The University of California San Diego’s Center for Medicinal Cannabis Research conducted a controlled clinical trial of CBD in boys with severe autism. Results from the research showed the therapeutic potential of CBD in reducing aggression and hyperactivity. Based on their findings, nearly two-thirds of participants demonstrating clinician-assessed improvement, and no serious side effects reported. 

This emerging research provides a timely backdrop for exploring CBDa (cannabidiolic acid), the raw, unheated precursor to CBD found in fresh hemp. Unlike CBD, CBDa retains its acidic form and may offer unique therapeutic properties such as potent anti-inflammatory, anti-anxiety, and potentially neuroprotective effects which could be useful in supporting children with ASD.

In this article, we dive into the evolving science on CBDa and autism, building directly on the momentum of the UC San Diego trial. We’ll explain how CBDa works in the endocannabinoid system, review the limited but promising research and expert commentary, assess safety considerations for children with ASD, and offer guidance on choosing high-quality raw hemp products. Whether you're a parent exploring CBDa for autism support or a healthcare provider assessing integrative options, this guide aims to present balanced and evidence-informed insights, without hype and without overpromising.

What Is CBDa?

Cannabidiolic acid (CBDa) is the natural, acidic precursor of cannabidiol (CBD). It is mostly abundant in raw hemp and cannabis plants before any exposure to heat or light. It is synthesized in the plant from cannabigerolic acid (CBGA) via specific plant enzymes. When exposed to heat through smoking, baking, or extraction processes, decarboxylation removes a carboxyl group from CBDa, converting it into neutral CBD. 

While most CBD products on the market come from processed hemp that has been heated to increase CBD concentration, CBDa remains in its natural, acidic form when extracted using cold or solventless methods. Recent research has shown that CBDa interacts differently with the body’s endocannabinoid system compared to CBD. It appears to influence serotonin receptors (5-HT1A) and inflammatory pathways more directly, which could be particularly relevant for individuals with autism who experience anxiety, mood dysregulation, or chronic inflammation.

CBDa vs. CBD

Although both CBDa and CBD come from the same hemp plant, their differences begin with how they’re processed and those differences significantly affect how they work in the body.

CBDa is found in raw, unheated hemp, while CBD is produced when CBDa undergoes heat treatment in a process called decarboxylation. This chemical change alters the way each compound interacts with the body’s systems. For example, CBDa appears to have a stronger effect on serotonin receptors and inflammatory pathways, which may be especially helpful in addressing symptoms like anxiety, nausea, and chronic inflammation.  Research shows that CBda is 1000 times more active than CBD in interacting with serotonin receptors. In contrast, CBD interacts more broadly with the endocannabinoid system (ECS) and has been widely studied for its potential benefits in conditions like seizures, chronic pain, and generalized anxiety. Another notable difference is bioavailability. This refers to the body’s ability to absorb and use a compound. Studies suggest that CBDa may have higher bioavailability than CBD, particularly when preserved in its raw form. This could mean that smaller doses of CBDa may offer more targeted effects with less risk of side effects. Follow this link to Learn more about CBDa vs. CBD. 

Understanding Autism Spectrum Disorder (ASD)

Autism Spectrum Disorder (ASD) is a developmental condition that affects how individuals communicate, interact, and process sensory information. The term “spectrum” reflects the wide variation in symptoms and severity from children who are nonverbal and require round-the-clock care, to those with high-functioning autism who may excel academically but struggle socially or emotionally.

Some of the most common symptoms include:

• Difficulty with verbal and nonverbal communication
• Repetitive behaviors and rigid routines
• Sensory processing challenges
• Delayed developmental milestones
• High levels of anxiety, agitation, or emotional dysregulation

Many children with autism also experience sleep disturbances, digestive issues, and co-occurring conditions such as ADHD, epilepsy, or intellectual disability. Managing these overlapping challenges often requires a team-based approach involving behavioral therapy, speech and occupational therapy, specialized education plans, and, in some cases, prescription medications. See our article on autism statistics for more information on autism. 

While medications like antipsychotics or stimulants may offer symptom control, they often come with side effects such as weight gain, fatigue, irritability, or even increased aggression over time. As a result, many families are exploring natural alternatives for autism, especially those that support neurological balance and reduce inflammation without compromising safety.

Relationship between autism spectrum disorder and endocannabinoid system

Scientific interest in the endocannabinoid system (ECS) has grown significantly in recent years, particularly in relation to neurological and developmental conditions such as Autism Spectrum Disorder (ASD). The ECS is a complex cell-signaling network found throughout the body. It plays a central role in regulating mood, sleep, appetite, immune response, pain, and neurological development.

