The appetite stimulating effect and safety of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in older patients with poor appetite: A triple-blinded, randomized, placebo-controlled, cross-over trial.

Background And Aims: Anorexia of aging is prevalent and constitutes a significant factor in the onset of malnutrition with limited effective interventions. Cannabis-based medicine (CBM) with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may have orexigenic properties in older patients with poor appetite. However, current evidence is insufficient regarding the impact of CBM in older patients with poor appetite. This trial aimed to assess the difference in caloric intake between an oromucosal spray containing CBM versus placebo. The secondary outcomes were safety parameters (tiredness, vertigo, nausea, euphoria, blood pressure, and heart rate). Methods: The trial is an investigator-initiated single-center, triple-blinded, randomized, placebo-controlled, superiority, cross-over trial with 17 patients >/=65 years with poor appetite. Patients received two dosages of CBM (8.1 mg THC and 7.5 mg CBD pr dosage) and placebo at two time points on two separate trial days, with a two-week washout period between trial days. The primary outcome, caloric intake, was measured with a controlled feeding study using standardized homogenous test meals. Safety parameters were assessed with 100 mm numerical visual analog scales. Results: No statically significant difference in mean caloric intake between CBM and placebo was observed (10 kilocalories (kcal) (CI: -55-75 kcal), favoring CBM). During the trial, 36 adverse events were classified as unrelated to CBM, while 16 were classified as possibly-related. Of the 16 possibly-related, five were during placebo conditions and one was reported prior to CBM. All possibly-related adverse events were mild and transient. No serious related adverse events were observed. Conclusions: In older patients with poor appetite, CBM administered buccally at two time points at the same day, with each dose containing 8.1 mg THC and 7.5 mg CBD, did not improve caloric intake compared to placebo. The observed safety parameters suggest that CBM is generally tolerated when administered according to this dosing regimen. The trial was registered at EudraCT (2021-002318-15) and Clinicaltrials. gov (NCT05503147).