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BMC Psychiatry
Published in: BMC Psychiatry 1/2019

Open Access 01-12-2019 | Autism Spectrum Disorder | Debate

Current state of evidence of cannabis utilization for treatment of autism spectrum disorders

Authors: Rumi Agarwal, Shanna L. Burke, Marlaina Maddux

Published in: BMC Psychiatry | Issue 1/2019

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Abstract

The core symptoms and co-morbidities associated with autism spectrum disorders (ASD) affect daily living and quality of life. Existing pharmacological interventions are only able to attenuate some related symptoms but are unable to address the underlying etiologies associated with ASD. Anecdotal evidence, which claims benefit from the use of cannabis to treat symptoms among this population, has been gaining popularity as families seek solutions.
This paper analyzed recent peer-reviewed literature to identify the current state of evidence regarding cannabis use for the ASD population. Systematic reviews, reports, and experimental studies were assessed to understand the current extent and nature of the evidence on the risks and benefits of cannabis use for ASD. At this time, three large-scale clinical trials are currently at varying stages of progress and publication of results. Only five small studies were identified that have specifically examined cannabis use in ASD. Given the sparse state of evidence directly assessed in this population, studies which examined effects of cannabis on shared pathological symptoms of ASD such as hyperactivity, sleep disorders, self-injury, anxiety, behavioral problems, and communication were also reviewed.
Studies revealed mixed and inconclusive findings of cannabis effects for all conditions, except epilepsy. Adverse outcomes were also reported, which included severe psychosis, increased agitation, somnolence, decreased appetite, and irritability. In addition, a wide range of cannabis compositions and dosage were identified within the studies, which impact generalizability.
There is currently insufficient evidence for cannabis use in ASD, which creates an urgent need for additional large-scale controlled studies to increase understanding of risks and benefits and also to examine the impact of “entourage effects.” This will support discussions of treatment options between health care providers and ASD patients and their families. Evidence may lead to a desired new line of treatment or prevent adverse outcomes from unsubstantiated use amongst families aiming for symptom reduction.
Literature
1.
Bridgeman MB, Abazia DT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. Pharm Ther. 2017;42:180–8.
2.
National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC: The National Academies Press; 2017. https://​doi.​org/​10.​17226/​24625.CrossRef
3.
4.
5.
Gregario J. Physicians, medical marijuana, and the law. Am Med Assoc J Ethics. 2014;16:732–8.
6.
7.
8.
9.
Russo EB. Cannabis and epilepsy: an ancient treatment returns to the fore. Epilepsy Behav. 2017;70:292–7.CrossRefPubMed
10.
Nuutinen T. Medicinal properties of terpenes found in cannabis sativa and humulus lupulus. Eur J Med Chem. 2018;157:198–228.CrossRefPubMed
11.
Baron EP. Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: an update on current evidence and cannabis science. Headache J Head Face Pain. 2018;58:1139–86.CrossRef
12.
13.
Abrams DI. The therapeutic effects of cannabis and cannabinoids: an update from the national academies of sciences, engineering and medicine report. Eur J Intern Med. 2018;49:7–11.CrossRefPubMed
14.
MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12–9.CrossRefPubMed
15.
16.
Gu B. Cannabidiol provides viable treatment opportunity for multiple neurological pathologies of autism spectrum disorder. Glob Drugs Ther. 2017;2:1–4.
