Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study / Adi ARAN in Journal of Autism and Developmental Disorders, 49-3 (March 2019)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 49-3 (March 2019) . - p.1284-1288 Titre : Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study Type de document : Texte imprimé et/ou numérique Auteurs : Adi ARAN, Auteur ; Hanoch CASSUTO, Auteur ; A. LUBOTZKY, Auteur ; N. WATTAD, Auteur ; E. HAZAN, Auteur Article en page(s) : p.1284-1288 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Cannabidiol  Disruptive behavior  Medical cannabis  Medical marijuana Index. décimale : PER Périodiques Résumé : Anecdotal evidence of successful cannabis treatment in autism spectrum disorder (ASD) are accumulating but clinical studies are lacking. This retrospective study assessed tolerability and efficacy of cannabidiol-rich cannabis, in 60 children with ASD and severe behavioral problems (age = 11.8 +/- 3.5, range 5.0-17.5; 77% low functioning; 83% boys). Efficacy was assessed using the Caregiver Global Impression of Change scale. Adverse events included sleep disturbances (14%) irritability (9%) and loss of appetite (9%). One girl who used higher tetrahydrocannabinol had a transient serious psychotic event which required treatment with an antipsychotic. Following the cannabis treatment, behavioral outbreaks were much improved or very much improved in 61% of patients. This preliminary study supports feasibility of CBD-based cannabis trials in children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-018-3808-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study [Texte imprimé et/ou numérique] / Adi ARAN, Auteur ; Hanoch CASSUTO, Auteur ; A. LUBOTZKY, Auteur ; N. WATTAD, Auteur ; E. HAZAN, Auteur . - p.1284-1288. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 49-3 (March 2019) . - p.1284-1288 Mots-clés : Autism spectrum disorder  Cannabidiol  Disruptive behavior  Medical cannabis  Medical marijuana Index. décimale : PER Périodiques Résumé : Anecdotal evidence of successful cannabis treatment in autism spectrum disorder (ASD) are accumulating but clinical studies are lacking. This retrospective study assessed tolerability and efficacy of cannabidiol-rich cannabis, in 60 children with ASD and severe behavioral problems (age = 11.8 +/- 3.5, range 5.0-17.5; 77% low functioning; 83% boys). Efficacy was assessed using the Caregiver Global Impression of Change scale. Adverse events included sleep disturbances (14%) irritability (9%) and loss of appetite (9%). One girl who used higher tetrahydrocannabinol had a transient serious psychotic event which required treatment with an antipsychotic. Following the cannabis treatment, behavioral outbreaks were much improved or very much improved in 61% of patients. This preliminary study supports feasibility of CBD-based cannabis trials in children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-018-3808-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Cannabinoid treatment for autism: a proof-of-concept randomized trial / Adi ARAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 6p. Titre : Cannabinoid treatment for autism: a proof-of-concept randomized trial Type de document : Texte imprimé et/ou numérique Auteurs : Adi ARAN, Auteur ; Moria HAREL, Auteur ; Hanoch CASSUTO, Auteur ; Lola POLYANSKY, Auteur ; Aviad SCHNAPP, Auteur ; Nadia WATTAD, Auteur ; Dorit SHMUELI, Auteur ; Daphna GOLAN, Auteur ; Francisco Xavier CASTELLANOS, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Behavior  Cannabidiol  Cannabinoids  Child psychiatry  Clinical trials randomized controlled  Developmental disorders  Entourage effect  Neuropsychology  Tetrahydrocannabinol Index. décimale : PER Périodiques Résumé : BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and ?9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and ?9-tetrahydrocannabinol at the same ratio. Participants (N?=?150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n?=?45) versus 21% on placebo (n?=?47; p?=?0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n?=?34) versus 3.6 points after placebo (n?=?36); p?=?0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n?=?95); 23% and 21% on pure-cannabinoids (n?=?93), and 8% and 15% on placebo (n?