In this study, cannabinoids were used for several indications, including spasticity, pain, restlessness, loss of appetite, agitation, anxiety, and paresis. The indications for the administration of a medication containing cannabinoids are in agreement with previous data [8,9,10,11,12,13]. We expected a positive development of the respective constellation of symptoms based on specific publications dealing with the administration of cannabinoids in the pediatric palliative setting [3,4,6].

Upon examining a putative improvement in aspects of daily structure, we found that patients with neurological diseases benefited the most from the medication. This can be related to the fact that these patients received the medication primarily due to symptoms of spasticity. Previous publications showed that cannabinoids had a therapeutic effect on treating refractory spasticity [4,5,14], a finding we could confirm in our cohort. The therapeutic goal was achieved in the majority of cases, so it seems to be safe to add cannabinoid medication to the existing therapeutic regimen to further improve specific symptoms. Studies have yet to show if they can replace other medications. Due to the multi-morbidity of many patients, a wide range of medications was used. We did not detect interactions and resulting adverse drug reactions.

Currently, there are no child-friendly methods of application for cannabinoids available. Sativex^® was discontinued mainly due to the time and effort required to dispense the medication, with 15 min between each spray burst, and the bitter taste of the spray. For a more suitable and reproducible use in pediatric palliative care, more child-friendly preparations are needed to ensure a consistent application of the medication.

Cannabinoids can cause adverse drug reactions. Some medications that affect the central nervous system impact the brain’s developmental capabilities [15,16]. There is a distinction between the short-term and long-term effects of cannabinoids. The short-term effects include dizziness, cognitive impairment, impaired free recall, impaired working memory and procedural memory, anxiety, and sedation [5,6,17]. These drug reactions are brief and reversible through abstinence. A small percentage of our patients exhibited some of the short-term effects identified in that study.

The younger the patients to whom cannabinoids are administered, the higher the risk of long-term effects [18], which include triggering psychosis and schizophrenia in individuals predisposed to mental illness [19]. There is a risk of unimpeded development, especially in children, due to medical malpractice in the form of, for example, a non-adapted dosage regimen or drug interactions [20]. Studies are needed so that pediatricians can make clear recommendations.

The chance of withdrawal due to adverse events is significantly higher for patients treated with cannabinoids than for controls. Before treatment with cannabinoids, a detailed evaluation should be conducted with the patient and the parents regarding potential improvements and common adverse events [21]. In our study, only one patient withdrew because of adverse events.

Other phytocannabinoids in the cannabis plant, such as tetrahydrocannabivarin, cannabigerol, and cannabichromene, may have additional effects of therapeutic interest [22]. To date, it remains unclear which part of the plant is most effective for treating a specific symptom. It could also be that a combination of different cannabinoids, a specific route of administration, or a given dosage might show the best effect [23]. Moreover, whether the best dose or combination of cannabinoids for one symptom complex are as effective as they would be for other indications has not been studied [5].

The demand for medical cannabis seems to be increasing, as demonstrated in a study from Australia that shows that since the legalization of medical cannabis in 2016, the number of prescriptions for medical cannabis has increased significantly [24]. Consistent with this trend, our study reflects a similar observation, as the majority of cannabinoid treatments commenced after the legalization of medical cannabis in Germany in 2017.

Due to the small number of patients, i.e., 31, our results cannot be considered nationally representative. Our study also included the treatment of young adults aged 18 to 33. These older patients were treated for a congenital disease by the SOPPC team. It was found that the treatments administered in our study were not influenced by age or developmental factors. For future studies, especially those designed to establish a dosing regimen, it is probably necessary to exclude patients over the age of 18 years. Since dronabinol has been used primarily to treat neurologically severely affected children with limited communication ability, dose finding with this medication highly depends on the child in question’s observation. Symptom control and the effects of medication are difficult to quantify. However, in the assessment of treatment efficacy, the Cohen’s Kappa value of 0.744 indicates a substantial degree of agreement between the two treating physicians [25]. A possible confirmation bias of parents and treating physicians based on expectations cannot be ruled out. Parents who wish for the medication to be effective might interpret their children’s behavior differently than those who doubt the efficacy of cannabinoid medication. More studies are needed in this area, with specialized analyses of symptoms using quantifiable methods. Spasticity could be monitored with the modified Ashworth scale [26]. In addition, it is difficult to monitor the number of days of treatment and compliance with a medication regimen, as there are patients currently not being cared for by the SOPPC team. Most of them are in a phase of their disease that does not require active care. These patients can be readmitted to active care as a crisis intervention. Prospective studies are required to ensure that medication is continuously monitored.

Based on our analysis, it seems to be safe to conclude that cannabinoids can be used safely and effectively in treating neurologic, oncologic, metabolic, and cardiologic pediatric disorders. In this study, we found that cannabinoids were used to relieve spasticity, pain, restlessness, or anxiety; increase appetite; or reduce seizure frequency in cases of treatment-refractory epilepsy. They showed a low spectrum of adverse events, and no obvious drug interactions, which generally must be considered, were found to be attributable to cannabinoid medication. Due to the lack of available data, cannabinoids should not be used as first-line therapy. However, they can be used, especially in the pediatric palliative setting, as an add-on therapy in multi-morbidity and less severely affected children to achieve a quality-of-life improvement. The aspects of daily structure improved in many cases, which is especially important for pediatric palliative patients.