17.
Siniscalco D. Current findings and research prospective in autism spectrum disorders. Autism. 2013;10:2165.
18.
Wei D, Dinh D, Lee D, Li D, Anguren A, Moreno-Sanz G, et al. Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment. Cannabis Cannabinoid Res. 2016;1:81–9.CrossRefPubMedPubMedCentral
19.
Salgado CA, Castellanos D. Autism spectrum disorder and cannabidiol: have we seen this movie before? Glob Pediatr Health. 2018;5:1–5.
20.
Kidd VD. Cannabinoids in the treatment of autism spectrum disorder: demanding data before using fad therapies. Pediatr Neurol. 2018;88:10–1.CrossRefPubMed
21.
22.
23.
24.
Maccarrone M, Rossi S, Bari M, De Chiara V, Rapino C, Musella A, et al. Abnormal mGlu 5 receptor/endocannabinoid coupling in mice lacking FMRP and BC1 RNA. Neuropsychopharmacol. 2010;35:1500–9.CrossRef
25.
Pietropaolo S, Guilleminot A, Martin B, D’Amato FR, Crusio WE. Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice. PLoS One. 2011;6:e17073.CrossRefPubMedPubMedCentral
26.
Jung K-M, Sepers M, Henstridge CM, Lassalle O, Neuhofer D, Martin H, et al. Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome. Nat Commun. 2012;3:1080.CrossRefPubMed
27.
Wang J, Ueda N. Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat. 2009;89:112–9.CrossRefPubMed
28.
29.
McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 2008;7:152–63.CrossRefPubMed
30.
Silverman JL, Tolu SS, Barkan CL, Crawley JN. Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. Neuropsychopharmacol. 2010;35:976–89.CrossRef
31.
Onaivi ES, Benno R, Halpern T, Mehanovic M, Schanz N, Sanders C, et al. Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders. Curr Neuropharmacol. 2011;9:209–14.CrossRefPubMedPubMedCentral
32.
McTighe SM, Neal SJ, Lin Q, Hughes ZA, Smith DG. The BTBR mouse model of autism spectrum disorders has learning and attentional impairments and alterations in acetylcholine and kynurenic acid in prefrontal cortex. PLoS One. 2013;8:e62189.CrossRefPubMedPubMedCentral
33.
Benno R, Smirnova Y, Vera S, Liggett A, Schanz N. Exaggerated responses to stress in the BTBR T+tf/J mouse: an unusual behavioral phenotype. Behav Brain Res. 2009;197:462–5.CrossRefPubMed
34.
Földy C, Malenka RC, Südhof TC. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron. 2013;78:498–509.CrossRefPubMedPubMedCentral
35.
Di Marzo V. Endocannabinoid signaling in the brain: biosynthetic mechanisms in the limelight. Nat Neurosci. 2011;14:9–15.CrossRefPubMed
36.
Li C, Jones PM, Persaud SJ. Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol Ther. 2011;129:307–20.CrossRefPubMed
37.
38.
Kerr DM, Downey L, Conboy M, Finn DP, Roche M. Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav Brain Res. 2013;249:124–32.CrossRefPubMed
39.
Roullet FI, Lai JKY, Foster JA. In utero exposure to valproic acid and autism — a current review of clinical and animal studies. Neurotoxicol Teratol. 2013;36:47–56.CrossRefPubMed
40.
Siniscalco D, Sapone A, Giordano C, Cirillo A, de Magistris L, Rossi F, et al. Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders. J Autism Dev Disord. 2013;43:2686–95.CrossRefPubMed
41.
Chakrabarti B, Kent L, Suckling J, Bullmore E, Baron-Cohen S. Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces. Eur J Neurosci. 2006;23:1944–8.CrossRefPubMed
42.
Domschke K, Dannlowski U, Ohrmann P, Lawford B, Bauer J, Kugel H, et al. Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in major depression. Eur Neuropsychopharmacol. 2008;18:751–9.CrossRefPubMed
43.
Schultz S, Siniscalco D. Endocannabinoid system involvement in autism spectrum disorder: an overview with potential therapeutic applications. AIMS Mol Sci. 2019;6:27–37.CrossRef
44.
Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30:1037–43.CrossRefPubMed
45.
Crippa JA, Zuardi AW, Guimaraes FS. Possible mechanisms involved in the antipsychotic effects of cannabidiol (CBD). Schizophr Bull. 2018;44(Suppl 1):S28.CrossRefPubMedCentral
46.
van der Stelt M, Di Marzo V. The endocannabinoid system in the basal ganglia and in the mesolimbic reward system: implications for neurological and psychiatric disorders. Eur J Pharmacol. 2003;480:133–50.CrossRefPubMed
47.
Fernández-Ruiz J, Hernández M, Ramos JA. Cannabinoid-dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther. 2010;16:e72–91.CrossRefPubMedPubMedCentral
48.
Busquets-Garcia A, Gomis-González M, Guegan T, Agustín-Pavón C, Pastor A, Mato S, et al. Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat Med. 2013;19:603–7.CrossRefPubMed
49.
Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacother J Hum Pharmacol Drug Ther. 2013;33:195–209.CrossRef
50.
51.
Siniscalco D, Bradstreet JJ, Cirillo A, Antonucci N. The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. J Neuroinflammation. 2014;11:78.CrossRefPubMedPubMedCentral
52.
Premoli M, Aria F, Bonini SA, Maccarinelli G, Gianoncelli A, Pina SD, et al. Cannabidiol: recent advances and new insights for neuropsychiatric disorders treatment. Life Sci. 2019;224:120–7.CrossRefPubMed
53.
54.
55.
Pretzsch CM, Freyberg J, Voinescu B, Lythgoe D, Horder J, Mendez MA, et al. Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacology. 2019;44:1398.CrossRefPubMedPubMedCentral
56.
57.
58.
59.
Bar-Lev Schleider L, Mechoulam R, Saban N, Meiri G, Novack V. Real life experience of medical cannabis treatment in autism: analysis of safety and efficacy. Sci Rep. 2019;9:200.CrossRefPubMedPubMedCentral
60.
61.
Chowdhury M, Aman MG, Lecavalier L, Smith T, Johnson C, Swiezy N, et al. Factor structure and psychometric properties of the revised home situations questionnaire for autism spectrum disorder: the home situations questionnaire-autism Spectrum disorder. Autism Int J Res Pract. 2016;20:528–37.CrossRef
62.
Silva LMT, Schalock M. Autism parenting stress index: initial psychometric evidence. J Autism Dev Disord. 2012;42:566–74.CrossRefPubMed
63.
King BH, Dukes K, Donnelly CL, Sikich L, McCracken JT, Scahill L, et al. Baseline factors predicting placebo response to treatment in children and adolescents with autism Spectrum disorders: a multisite randomized clinical trial. JAMA Pediatr. 2013;167:1045–52.CrossRefPubMedPubMedCentral
64.
Kuester G, Vergara K, Ahumada A, Gazmuri AM. Oral cannabis extracts as a promising treatment for the core symptoms of autism spectrum disorder: preliminary experience in Chilean patients. J Neurol Sci. 2017;381:932–3.CrossRef
65.
Guy W, National Institute of Mental Health (U.S.). Psychopharmacology Research Branch. Division of Extramural Research Programs. ECDEU assessment manual for psychopharmacology. Rockville, Md. : U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. http://​archive.​org/​details/​ecdeuassessmentm​1933guyw. Accessed 22 Jul 2019.
66.
Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985;89:485–91.PubMed
67.
Kurz R, Blaas K. Use of dronabinol (delta-9-THC) in autism: a prospective single-case-study with an early infantile autistic child. Cannabinoids. 2010;5:4–6.
68.
Poleg S, Golubchik P, Offen D, Weizman A. Cannabidiol as a suggested candidate for treatment of autism spectrum disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;89:90–6.CrossRef
69.
Anderson CL, Evans VF, DeMarse TB, Febo M, Johnson CR, Carney PR. Cannabidiol for the treatment of drug-resistant epilepsy in children: current state of research. J Pediatr Neurol. 2017;15:143–50.CrossRef
70.
Sulak D, Saneto R, Goldstein B. The current status of artisanal cannabis for the treatment of epilepsy in the United States. Epilepsy Behav. 2017;70:328–33.CrossRefPubMed
