Endocannabinoid System, Autism, and Disabilities

Radically important information for people with disabilities and mental health issues, with huge implications for holistic health and wellness.

What is the Endocannabinoid (EC) System?

And what implications does its discovery and utility have for people with many different types of disabilities in Australia? Is this system potentially important in one way or other to help people with Autism, Intellectual Disability, Social Phobia, Anxiety, Depression, Prader-Willi, Fragile X, rare genetic conditions, and a wide range of physical and/or mental disabilities?

This article does not claim to answer these questions adequately. Rather we seek to raise these and other questions to begin the process of raising awareness – with the hope that you will continue being curious and to research these developments as they come to light in the months and years ahead.

Photo by Samuel Theo Manat Silitonga

What is the Endocannabinoid (EC) System?

The Endocannabinoid (EC) System is a biological system composed of endocannabinoids. These are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors in the brain and neurological system. As part of this function, endocannabinoids also bind to cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system and peripheral nervous system (Wikipedia 2022). In this sense, they have an all-of-body presence and function.

The EC system is subject to further exploratory research but has been identified with a wide range of functions. The impressive list of known functions include,

  1. Regulating physiological processes including,
    1. Fertility.
    2. Pregnancy.
    3. Pre- and postnatal development.
    4. Various immune system functions.
    5. Mediating the pharmacological effects of cannabis.
    6. Influence of sleep and relaxation responses.
  2. Regulating cognitive processes including,
    1. Appetite. 
    2. Pain-sensation. 
    3. Mood.
    4. Memory.
    5. Depression and anxiety.
    6. Social phobia and social anxiety.
  3. Multiple aspects of neural functions including,
    1. Control of movement and motor coordination.
    2. Learning and memory.
    3. Emotion and motivation.
    4. Addictive-like behaviour and
    5. Pain modulation.

When you contemplate how this list presents, you see themes related to how the EC system modulates between brain and body, cognitive and kinaesthetic systems. And of course, many describe the EC system as having an overarching orchestral modulating function that provides and maintains global, regional, and specific levels of homeostasis.

Photo by Inimafoto

Homeostasis

Homeostasis is a central concept in physical and mental health that speaks of not only balance but also the ongoing, moment to moment, fluctuations of the human system that deals with hundreds if not multiple thousands of chemical, neuronal, muscular, mental, environmental, social, and relational factors in any given millisecond. We rarely appreciate how complex and beautiful the human system truly is until we gaze at the functional capacity of the body-mind-heart-soul to maintain health and wellness or deal with illness and acute crisis.

No other system of the body, including past conceptions of the neurological system, have come this close to expressing this level of orchestration of complexity and harmony, modulation and healing synthesis, that appears within the EC system.

Photo by Spencer Selover

Potential and Risk in Disability Support

Also as you contemplate the above list of functions of the EC system, you can imagine that there may be many if not hundreds or thousands of potential connections to many and varied disabilities. These synergies are yet to be discovered in science. Some may already be partially understood by existing studies as well as by personal and anecdotal experience.

However, we have a very long way to go. This is true especially because science like medicine tends to not take a holistic and ecological perspective on issues. The current western model, as truncated as it remains, tends to focus their efforts on innumerable microcosms with such highly targeted focus on research objectives and interventions. Studies that take a more functional perspective on ways to influence and support social and emotional capacities, risks, and behavioural patterns are more likely to yield helpful insights in the short to medium term. Given the limitations of this article, we only explore new studies that cover three themes, depression, autism, and multiple sclerosis (MS).

Depression

For example, Sharafi et al (2022) showed potential for the therapeutic affect of the EC system with depression, including within critical periods of acute self-harm and suicide. The authors showed that existing pharmacological interventions tend to rely on indeterminate timeframes for activation of neurological changes that settle a person during an acute phase of anxiety and depression leading to risk of self-harm. When administered with a substance such as CBD oil, a non-psychoactive substance derived from the cannabis plant, to partially activate the EC system, they found that the timeframe was considerably reduced to seeing a calming affect that led to reduced subjective experience of depression and existential anxiety as well as a reduced risk of harm.

Photo by cottonbro

Autism

Colizzi et al (2022) explored some of the underlying neurological functions of the endocannabinoid system in modulating neural circuits during the early stage of neurodevelopment. They postulated “potential common markers of disease have been investigated in both autism and psychosis spectrum disorders.” Their review found that “a developmental and transgenerational trajectory between autism and schizophrenia is supported by evidence” that they say appears through an “exogenous alteration of the endocannabinoid system” during developmental stages. This “promotes progression to inheritable psychosis phenotypes in the context of biobehavioral autism vulnerability.” The implications of this suggestion is that there may be a “developmental continuum between autism and psychosis” as one function of the dysregulation of the endocannabinoid system. One would wonder whether early to middle and late childhood interventions that support the EC system may address these underlying developmental mechanisms.

Photo by cottonbro

Babayeva et al (2022) correctly explain that “no medicine has been formed for the management of the ASD primary symptoms.” However, various aspects of the prognosis as well as social, emotional, and behaivoural presentations are treated by a host of on and off label medications. The authors suggest that the “endocannabinoid system has a central role in ruling emotion and social behaviours.” We would not put the situation in this concrete operational and highly simplistic way. You will likely understand our critique after having read our description of the dynamic and nuanced EC system above.

