In May 2021, MR, a 42-year-old male previously fit and well mathematics teacher, was diagnosed with metastatic MMR proficient RAS mutant BRAF wild-type rectosigmoid adenocarcinoma with multiple lung metastases. He commenced palliative FOLFIRI chemotherapy. In August 2021, MR was admitted as an emergency with bowel perforation after two cycles of chemotherapy. A Hartmann's procedure was performed, removing the primary tumor (ypT3 N2a) and controlling sepsis. FOLFIRI chemotherapy was resumed in December 2021 and 10 additional cycles were completed by May 2022. Progression of lung metastasis necessitated the start of second-line chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) in September 2022. After completing FOLFOX chemotherapy in February 2023, MR underwent radiofrequency lung ablation.

Management of CINV with THC-predominant flowers

MR reported severe nausea and vomiting associated with the initial FOLFIRI treatment. He was prescribed metoclopramide and aprepitant, which offered limited benefit, and ondansetron, which resulted in constipation and was discontinued after his Hartmann's procedure. After resuming FOLFIRI chemotherapy, MR sought a private consultation and in May 2022, he obtained his first private prescription for THC-predominant cannabis flowers for inhalation. In the UK, the majority of CBMPs are unlicensed medicines or “specials” and while they can be prescribed by clinicians complying with strict guidance from NHS England, the Medicines and Healthcare Products Regulatory Agency (MHRA), and the General Medical Council (GMC), funding of these medications is challenging due to the lack of National Institute for Health and Care Excellence (NICE) formal guidelines. Unlicensed CBMPs most frequently prescribed in the UK are dried flowers for inhalation and oral extracts, and are usually identified by the relative composition of their active ingredients, i.e., THC and cannabidiol (CBD), and classified by chemotype as follows: chemotype-1 (THC-predominant, THC>>>CBD); chemotype-2 (balanced, THC≈CBD); and chemotype-3 (CBD-predominant, THC<<<CBD) [5].

After initiating the second-line FOLFOX chemotherapy in September 2022, MR was prescribed levomepromazine, which resulted in severe drowsiness, and nabilone, which did not help with CINV. To provide a comparative assessment of the efficacy of the interventions tested, MR retrospectively completed the revised Edmonton Symptom Assessment Scale (ESASr) in May 2023 [6]. Results are expressed in Table 1 and show that inhalation of cannabis flowers together with metoclopramide and aprepitant was the most successful combination for controlling CINV.

Funding of THC-predominant cannabis flowers by the NHS

In July 2022, MR requested his general practitioner to submit an individual funding request (IFR) to the NHS South, Central, and West Commissioning and Support Unit to cover the cost associated with his medicinal cannabis flowers. This amounted to £388 per month for the 24 months his oncologist had estimated his prognosis to be. In October 2022, the panel denied his petition considering by mistake that MR was requesting funding for the use of Sativex. Sativex is a CBMP authorized for the treatment of spasticity associated with multiple sclerosis, and the funding panel argued that Sativex was not approved for the indication of CINV. In November 2022, the IFR was resubmitted, clarifying that the application was for medicinal cannabis flowers, an unlicensed CBMP. The panel then denied this second request because MR had not exhausted other authorized options like nabilone.

In March 2023, after trialing nabilone and finding it of minimal efficacy, MR’s general practitioner resubmitted the IFR, emphasizing that the use of cannabis flowers together with prescription antiemetics allowed the patient to complete his course of FOLFOX chemotherapy. This was further corroborated by MR’s oncologist in a letter to The Shirley Health Partnership supporting MR’s IFR. On April 20th, 2023, the funding panel met and agreed to fund MR’s request. The panel also agreed to fund the cost of a certified medical device, an herbal vaporizer, for the administration of medicinal cannabis flowers in compliance with current UK legislation set forth by the Home Office in 2018, which prohibits smoking of CBMP.

Palliative use of THC-predominant cannabis flowers in advanced or metastatic cancer

Besides offering control of CINV, the use of CBMP allowed MR to tolerate other symptoms associated with his cancer and its treatment. In MR’s words, “using medical cannabis transforms me from an anxiety-ridden, vomiting, fatigued wreck into an active family participant, playing with my kids, chatting with my wife and friends, cooking meals, and cleaning the house. It enables me to make the most of the time I have left, whether I'm on chemo or recovering from it. I want to use medical cannabis to have the best possible quality of life for my remaining years.” Patient-reported outcome measures were collected at the onset of treatment and at two- and four-month follow-ups as part of the standard of care received at the private clinics where MR obtained his prescription for CBMP. Validated questionnaires, including the General Anxiety Disorder-7 (GAD-7) and the single-item Sleep Quality Scale (SQS), were used [7,8]. Results reported in Table 2 show improvements in anxiety and quality of sleep associated with the addition of CBMP to the standard of care management. These improvements mirror what was reported by the patient in the ESASr following the usage of chemotype-1 cannabis flowers, as shown in Table 1. Coincidentally, the patient was able to discontinue the use of prescription drugs, such as diazepam and zopiclone, and to reduce the dose of fluoxetine. Administration of cannabis flowers was performed “on demand” and amounted typically to one gram per day. Varieties of​​​ ​​​​Cannabis sativa L. used were of chemotype-1 (THC-predominant) and contained an average of 20% of THC and less than 1% of CBD in dry weight. Individual dosing size was 0.2 grams, which amounts to a maximum of 40 mg of THC per administration. However, the actual absorption of THC largely depends on the number of inhalations and the temperature used [5,9].