The ECS consists of three main components:

• Endocannabinoids: these are naturally produced molecules (such as anandamide and 2-AG) that bind to cannabinoid receptors to help maintain internal balance. So far, scientists have identified more than 10 of these molecules. 
• Cannabinoid receptors: these are mainly CB1 (in the brain and nervous system) and CB2 (in the immune system). The work to regulate internal balance and control several life processes. 
• Enzymes: Enzymes are responsible for breaking down endocannabinoids once they've completed their function. The help to regulate the activity of cannabinoids making sure they don’t constitute a nuisance once their role is completed. 

Together, these components regulate a wide range of physiological processes, including neuronal signaling, inflammation, and emotional response.

Information from a 2021 research suggests that individuals with autism may experience dysfunction or imbalance like lower levels of anandamide in their endocannabinoid system. 

Anandamide plays a critical role in regulating mood, cognition, inflammation, and social behavior. This reduced "endocannabinoid tone" in ASD has been linked to core behavioral symptoms and immune dysregulation. Animal studies have further supported these findings, showing that decreased anandamide in brain regions like the hippocampus leads to social and cognitive impairments. Notably, enhancing AEA levels through FAAH (fatty acid amide hydrolase) inhibition has reversed these deficits in ASD models, highlighting a potential therapeutic target.

Beyond anandamide alone, broader disruptions in the endocannabinoidome (eCBome), including other lipid mediators such as PEA, OEA, and 2-AG, along with altered CB₁/CB₂ receptor activity and enzyme expression may further contribute to autism pathology. These molecular changes can influence not only neurological function but also the gut-brain axis and systemic inflammation, both of which are commonly affected in ASD. 

Why This relationship between ECS and Autism Matters for CBDa

While CBD is known to indirectly influence the ECS by inhibiting the breakdown of anandamide, CBDa was observed to act more directly on serotonin (5-HT1A) receptors and may also contribute to ECS modulation via anti-inflammatory and COX-2 inhibitory pathways. By supporting ECS function, CBDa may help regulate mood, reduce anxiety, modulate inflammation, and improve neurological signaling in individuals with autism. This biological synergy between the ECS and cannabinoids can lead to the following effects on individuals with ASD. 

• Anxiety and Emotional Regulation

Children with autism often experience intense anxiety, especially in social settings or sensory-overloaded environments. In fact, studies estimate that up to 40–50% of people with autism spectrum disorder (ASD) meet the criteria for an anxiety disorder, significantly higher than in neurotypical children. This population can benefit from the therapeutic potentials of CBDa especially since it interacts with serotonin receptors, which are important in regulating mood and anxiety. Unlike CBD, which influences this receptor indirectly, CBDa appears to bind more directly and potently, potentially offering a calming effect without the sedative side effects seen with some medications. This mechanism makes CBDa a promising option for children who experience frequent emotional meltdowns, difficulty self-regulating, or persistent anxiety that interferes with daily activities. 

• Sleep Support

Individuals with autism struggle to fall or stay asleep, often due to heightened stress responses, sensory sensitivities, or disruptions in melatonin production. A 2024 research shows that 40% to 80% of children with autism spectrum disorder (ASD) experience sleep disturbances, including difficulty falling asleep, frequent night wakings, and reduced overall sleep duration. These issues can significantly affect behavior, mood, and daytime functioning for both the child and their caregivers.

While formal clinical studies on CBDa and sleep are still emerging, its ability to reduce anxiety and lower inflammation suggests it may indirectly support better sleep quality. CBDa interacts with serotonin pathways (5-HT1A receptors), which are also involved in regulating the sleep-wake cycle. By promoting a sense of calm and reducing stress responses, CBDa offers potential as a non-sedating, plant-based option for managing sleep-related challenges in individuals with autism, especially when anxiety is a contributing factor.

• Inflammation and Gut Health

Emerging evidence suggests that chronic inflammation and gut-brain axis imbalances play a significant role in the severity and expression of autism symptoms. In fact a 2022 study published in Frontiers in Psychiatry indicate that up to 70% of children with autism spectrum disorder (ASD) experience gastrointestinal (GI) issues, such as constipation, diarrhea, bloating, and food sensitivities. These gut-related symptoms are not only uncomfortable but are also linked to increased irritability, anxiety, and cognitive challenges in affected children.

