Medical cannabis

Contact

Mr Mikael Sodergren
m.sodergren@imperial.ac.uk

0203 313 8542 

What we do

Cannabis-based medicines were rescheduled under UK law in 2018 allowing doctors to prescribe these treatments to patients for a wide range of conditions. We are interested in the evaluation and development of novel cannabinoid therapies targeting: 1) inflammation & cancer, with a current focus on pancreatic ductal adenocarcinoma (PDAC) and 2) acute/post-surgical, neuropathic and cancer-related pain. We are also interested in clinical outcomes-based research and the use of Real World Evidence (RWE) in cannabinoid drug development.  

Inflammation & Cancer 
We investigate the mechanism of action of cannabinoids and relevant compounds at a molecular level through the study of relevant oncological signalling pathways. We also evaluate the efficacy and interaction of cannabinoids in combination with cytotoxic and immune-modulating therapies for the treatment of cancer.  

Pain 
We aim to test the efficacy and potency of a range of novel cannabinoid related compounds, including those that target receptors such as the cannabinoid receptors CB1 and CB2, and to develop new analgesic treatments for use in the clinic. These novel agents are evaluated using in vitro models of hypersensitivity in cultured neurons from rodent and human sensory ganglia.  We have recently shown that Cannabidiol (CBD) at low doses, corresponding to plasma concentrations observed physiologically, inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization.  CBD also facilitated calcineurin-mediated TRPV1 inhibition.  These mechanisms may underlie nociceptor desensitization, and the therapeutic effect of CBD in animal models and patients with acute and chronic pain. 

Real World Evidence
We use health data sourced from non-interventional studies, registries, electronic health records and administrative datasets to broaden and streamline the process of evidence generation for cannabis-derived medicinal product development. We evaluate the use of RWE as an additional tool in the drug development pipeline.

Why it is important

Inflammation & Cancer 
Cannabinoids have shown merits in not only alleviating the unwanted side-effects of cancer treatments but have also displayed promising pre-clinical antitumour properties, through modulating processes which include apoptosis and autophagy. Co-administration of cannabinoids with cytotoxic therapies may enhance the potency of these outcomes. In cancers that are refractory to systemic therapy, these synergistic effects warrant further investigation to select combinations for clinical translation and evaluation.  

Pain 
There is an increasing unmet clinical need for several types of pain treatment. Many current pharmacological treatments have limited efficacy and significant side-effects.  Chronic neuropathic pain represents a great need - between 4 and 12 patients are treated before a single patient reports 50% pain relief, and clinical trials in chemotherapy-induced painful neuropathy have been disappointing.  Advances in the non-opioid treatment of acute and chronic pain, such as with novel cannabinoids, are therefore urgently needed. 

Real World Evidence
Access to cannabis-based medicinal products has increased globally as more countries have revised scheduling laws however one of the main barriers for patient access remains a paucity of high-quality clinical evidence. RWE can provide immediate impact on clinical care, inform well-conducted RCTs and contribute to market authorisation dossiers.

How it can benefit patients

Inflammation and Cancer 
Understanding the specific molecular and biological actions of cannabinoids in the context of inflammation and cancer will help to reveal novel targets for therapeutic interventions. The study of combination treatments will provide data to accelerate translation to clinical trials.     

Pain 
Up to 50% of all cancer patients experience pain, and as many as 90% with advanced cancer live with chronic debilitating pain that can be difficult to treat.  The pain contributes significantly to increased morbidity and reduced quality of life, characterised by fatigue, depression, insomnia, and weight loss.  The evaluation and development of cannabinoid compounds may lead to novel therapies which provide better pain relief and improve the quality of life in patients with chronic pain conditions. 

Real World Evidence
Cannabis-based medicinal products are a complex range of pharmaceuticals which pose challenges to traditional pathways of drug development and translation. The Medicines and Healthcare Products Regulatory Agency (MHRA) has issued new guidance to confirm that RWE can be used to support regulatory approval, helping to bring medicines to patients who need them in a quicker and more cost-effective way.

