Patient population

During the study period, 188 ASD patients initiated the treatment. Diagnosis of ASD was established in accordance with the accepted practice in Israel; six board certified paediatric psychiatrists and neurologists were responsible for treatment of 125 patients (80.6%), the remaining 30 children were referred by 22 other physicians. Table 1 shows demographic characteristics of the patient population. The mean age was 12.9 ± 7.0 years, with 14 (7.4%) patients being younger than the age of 5, 70 patients (37.2%) between 6 to 10 years and 72 (38.2%) aged 11 to 18. Most of the patients were males (81.9%). Twenty-seven patients (14.4%) suffered from epilepsy and 7 patients (3.7%) from Attention Deficit Hyperactivity Disorder (ADHD).

Table 1 Demographic and clinical characteristics of patients at intake. Full size table

At baseline parents of 188 patients reported on average of 6.3 ± 3.2 symptoms. Table 2 shows the prevalence of symptoms with most common being restlessness (90.4%), rage attacks (79.8%) and agitation 78.7%.

Table 2 Symptom prevalence and change. Full size table

Cannabis products recommended to the patients were mainly oil applied under the tong (94.7%). Seven patients (3.7%) received a license to purchase oil and inflorescence and three patients (1.5%) received a license to purchase only inflorescence. Most patients consumed oil with 30% CBD and 1.5% THC, on average 79.5 ± 61.5 mg CBD and 4.0 ± 3.0 mg THC, three times a day (for a more detailed distribution of CBD/THC consumptions see Supplementary Fig. S1). Insomnia recorded in 46 patients (24.4%) was treated with an evening does of 3% THC oil with on average additional 5.0 ± 4.5 mg THC daily. All the products content was validated by HPLC (High Performance Liquid Chromatography) in each production cycle. The cannabis dose was not significantly associated with weight (r correlation coefficient = −0.13, p = 0.30), age (r correlation coefficient = −0.10, p = 0.38), or gender (p = 0.38).

Follow-up, one month

After one month, out of 188 patients, 8 (4.2%) stopped treatment, 1 (0.5%) switched to a different cannabis supplier, and 179 patients (94.6%) continued active treatment (Fig. 1). Of the latter group, 119 (66.4%) responded to the questionnaire with 58 patients (48.7%) reporting significant improvement, 37 (31.1%) moderate improvement; 7 patients (5.9%) experienced side effects and 17 (14.3%) reported that the cannabis did not help them.

Figure 1 The study population in the three follow-up periods, at intake, after one month and after six months of medical cannabis treatment. Full size image

The reported side effects at one month were: sleepiness (1.6%), bad taste and smell of the oil (1.6%), restlessness (0.8%), reflux (0.8%) and lack of appetite (0.8%).

Follow-up, six months

After six months, of the 179 patients assessed in the one-month follow-up, 15 patients (8.3%) stopped treatment, 9 (4.9%) switched to a different cannabis supplier and 155 patients (86.6%) continued treatment (Fig. 1). Of the latter group, 93 (60.0%) responded to the questionnaire with 28 patients (30.1%) reporting a significant improvement, 50 patients (53.7%) moderate improvement, 6 patients (6.4%) slight improvement and 8 (8.6%) having no change in their condition. None of the variables entered to the multivariate analysis to predict treatment success was statistically significant.

To assess the potential response bias, we have compared baseline characteristics between 93 respondents and 62 non-respondents to the 6-month questionnaire. The former group was slightly older (13.7 ± 0.8 vs. 10.8 ± 0.5, p = 0.004).

Quality of Life

Quality of life, mood and ability to perform activities of daily living were assessed before the treatment and at six months. Good quality of life was reported by 31.3% of patients prior to treatment initiation while at 6 months good quality of life was reported by 66.8% (p < 0.001, Supplementary Fig. S2). Positive mood was reported by the parents on 42% before treatment and 63.5% after 6 months of treatment (p < 0.001). The ability to dress and shower independently was significantly improved from 26.4% reported no difficulty in these activities prior to the treatment to 42.9% at six months (p < 0.001). Similarly, good sleep and good concentration were reported by 3.3% and 0.0% (respectively) before the treatment and on 24.7% (p < 0.001) and 14.0% (p < 0.001) during an active treatment (Table 3).

Table 3 Assessment of daily activities. Full size table

The improved symptoms at 6 months included seizures, of the 13 patients on an active treatment at six months 11 patients (84.6%) reported disappearances of the symptoms and two patients reported improvement; restlessness and rage attacks were improved in 72 patients (91.0%) and 66 (90.3%) respectively (Table 2).

Medications Use

The most common concomitant chronic medications on the intake were antipsychotics (56.9%), antiepileptics (26.0%), hypnotics and sedatives (14.9%) and antidepressants (10.6%). Out of 93 patients responding to the follow-up questionnaire, 67 reported use of chronic medications at intake. Overall, six patients (8.9%) reported an increase in their drugs consumption, in 38 patients (56.7%) drugs consumption remained the same and 23 patients (34.3%) reported a decrease, mainly of the following families: antipsychotics, antiepileptics antidepressants and hypnotics and sedatives (Table 4). Antipsychotics, the most prevalent class of medications taken at intake (55 patients, 33.9%); at 6 months it was taken at the same dosage by 41 of them (75%), 3 patients (5.4%) decreased dosage and 11 patients (20%) stopped taking this medication (Table 4).

Table 4 Concomitant medications. Full size table

Side Effects

The most common side effects, reported at six months by 23 patients (25.2%, with at least one side effect) were: restlessness (6 patients, 6.6%), sleepiness (3, 3.2%), psychoactive effect (3, 3.2%), increased appetite (3, 3.2%), digestion problems (3, 3.2%), dry mouth (2, 2.2%) and lack of appetite (2, 2.2%).

Out of 23 patients who discontinued the treatment, 17 (73.9%) had responded to the follow-up questionnaire at six months. The reasons for the treatment discontinuation were: no therapeutic effect (70.6%, twelve patients) and side effects (29.4%, five patients). However, 41.2% (seven patients) of the patients who discontinued the treatment had reported on intentions to return to the treatment.