Pre-clinical studies on CBDa has revealed its potent anti-inflammatory properties. It works in part by inhibiting COX-2 enzymes and reducing pro-inflammatory cytokines, which are often elevated in both the gut and brain of individuals with ASD. By addressing inflammation at its root, CBDa may offer a natural way to support both digestive health and neurological balance, making it a promising therapeutic candidate for children with autism who experience GI distress alongside behavioral symptoms.

• Focus and Repetitive Behaviors

Some caregivers and parents of children with autism report noticeable improvements in attention span, as well as reductions in repetitive or compulsive behaviors, when using cannabinoid-based support. While much of the existing data focuses on CBD, early research and anecdotal evidence point to CBDa as a promising alternative due to its higher bioavailability and stronger interaction with serotonin receptors (5-HT1A).

Studies show that repetitive behaviors affect up to 98% of individuals with autism, and attention deficits are also commonly observed, often overlapping with ADHD diagnoses. CBDa’s ability to modulate serotonin, reduce neuroinflammation, and promote neurological balance may help minimize overstimulation and improve cognitive regulation. 

What Does Research Say About CBD and Autism?

Over the past decade, there has been a growing body of research exploring the effects of CBD and CBD-enriched cannabis extracts on symptoms associated with Autism Spectrum Disorder (ASD). While more large-scale clinical trials are still needed, early findings from observational studies, case series, and preclinical data point to promising results.

• CBD-rich extracts improve behavior and emotion of people with ASD

Multiple studies have reported significant reductions in aggression, hyperactivity, and self-injurious behaviors in children with ASD following treatment with CBD-rich cannabis extracts. In a retrospective study published in Frontiers in Neurology, 14 out of 15 children with ASD showed improvements across symptoms like ADHD, behavioral disorders, communication deficits, and sleep disturbances after 6 to 9 months of treatment, with only mild and infrequent side effects.

Another study published in Scientific Reports noted that restlessness, irritability, and aggression showed the most improvement among participants, with more than 80% of parents reporting better quality of life, sleep, mood, and social interaction in their children.

• Communication and Social Interaction

Several studies also highlight improvements in communication skills and social behaviors, which are core challenges in autism. In a 2023 study in Frontiers in Psychiatry, 18 out of 20 children treated with a full-spectrum CBD-rich extract showed measurable improvements in social interaction, communication deficits, and sleep problems.

• Anxiety and Sleep Regulation

Anxiety is a major co-occurring condition in ASD, and many children with autism struggle with sleep disturbances. A systematic review from 2020, summarized how CBD helped reduce anxiety symptoms in up to 39% of participants, while also enhancing sleep quality, reducing agitation, and promoting relaxation.

Safety and Tolerability of CBD-Rich Extracts in People with Autism Spectrum Disorder (ASD)

Importantly, across most clinical and observational studies, CBD-enriched extracts have demonstrated a strong safety profile in individuals with autism spectrum disorder (ASD). Research consistently shows that these extracts are well tolerated, with mild and infrequent adverse effects, such as drowsiness, changes in appetite, or gastrointestinal discomfort. In fact, a widely cited 2019 observational study from Israel involving 188 children with ASD found that over 80% of participants experienced moderate to significant improvement in symptoms such as anxiety, communication difficulties, and behavioral outbursts after using CBD-rich cannabis oil. Adverse effects were reported in less than 25% of participants, and they were mostly mild and temporary.

The recent study from UC San Diego involving 30 boys with severe autism spectrum disorder (ASD) found that CBD was well tolerated and led to meaningful behavioral improvements in about two-thirds of participants. These included reduced aggression, hyperactivity, and better communication. While a strong placebo effect was observed, many families reported being able to reduce or discontinue other medications that often carry more serious side effects. 

Furthermore, the study reported how participants were able to reduce or completely discontinue other medications, including antipsychotics, mood stabilizers, and sedatives, which are often associated with more severe side effects such as weight gain, hormonal imbalances, or increased risk of metabolic syndrome.

Overall, the emerging body of evidence highlights CBD’s favorable safety profile, especially in pediatric ASD populations, and calls for larger, randomized controlled trials to further evaluate the efficacy and long-term safety of CBD and CBDa in this context.

CBD vs. Full-Spectrum and CBDa Extracts and Autism Spectrum Disorder

While most studies focus on CBD or CBD-enriched cannabis with a high CBD to low THC ratio (often 20:1), emerging research is now exploring raw cannabinoids like CBDa, which may offer even greater bioavailability and gentler interaction with the serotonin system. One preclinical study observed that administration of high CBDa extracts significantly reversed autism-like behaviors in animal models, including self-grooming and social withdrawal.

