cbd autism research

December 15, 2021 By admin Off

‘Hemp oil’, ‘whole hemp extract’, ‘CBD oil‘(*), ‘CBD full spectrum oil ‘are all names for oil that has been extracted from cannabis/hemp plant. As in most cases such oils contain only negligible levels of THC, they can be sold and purchased legally in most countries (while cannabis strains with high levels of THC are legal in some countries, they usually cannot be imported into UK without medical prescription or special approval).

The benefits, difficulties, challenges of using and matching the right type of cannabis-derived product to each individual and their specific symptoms in real life are best illustrated in this article by Dr Alan Flashman, and experienced clinician who has treated over 500 children with autism with medical cannabis:

(also see ‘What is medicinal cannabis’ section above)

What is the difference between THC and THCA? Does THCA have any health benefits?

“…I try to make the treatment as systematic as possible, despite our ignorance regarding more of the compounds in the cannabis plants we use. I try to get an optimal effect of the appropriate oil (60% of the time the CBD rich oil, 20% of the time the THC rich oil) in the morning dose by increasing by a drop every few days until increase yields no improvement. Then I try to “fine tune” the CBD:THC ration with the other oil in the same way until optimal effect is reached…My experience suggests that this systematic approach creates the most reliable results.

In those at risk , younger age of first cannabis use is associated with earlier onset of schizophrenia and bipolar disorder and worse outcomes. CBD-predominant preparations, and even THCA, may be a useful therapy for children (or adults) with severe developmental/self-harm, schizophrenia, seizures, brain tumors, refractory or rare diseases. In these conditions, CBD (with low or no THC) may be more efficacious with fewer AEs than traditional therapies. (i.e., opioids, antiepileptic etc). Risks and benefits need to be considered.”

In this way endocannabinoids help regulate the functioning of the brain, the gut, the immune and other systems, as well as processing of sensory information, sensation of pain, stress response and recovery, memory and cognitive function, mood and behaviours, including social behaviours , anxiety , appetite and metabolic function, motor function and many others.

NOTE: The information on this page should in no way be seen as a medical advice. Cannabis and cannabis-derived products can have possible contraindications, drug interactions and side-effects, and should therefore only be used under supervision of a qualified practitioner.

“Use of cannabis as medicine in children remains another forbidden territory, but as in any other context, the relative risks and benefits must be weighed… It should be stated emphatically that there is a world of difference scientifically and ethically between judicious administration of low doses of cannabinoids for therapeutic purposes as compared to chronic use of high-dose THC for recreational purposes by teenagers .

Even though TCHA and CBDA , the acidic precursor of CBD found in raw cannabis plant , are not as well researched as their activated forms, there are strong indications that they have numerous health benefits of their own.

Amongst its many actions in the body THC is known to bind to cannabinoid and other receptors that are present on the neurons and in this way it regulates the functioning of the brain .

What are the possible risks and dangers? Does cannabis use lead to brain damage?

Endocannabinoids, as well as plant cannabinoids, also interact and influence the functioning of many other receptors and signalling molecules that are important in autism, such as GABA/glutamate, oxytocin (the social attachment hormone) serotonin and dopamine.

Cannabis-based products that are meant to be applied like a cream and absorbed through the skin are also becoming increasingly available. However, the CBD molecule is not readily absorbed through the skin, and again in most cases only a small amount will reach the bloodstream. For this reason many manufacturers are actively exploring and developing special formulations to improve the skin absorption rate of cannabis compounds. In addition, according to some practitioners and researchers, the site of administration of CBD topical products is just as important. (One experienced clinician for example recommends to his patients to apply creams and oils on the back of the neck and hairline).

Oils that have been extracted from cannabis strains with low levels of THC are usually called CBD oils(*), hemp oils or hemp extracts. The names ‘full spectrum cannabis oil’ or ‘full spectrum cannabis extract’ are sometimes used for oils derived from cannabis strains with higher levels of THC, but in most cases ‘full-spectrum’ refers to a product that has been processed in a way that preserved all the original constituents that were present in the raw plant (see below).

CBD , or cannabidiol, is another cannabinoid compound present in cannabis plants that has been well studied for its effects in the human body. It binds to types of cell receptors that are present on the surface of the immune cells (including the brain immune cells called microglia), gut lining, sensory organs, bone and many other types of tissue.

