Cannabis-Responsive™ Biomarkers Autism Spectrum Disorder Pilot Study
Why is Cannformatics focused on developing technology to evaluate medical cannabis (MC) products and treatments?
Many medical conditions being treated by MC; autism, anxiety, neurodegenerative diseases, epilepsy, chronic pain, sleep disorders, chemotherapy-induced nausea, vomiting and pain, etc. are complex medical conditions involving the central nervous system and other physiological systems. The complexity of these conditions are why some patients are successful in using MC and others are not. When medical cannabis products are developed to specifically target the mechanism of actions that alleviate symptoms, patient success rates will significantly improve. Going beyond that to providing patients and their HCPs with personalized recommendations that optimize MC treatment to address the unique needs of a patient will further improve positive outcomes.
What is the definition of a Cannabis-Responsive™ biomarker (C-ReB™)?
A C-ReB™ is any metabolite which changes value in response to the presence of at least one cannabinoid.
What technology did Cannformatics develop for identifying, analyzing, and applying C-ReBs?
Cannformatics technology is rooted in metabolomics and lipidomics, the process of detecting, quantifying, and analyzing saliva-based metabolites that change after medical cannabis (MC) treatment.
How long did the technology take to develop? Who is the team behind the technology?
Cannformatics spent over three-years in research and development developing and implementing its technology and methodologies with a multi-disciplinary team of experts in biochemistry, bioinformatics, data science, neuropsychology, pediatrics, integrative medicine, emergency medicine and the medical cannabis industry prior to conducting the ASD Pilot Study.
What are the potential applications of Cannformatics technology?
Cannformatics technology was developed to show how all cannabis/CBD products (flower, edibles, tinctures, beverages, etc.) and consumption methods impact the body. The technology can be used to develop new cannabis and CBD products, optimize the use of medical cannabis in reaching wellness goals, personalize MC treatment for complex medical conditions, as well as to determine levels of THC-related intoxication.
How will C-ReBs help to reduce the stigma holding back broader acceptance of MC treatment?
There are a lot of factors that contribute to the stigma surrounding MC. One factor we can help address is by providing data in the same format doctors and patients are used to seeing when evaluating the impact of any medical treatment. C-ReB data changes the conversation from “we need more research” to “let’s look at the data.” We believe when doctors, patients and policymakers have access to objective quantitative evidence that MC treatment moves relevant biomarkers to a healthy physiological range, similar to tools currently used to evaluate prescription medication, there will be less stigma around patients taking MC and providers recommending it.
Why was this study important for Cannformatics?
This study validates that our technology and methodology are effective in evaluating medical cannabis treatment. It shows that C-ReBs can determine if a dose is the correct amount and how often a patient should take MC to manage their symptoms.
Future studies will provide the data necessary for determining what cannabinoids will have the greatest impact in helping you manage your medical condition.
The technology and methodologies developed for the ASD study establishes a roadmap for future studies of other medical conditions.
ABOUT THE ASD PILOT STUDY
Why did you choose ASD as your first study?
We are fortunate to have Dr. Bonni Goldstein on our Advisory Board. Dr. Goldstein is a pediatrician, who is also recognized as a leading expert in medical cannabis treatments. Dr. Goldstein suggested that the families she works with as well as other families in the ASD community would be excited to participate in a study that would start to shed light on how MC was physiologically impacting children with ASD. In addition, because children with ASD often have a wide range of neurological symptoms we anticipated we would find C-ReBs related to various aspects of the central nervous system’s metabolic pathways.
What were the study objectives?
Cannformatics had two objectives for the ASD Pilot Study. First, to conclusively demonstrate the company’s technology and saliva-based methodology were effective in identifying and analyzing C-ReBs, a new class of biomarkers. Second, to demonstrate C-ReBs’ ability to suggest the metabolic pathways of children with ASD that respond to MC treatment.
Does this study conclusively show MC is effective at treating ASD?
No. This study showed that MC treatment is impacting children with ASD at the metabolic level and that the changes observed correlate with changes in behavioral surveys. To determine MC effectiveness conclusively would require a double-blind clinical study. This study was an observational study of children who are successfully using cannabis. The study was not designed to conclusively prove MC effectiveness.
Who were the study participants?