71.
Gaston TE, Friedman D. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav. 2017;70:313–8.CrossRefPubMed
72.
Suraev AS, Todd L, Bowen MT, Allsop DJ, McGregor IS, Ireland C, et al. An Australian nationwide survey on medicinal cannabis use for epilepsy: history of antiepileptic drug treatment predicts medicinal cannabis use. Epilepsy Behav. 2017;70:334–40.CrossRefPubMed
73.
74.
Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456–73.CrossRefPubMed
75.
Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med Rev. 2014;18:477–87.CrossRefPubMed
76.
Nicholson AN, Turner C, Stone BM, Robson PJ. Effect of Δ-9-tetrahydrocannabinol and Cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol. 2004;24:305–13.CrossRefPubMed
77.
Richards C, Moss J, Nelson L, Oliver C. Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: A prospective cohort study of risk markers. J of Neurodev Disord. 2016;8:21.
78.
Bergamaschi MM, Queiroz RHC, Chagas MHN, de Oliveira DCG, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-Naïve social phobia patients. Neuropsychopharmacology. 2011;36:1219–26.CrossRefPubMedPubMedCentral
79.
Blanco C, Hasin DS, Wall MM, Flórez-Salamanca L, Hoertel N, Wang S, et al. Cannabis use and risk of psychiatric disorders: prospective evidence from a US national longitudinal study. JAMA Psychiatry. 2016;73:388–95.CrossRefPubMed
80.
Feingold D, Weiser M, Rehm J, Lev-Ran S. The association between cannabis use and anxiety disorders: results from a population-based representative sample. Eur Neuropsychopharmacol. 2016;26:493–505.CrossRefPubMed
81.
Sagar A, Bishop JR, Tessman DC, Guter S, Martin CL, Cook EH. Co-occurrence of autism, childhood psychosis, and intellectual disability associated with a de novo 3q29 microdeletion. Am J Med Genet A. 2013;161:845–9.CrossRefPubMedCentral
82.
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2017;175:225–31.CrossRefPubMed
83.
Rubino T, Parolaro D. The impact of exposure to cannabinoids in adolescence: insights from animal models. Biol Psychiatry. 2016;79:578–85.CrossRefPubMed
84.
D’Souza DC, Ranganathan M. Medical marijuana: is the cart before the horse? JAMA. 2015;313:2431–2.CrossRefPubMed
85.
De Alwis D, Agrawal A, Reiersen AM, Constantino JN, Henders A, Martin NG, et al. ADHD symptoms, autistic traits, and substance use and misuse in adult Australian twins. J Stud Alcohol Drugs. 2014;75:211–21.CrossRefPubMedPubMedCentral
86.
Cooper RE, Williams E, Seegobin S, Tye C, Kuntsi J, Asherson P. Cannabinoids in attention-deficit/hyperactivity disorder: a randomised-controlled trial. Eur Neuropsychopharmacol. 2017;27:795–808.CrossRefPubMed
87.
Harrison KL, Zane T. Focus on science: is there science behind that?: autism and treatment with marijuana. Sci Autism Treat. 2017;14:12–5.
88.
Dryburgh LM, Bolan NS, Grof CPL, Galettis P, Schneider J, Lucas CJ, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Br J Clin Pharmacol. 2018;84:2468–76.CrossRefPubMedPubMedCentral
89.
Arora M, Reichenberg A, Willfors C, Austin C, Gennings C, Berggren S, et al. Fetal and postnatal metal dysregulation in autism. Nat Commun. 2017;8:15493.CrossRefPubMedPubMedCentral
90.
Duvall SW, Lindly O, Zuckerman K, Msall ME, Weddle M. Ethical implications for providers regarding Cannabis use in children with autism Spectrum disorders. Pediatrics. 2019;143:e20180558.CrossRefPubMed
Metadata
Title
Current state of evidence of cannabis utilization for treatment of autism spectrum disorders
Authors
Rumi Agarwal
Shanna L. Burke
Marlaina Maddux
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2019
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-019-2259-4

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