Some data also exists pointing to possible interactions of cannabinoids with blood thinning medicine such as warfarin .

What is a full-spectrum cannabis/CBD extract?

Terms such as medical cannabis, medicinal cannabis, or medical marijuana, are broad terms that can be used to describe any type of cannabis-based product that is used to relieve symptoms . Sometimes the terms ‘medical cannabis, or ‘medicinal cannabis’ simply means that the product has been prescribed by a doctor .

Cannabis is a genus of flowering plants in the family Cannabaceae. The two main species of cannabis genus of plants are Cannabis sativa and Cannabis indica. Thousands of variations and hybrids of those and other cannabis strains have been cultivated and are in use today.

Borneol has been found in to relieve symptoms of autism – one study observed improved inhibitory control, mental flexibility, and planning in children with autism who were given borneol nasal drops for a period of six months. The improvement in executive functioning were paralleled by activation in the brain networks involved in executive functions. In another study children with autism receiving borneol nasal drops experienced significant improvements in their social and self-control abilities, as well as in their immunologic function.

… It is crucial that autistic children have access to a variety of different whole plant strains. While it is not possible to specify which strains affect which children, I can state as an observed fact that some children respond differentially to different strains despite a similarity in CBD:THC ratios.”

To date several small-scale studies have been published on treatment trials that used cannabis-based products for reducing symptoms of autism. The results of all of those studies were extremely positive and encouraging. Significant reduction in core and comorbid autism symptoms was seen in most participants.

Epidiolex and Sativex, for example, are medical formulation by GW Pharmaceuticals that have undergone extensive clinical trials. Epidiolex has been approved in many countries for treating severe treatment-resistant epilepsy syndromes. It is very expensive, even though it contains only a highly purified form of CBD isolate (see below for detailed explanation of what a CBD isolate is) and not much else. In this way this product does not differ much from many other products that contain CBD isolate and that cost much less than Epidiolex. Sativex on the other hand, is a proprietary whole-plant full-spectrum cannabis extract, which again means that it is not different from many other similar products in a substantial manner. However since most of those other products have not undergone extensive clinical trials, many clinicians would be unable or reluctant to prescribe or recommend them to their patients.

McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347(5):314–21.

Studies in animal models suggest a reduced endocannabinoid tone in ASD [16,17,18,19]. Stimulation of the endocannabinoid system [16,17,18,19] and administration of CBD [17] have improved social deficits in some models. Additionally, children with ASD have been found to have lower peripheral endocannabinoid levels [20, 21].

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Cannabis plants (Topaz strain; BOL Pharma, Israel) were subjected to CO 2 extraction. The extract was either immediately dissolved in olive oil (BOL-DP-O-01-W) or underwent further purification to 99% pure CBD and then was dissolved in olive oil (BOL-DP-O-01). The final concentrations of CBD and THC in both solutions were 167 mg/ml CBD and 8.35 mg/ml THC. Flavorings were added to all three solutions to make taste and scent uniform.

Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY, USA.

Ethics approval and consent to participate.

Adi Aran, Moria Harel, Hanoch Cassuto, Lola Polyansky, Aviad Schnapp & Nadia Wattad.

Wei D, Allsop S, Tye K, Piomelli D. Endocannabinoid signaling in the control of social behavior. Trends Neurosci. 2017;40(7):385–96.

All research procedures were approved by the Shaare Zedek Medical Center Review 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.

You can also search for this author in PubMed Google Scholar.

Aran, A., Harel, M., Cassuto, H. et al. Cannabinoid treatment for autism: a proof-of-concept randomized trial. Molecular Autism 12, 6 (2021). https://doi.org/10.1186/s13229-021-00420-2.

Males were more likely to improve on the HSQ-ASD and SRS-2. Younger children were more likely to improve on the CGI-I and APSI. Participants who had somnolence during cannabinoid treatment were more likely to respond per the CGI-I assessment. However, treatment with the whole-plant extract remained significantly associated with improvement on the CGI-I and SRS-2 after controlling for somnolence and for concomitant use of medications during treatment [Odds Ratio of 6.08 ( p = 0.003) and 3.56 ( p = 0.015), respectively].

The clinician assessment was based on a detailed description of the most bothersome behavioral problems at baseline and an extensive interview at the end of each treatment period focused on those problems. Using this patient- and family-centered tool customized for each participant, we found that 49% of participants receiving the whole-plant extract treatment responded versus 21% on placebo ( p = 0.005).

