Congress Program

National University of Ireland (NUI) Galway, Ireland
Cannabidiol: Pharmacology and Therapeutic Potential
David P. Finn
Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, National University of Ireland Galway, University Road, Galway, Ireland.
Recent years have witnessed intense interest in cannabidiol (CBD) as a therapeutic for a variety of disorders including, but not limited to, epilepsy, multiple sclerosis, chronic pain, inflammatory disorders, anxiety, psychosis, sleep disorders and depression. Patients worldwide are using a large array of different CBD products including oils, creams, patches, oral capsules and inhaled extracts amidst some uncertainty and controversy on the efficacy, safety and appropriate use of CBD for therapeutic purposes. CBD is a phytocannabinoid found in the cannabis plant. It has low affinity for, and activity at, the cannabinoid receptors, CB1 and CB2, but there is some evidence for negative allosteric modulation of cannabinoid receptors. CBD binds to a number of other receptors and channels and has a complex pharmacology. It lacks the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC), but clearly acts within the brain given its anti-epileptic, anxiolytic and possible anti-psychotic effects. This talk will provide an overview of the pharmacology of CBD, its sites and mechanisms of action, pharmacokinetics, efficacy in preclinical models and clinical trials, and its side-effect profile. The talk will have a particular emphasis on chronic pain, given the interest and controversy around this indication. Preclinical studies support the contention that CBD may be a promising novel analgesic agent. Further clinical research and trials with CBD are warranted, alongside continued preclinical elucidation of its targets and mechanisms of action.

McGill University, Canada

Sheba Medical Center, Israel

University of Turin Medical School and Plateau Rosà Hypoxia Medicine, Italy/Switzerland
Placebo effects represent one of the most important confounding variables in the design and interpretation of clinical trials, thus their understanding is today a priority in biomedical research. In this talk, I will present some examples of how recent research and insights into the neurobiological mechanisms of placebo effects provide some interesting information that may help better design and interpret clinical trials. This is particularly important for trials on cannabis, which is quite an unexplored field of clinical research. First, patients’ expectations have been found to be the main mediators of placebo effects, thus their assessment should be the rule in any clinical trial. Second, previous exposure to active treatments may lead to substantial placebo responses, thus the history of pre-trial pharmacological and non-pharmacological treatments should be assessed very carefully. Third, communication across the participants of a trial has been found to affect several outcome measures, thus communication across participants should be avoided. Fourth, today we can identify and create placebo responders and non-responders in the lab by using both learning procedures and genetics, which indicates that placebo effects can be manipulated. These four examples suggest that this new scientific knowledge may have profound implications for clinical trials, including cannabis trials, thus moving trial design from speculative to evidence-based.

University of Bern, Switzerland
Jürg Gertsch
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland
The botanical drug cannabis flos has a unique popular status as being a potent recreational drug and bona fide universal remedy (panacea). Generally, cannabinoids exert therapeutic effects in a broad range of pathophysiologies related to inflammation, pain, neuropsychiatric, metabolic and stress-related conditions in preclinical animal models. However, the translation of such data to humans still lacks an evidence-based foundation. While undoubtedly cannabis products have a pharmaceutical potential in very diverse therapeutic settings, it remains unclear how different patients react to the complex cannabimimetic pharmacology and how this affects the outcome. Motivated by the booming cannabis manufacturing industry and the increasing worldwide self-therapy by patients, there are cumulative accounts about broad therapeutic effects of cannabis and legal cannabinoids like cannabidiol (CBD) beyond statistical evidence. The numerous affirming anecdotal reports by patients pose a challenge to physicians and legal authorities. Given the recent insight that the endocannabinoid system is mediating, at least in part, a placebo effect, psychoactive cannabis and cannabinoids could exert complex neuropharmacological actions. As will be outlined, placebo effects may play a role in the broad palliative and therapeutic effects of medical cannabis unprecedented by other phytopharmaceuticals. The urgent need for human biomarkers to improve clinical trials will be discussed.

Technical University Munich, Germany

Department of Health, Australia
Implementation of a Regulatory Framework for Medicinal Cannabis – Evidence Reviews, Clinical Guidance and Patient Access – the Australian Experience
Adjunct Professor John Skerritt, Deputy Secretary, Australian Department of Health
Australian Government policy treats medicinal cannabis products as prescription medicines, and several steps have been taken to improve patient access. These included introduction of a regulatory scheme for cultivation and manufacture as well as patient access schemes. Under an “Authorised prescriber” route prescribers are approved for a particular product for set of conditions while “Special Access” Schemes (SAS) enable individual patient access. Typically online SAS applications require review (in under 48 hours) by departmental health care professionals since these products have not been assessed for safety, quality and efficacy. Australian state and territory laws also require assessment of the doctor and patient for diversion or dependency risks for THC-containing medicines.
Our department has worked with universities, clinical and patient groups on reviews of the efficacy evidence for medicinal cannabis components and products in epilepsies, multiple sclerosis, chemotherapy-induced nausea and vomiting, pain types and palliative care. Annotated bibliographies of relevant publications as well as prescriber and patient guidance documents that provide information about the current state of clinical evidence were first published in December 2017 and are currently being updated, along with information on clinical trials of medicinal cannabis products. They are provided on the TGA website along with other educational and information resources.
The ultimate goal is to have a wider range of medicinal cannabis products available as market authorised medicines following review of their quality, safety and efficacy for the proposed indication/s.

