Dopaminergic disorders with endocannabinoid involvement
Endocannabinoids have been implicated in a variety of disorders, including several that typically correlate with increased (bold) or decreased (italics) or decreased or increased (italics and bold) dopamine levels:123
- 1. Endocannabinoids for various disorders
- 2. Cannabinoids for Parkinson’s disease
- 3. Psychosis risk factors for cannabis use
1. Endocannabinoids for various disorders
| Disorder | Dopamine | AEA | 2-AG | CB1R | CB2R |
|---|---|---|---|---|---|
| ADHD | DA decreased | AEA increased4 | CB1R agonist improved hyperactivity/impulsivity5 | ||
| Cardiovascular Disorders6 | |||||
| ASS7 8 9 10 11 12 13 14 15 | AEA decreases16, endocannabinoids decreases17 | ||||
| Parkinson’s18 19 | DA decreased | AEA increased20 | 2-AG increased21 | CB1R expression in basal ganglia increased2223 24 | CB2R increased2526 |
| Alzheimer’s2728 | AEA increase helpful2930 | CB1R decreased31 | CB2R increased32 | ||
| Huntington28 | Reduced to completely lost CB1R and D1R33 | ||||
| Multiple sclerosis34 | AEA increased in CSF and peripheral lymphocytes increased35 | 2-AG unchanged in CSF and peripheral lymphocytes35 | |||
| Fragile X syndrome34 | 2-AG elevation helpful in animal model36 | CB1R reduced due to overstimulation. CBD could be helpful37 | |||
| amyotrophic lateral sclerosis | |||||
| traumatic brain injuries | |||||
| Stroke | |||||
| Epilepsy | DA decreased | AEA increased after seizures | 2-AG increased after seizures | ||
| Glioblastoma | DA reduced | ||||
| Anxiety disorders | AEA reduced3839 AEA increase helpful40 | 2-AG increase helpful40 | CB2R antagonists helpful41 | ||
| PTSD and erroneous deletion of aversive memories42 | decreased | AEA decreased4344 AEA unchanged45 AEA stress response unchanged4647 | 2-AG decreased45 2-AG stress response decreased4647 | CB1R increased4344 | |
| Depression4849 | DA decreased | AEA increased in mild depression, more likely unchanged in severe depression39 AEA increase helpful50 Fluoxetine decreased AEA in limbic regions50 Tianeptine increased AEA in hippocampus and dorsal striatum50 Imipramine increased endocannabinoids in dorsal striatum50 Escitalopram increased endocannabinoids in hippocampus and dorsal striatum OR decreased them in cortex and cerebellum50 | 2-AG decreased50 in women with major depression3938 2-AG tended to be increased in mild depression39 Fluoxetine increased 2-AG in PFC50 Tianeptine increased 2-AG in dorsal striatum and PFC50 Imipramine increased endocannabinoids in dorsal striatum50 Escitalopram increased endocannabinoids in hippocampus and dorsal striatum{ OR decreased them in cortex and cerebellum50 | ||
| Bipolar Disorder51 | |||||
| Eating disorders5253 54 | |||||
| Psychosis55 | DA increased | AEA decreased in CSF56 and blood57 | |||
| Schizophrenia | Negative symptoms: DA decreased in PFC / positive symptoms: DA increased in dorsomedial striatum5859 60 61 62 63 64 | AEA increased 8-fold in brain65 to 10-fold66 | CB1R increased65 |
2. Cannabinoids for Parkinson’s disease
Cannabinoids for Parkinson’s disease
Parkinson’s is caused by a gradual degeneration of dopaminergic neurons in the substantia nigra, which increasingly restricts dopaminergic neurotransmission in the striatum.67
It is possible that impaired endocannabinoid signaling in the basal ganglia is the cause of Parkinson’s disease. Cannabinoids are being discussed and tested for the treatment of Parkinson’s symptoms and to delay the development of Parkinson’s disease.68697071
- CB1R agonists
- Antioxidant phytocannabinoids appear to inhibit the degeneration of Parkinson’s dopaminergic neurons in animal models of Parkinson’s disease79
- other studies have found no strong antioxidant effect of cannabinoids80
- CB2Rs are involved in the control of motor effects8182
- Cannabinoids have a neuroprotective effect8384 85 and inhibit the development of Parkinson’s disease in animal models of Parkinson’s disease86
Cannabis use in Parkinson’s disease shown in studies
- 45.9%87 to 78%88 improvements through cannabis use
- Motor skills
- less pain89
- improved sleep89 through nabilone93
- reduced anxiety due to nabilone93
CBD had an effect on Parkinson’s
- a reduction in the overall Parkinson’s values94
- a significant reduction in psychotic symptoms94
- no improvement in motor or general symptoms in double-blind study9594
Significantly increased levels of TRPV1 were found in a Parkinson’s animal model, which could explain the increased sensitivity to pain in Parkinson’s disease.96
3. Psychosis risk factors for cannabis use
Special psychosis risk factors for cannabis use:9798
- frequent consumption
- Consumption of cannabis with a high Δ9-THC content
- early consumption (adolescence)
- family history of psychosis
- Psychosis prodromal symptoms
- Nervousness
- Anxiety
- Restlessness
- Anxiety or depression
- Withdrawal from social ties
- reduced zest for life and performance
- Limited ability to cope with training or work compared to before
- Carrier of the Val allele of COMT
- Hallucinations with cannabis use99
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