=?94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226. En ligne : http://dx.doi.org/10.1186/s13229-021-00420-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Cannabinoid treatment for autism: a proof-of-concept randomized trial [Texte imprimé et/ou numérique] / Adi ARAN, Auteur ; Moria HAREL, Auteur ; Hanoch CASSUTO, Auteur ; Lola POLYANSKY, Auteur ; Aviad SCHNAPP, Auteur ; Nadia WATTAD, Auteur ; Dorit SHMUELI, Auteur ; Daphna GOLAN, Auteur ; Francisco Xavier CASTELLANOS, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 6p. Mots-clés : Autism spectrum disorder  Behavior  Cannabidiol  Cannabinoids  Child psychiatry  Clinical trials randomized controlled  Developmental disorders  Entourage effect  Neuropsychology  Tetrahydrocannabinol Index. décimale : PER Périodiques Résumé : BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and ?9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and ?9-tetrahydrocannabinol at the same ratio. Participants (N?=?150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n?=?45) versus 21% on placebo (n?=?47; p?=?0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n?=?34) versus 3.6 points after placebo (n?=?36); p?=?0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n?=?95); 23% and 21% on pure-cannabinoids (n?=?93), and 8% and 15% on placebo (n?=?94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226. En ligne : http://dx.doi.org/10.1186/s13229-021-00420-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Lower circulating endocannabinoid levels in children with autism spectrum disorder / Adi ARAN in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 2 p. Titre : Lower circulating endocannabinoid levels in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Adi ARAN, Auteur ; M. EYLON, Auteur ; M. HAREL, Auteur ; L. POLIANSKI, Auteur ; A. NEMIROVSKI, Auteur ; S. TEPPER, Auteur ; A. SCHNAPP, Auteur ; Hanoch CASSUTO, Auteur ; N. WATTAD, Auteur ; J. TAM, Auteur Article en page(s) : 2 p. Langues : Anglais (eng) Mots-clés : *2-arachidonoylglycerol  *Anandamide  *Arachidonic acid  *Autism spectrum disorder  *Biomarkers  *Cannabinoids  *Endocannabinoid system  *N-arachidonoylethanolamine  *N-oleoylethanolamine  *N-palmitoylethanolamine  Board and Israeli Ministry of Health prior to participant enrollment.  Participants' parents provided written consent prior to initiation of any  experimental procedures, and written assent was obtained from participants when  appropriate.Not applicable.The authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods: Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 +/- 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 +/- 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results: Children with ASD had lower levels (pmol/mL, mean +/- SEM) of AEA (0.722 +/- 0.045 vs. 1.252 +/- 0.072, P < 0.0001, effect size 0.91), OEA (17.3 +/- 0.80 vs. 27.8 +/- 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 +/- 0.32 vs. 7.15 +/- 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions: We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0256-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Lower circulating endocannabinoid levels in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Adi ARAN, Auteur ; M. EYLON, Auteur ; M. HAREL, Auteur ; L. POLIANSKI, Auteur ; A. NEMIROVSKI, Auteur ; S. TEPPER, Auteur ; A. SCHNAPP, Auteur ; Hanoch CASSUTO, Auteur ; N. WATTAD, Auteur ; J. TAM, Auteur . - 2 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 2 p. Mots-clés : *2-arachidonoylglycerol  *Anandamide  *Arachidonic acid  *Autism spectrum disorder  *Biomarkers  *Cannabinoids  *Endocannabinoid system  *N-arachidonoylethanolamine  *N-oleoylethanolamine  *N-palmitoylethanolamine  Board and Israeli Ministry of Health prior to participant enrollment.  Participants' parents provided written consent prior to initiation of any  experimental procedures, and written assent was obtained from participants when  appropriate.Not applicable.The authors declare that they have no competing  interests.Springer Nature remains neutral with regard to jurisdictional claims in  published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods: Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 +/- 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 +/- 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results: Children with ASD had lower levels (pmol/mL, mean +/- SEM) of AEA (0.722 +/- 0.045 vs. 1.252 +/- 0.072, P < 0.0001, effect size 0.91), OEA (17.3 +/- 0.80 vs. 27.8 +/- 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 +/- 0.32 vs. 7.15 +/- 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions: We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD. En ligne : https://dx.doi.org/10.1186/s13229-019-0256-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

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