University Göttingen, Germany

McGill University, Canada

Tel Aviv Medical Center, Israel

Kantonsspital St. Gallen, Switzerland
Cannabis-Based Medicines in Neurology – Beyond Spasticity in Multiple Sclerosis
Basic research has revealed a huge potential for cannabinoid-based medications. This is particular the case for neurological diseases. In general one may distinguish between symptomatic treatment for symptom control and disease – modifying treatments. The latter is especially relevant for neurodegenerative diseases such as amyotrophic lateral sclerosis.
While for spasticity numerous well-conducted studies have been performed and in addition CBD-based medications have been approved for certain forms of epilepsy for most other possible indications clinical trials are lagging behind the basic science.
The presentation will review current knowledge of clinical trials for neurological symptoms beyond spasticity and highlight ongoing research in neurodegeneration.

National Drug and Alcohol Research Centre, Australia

University of Lethbridge, Canada
Neuropathic pain is a chronic pain condition caused by a lesion or disease of the somatosensory nervous system. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia and central poststroke pain. Several randomized placebo-controlled trials (RCTs) of 3 to 15 weeks-duration have examined the effect of sativex, an oromucosally delivered spray prepared from cannabis sativa extract containing mainly tetrahydrocannabinol (THC) and cannabidiol (CBD), and synthetic THC for the treatment of neuropathic pain. These trials show lack of clinical relevant effects. Because of the negative results, potential misuse, and possible long-term health risks, the Special Interest Group of Neuropathic Pain (NeuPSIG) provided a weak recommendation against the use of cannabis-based medicinal products for neuropathic pain. Inhaled cannabis has shown some effect for chronic neuropathic pain in short-duration RCTs (hours or days) and is associated with psychological and cognitive side effects. Few drugs that potentiate the action of endocannabinoids have been tested and studies have so far not provided consistent evidence of effect for neuropathic pain. Currently, there is no evidence for a long-term clinical relevant effect or safe use of cannabis-based medicinal products or medicinal cannabis for the treatment of chronic neuropathic pain.

Sheba Medical Center, Israel

King's College London, UK

Ministry of Health, Luxembourg

Ministry of Health, Luxembourg
Medicinal cannabis is available in Luxembourg since February 2019 for 3 restricted medical indications in the context of a 2-year pilot phase.
We will present the context of medicinal Cannabis in Luxembourg and an overview of the data collected after one year.
We will draw the first lessons learned from 1-year implementation, highlighting the challenges we face for the end of the pilot phase and then present our tools and strategy for the management of potential abuse and misuse of medicinal cannabis.

Imperial College Healthcare NHS Trust, UK
The Government announced in mid-2018 from 01 November 2018 that 80,000 doctors in the UK would be able to prescribe medicinal cannabis. This was preceded by a communication from the Chief Medical Officer that cannabis is no longer a Schedule A drug. Understandably there was a lot of interest from the patients who had benefit from using cannabis and were keen on getting the prescription on the NHS. The various Royal Colleges and other stake holders representing various medical specialities issued position statements indicating the paucity of evidence for medicinal cannabis based on robust clinical trials and called for better quality clinical trials to gather evidence for the use of medicinal cannabis. In November 2019, NICE brought out their recommendations on chemotherapy-induced nausea & vomiting, treatment resistant epilepsy, spasticity in multiple sclerosis and chronic pain. The general feeling was that there were not enough clinical trials on the safety and efficacy for cannabis-based medicinal products that met the rigorous criteria NICE stipulates for their guidance. There are research recommendations for medicinal cannabis and hence clinical trials are underway in the UK. The British Pain Society in its updated position statement recognises that there could be a role for cannabis-based medicinal products in the management of chronic pain, but recommends that this should be part of a clinical trial and that data should be collected to evaluate the safety and efficacy profile.

