Brief report: Cannabidiol rich cannabis in children with autism spectrum disorder and severe behavioral problems--a retrospective feasibility study Aran et al., 201817
|
Israel |
60 children (mean 11.8 years old, SD 3.5 years), 83% male, 77% with low cognitive function (according to ADOS or CARS), all with severe behavior problems (6 or 7, according to CGI-S). |
Retrospective analysis of autistic children with behavioral changes refractory to conventional treatment at the Shaare Zedek Medical Center (Jerusalem, Israel), with medical prescription of cannabis for 7 to 13 months with plant extract containing CBD and THC at 20:1 (in poorly responsive cases, 6:1). |
The average daily dose was 3.8±2.6 mg/kg/day of CBD and 0.29±0.22 mg/kg/day of THC for the 44 children who received three doses/day. For the 16 who received two doses, 1.8±1.6 mg/kg/day of CBD and 0.22±0.14 mg/kg/day of THC was the average dose received. 51% presented one side effect, the most common being: sleep disorders (14%), restlessness (9%), nervousness (9%), and loss of appetite (9%). In the HSQ score, 29% had an average improvement of 1.38±1.79 (median = 0.81). In the APSI score, it was 0.66±0.74 (median = 0.53). |
There was a significant improvement in behavioral problems that was reported in 61% of children, in the CGIC; in anxiety: 39% and in communication problems: 47%. High concentration of THC (6:1-CBD) can lead to a psychotic episode. |
Oral cannabidiol use in children with autism spectrum disorder to treat related symptoms and comorbidities Barchel et al., 201816
|
Israel |
53 children (mean 11 years of age, SD 4 to 22 years) received CBD for an average of 66 days (SD 30-588 days). |
Administration of oil with CBD and THC (20:1), orally, with telephone interviews conducted every two weeks with parents or caregivers, asking about changes in symptoms, the data obtained were analyzed independently by specialists in search of these changes in symptoms and safety of medicines. The improvement resulting from CBD was also compared with conventional treatment for ASD. |
Self-harm and anger bouts (n = 34) improved in 67.6% and worsened in 8.8% of the participants. Symptoms of hyperactivity (n = 38) improved in 68.4%, did not change in 28.9%, and worsened in 2.6% of the subjects. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5% of the participants. Adverse effects, mostly somnolence and change in appetite, were mild. |
A comparison of symptom improvement between CBD treatment and conventional treatment was analyzed using the binomial test. Parents’ reports suggest that CBD may improve symptoms related to ASD. |
Effects of cannabidiol on brain excitation and inhibition systems: a randomized placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder Pretzsch et al., 201926
|
England |
34 people (neurotypical control n = 17, ASD n = 17). All with IQ greater than 70. |
Patients were allocated in a randomized order: about half in each group participated in the placebo before CBD (600 mg oral solution) and the other half participated in CBD before the placebo. After administration, placebo or CBD, a check was scheduled to coincide with the maximum plasma concentration (2 h). It was evaluated by magnetic resonance spectroscopic imaging. |
It was seen that patients with ASD had a drop in IQ compared to neurotypical controls (F1 = 5,781; p = 0.022), but the difference in IQ did not influence the results: ASD (r < -0.008; p > 0.698); neurotypical (r < 0.068; p > 0.235). The excitatory mechanisms of response to glutamate were comparable, regardless of diagnosis, however the inhibitory response by GABA + was altered in ASD. There was a difference in the results found in the images in relation to the placebo group. |
CBD can change the levels of glutamate, glutamine and GABA +, regulators of excitatory and inhibitory neurotransmission. The autistic brain reacts differently to GABA+, which helps to understand the mechanisms and targets of treatment for ASD. |
The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) Pretzsch et al., 201928
|
England |
34 people (17 with ASD and 17 without). |
CBD 600 mg oral solution. Functional magnetic resonance imaging was used for evaluation. |
CBD is able to alter the fALFF in the cerebellar vermis, center of perception of gravity, right fusiform gyrus. The connectivity function (FC) in the vermis increased in the left and right caudal portion, however it reduced between the vermis and the occipital temporal part of the left middle temporal gyrus, the right supramarginal anterior gyrus, the left upper parietal lobe and the gyrus upper left front; none of these effects were observed significantly in the brains of healthy people. There was a difference in the results found in the images in relation to the placebo group. |
First evidence of neuromodulation made from the administration of CBD in fALFF and FC in the brains of adults with autism. CBD was able to alter crucial properties of brain function in key areas that are altered in ASD. |
Real life experience of medical cannabis treatment in autism: analysis of safety and efficacy Bar-Lev Schleider et al., 201929
|
Israel |
188 patients with ASD with a mean age of 12 years, SD ± 7 years, younger than 5 years (14). 81.9% of the male gender. |
Cannabis oil enriched with 30% CBD and 1.5% THC (3 times a day, sublingual) was used, oil enriched by an average of 61.5 + -79.5 mg CBD and 3 + -4 mg THC. The team initially and periodically evaluated the health status, assessed the medical history and administered medical questionnaires. |
In 6 months (49.5% of sample loss), 91% of cases of restlessness improved; 90.3% of anger bouts; 85.2% of agitation; 78.1% problems with sleep; among other symptoms. There was at least one side effect in 25.2%, which were: restlessness (6.6%), drowsiness (3.2%), psychoactive effect (3.2%), increased appetite (3.2%), digestive problems (3.2%), dry mouth (2.2%) and lack of appetite (2.2%). |