The study participants were a racially, ethnically, socio-economic diverse group of 15 children ages 6-12 years old, 13 boys and 2 girls, with moderate-to-severe ASD symptoms. All the participating children were being successfully treated with MC and/or CBD for at least a year. In addition, nine typically developing (TD) children of a similar age and gender mix provided saliva samples and behavior surveys to establish a TD physiological range.
Has anyone else done a similar study?
To our knowledge this is the first study to ever examine the metabolic response of children with ASD treated with widely available off-the-shelf MC or CBD products sold by state licensed dispensaries.
Why is this study important?
Whether it is traditional pharmaceuticals (anti-anxiety, antipsychotics, anti-depressive) or MC none of these treatments have been studied in terms of understanding how any of these drugs metabolically impact children with ASD. This study begins to provide the autism community, healthcare providers and policymakers with objective data demonstrating the physiological impact of MC/CBD on children with ASD. While this was a small study in terms of participants, it is a giant leap forward towards giving families peace of mind that we are seeing changes at the metabolic level in response to MC treatment.
What MC/CBD products were used in the study?
Participants in the study took the MC/CBD products they have been successfully using for at least a year. Each child had their own unique formulation some with and without THC. Please see Table 1 in the paper to see each child’s cannabinoid mix.
How does Cannformatics determine what C-ReBs are relevant for ASD?
There are three critical datasets needed to determine what metabolites are C-ReBs and if those C-ReBs are relevant for patients with ASD. The first dataset comes from the saliva samples collected before the patients take their first daily dose of cannabis. In the study this data is referred to as the “PRE” meaning pre-dose. The second dataset comes from the saliva samples taken 90-120 minutes after the first dose. In the study this data is referred to as the “PEAK” meaning the approximate time when the first dose is fully impacting the body. The third dataset comes from the saliva samples of typically developing (TD) children the same age and gender mix as the study participants. The data from the TD group establishes a physiological range for the metabolites. We then compare the participants PRE and PEAK data to the physiological range. When we find a metabolite that is present in at least 70% of the participants that was out range in the PRE sample and moves to the TD physiological range in the PEAK sample, we recognize it as a relevant C-ReB in this study.
How many C-REBs were identified? What do the biomarkers indicate?
The Study identified 65 potential C-ReBs. 23 of the C-ReBs were categorized as anti-inflammatory, bioenergy-associated, neurotransmitters, amino acids, and endocannabinoids. Three C-ReBs; N-acetylaspartic acid (NAA), spermine and dehydroisoandrosterone 3-sulfate (DHEA-sulfate) were previously linked to behavioral symptoms commonly observed in individuals with ASD and/or neurological disorders. Importantly, qualitative behavioral studies correlated with the C-ReBs show that participants in the study treated with MC saw improved behavior trends.
Do you anticipate publishing additional findings from this study?
This study demonstrates that C-ReBs found in the saliva of children with ASD being treated with MC can be objectively quantified. It is well documented that autism is associated with abnormal lipid metabolism. Therefore, we applied lipidomics to the participant samples to see if we could identify additional C-ReBs and provide early insights into the role of MC treatment on lipid metabolism. A lipidomics-based paper is currently in preparation and is expected to be published in the coming months.
Do the results from the pilot study have implications for other medical conditions?
The variety of C-ReBS that were identified give us confidence that our technology and methodology can be applied to any medical condition treated by MC. Further, study results show the potential of C-ReBs to provide insights into the central nervous system’s metabolic pathways. Our aim is to open the potential to improve medical cannabis treatment for people with autism of all ages as well as to expand our platform to provide insights for chronic neuropathic pain, anxiety, and chemotherapy-induced nausea and vomiting.
How will the results from this study be used for personalizing MC treatment?
The identified C-ReBs lay the foundation of Cannformatics proprietary AI-driven bioinformatics platform to predict, without using medical cannabis (pre-dosing), the impact of MC treatment on an individual. In addition, we plan to provide personalized recommendations on the best fit product, dosage and consumption method based on a patient’s own C-ReBs and our database.
What are the next steps for the ASD Study?
Cannformatics is currently seeking funding to conduct a larger study with individuals of all ages with ASD using MC treatment to manage symptoms. This larger study is necessary to confirm the suggested findings from the pilot study and establish a database significant enough to provide recommendation services to the ASD community.