Unlike CBD, which requires metabolic conversion, CBDa is absorbed more efficiently, offering up to 11 times more bioavailability than CBD in some studies. This allows lower doses to achieve therapeutic effects, making it a gentler yet more potent option for sensitive populations like children with autism. It is also pertinent to note that CBDa interacts more directly with the 5-HT1A serotonin receptor, which plays a key role in mood regulation, anxiety, and social behavior. Full-spectrum CBDa extracts, which preserve the natural acidic form along with minor cannabinoids and terpenes, may enhance these effects through the entourage effect. 

References 

1. UC San Diego Health. (2023, January 3). CBD might help children with autism, but more research needed. UC San Diego Today. https://today.ucsd.edu/story/cbd-might-help-children-with-autism-but-more-research-needed
2. Medical News Today. (2023). CBDa: What to know. https://www.medicalnewstoday.com/articles/cbda
3. Aran, A., Cassuto, H., Lubotzky, A., Wattad, N., & Hazan, E. (2021). Cannabidiol-Based Medical Cannabis in Children with Autism- A Retrospective Feasibility Study. Journal of Autism and Developmental Disorders, 51(4), 1056–1066. https://pmc.ncbi.nlm.nih.gov/articles/PMC7498943/
4. Nesas Hemp. CBDa vs CBD: What’s the Difference? https://www.nesashemp.com/cbda-vs-cbd/
5. Nesas Hemp. Autism statistics. https://www.nesashemp.com/blog/autism-statistics/
6. Gabriele, S., Sacco, R., Persico, A. M., & Muratori, F. (2021). Alterations of the endocannabinoid system in autism spectrum disorders: A systematic review. Psychiatry Research, 304, 114161. https://www.sciencedirect.com/science/article/abs/pii/S0165178121005515
7. van Steensel, F. J. A., Bögels, S. M., & Perrin, S. (2011). Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clinical Child and Family Psychology Review, 14(3), 302–317. https://pmc.ncbi.nlm.nih.gov/articles/PMC6596989/
8. Díaz-Román, A., Zhang, J., & Delorme, R. (2024). Sleep problems in autism spectrum disorder: Prevalence and associated features. Journal of Clinical Medicine, 13(3), 211. https://pmc.ncbi.nlm.nih.gov/articles/PMC11046719/
9. Aran, A., Eylon, M., Harel, M., Politi, M., & Meiri, G. (2022). Cannabis in autism: What do we know so far? Frontiers in Psychiatry, 13, 963102. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.963102/full
10. Di Giacomo, D., Zilli, C., Mongiovi, C., et al. (2023). CBDA in neurodegenerative diseases: Recent findings and future directions. Frontiers in Psychiatry, 14, 10095267. https://pmc.ncbi.nlm.nih.gov/articles/PMC10095267/
11. Hausman-Kedem, M., Menascu, S., & Kramer, U. (2023). Oral cannabidiol use in children with autism spectrum disorder. Israel Medical Association Journal, 25(3), 186–191. https://pmc.ncbi.nlm.nih.gov/articles/PMC9887656/
12. Barchel, D., Stolar, O., De-Haan, T., Ziv-Baran, T., Saban, N., Fuchs, D. O., & Berkovitch, M. (2019). Cannabidiol use in children with autism spectrum disorder: An observational study. Molecular Autism, 10, 1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8224357/
13. Bar-Lev Schleider, L., Mechoulam, R., Saban, N., Meiri, G., & Novack, V. (2019). Real life experience of medical cannabis treatment in autism: Analysis of safety and efficacy. Frontiers in Neurology, 10, 1145. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01145/full
14. Pretzsch, C. M., Freyberg, J., Voinescu, B., Lythgoe, D. J., Horder, J., Mendez, M. A., ... & McAlonan, G. M. (2019). Effects of cannabidiol on brain excitation and inhibition systems: A randomized placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Scientific Reports, 9, 20351. https://www.nature.com/articles/s41598-018-37570-y
15. Bagasra, O., Prillaman, A., & Williams, J. A. (2023). Cannabinoid modulation in autism: What does current clinical and pre-clinical evidence suggest? Frontiers in Psychiatry, 14, 1210155. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1210155/full