Federal Institute for Drugs and Medical Devices, Germany
Background Medical doctors who prescribe cannabis medicines at the expense of the German statutory health insurance are obliged to take part in a non-interventional survey, which runs until 31 March 2022.
Objectives The survey serves the collection and evaluation of anonymized treatment data.
Methods The transmission of the data for the survey takes place via an online portal operated by the BfArM (Federal Institute for Drugs and Medical Devices). The first data transmission takes place after a treatment period of one year or, if the treatment discontinued before the end of one year, directly after discontinuation of therapy. Demographic data and information on the treated disease or symptoms, previous treatment, co-treatment, adverse reactions, treatment success and change of quality of life are evaluated.
Results Most frequently, the symptom “pain” was treated, followed by “spasticity” and “anorexia/wasting”. The observed adverse reactions correspond with those listed in the product information for the two cannabis-based proprietary medicinal products, Sativex® and Canemes®. In most cases, insufficient efficacy was the reason for a discontinuation of treatment.
Conclusion Preliminary evaluation of the treatment success supports the use of cannabis-based medicines as individual therapeutic trial, last-line, in non-nociceptive pain and spasticity. The most frequent side effects concern vigilance and are therefore highly relevant.
References Schmidt-Wolf, G. & Cremer-Schaeffer, P. Begleiterhebung zur Anwendung von Cannabisarzneimitteln in Deutschland – Zwischenauswertung. Bundesgesundheitsbl (2019) 62: 845. https://doi.org/10.1007/s00103-019-02968-0
Cremer-Schaeffer, P., Schmidt-Wolf, G. & Broich, K. Cannabisarzneimittel in der Schmerztherapie – Zwischenauswertung der Cannabisbegleiterhebung hinsichtlich der primär behandelten Symptomatik Schmerz. Schmerz (2019) 33: 415. https://doi.org/10.1007/s00482-019-00399-z

New South Wales Cannabis Medicines Advisory Service, Australia
Background
The New South Wales (NSW) Cannabis Medicines Advisory Service (CMAS) is an Australian State government-funded medical advisory service. To our knowledge, this service is the first of its kind in the world. The NSW CMAS provides free clinical advice and guidance to NSW-registered health professionals regarding:
- Information about cannabis medicines (formulations, dosing, potential drug interactions)
- Advice tailored to patient-specific clinical contexts
- Current scientific evidence, to support prescribing decisions
- Guidance, tools for monitoring potential therapeutic and adverse effects
- Information on open clinical trials using cannabis medicines
Aims
- Outline service methodology and resources provided to clinicians considering prescribing a cannabis medicine.
- Describe service enquiry themes, trends and outcomes.
Methods
Following the provision of a comprehensive clinical history, NSW CMAS performs a patient-specific literature review, to determine what evidence currently exists for the proposed indication and to highlight important clinical considerations and monitoring strategies. NSW CMAS supports health practitioners during every step of the process from compilation of the literature, to prescribing processes and subsequent follow-up.
Results
The first data regarding the effects of Medicinal Cannabis in NSW Australia, based on an interim audit of enquiry trends, will be presented. De-identified data that will be analysed include but are not limited to clinical indications and product formulations being prescribed in clinical practice.
Conclusion
The NSW CMAS service model has played a key role in the translation of cannabis medicine research into clinical practice in NSW, Australia. The model focuses on best patient care practices, patient safety, and evidence-based clinical practice. The NSW CMAS data provides an innovative and much-needed insight into how prescribed cannabis medicines are being used in real-world settings.

National Institute of Health, Italy

Copenhagen Research Center for Mental Health - CORE and University of Copenhagen, Denmark
In January 2018, a pilot program was launched in Denmark with medicinal cannabis. We will present results from the ongoing evaluation of this program.
The pilot program is being evaluated with a triangulation of methods. Patients who have redeemed a prescription of medicinal cannabis have been identified from the nationwide Danish registers. A random selection of nine patients have been included for qualitative interviews. A larger selection have been randomly selected for quantitative interviews and surveys. These have been matched using propensity score matching to controls who have not used medicinal cannabis, but who have received other types of medication for the same disorders. Finally, all patients redeeming at least one prescription for medicinal cannabis, and matched controls, have been tracked in the nationwide Danish registers.
Results will be ready in April 2020, as per demand from the Ministry of Health which funded the evaluation.
The triangulation of methods we apply allow for the best possible evaluation of the Danish pilot program. The register-based assessment is free from selection bias, but is limited regarding the depth of information; the quantitative interview-and-survey assessment comes with a potential selection bias, but has a thorough level of information; finally, the qualitative assessment is not necessarily generalizable, but provides in-depth information which could not be obtained in a structured or even semi-structured manner.

Monash University, Australia
Whether or not cannabinoids represent an effective strategy to reduce opioid use and opioid-related harm, either at the individual or population level, has been the topic of much debate in recent years. This presentation will summarise the results of two reviews that synthesise what is known about the potential for cannabinoids to reduce opioid-related harm. The first systematic review and meta-analyses examined evidence from 28 pre-clinical and clinical studies to determine whether cannabinoids may have an opioid-sparing effect. Preclinical studies consistently demonstrated synergistic effects of concurrent cannabinoid and opioid administration. Yet, the findings from clinical studies were inconsistent. A second comprehensive review examined the epidemiological and ecological evidence from 25 studies to consider whether cannabis use and availability was associated with reduced opioid-related harms. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and related harms, although important methodological weaknesses were identified, and recent research has produced conflicting results. Taken together, this work may help identify where further clinical research could be conducted to inform the debate as to whether cannabinoids may have an important role in reducing opioid use and harm from either a clinical or population health perspective.

Tel Aviv Medical Center, Israel

Clinic Horsted, Denmark
North American Perspective – Mary-Ann Fitzcharles, Canada
European Perspective – Frank Petzke, Germany
Australian Perspective – TBD
Israeli Perspective – Silviu Brill, Israel
Danish Perspective – Tina Horsted, Denmark