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 two main areas: 1) inflammation & cancer, with a current focus on pancreatic ductal adenocarcinoma (PDAC) and 2) acute/post-surgical, neuropathic and cancer-related pain.  

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. 

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 outcomesIn 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.     

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. 

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.  

Additional information

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

  1. Anand U, Pacchetti B, Anand P, Sodergren MH. Cannabis-based medicines and pain: a review of potential synergistic and entourage effects. Pain Manag. 2021 Mar 11. doi: 10.2217/pmt-2020-0110.
  2. 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. 
  3. Erridge S, Mangal N, Salazar O, Pacchetti B, Sodergren MH. Cannflavins - From plant to patient: A scoping review. Fitoterapia. 2020 Oct;146:104712 
  4. Sodergren MH, Mangal N, Wasan H, Sadanandam A, Balachandran VP, Jiao LR, Habib N. Immunological combination treatment holds the key to improving survival in pancreatic cancer. J Cancer Res Clin Oncol. 2020 Nov;146(11):2897-2911 
  5. Tagne AM, Pacchetti B, Sodergren MHCosetino M, Marino F. Cannabidiol for Viral Diseases: Hype or Hope? Cannabis Cannabinoid Res. 2020 Jun 5;5(2):121-131 
  6. 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 
  7. 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. 
  8. Anand U : Mechanisms and Management of cancer pain. In The Cancer Handbook. Volume Chapter 98. 2 edition. Edited by: Alison, MR . Publishers John Wiley and Sons Ltd. Chichester; 2007. 
  9. 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.  
  10. Furgiuele A, Tagne AM, Pacchetti B, Sodergren M, Cosentino M, Marino FImmunomodulatory Effects of Cannabidiol: Relevance in Multiple Sclerosis at the International Association for Cannabis as Medicine (IACM) 10th Conference on Cannabinoid in Medicine, in Berlin. 
  11. 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. 
  12. 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.  
  13. Anand U, Otto WR, Anand P. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons. Mol Pain 2010; 6:82. 
  14. 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.  

Our researchers

Oliver Salazaar

Oliver Salazaar

Oliver Salazaar
Research Fellow