The treatment in the majority of the patients was based on hemp oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires.

After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition.

Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Hemp in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.

In this retrospective study on 60 children, behavioral outbreaks were improved in 61% of patients, communication problems in 47%, anxiety in 39%, stress in 33% and disruptive behavior in 33% of the patients. The rationale for this treatment is based on the previous observations and theory that cannabidiol effects might include alleviation of psychosis, anxiety, facilitation of REM sleep and suppressing seizure activity.

Beginning treatment with hemp

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 pediatric psychiatrists and neurologists were responsible for the treatment of 125 patients (80.6%), the remaining 30 children were referred by 22 other physicians.

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).

Hemp 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 the 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 dose 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 hemp 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).

Results after 1 month

After one month, out of 188 patients, 8 (4.2%) stopped treatment, 1 (0.5%) switched to a different hemp 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 hemp did not help them.

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%).

Results after 6 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 hemp supplier and 155 patients (86.6%) continued treatment. 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.

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 the good quality of life was reported by 66.8%. Positive mood was reported by the parents on 42% before treatment and 63.5% after 6 months of treatment. 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. Similarly, good sleep and good concentration were reported by 3.3% and 0.0% (respectively) before the treatment and on 24.7% and 14.0% during active treatment.

The improved symptoms at 6 months included seizures, of the 13 patients on 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.

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.

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.

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%).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.

Discussion about the study

Hemp as a treatment for autism spectrum disorders patients appears to be well-tolerated, safe and seemingly effective option to relieve symptoms, mainly: seizures, tics, depression, restlessness and rage attacks. The compliance with the treatment regimen appears to be high with less than 15% stopping the treatment at six months follow-up. Overall, more than 80% of the parents reported at a significant or moderate improvement in the child global assessment.

The hemp treatment appears to be safe and side effects reported by the patients and parents were moderate and relatively easy to cope with. The most prevalent side effects reported at six months was restlessness, appearing in less than 6.6% of patients. Moreover, the compliance with the treatment was high and only less than 5% have stopped the treatment due to the side effects.

Study outcomes

For safety analysis, we have assessed the frequency of the following side effects at one and at six months: physiological effects – headaches, dizziness, nausea, vomiting, stomach ache, heart palpitation, drop in blood pressure, drop in sugar, sleepiness, weakness, chills, itching, red/irritated eyes, dry mouth, cough, increased appetite, blurred vision, slurred speech; cognitive side effects – restlessness, fear, psycho-active effect, hallucinations, confusion and disorientation, decreased concentration, decreased memory or other. The patient parents were asked to provide details of the incidence, duration, and severity of the reported side effect.

For the efficacy analysis, we used the global assessment approach where the patient parents were asked: “How would you rate the general effect of hemp on your child condition?” the options were: significant improvement, moderate improvement, slight improvement, no change, slight deterioration, moderate deterioration, and significant deterioration. Autism symptoms severity assessment included the following items: restlessness, rage attacks, agitation, speech impairment, cognitive impairment, anxiety, incontinence, depression and more. Quality of life was assessed on a Likert scale ranging from very poor to poor, neither poor nor good and good to very good.

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Declaration

The study was approved by the Soroka University Medical Center ethics committee (study number: SCRC-0415-15) and the need for informed consent was abandoned due to the retrospective nature of data analysis.

Data availability

The dataset created and/or analyzed during the current study is not publicly available for medical confidentiality but is available from the first author on a reasonable request in summary form prior to IRB approval.

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