Dados do Trabalho

Título

IMPACT OF CBD-DOMINANT FULL-SPECTRUM PHYTOCANNABINOID EXTRACT ON NEUROBEHAVIORAL MANAGEMENT IN CHILDREN AND ADOLESCENTS WITH MODERATE TO SEVERE NON-SYNDROMIC AUTISM SPECTRUM DISORDER: CLINICAL AND FAMILY IMPLICATIONS"

Introdução

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, and behavior. Current pharmacological treatments are limited and often associated with significant side effects. As interest in alternative therapies grows, cannabidiol (CBD)-dominant extracts have emerged as a potential treatment for managing ASD symptoms.

Objetivo

The study aims to evaluate the effectiveness and safety of a CBD-dominant full-spectrum phytocannabinoid extract in improving neurobehavioral symptoms in children and adolescents with moderate to severe non-syndromic ASD. The study also seeks to explore whether this treatment can enhance the overall quality of life for both patients and their families.

Método

This was a retrospective, observational, and cross-sectional cohort study conducted at the University Hospital of Brasília. A total of 30 participants, aged 5 to 18 years, diagnosed with moderate to severe ASD, were treated with individualized doses of a CBD-dominant extract containing THC in a 33:1 ratio. Clinical assessments were performed regularly, and caregivers were interviewed to obtain their perceptions of the treatment's impact on the patients' symptoms and quality of life.

Resultados

The study found significant improvements in several key areas, including communication skills, attention, learning abilities, and social interactions. Additionally, reductions in aggression, irritability, and other maladaptive behaviors were observed. Statistically, 70% of participants showed improvements in these domains, with minimal side effects, which were manageable by adjusting the dosage of the extract. These improvements were reflected not only in clinical assessments but also in the caregivers' reports, which indicated enhanced quality of life for both the patients and their families.

Conclusão

In the present study, we show that the benefits of treatment with full-spectrum CBD
oil for non-syndromic individuals with ASD are not only noticeable to the clinical eye but are also perceived and experienced by the families and caregivers. In short, the findings corroborate that this treatment, combined with a gradual and individualized dosage regimen, is safe and efficient for broader treatment of central and comorbid symptoms associated with ASD, being able to improve aspects such as social interaction, communication and quality of life.

