The patient list of the pharmacy included data on 205 children or adolescents who were treated with THC- or CBD-containing preparations between February 2008 and June 2019. The first prescription to a child or adolescent was in 2013. Initially, we received 77 responses from caregivers. After the reminders, 90 caregivers (43.9%) agreed to participate in the study. Figure 1 shows the recruitment into the study. We compared the characteristics of the 90 participating children or adolescents to the 115 patients who did not participate. There were no differences in age and the type of medical cannabis prescribed. Compared to non-responders, participants were more likely to be male, to have more than one ICD-10 diagnosis, to have a disease of the nervous system or an endocrine, nutritional and metabolic disease, and have multiple prescriptions of medical cannabis products. According to the ICD-10 classification, the most common diseases among the 205 children or adolescents were diseases of the nervous system (120; 59%), mental and behavioural disorders (26; 13%), cancer (15; 7%), congenital malformations, deformations and chromosomal abnormalities (15; 7%), and endocrine, nutritional, and metabolic diseases (11; 5%). For 34 (17%), the diagnosis was missing (Table S2).
The median age at the first prescription of the 90 participants was 11.5 years (interquartile range 6–15), and 32 were female (36%, Table 1). The youngest participant was 4 months old with a neurodegenerative disease and the oldest 17 years old with epilepsy. Both received CBD only to treat seizures. More than half of the participants (57%) suffered from more than one disease. The most common diagnosis were epilepsy (66; 73%), cerebral palsy (32; 36%), encephalopathy (15; 17%), metabolic diseases (8; 9%), and autism (7; 7%). Among the 66 participants with epilepsy, 24 (36%) had only epilepsy, whereas 42 (64%) had epilepsy with additional diseases (Table S3).
Fifty-one participants (57%) were treated with CBD only and 39 (43%) with a THC preparation. Six patients who received a THC-containing preparation and pure CBD (three received dronabinol and 2.5%, 5%, or 10% pure CBD; two cannabis tincture and 5% or 10% pure CBD; and one cannabis oil and 2.5% CBD) were included in the THC group. When analysing the groups ‘THC only’ and ‘THC and CBD’, we found no statistical difference (Table S4). THC was more commonly prescribed to participants with cancer (p = 0.03), whereas CBD only was more frequently prescribed to participants with epilepsy (p < 0.001). Participants were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, loss of appetite, vomiting, or nausea, whereas seizures were the dominant indication for CBD only therapy. The daily dosage of medical cannabis preparations increased over time for both THC- and CBD-only preparations (Fig. 2).
The majority of participants (72; 80%) received at least one concomitant medication. The most frequent medication categories were antiepileptic drugs (60; 67%), followed by muscle relaxants (10; 11%), analgesics (10; 11%), and other drugs (25; 28%). Also, 63 (70%) participants received physical therapy, 46 (51%) occupational therapy, and 23 (26%) osteopathy (Table 1).
Treatment interruption and side effects
During medical cannabis treatment, 39 of the 90 participants (43%) reported a treatment interruption (Tables 2 and S5). Twenty-two stopped treatment definitively, and 17 resumed treatment (six continued with the same preparation and dosage, seven continued with the same preparation but a different dosage, four continued with another preparation). The median time from treatment initiation to treatment interruption was eight weeks (IQR 3–32 weeks). The reasons given for the treatment interruption included lack of improvement in 22 patients (56%), side effects in 18 (46%), the need for a gastric tube in 17 cases (44%) preventing the continuation of treatment, and cost considerations in 9 patients (23%, Tables 2 and S5). Side effects were observed in 25 of the 90 participants (28%) and similar in the THC and CBD group. The three most common side effects were tiredness, sedation, and dry mouth (Tables 2 and S5).
Awareness, prescription, and cost modalities
Caregivers learned about medical cannabis therapy through the media (44; 49%), their family doctor or medical specialist (37; 41%), and friends or family members (21; 23%). In most cases (82; 91%), specialist doctors, neuropaediatricians, neurologists, oncologists, or palliative care specialists prescribed the preparation. The cost of the first prescription was reimbursed by the invalidity insurance (insurance covering some chronic diseases such as epilepsy or cerebral palsy) in 50 participants (56%), and the health insurance covered the cost for ten patients (11%, Table 3). For 27 participants (30%), caregivers paid out of their pocket. This situation persisted during the treatment. The monthly cost was below 300 USD for 24 participants (27%), between 301 to 600 USD for 22 (24%), more than 600 USD for 25 (28%). The cost was unknown for the remaining 19 children or adolescents. Many caregivers were concerned about the high cost of medical cannabis preparations. Table S3 gives further details about costs.
Treatment effects of medical cannabis preparations
In 59 of 90 participants (66%), the treatment with medical cannabis was reported to be successful by the caregivers (Tables 2 and S5). Participants treated with THC products most frequently reported a reduction of pain, spasticity, seizures, and a reduction in the number of drugs taken. Participants treated with pure CBD-containing products most commonly reported a reduction in the frequency of seizures. Irrespective of treatment with THC or CBD only, caregivers felt that their children or adolescents were more relaxed, more satisfied, and in better general condition than before the therapy with medical cannabis (Fig. 3, Table S6). The use of other therapies like physiotherapy, osteopathy, speech, or occupational therapy did not change, regardless of whether the patients received THC or CBD only (Fig. 3).