Summary of current research

Inflammation and Cancer 

 In vitro:  

  • Pharmacological evaluation of cannabinoids in PDAC cell lines by analysis of cell viability, cytotoxicity, cell proliferation, cell death and cell cycle state 
  • Identification of oncological signalling pathways and targets which maybe upregulated or downregulated using qt-PCR, western blots and FACS analysis 
  • Defining and comparing molecular pathway changes of cannabinoid treatment in chemotherapy resistant versus chemotherapy sensitive cell lines  
  • Investigate synergistic effects of cannabinoids in combination with standard cytotoxic therapy using Combenefit analysis 

In vivo:  

  • Investigate the effects of single agent cannabinoid therapy and in combination with cytotoxic treatment in syngeneic PDAC mouse models by analysing changes in tumour burden and survival  
  • Gene expression profiles of whole tumour biopsies is performed using a specific panel of immune genes and its reduced versions using nCounter platform (NanoString Technologies). This analysis provides an extensive view of immune microenvironment changes and the mechanisms associated with them. 
  • Quantifying and analysing the immune landscape of cannabinoid treatment by immunohistochemistry (IHC) and FACs analysis using a panel of T cells, B cells, neutrophils and macrophages  

Pain 

  • We model specific disease-related conditions (e.g. cancer chemotherapy with oxaliplatin or Ara C, co-cultures of sensory neurons with cancer cells, and metabolic conditions such as uraemia).  These provide in vitro models of pain, to enable a “clinical trial in a dish”.  The neurons are stimulated with a “painful” stimulus, such as capsaicin, that activates the pain receptor TRPV1.   
  • We are using these in vitro models to evaluate cannabinoids as analgesic agents, which can be compared with the effects of endocannabinoid molecules Anandamide and 2-Arachchidonyl glycerol.   
  • We have established target validation studies of the CB2 receptor, described its histological localization in rats and humans, and observed increased CB2 expression in painful human neuromas.  We also assayed the inhibitory effect of CB2 agonists in blocking capsaicin mediated calcium influx in nociceptors, via the TRPV1 receptor.  

Real World Evidence

  • Evaluate terminology to define cannabis-based medicines accurately and a global, common dataset for reporting of clinical outcomes as RWE
  • We use large registry-based datasets from the UK to analyse clinical outcomes for several different conditions following the initiation of cannabinoid therapies
  • Use RWE to investigate cannabinoid interventions in chronic disease states with identification of causative and therapeutic components
  • Investigate novel methods of multi-modal RWE data integration and analysis

Additional information

Funders & Related Centres
Funders
Related Centres

 

Collaborators
External
 
Internal
Clinical trials

We are in the development phase for a randomised controlled trial evaluating cannabis-based medicinal products in the treatment of acute post-operative pain, nausea and vomiting. The first stage of this process which involves a comprehensive patient and public involvement program has been completed and published in Cannabis and Cannabinoids Research.

There are a number of other ongoing translational projects and we welcome industry/academic collaborations to accelerate this process. These include a collaborative protocol for a placebo-controlled double-blind Phase II virtual trial with a pilot & feasibility phase to assess the efficacy and safety of cannabidiol (CBD) for the treatment of home self-isolating health care worker patients with mild COVID-19 .

PhD students

When we have funding for PhD studentships, we advertise them through central channels such as Find a PhD. Information is also available on the Surgery and Cancer study page. If no studentships are currently advertised, please get in touch with the group lead with proposed project titles to discuss further.   

