vitro more or less than to the tumor subtype. These data should reveal how to personalize potential cannabiboids' therapy to be most effective.

The lecture briefly summarizes the history of cannabis in treatment, the discovery of cannabinoids and the entire endocannabinoid system. Then it deals with the treatment of cancer, autism and female diseases and importance of correct chemotypes of this plant in the treatment of the patient.

Legal cannabis is now a reality in Canada as it soon will be for many other countries around the world. But what does this mean for the medical user, through the transition to legality and beyond?

There was a time in Canada that people would go to jail for possession of cannabis, but it was only through precedent setting court cases, persons with AIDS or epilepsy, for example, standing up for their rights, that cannabis is now legal. And, of course, this was backed by the mushrooming scientific evidence that had been accumulating since the discovery of the receptor that binds thc and the subsequent endocannabinoid system.

This major medical find (as big as DNA and insulin), has received much attention in the past two decades and there is still much more to learn. Now that cannabis is legal in Canada we have an opportunity to study its effects, with groups of people that did not present with prohibition.

We are currently beginning project with the Mohawk Nation in Ontario, Canada. The organization is called the National Indigenous Medical Cannabis Association, that has been distributing cannabis to a membership for a number of years.

Nimca, has full laboratory capabilities (HPLC, GC/MS) to quality control and standardize its cannabis. The purpose is to use the Nimca dispensary (Legacy 420) as a hub for a harm reduction study using cannabis to curb the number of opiate related deaths, that is currently epidemic in Canada, particularly among the indigenous.

In this presentation we will outline our reasons for using cannabis as a harm reduction agent, its relationship to opiate use, pain and opiate withdrawal. And how we are putting cannabis medicine to work in the legal environment.

Highlight certain observations based on the relatively recent statement on the issue by the World Health Organization. Observations in context and discuss the role of the medical establishment in the assimilation of cannabis based products into the field of standard medicine.

Any health-related decisions should be made in partnership between the patient and the doctor. Both parties take steps to participate in the process of decision making. There is growing evidence that the public want more involvement in treatment decisions. Shared decisions may be harder to achieve when the patient is faced with a shocking, serious or life threatening diagnosis.During recent years, more and more clinical research affirms that cannabis can safely and effectively alleviate symptoms of serious and chronic medical conditions. Nevertheless, many patients, their relatives and caregivers are still hesitate, whether try is or not try a cannabis as a valuable remedy. They are routinely apply for this to their health care providers, but, unfortunately, despite all previous and, most important, recent achievements in this area, majority of physicians are unable to advise their patients anything clear and prefer to avoid or even ignore any discussion on this topic.

In contemporary patient-centered care, an individual’s specific health needs (including cannabis-based therapy) and desired health outcomes are the driving force behind all health care decisions. Facing the further ongoing and increasing progress in cannabinoid medicine, responsible clinicians should educate themselves in this are in order to be able to maintain professional dialog and to practice well-balanced comprehensive shared decision making with their patients upon their demands and even to initiate a cannabis-based treatment to suitable for it patients.

Mitochondria are dynamic and complex cellular organelles that are involved in a wide range of cellular events and are essential for tissue adaptation, survival, death, and renewal. In addition to their important role in energy metabolism making them popularly known as the cellular powerhouse, mitochondria are malleable structures that are also intimately involved in controlling cellular redox status, cellular signaling, calcium homeostasis, and cell death and autophagy processes. Thus, mitochondria have emerged from simply being the powerhouse of the cell to being at the forefront of numerous research avenues. In fact, mitochondrial perturbations evoked by physiological and pathological stimuli have been shown to contribute towards the pathogenesis of many diseases and mitochondrial research now constitutes a very significant and ever-expanding research area. It is now understood that mitochondria and their associated pathways may represent areas for the development of preventive and therapeutic strategies to potentially mitigate diseases/disorders such as diabetes, obesity, neurodegeneration, epilepsy, sarcopenia and many others. Cannabis sativa L. with its myriad of bioactive molecules is showing very promising potentials to modulate the function and dysfunction of mitochondria, thereby enhancing heath and positively influencing disease progression. Understanding how omega 3 and cannabinoids alter the cellular powerhouse-mitochondria is also adding substantially to our understanding of how these molecules effect our biochemistry.

As population gets older, healthcare systems and governments are seeking for solutions to reduce healthcare costs and improve the quality of life of patients. With more than 10 years of clinical and research experience, and as the first to start treating older adults with cannabis, Inbal provides a very broad and interesting prospective regarding medical cannabis and its place as part of the overall medical care of patients.   

• Our experience - Hadarim Project and how did it all start.
• NiaMedic - Research & Healthcare.
• Geriatric medicine and medical cannabis.
• Research - results and insights.