Accepted : 27 January 2021.

Intriguingly, one of our secondary outcomes, the SRS-2, provided preliminary evidence that cannabinoid treatment might improve core symptoms of ASD (Table 4). This finding could be of high importance if confirmed in future studies, as studies exploring pharmacological interventions for the ASD core symptoms are scarce.

Screening, randomization and attrition are shown in Fig. 2 and participant characteristics are provided in Table 2. Fifty participants were randomly assigned to each of the 3 treatments in Period-1 and 44 per group completed the study (12% overall attrition).

Background.

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).

The endocannabinoid system is a cell-signaling system composed of the cannabinoid receptors, their endogenous ligands (endocannabinoids, mainly anandamide and 2-AG), transporters, and enzymes which produce and degrade the endocannabinoids [15].

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Keller R, Basta R, Salerno L, Elia M. Autism, epilepsy, and synaptopathies: a not rare association. Neurol Sci. 2017;38(8):1353–61.

Ferber SG, Namdar D, Hen-Shoval D, Eger G, Koltai H, Shoval G, et al. The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol. 2020;18(2):87–96.

Campos AC, Fogaca MV, Scarante FF, Joca SRL, Sales AJ, Gomes FV, et al. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Front Pharmacol. 2017;8:269.

HSQ-ASD [33] is a 24-item parent-rated measure of noncompliant behavior in children with ASD. The scale yields per-item mean scores of 0 to 9 (higher is worse) [33].

Additional file 2.

Aran A, Eylon M, Harel M, Polianski L, Nemirovski A, Tepper S, et al. Lower circulating endocannabinoid levels in children with autism spectrum disorder. Mol Autism. 2019;10:2.

Primary outcomes: We designated two co-primary outcome measures to assess ASD associated disruptive behaviors: Home Situations Questionnaire-ASD (HSQ-ASD) and CGI-Improvement (CGI-I) targeting behavioral problems.

These preclinical data and case-series, reporting treatment with artisanal CBD-rich, cannabis strains [22,23,24,25,26] have triggered widespread use of various cannabis strains in children with ASD, despite a lack of controlled studies. Furthermore, the cannabis plant contains a wide range of minor cannabinoids, terpenes, and flavonoids which differ by strain. These components have also been reported to impact human behaviour [27, 28]. Various combinations of these components have been proposed to have a synergistic pharmacological effect (‘the entourage effect’) [29]. Whether presumed effects of cannabis in ASD should be attributed to CBD or THC, or whether minor cannabinoids, terpenes, and flavonoids also contribute therapeutically remains unclear. Accordingly, we performed a proof-of-concept, placebo-controlled trial of whole-plant extract and pure cannabinoids in children and adolescents with ASD. We hypothesized that whole-plant extract, per the entourage effect, would be more effective than placebo for disruptive behaviors; assessing this hypothesis was our primary objective. A secondary objective was to assess the efficacy of pure cannabinoids which are more standardized and repeatable than whole-plant extracts and hence more suitable for pharmacotherapy.

Fleury-Teixeira P, Caixeta FV, Ramires da Silva LC, Brasil-Neto JP, 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.

The primary objective was to evaluate whether whole-plant cannabis extract would induce a significant improvement in behavioral assessments compared to placebo. We used the same CBD: THC ratio as in previous open-label case series [22,23,24]. We did not use a ‘CBD only’ arm in this initial study, as we hypothesized that the CBD-THC combination would be more efficacious because of direct effects of THC on the endocannabinoid system.

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There were no treatment-related severe or serious AEs. Six participants had an unrelated serious event (Additional file 1: Table S1). Overall, mild AEs were not significantly more frequent during cannabinoid treatment (mild AEs were reported 383, 388, and 353 times, in 89, 79, and 78 participants during treatment with whole-plant extract, pure cannabinoids, and placebo, respectively). Moderate AEs were reported 80, 78, and 57 times, in 44, 45, and 26 participants during treatment with whole-plant extract, pure cannabinoids, and placebo, respectively. AEs that were more common during cannabinoid treatment are presented in Table 3. The full list of adverse events and correlations with age, sex, treatment dose, and concomitant medications appears in Additional file 1: Table S2.

Published : 03 February 2021.