Current PhD Students
  • Nagina Mangal 
 
Publications

Journal publications

  1. Nimalan D, Kawka M, Erridge S, Ergisi M, Harris M, Salazar O, Ali R, Loupasaki K, Holvey C, Coomber R, Platt M, Rucker JJ, Khan S, Sodergren MH. UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes. J Cannabis Res. 2022 Jan 4;4(1):3. doi: 10.1186/s42238-021-00114-9.
  2. Harris M, Erridge S, Ergisi M, Nimalan D, Kawka M, Salazar O, Ali R, Loupasaki K, Holvey C, Coomber R, Usmani A, Sajad M, Hoare J, Rucker JJ, Platt M, Sodergren MH.
    UK Medical Cannabis registry: an analysis of clinical outcomes of medicinal cannabis therapy for chronic pain conditions. Expert Rev Clin Pharmacol. 2021 Dec 31:1-13. doi: 10.1080/17512433.2022.2017771.
  3. Ergisi M, Erridge S, Harris M, Kawka M, Nimalan D, Salazar O, Loupasaki K, Ali R, Holvey C, Coomber R, Platt M, Rucker JJ, Sodergren MH. UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder. Expert Rev Clin Pharmacol. 2021 Dec 23. doi: 10.1080/17512433.2022.2020640.
  4. Anand U, Oldfield C, Pacchetti B, Anand P, Sodergren MH. Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons. J Pain Res. 2021 Nov 24;14:3603-3614
  5. Banerjee R, Erridge S, Salazar O, Mangal N, Couch D, Pacchetti B, Sodergren MH. Real World Evidence in Medical Cannabis Research. Ther Innov Regul Sci. 2022 Jan;56(1):8-14
  6. Hammond S, Erridge S, Mangal N, Pacchetti B, Sodergren MH. The Effect of Cannabis-Based Medicine in the Treatment of Cachexia: A Systematic Review and Meta-Analysis. Cannabis Cannabinoid Res. 2021 Dec;6(6):474-487
  7. Kawka M, Erridge S, Holvey C, Coomber R, Usmani A, Sajad M, Platt MW, Rucker JJ, Sodergren MH. Clinical Outcome Data of First Cohort of Chronic Pain Patients Treated With Cannabis-Based Sublingual Oils in the United Kingdom: Analysis From the UK Medical Cannabis Registry. J Clin Pharmacol. 2021 Dec;61(12):1545-1554
  8. Mangal N, Erridge S, Habib N, Sadanandam A, Reebye V, Sodergren MH. Cannabinoids in the landscape of cancer. J Cancer Res Clin Oncol. 2021 Sep;147(9):2507-2534
  9. Erridge S, Salazar O, Kawka M, Holvey C, Coomber R, Usmani A, Sajad M, Beri S, Hoare J, Khan S, Weatherall MW, Platt M, Rucker JJ, Sodergren MH. An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients. Neuropsychopharmacol Rep. 2021 Sep;41(3):362-370
  10. Anand U, Pacchetti B, Anand P, Sodergren MH. Cannabis-based medicines and pain: a review of potential synergistic and entourage effects. Pain Manag. 2021 Apr;11(4):395-403
  11. Anand, U, Jones B, Korchev Y, Bloom S.R, Pacchetti B, Anand P, Sodergren MH. (2020) CBD Effects on TRPV1 Signaling Pathways in cultured DRG neurons.  J Pain Res 13; 2269–2278. 
  12. Erridge S, Mangal N, Salazar O, Pacchetti B, Sodergren MH. Cannflavins - From plant to patient: A scoping review. Fitoterapia. 2020 Oct;146:104712 
  13. Tagne AM, Pacchetti B, Sodergren MH, Cosetino M, Marino F. Cannabidiol for Viral Diseases: Hype or Hope? Cannabis Cannabinoid Res. 2020 Jun 5;5(2):121-131 
  14. Erridge S, Miller M, Gall T, Costanzio A, Pacchetti B, Sodergren MH. A Comprehensive Patient and Public Involvement Program Evaluating Perception of Cannabis-Derived Medicinal Products in the Treatment of Acute Postoperative Pain, Nausea, and Vomiting Using a Qualitative Thematic Framework. Cannabis Cannabinoid Res. 2020 Feb 27;5(1):73-80 
  15. Anand U, Otto WR, Casula MA, et al. The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. Neurosci Lett. 2006; Neurosci Lett. 2006;399 (1–2):51–56. 
  16. Anand U : Mechanisms and Management of cancer pain. In The Cancer Handbook. Volume 2 Chapter 98. 2 edition. Edited by: Alison, MR . Publishers John Wiley and Sons Ltd. Chichester; 2007. 
  17. Anand U, Otto WR, Sanchez-Herrera D, et al. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain. 2008;138(3):667–680.399 (1–2):51–56.  
  18. Anand U, Otto WR., Bountra C, Chessell IP, Sinisi M, Birch R, Anand P.  Cytosine arabinoside affects the heat and capsaicin receptor TRPV1 localisation and sensitivity in human DRG neurons. J Neurooncol. 2008; 89 (1): 1-7. 
  19. Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev. 2009;60(1):255–266.  
  20. Anand U, Otto WR, Anand P. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons. Mol Pain 2010; 6:82. 
  21. Anand U, Korchev Y, Anand P. The role of urea in neuronal degeneration and sensitization:an in vitro model of uremic neuropathy. Mol Pain. 2019; 15: 1-12. 

