The 3rd International Annual Congress on

Controversies on

Cannabis-Based Medicines

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.

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.

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.

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

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.

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.

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.

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