The mechanism by which cannabinoids could be utilized for treating ASD and its associated disorders, including epilepsy, may possibly be through the synthetic modulation of the ECS, which can help regulate social responses, pleasure, cognition, concentration, body movement, gastrointestinal function, pain, seizures, and the five senses [
7,
43]. Unlike THC, CBD is a serotonin (5-hydroxytryptamine) receptor agonist, which is a non-cannabinoid receptor, but may explain the facilitation of the anxiolytic effect [
44]. Its antipsychotic effect is attributed to partial agonism at dopamine D2 receptors [
45‐
47], similar to the antipsychotic action of aripiprazole [
45]. Additionally, CBD modulates glutamate-GABA systems that may be altered in ASD [
48]. Importantly, CBD inhibits the enzyme FAAH that degrades AEA, one of the main endocannabinoids. The modulation of the ECS is primarily targeted to CB1R and CB2R, and synthetic introduction of cannabinoids facilitates a process that mimics natural eCBs signaling to affect physiological factors [
49]. THC is more effective in binding to CB1R when compared to binding to CB2R [
44]. A high density of CB1R can be found in the basal ganglia, hippocampus, neocortex, hypothalamus, and limbic cortex. These neuron terminals affect motor activity, motor coordination, thinking, appetite, and sedation respectively. CB2R can be found on immune cells and tissues, which affect inflammation and immunosuppression [
49], as well as the tonsils and spleen, the central nervous system, and in glial and neuronal cells [
50]. These interactions, potentiated by cannabinoid treatment, may offer a prospective treatment option for management of ASD related symptoms in the future. Though CB2R is not expressed in neurons under normal conditions, it is highly expressed under pathological conditions (i.e. psychiatric and neurological diseases) [
50], and this warrants further investigation. At this time, although still controversial, immune system dysregulation is beginning to receive attention as having a possible role in ASD [
51]. The role of CB2R in regulating the immune system and inflammation offers a potentially promising therapeutic mechanism for managing the symptoms associated with ASD etiology [
40,
51]. Previous studies have noted an upregulation of CB2R density and an increase in CB2R protein levels in the PBMC of all of the subjects with ASD, while there were no reported differences in CB1R, nor FAAH levels [
40]. No significant intragroup variances were also reported for the control group. These results indicate an endocannabinoid-CB2 signaling dysregulation in ASD, though CB2R has not shown good cannabinoidergic activity [
52]. Despite this, there is a hypothesized treatment opportunity for synthetic eCBs manipulation via CBD administration. CBD thus, could offer a therapeutic potential for improving motor skill and sleep, while also supporting anxiolytic, antipsychotic [
45], and anticonvulsant symptoms [
16].