Mental Health and the ECS

Mental Health

The endocannabinoid system (ECS) is immensely seen in areas of the brain implicated in processing of emotional information as well as memory and learning, such as the cortex, amygdala circuit, and hippocampus. Cognitive deficits and abnormal emotional processing are fundamental characteristics of numerous neuropsychiatric conditions, including schizophrenia and mood disorders. This helps the implication that the ECS plays a role in the neurobiology of these disorders. Preclinical and clinical data support the involvement of the endocannabinoid system in the etiopathogenesis of several mental diseases. Both animal and human studies seem to suggest that pharmacological modulation of this system might represent a novel approach for treatment. (springer)

• Diseases such as ADHD, depression, and PTSD are affected by the ECS.
• The ECS has a major impact on the mental health of individuals across a wide spectrum of mental health issues including fear, anxiety and stress
• There has been an explosion in mental health issues that can be partially attributed to the western diet that is high in processed sugars and alcohol and low in Omega 3 and 6 fatty acids

• Endocannabinoids were mainly derivatives of the n-6 fatty acid arachidonic acid however, recent data have shown that they are also derivatives of n-3 fatty acids
• A ratio of 3:1 Omega 6: Omega 3 is needed for proper ECS activation.

• Stress exposure has been shown to reduce endocannabinoid levels of AEA and increase 2-AG levels.Exposure to chronic stress causes a downregulation, or loss, of CB1 receptors.
• Studies show that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior.
  • This shows why activation of the ECS through exercise, which produces AEA in the body, is so effective for mental health disorders.

• Current studies implicate that disfunction of the Endocannabinoid system plays a role in the neurobiology of both psychosis and mood disorders.
• Published data identifies enhancing the EC signaling would represent a new approach for the treatment of depression and anxiety.
• Studies implicate a hypo-functionality of the ECS in these ailments. Current clinical trials in psychosis are needed to be aimed at blocking CB1 signaling or increasing AEA levels. Since these are the positive results observed in manipulation of the ECS in psychosis.

Autism

There is increasing evidence that the ECS has a role in social and emotional processing.  Several studies point to a correlation between the ECS and autism pathophysiology. The ECS is a key modulator of cellular pathways and metabolic activity in autism. Current studies are directly examining the role of this system in autism. The ECS dysfunction may also underlie the behavioral abnormalities observed in autism spectrum disorders.

• Lower circulating endocannabinoid levels in children with autism spectrum disorder The (ECS) plays a major role in regulation of synaptic plasticity and neuromodulation.
  • Variations of the ECS have been exhibited in several animal models of autism spectrum disorder (ASD).
  • In some of these models, activating the ECS rescued the social deficits.
  • Lower serum levels of AEA, PEA, and OEA have been seen in children with ASD.
• Endocannabinod Signal Dysregulation in Autism Spectrum Disorders: A Correlation Link between Inflammatory State and Neuro-Immune AlterationsAlteration of CB2 receptor signaling could offer a promising option.
  • FAAH inhibition, as well as PEA supplementation, can offer two other promising EC targets.
  • EC system alteration has been shown to be an effective treatment in vivo and in vitro models.

Addiction 

The ECS plays different roles in the stages of addiction, dependency and withdrawal through interactions of the CB1 and CB2 receptors.  Various substances such as crack, heroine, alcohol and nicotine have links to CB1 and CB2 receptor interactions. CB1 receptors are abundant in the brains reward circuitry

• Cannabis was shown to decrease crack use, cravings, and produce concrete and subjective changes in the behavior of crack addicts by 68%.
• The CB2 receptor in the brain was linked to modulating cocaine’s effects.
  • This is likely through a dopamine-dependent mechanism.
  • This would suggest CB2 would be an ideal target for new drug therapy.

• CBD reduces craving in drug-abstinence individuals with heroin dependency.
  • CBD would support a treatment option for opioid use disorder.

• Extinction of both cocaine and amphetamine induced conditions was seen with high doses of CBD and THC

• Cannabidiol (CBD) inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances.The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.

• Volunteers smoking high CBD content cannabis were found to reduce their desire for drug related stimuli.
  • “The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders.”
• Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice.
  • “Delta9-THC also ameliorated the aversive motivational consequences of nicotine withdrawal.”