The use of cannabis for ASD is well tolerated, safe and appears to be effective in relieving symptoms (especially seizures, depression, restlessness and bouts of anger). There was great acceptability of the treatment, with only less than 15% of dropouts in a 6-month follow-up. More than 80% of parents reported a significant global improvement in children. |
Use of dronabinol (delta-9-THC) in autism: A prospective single-case-study with an early infantile autistic child Kurz & Blaas, 201027
|
Austria |
Boy, 6 years old, (diagnosed at 3) via DSM-IV criteria and confirmed by ADOS and ADI. |
Drops of dronabinol dissolved in sesame oil, with one drop initially (0.62 mg) in the morning up to the maximum dose of 2 drops in the morning, with a total daily dose of 3.62 mg of dronabinol. 6-month follow-up (without adding other new therapies or changing existing care measures). Symptom severity was assessed using the ABC questionnaire. |
Hyperactivity decreased by 27 points, lethargy reduced by 25 points, irritability decreased by 12 points, stereotypy reduced by 7 points and inappropriate speech decreased by 6 points in six months. |
This isolated case suggests that dronabinol may reduce the symptoms of autism in children, perhaps by modifying cannabinoid levels in the central nervous system. |
Rating of the safety and effectiveness of marijuana, THC/CBD, and CBD for autism spectrum disorders: results of two national surveys Adams et al., 201930
|
United States |
156 participants who already used cannabis in its derived forms. |
The National Survey on Treatment Effectiveness for Autism (NSTEA) started collecting data in 2017 and continues to collect online. Marijuana is studied in the following forms: flower, edible, vaporized, gums, tincture, leaf and other forms; THC/CBD combination in the following forms: oil, gums, edible, tincture, vaporized and all methods; and only CBD in the following forms: oil, tincture, gums and others. |
Reported improvements: calm (58-71%); irritability (46-65%); aggression/agitation (43-58%); sleep (30-58%); drowsiness (32-46%); hyperactivity (26-39%); sensory sensitivity (28-32%); cognition (32-46%); attention (26-42%); social interaction (26-42%); language (26-38%); perseverance (22-27%); depression (16-41%). Adverse effects of CBD, uncommon: behavioral problems (5%), decreased cognition (4%), fatigue (4%), aggression/agitation (4%). All these side effects were mild and/or transient. |
The primary reported benefits were calming effects, including improved anxiety, irritability, aggression/agitation, hyperactivity, and sleep. There were also improvements in the symptoms of ASD. There were few adverse effects for THC/CBD and CBD and mild for marijuana. |
Effects of CBD-enriched Cannabis sativa extract on autism spectrum disorder symptoms: an observational study of 18 participants undergoing compassionate use Fleury-Teixeira et al., 201931
|
Brazil |
18 patients: 11 without a history of epilepsy, 2 with a previous history of epilepsy but without seizures for over a year, and 5 with epilepsy and still with seizures. |
Extract enriched with CBD in the ratio CBD/THC 75:1. Average of 4.6 mg/kg/day of CBD and 0.06 mg/kg/day of THC. The individual doses were based on previous studies with patients with refractory epilepsy associated with autism. The average initial dose was 2.9 mg/kg/day and dose adjustments were made throughout the treatment. |
80% of patients improved in more than 30% of the three items assessed: sleep disorders, epileptic seizures, and behavioral changes. In addition, signs of improvement were reported for motor development; communication and interaction; and cognitive performance. The adverse effects were: moderate drowsiness and irritability (three cases each), diarrhea, increased appetite, conjunctival hyperemia, and increased body temperature (one case each). All these side effects were mild and/or transient. |
Several therapeutic benefits of the CBD-enriched preparation that extends to ASD symptoms have been noted, even in non-epileptic patients. This study pointed to a potential risk of paradoxical effects when introducing cannabinoids to a patient using a combination of drugs that include antipsychotics. This highlights the need for extra vigilance and a gradual increase in the dosage of cannabinoids in patients receiving many medications. |
Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without autism spectrum disorder (ASD): a single dose trial during magnetic resonance spectroscopy Pretzsch et al., 201932
|
England |
34 participants, around 28.47 (6.55) years old in the control group and 31.29 (9.94) in those with ASD, among them 17 people, diagnosed by ICD-10, with severe symptoms evaluated by ADOS and ADI. |
Randomized, double-blind, crossover study using magnetic resonance spectroscopic imaging comparing glutamate and GABA levels after the use of placebo and 600 mg CBDV. Information was collected from the dorsomedial region of the prefrontal cortex and the left basal ganglia (areas related to ASD) after 2 h (plasma peak of the substance) of administration. |
Tests performed at least 13 days after using the drug/placebo indicated that CBDV increased the levels of glutamate in the left basal ganglia in both groups, but in those with ASD despite this increase, the basal concentration of the substance decreased. CBDV did not alter the levels of glutamate or GABA in the medial dorsal region of the prefrontal cortex of either group. There was a difference in the results found in the images in relation to the placebo group. |
CBDV modulates the levels of glutamine/GABA in the left basal ganglia, with individual variations depending on the biochemistry of the individual base (CBDV increased the levels of glutamate in autistic low baseline amounts, opposite to those who already had it high in baseline). Future studies should evaluate the effect of CBDV on behavior and whether the response to an acute dose can predict therapeutic success in patients with ASD. |