Conference abstracts 

  1. Kawka M, Erridge S, Holvey C, Coomber R, Usmani A, Sajad M, Platt MW, Rucker J, Sodergren MH. Clinical outcome data of first cohort of chronic pain patients treated with cannabis-based sublingual oils in the United Kingdom – Analysis from the UK Medical Cannabis Registry. Oral presentation and abstract at 93rd European General Practice Research Network Conference (EGPRN), November 2021, Halle, Germany
  2. S Hammond, S Erridge, N Mangal, B Pacchetti, M H Sodergren. The Effect Of Cannabis-Based Medicine In The Treatment Of Cachexia: A Systematic Review And Meta-Analysis. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  3. S Erridge, N Mangal, B Pacchetti, M H Sodergren. Cannflavins – From plant to patient: a scoping review. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  4. Mangal N, Lawrence P, Ragulan C, Desai C, Pacchetti B, Reebye V, Sadanandam A, Sodergren MH. Therapeutic Effect of Cannabidiol in Combination with Chemotherapy in Pancreatic Ductal Adenocarcinoma. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids.
  5. Erridge S, Salazar O, Kawka M, Holvey C, Coomber R, Usmani A, Sajad M, Beri S, Hoare J, Khan S, Weatherall MW, Platt M, Rucker JJ, Sodergren MH. An Initial Analysis of the UK Medical Cannabis Registry. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  6. Ergisi M, Erridge S, Harris M, Kawka M, Nimalan D, Salazar O, Loupasaki K, Ali R, Holvey C, Coomber R, Usmani A, Sajad M, Beri S, Hoare J, Khan S, Weatherall MW, Platt M, Rucker JJ, Sodergren MH. An Updated Analysis of General Clinical Outcome Measures Across Patient Groups in the UK Medical Cannabis Registry. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  7. Ergisi M, Erridge S, Harris M, Kawka M, Nimalan D, Salazar O, Loupasaki K, Ali R, Holvey C, Coomber R, Platt M, Rucker JJ, Sodergren MH. UK Medical Cannabis Registry: An Analysis of Clinical Outcomes of Medicinal Cannabis Therapy for Anxiety. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  8. Harris M, Erridge S, Ergisi M, Nimalan D, Nimalan D, Salazar O, Ali R, Loupasaki K, Ali R, Holvey C, Coomber R, Usmani A, Sajad M, Rucker JJ, Platt M, Sodergren MH. Exploring Quality of Life Outcomes of Chronic Pain Patients from The UK Medical Cannabis Registry. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  9. Nimalan D, Kawka M, Erridge S, Ergisi M, Harris M, Salazar O, Loupasaki K, Ali R, Holvey C, Coomber R, Platt M, Rucker JJ, Khan S, Sodergren MH. Analysis of Palliative Care Patients from the UK Medical Cannabis Registry: Initial Experience and Outcomes. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  10. Erridge S, Coomber R, Sodergren MH. Medical Cannabis, Over-The-Counter CBD And Public Opinion in the United Kingdom. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  11. Mangal N, Reebye V, Pacchetti B, Sadanandam A, Sodergren MH. Ceramide synthase isoforms are upregulated by cannabidiol resulting in cytotoxic effect in pancreatic ductal adenocarcinoma. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  12. Anand U, Pacchetti B, Anand P, Sodergren MH. Investigating cannabinoid entourage effects in cultured DRG neurons. Abstract ICRS 2021-The 31st Annual ICRS Symposium on the Cannabinoids
  13. A Furgiuele, A M Tagne, B Pacchetti, M H Sodergren, M Cosentino, F Marino. Effect of Cannabidiol on Human Peripheral Blood Mononuclear Cell and Relevance for Immunomodulation in Multiple Sclerosis. IACM 10th Conference on Cannabinoids in Medicine. 
  14. F Marino, A Luini, M Legnaro, B Pacchetti, M H Sodergren, M Cosentino. Cannabidiol modulates human polymorphonuclear leukocyte functions: experimental evidence and clinical implications. Abstract and Oral communication - 19th Annual National Congress of the Italian Society of Neuroscience (SINS)
Further information & industry

Our researchers

Mr Mikael Sodergren

Mr Mikael Sodergren
Principal investigator

Dr Uma Anand

Dr Uma Anand
Post-Doc Fellow

Dr Simon Erridge

Dr Simon Erridge
Clinical Research Fellow

Dr Vikash Reebye

Dr Vikash Reebye
Senior Research Fellow

Oliver Salazaar

Oliver Salazaar
Research Fellow

Nagina Mangal

Nagina Mangal
PhD student