There is considerable danger that medical science and intervention will seek an easy fix, without any adequate comprehension of the complexity and underlying mechanisms of the human system. The same conundrum has happened with the cholesterol debate with an over simplification and too many false assumptions leading to over use of statins (see our prior article published earlier this month).

The authors appear to assume that dysfunctions of the EC system contribute to the behavioural deficits in autism. We would not jump to this conclusion this early in the development of research, even as much as the theory makes a lot of sense. They then present the hypothesis that EC system represents a potential target for the development of a novel autism therapy.

They point to the research suggesting that cannabis-based compounds have shown novel efficacy in several studies of neurobehavioral and neurological syndromes. The assumption of medical science, and to a large extent also behavioural science, is that Autism is primarily if completely based in a neurological dysfunction. Having worked as therapists in the field for some time, we do not share this view. Autism may include neurobiological layers but is also much more not that than that.

While we think the ways the authors express these issues are preliminary, the utility of the paper is that they reviewed the therapeutic potential of medical cannabis and its related compounds in the treatment of symptoms associated with Autism and concurrent disorders. This work needs to be done at this time, and further research is very much warranted.

The authors then table the existing research which has a preponderance of animal-based studies, but also more recent work on human-based studies in the wake of legalisation of medical cannabis overseas as well as further legalisation for recreational use in some jurisdictions. They describe the use of CBD and its roles in helping to modulate the EC system that has lead-on affects in Autism and associated conditions including Attention Deficit and Hyperactivity Disorder (ADHD), Seizure Disorders, Anxiety, Sleep Disorders, and Mood Disorders.

The authors conclude that because of the central role of the EC system in modulating mood, emotion and social behaviours, there is mounting evidence that the EC system’s dysfunction is central to how Autism presents in pathways of “pathogenesis…” and how this dysfunction contributes to behavioural deficits and neurological inflammation that is observed in Autism. They suggest that “cannabis and cannabinoids… may improve Autism associated social and cognitive impairments.”

While there appears to be therapeutic potential for cannabinoids to help to modulate the EC system, the authors do not address the problem of down regulation. We suspect that the EC system which focuses on maintaining homeostasis would down regulate with extended use of cannabinoidal products, leading to potential lessening of efficacy over time and/or to needing to increase dosages and towards a possible functional dependence.

The authors rightly suggest that “there are limited data supporting clear effect of cannabis/cannabinoids in different phenotypes of ASD.” They propose that more clinical investigations are needed. We agree that there is a lot of work to be done to discover the efficacy, safety, and dosing of novel therapies. The authors express the hopeful view that this “would be a significant advance in the treatment of Autism and could lead to improved functioning and quality of life for the patients and their families.”

While taking a cautious approach, we tend to agree as long as people understand that use of most of these substances needs to be understood in light of the growing knowledge and appreciation for the EC system itself, and how it functions, this will have flow-on effects in how we use cannabinoidal treatments which may need to be periodic, intermittent, and with breaks that allow the EC body-system to remodulate and maintain balance apart from the influence of the plant-based intervention.

Photo by Mike

Multiple Sclerosis

Khan et al (2022) explore promising therapeutic interventions with multiple sclerosis. MS is a chronic and complex neurodegenerative disease. MS is distinguished by the presence of lesions in the central nervous system. They observed that Cannabis sativa has a role in relieving pain, tremors and spasticity. The substance also prevents exaggerated immune responses in the central nervous system due to chronic and acute inflammatory processes common in MS and that also influence the blood-brain barrier. They suggested that “various CB1/CB2 receptors agonists… showed anti-inflammatory properties and are considered to be effective as potential therapeutics for MS.”

Bibliography

AmirMohammad Sharafi, Sina Pakkhesal, Ali Fakhari, Nazli Khajehnasiri, Ali Ahmadalipour,
Rapid treatments for depression: Endocannabinoid system as a therapeutic target, Neuroscience & Biobehavioral Reviews, Volume 137, 2022, 104635, ISSN 0149-7634, https://doi.org/10.1016/j.neubiorev.2022.104635.

Mariana Babayeva, Haregewein Assefa, Paramita Basu, Zvi Loewy. Autism and associated disorders: cannabis as a potential therapy. Front. Biosci. (Elite Ed) 2022, 14(1), 001. https://doi.org/10.31083/j.fbe1401001.

Colizzi M, Bortoletto R, Costa R, Bhattacharyya S, Balestrieri M. The Autism–Psychosis Continuum Conundrum: Exploring the Role of the Endocannabinoid System. International Journal of Environmental Research and Public Health. 2022; 19(9):5616. https://doi.org/10.3390/ijerph19095616.

Khan, H., Ghori, F.K., Ghani, U. et al. Cannabinoid and endocannabinoid system: a promising therapeutic intervention for multiple sclerosis. Mol Biol Rep (2022). https://doi.org/10.1007/s11033-022-07223-5.

Featured Photo by Pixabay

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