Referências

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association Publishing: Washington, DC, USA, 2022; ISBN 0-89042-575-2.
2. Shuster, J.; Perry, A.; Bebko, J.; Toplak, M.E. Review of Factor Analytic Studies Examining Symptoms of Autism Spectrum Disorders. J. Autism Dev. Disord. 2014, 44, 90–110. [CrossRef]
3. Turnock, A.; Langley, K.; Jones, C.R.G. Understanding Stigma in Autism: A Narrative Review and Theoretical Model. Autism Adulthood 2022, 4, 76–91. [CrossRef] [PubMed]
4. Elsabbagh, M.; Divan, G.; Koh, Y.; Kim, Y.S.; Kauchali, S.; Marcín, C.; Montiel-Nava, C.; Patel, V.; Paula, C.S.; Wang, C.; et al. Global Prevalence of Autism and Other Pervasive Developmental Disorders. Autism Res. 2012, 5, 160–179. [CrossRef] [PubMed]
5. Khachadourian, V.; Mahjani, B.; Sandin, S.; Kolevzon, A.; Buxbaum, J.D.; Reichenberg, A.; Janecka, M. Comorbidities in Autism
Spectrum Disorder and Their Etiologies. Transl. Psychiatry 2023, 13, 71. [CrossRef] [PubMed]
6. Takarae, Y.; Sweeney, J. Neural Hyperexcitability in Autism Spectrum Disorders. Brain Sci. 2017, 7, 129. [CrossRef] [PubMed]
7. Chez, M.G.; Chang, M.; Krasne, V.; Coughlan, C.; Kominsky, M.; Schwartz, A. Frequency of Epileptiform EEG Abnormalities in a
Sequential Screening of Autistic Patients with No Known Clinical Epilepsy from 1996 to 2005. Epilepsy Behav. 2006, 8, 267–271.
[CrossRef] [PubMed]
8. Markram, K.; Markram, H. The Intense World Theory—A Unifying Theory of the Neurobiology of Autism. Front. Hum. Neurosci.
2010, 4, 224. [CrossRef]
9. Devlin, B.; Scherer, S.W. Genetic Architecture in Autism Spectrum Disorder. Curr. Opin. Genet. Dev. 2012, 22, 229–237. [CrossRef]
[PubMed]
10. Siniscalco, D.; Sapone, A.; Giordano, C.; Cirillo, A.; de Magistris, L.; Rossi, F.; Fasano, A.; Bradstreet, J.J.; Maione, S.; Antonucci, N.
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, 2686–2695. [CrossRef]
11. Szabo, B.; Schlicker, E. Effects of Cannabinoids on Neurotransmission. In Cannabinoids; Springer: Berlin/Heidelberg, Germany,
2005; pp. 327–365.
12. Aran, A.; Eylon, M.; Harel, M.; Polianski, L.; Nemirovski, A.; Tepper, S.; Schnapp, A.; Cassuto, H.; Wattad, N.; Tam, J. Lower
Circulating Endocannabinoid Levels in Children with Autism Spectrum Disorder. Mol. Autism 2019, 10, 2. [CrossRef]
13. Adler, B.A.; Wink, L.K.; Early, M.; Shaffer, R.; Minshawi, N.; McDougle, C.J.; Erickson, C.A. Drug-Refractory Aggression, Self-Injurious Behavior, and Severe Tantrums in Autism Spectrum Disorders: A Chart Review Study. Autism 2015, 19, 102–106.
[CrossRef] [PubMed]
14. Hirota, T.; Veenstra-VanderWeele, J.; Hollander, E.; Kishi, T. Antiepileptic Medications in Autism Spectrum Disorder: A Systematic
Review and Meta-Analysis. J. Autism Dev. Disord. 2014, 44, 948–957. [CrossRef]
15. Fung, L.K.; Mahajan, R.; Nozzolillo, A.; Bernal, P.; Krasner, A.; Jo, B.; Coury, D.; Whitaker, A.; Veenstra-Vanderweele, J.; Hardan,
A.Y. Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-Analysis.
Pediatrics 2016, 137, S124–S135. [CrossRef] [PubMed]
16. Alsayouf, H.A.; Talo, H.; Biddappa, M.L.; De Los Reyes, E. Risperidone or Aripiprazole Can Resolve Autism Core Signs and
Symptoms in Young Children: Case Study. Children 2021, 8, 318. [CrossRef]
17. Pandina, G.; Ring, R.H.; Bangerter, A.; Ness, S. Current Approaches to the Pharmacologic Treatment of Core Symptoms Across
the Lifespan of Autism Spectrum Disorder. Psychiatr. Clin. N. Am. 2020, 43, 629–645. [CrossRef]
18. Schnabel, A.; Youssef, G.J.; Hallford, D.J.; Hartley, E.J.; McGillivray, J.A.; Stewart, M.; Forbes, D.; Austin, D.W. Psychopathology in Parents of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Prevalence. Autism 2020, 24,
26–40. [CrossRef] [PubMed]
19. Poleg, S.; Golubchik, P.; Offen, D.; Weizman, A. Cannabidiol as a Suggested Candidate for Treatment of Autism Spectrum
Disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 2019, 89, 90–96. [CrossRef] [PubMed]
20. White, C.M. A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. J. Clin. Pharmacol.
2019, 59, 923–934. [CrossRef] [PubMed]
21. Chesney, E.; Oliver, D.; Green, A.; Sovi, S.; Wilson, J.; Englund, A.; Freeman, T.P.; McGuire, P. Adverse Effects of Cannabidiol: A
Systematic Review and Meta-Analysis of Randomized Clinical Trials. Neuropsychopharmacology 2020, 45, 1799–1806. [CrossRef]
22. da Silva Junior, E.A.; Medeiros, W.M.B.; dos Santos, J.P.M.; de Sousa, J.M.M.; da Costa, F.B.; Pontes, K.M.; Borges, T.C.; Espínola Neto Segundo, C.; Andrade e Silva, A.H.; Nunes, E.L.G.; et al. Evaluation of the Efficacy and Safety of Cannabidiol-Rich Cannabis Extract in Children with Autism Spectrum Disorder: Randomized, Double-Blind and Controlled Placebo Clinical Trial. Trends
Psychiatry Psychother 2024, 46, e20210396. [CrossRef]
23. Mostafavi, M.; Gaitanis, J. Autism Spectrum Disorder and Medical Cannabis: Review and Clinical Experience. Semin. Pediatr.
Neurol. 2020, 35, 100833. [CrossRef] [PubMed]
24. Malcher-Lopes, R. Canabinoides Ajudam a Desvendar Aspectos Etiológicos Em Comum e Trazem Esperança Para o Tratamento
de Autismo e Epilepsia. Rev. Biol. 2014, 13, 43–59. [CrossRef]
25. 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. [CrossRef] [PubMed]
26. Aran, A.; Cassuto, H.; Lubotzky, A.; Wattad, N.; Hazan, E. Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems—A Retrospective Feasibility Study. J. Autism Dev. Disord. 2019, 49, 1284–1288. [CrossRef] [PubMed]
27. Fleury-Teixeira, P.; Caixeta, F.V.; Ramires da Silva, L.C.; Brasil-Neto, J.P.; Malcher-Lopes, R. Effects of CBD-Enriched Cannabis Sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use. Front. Neurol. 2019, 10, 1145. [CrossRef] [PubMed]
28. Aran, A.; Harel, M.; Cassuto, H.; Polyansky, L.; Schnapp, A.; Wattad, N.; Shmueli, D.; Golan, D.; Castellanos, F.X. Cannabinoid Treatment for Autism: A Proof-of-Concept Randomized Trial. Mol. Autism 2021, 12, 6. [CrossRef] [PubMed]
29. Barchel, D.; Stolar, O.; De-Haan, T.; Ziv-Baran, T.; Saban, N.; Fuchs, D.O.; Koren, G.; Berkovitch, M. Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-Morbidities. Front. Pharmacol. 2019, 9, 1521. [CrossRef] [PubMed]
30. Ziats, C.A.; Patterson, W.G.; Friez, M. Syndromic Autism Revisited: Review of the Literature and Lessons Learned. Pediatr. Neurol. 2021, 114, 21–25. [CrossRef] [PubMed]
31. Montagner, P.S.S.; Medeiros, W.; da Silva, L.C.R.; Borges, C.N.; Brasil-Neto, J.; de Deus Silva Barbosa, V.; Caixeta, F.V.; Malcher- Lopes, R. Individually Tailored Dosage Regimen of Full-Spectrum Cannabis Extracts for Autistic Core and Comorbid Symptoms: A Real-Life Report of Multi-Symptomatic Benefits. Front. Psychiatry 2023, 14, 1210155. [CrossRef]
32. Russo, E.B. The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain”, No Gain. Front. Plant Sci. 2019, 9, 1969. [CrossRef]
33. Seeman, P. Cannabidiol Is a Partial Agonist at Dopamine D2High Receptors, Predicting Its Antipsychotic Clinical Dose. Transl. Psychiatry 2016, 6, e920. [CrossRef] [PubMed]
34. Hacohen, M.; Stolar, O.E.; Berkovitch, M.; Elkana, O.; Kohn, E.; Hazan, A.; Heyman, E.; Sobol, Y.; Waissengreen, D.; Gal, E.; et al. Children and Adolescents with ASD Treated with CBD-Rich Cannabis Exhibit Significant Improvements Particularly in Social Symptoms: An Open Label Study. Transl. Psychiatry 2022, 12, 375. [CrossRef] [PubMed]
35. Schnitzler, E. The Neurology and Psychopathology of Pica. Curr. Neurol. Neurosci. Rep. 2022, 22, 531–536. [CrossRef] [PubMed

Palavras Chave

Autism Spectrum Disorder (ASD); CBD-dominant full-spectrum; Clinical and Family Implications of Cannabidiol (CBD)