16. Aran, A., Harel, M., Cassuto, H., Polyak, A., & Meiri, G. (2020). Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems–A retrospective feasibility study. Journal of Cannabis Research, 2, 3. https://www.sciencedirect.com/science/article/abs/pii/S1071909120300449
17. Abu‐Serriah, M., Lynch, J. A., & Sharif, K. (2023). Cannabinoid-related neuroprotective mechanisms in ASD. IBRO Neuroscience Reports, 15, 245–255. https://www.ibroneuroreports.org/article/S2667-2421(23)00211-7/fulltext
18. Medical News Today. (2023). CBDa: What to know. https://www.medicalnewstoday.com/articles/cbda
19. Aran, A., Cassuto, H., Lubotzky, A., Wattad, N., & Hazan, E. (2021). Cannabidiol-Based Medical Cannabis in Children with Autism- A Retrospective Feasibility Study. Journal of Autism and Developmental Disorders, 51(4), 1056–1066. https://pmc.ncbi.nlm.nih.gov/articles/PMC7498943/
20. Nesas Hemp. CBDa vs CBD: What’s the Difference? https://www.nesashemp.com/cbda-vs-cbd/
21. Nesas Hemp. Autism statistics. https://www.nesashemp.com/blog/autism-statistics/
22. Gabriele, S., Sacco, R., Persico, A. M., & Muratori, F. (2021). Alterations of the endocannabinoid system in autism spectrum disorders: A systematic review. Psychiatry Research, 304, 114161. https://www.sciencedirect.com/science/article/abs/pii/S0165178121005515
23. van Steensel, F. J. A., Bögels, S. M., & Perrin, S. (2011). Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clinical Child and Family Psychology Review, 14(3), 302–317. https://pmc.ncbi.nlm.nih.gov/articles/PMC6596989/
24. Díaz-Román, A., Zhang, J., & Delorme, R. (2024). Sleep problems in autism spectrum disorder: Prevalence and associated features. Journal of Clinical Medicine, 13(3), 211. https://pmc.ncbi.nlm.nih.gov/articles/PMC11046719/
25. Aran, A., Eylon, M., Harel, M., Politi, M., & Meiri, G. (2022). Cannabis in autism: What do we know so far? Frontiers in Psychiatry, 13, 963102. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.963102/full
26. Di Giacomo, D., Zilli, C., Mongiovi, C., et al. (2023). CBDA in neurodegenerative diseases: Recent findings and future directions. Frontiers in Psychiatry, 14, 10095267. https://pmc.ncbi.nlm.nih.gov/articles/PMC10095267/
27. Hausman-Kedem, M., Menascu, S., & Kramer, U. (2023). Oral cannabidiol use in children with autism spectrum disorder. Israel Medical Association Journal, 25(3), 186–191. https://pmc.ncbi.nlm.nih.gov/articles/PMC9887656/
28. Barchel, D., Stolar, O., De-Haan, T., Ziv-Baran, T., Saban, N., Fuchs, D. O., & Berkovitch, M. (2019). Cannabidiol use in children with autism spectrum disorder: An observational study. Molecular Autism, 10, 1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8224357/
29. Bar-Lev Schleider, L., Mechoulam, R., Saban, N., Meiri, G., & Novack, V. (2019). Real life experience of medical cannabis treatment in autism: Analysis of safety and efficacy. Frontiers in Neurology, 10, 1145. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01145/full
30. Pretzsch, C. M., Freyberg, J., Voinescu, B., Lythgoe, D. J., Horder, J., Mendez, M. A., ... & McAlonan, G. M. (2019). Effects of cannabidiol on brain excitation and inhibition systems: A randomized placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Scientific Reports, 9, 20351. https://www.nature.com/articles/s41598-018-37570-y
31. Bagasra, O., Prillaman, A., & Williams, J. A. (2023). Cannabinoid modulation in autism: What does current clinical and pre-clinical evidence suggest? Frontiers in Psychiatry, 14, 1210155. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1210155/full
32. Aran, A., Harel, M., Cassuto, H., Polyak, A., & Meiri, G. (2020). Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems–A retrospective feasibility study. Journal of Cannabis Research, 2, 3. https://www.sciencedirect.com/science/article/abs/pii/S1071909120300449
33. Abu‐Serriah, M., Lynch, J. A., & Sharif, K. (2023). Cannabinoid-related neuroprotective mechanisms in ASD. IBRO Neuroscience Reports, 15, 245–255. https://www.ibroneuroreports.org/article/S2667-2421(23)00211-7/fulltext