The cognitive changes in the brains of people with Down syndrome may be helped by cannabinoid therapy that corrects memory deficits.
Down Syndrome, or Trisomy 21, is one of the main genetic causes of intellectual disability. It has a frequency of 1 in 700 to 1000 live births. Intellectual disability is displayed by learning and memory deficits that can be pinpointed to occur in specific areas of the brain, called the ‘hippocampus cognitive domains’.
The mouse is the model for the study of trisomy conditions. Trisomy 21 is analogous to Trisomy 16 in mice as the gene loci are very similar. And this is how researchers came to understand how the endocannabinoid system is involved in the regulation of neurological processes that underlie cognitive deficits in Trisomy 21.
Cognitive Problems Caused By Changes in Neurons
Researchers have found several reasons for the intellectual disability that can accompany Down Syndrome. There are changes in the communication between neurons in the hippocampus as well as an imbalance between neurons that excite and those that inhibit. The endocannabinoid system has emerged as one of the main regulators of all these processes, prompting one group of researchers to investigate its involvement in Down syndrome.
Too Many CB1 Receptors Leads to Cognitive Problems
Researchers identified that CB1 receptors play a role in characteristic cognitive patterns seen in two different mouse models for Down syndrome. The first observation they made is that there seems to be an overabundance of CB1 in neurons of the hippocampus, and these are overly activated. The result is this serious dampening of connecting neurons that convey cognitive abilities.
When they tested this theory by using knockdown trisomy mice that were bred to have decreased CB1 receptors, the memory deficits were gone. The assessment of this change was looked at over two tests: novel object recognition test and novel place recognition test. During the tests, mice that had memory deficits performed poorly, and couldn’t recognize the objects or places that they were previously introduced to. On the contrary, when CB1 receptor activity was decreased, the memory was rescued. The same results were obtained when CB1 was activated using a pharmaceutical called Rimonabant.
These results suggest that increased number CB1 receptors and their hyperexcited state in the hippocampus creates imbalance in neurotransmission. And that this is responsible for lowered cognitive abilities.
Other Receptors Problems May Be Involved
There is some evidence that other components of the endocannabinoid system, such as CB2 receptor and fatty acid amide hydrolase (FAAH) could be implicated in Down Syndrome. Post-mortem analysis of brains from individuals with Down syndrome identified that Alzheimer-like beta amyloid plaques are evident, and that specific brain cell types associated with the plaques have excess CB2 and FAAH. Although scientists can’t definitively say whether these changes are a cause or a consequence of amyloid beta deposition in Down syndrome, it could suggest novel therapeutic targets to prevent cognitive decline in these patients.
What Can Cannabis Do About It?
Given that CB2 activation is associated with anti-inflammatory effects, CB2 agonists may have a neuroprotective effect. Likewise, since FAAH levels are high, endocannabinoid levels are likely chronically reduced and supplementation with exogenous cannabinoids may have therapeutic benefits.
Additionally, by the age of 30 to 40, people with Down Syndrome have a significant build up of these sticky amyloid plaques that are also found in Alzehimer’s. In fact, a study at the University of South Florida declared these two disorders to be variations of the same disease. Cannabinoid therapy has been found to be enormously helpful in preventing and breaking down these plaque in vivo and in vitro.
Pre-clinical studies have shown that administration of THC at 3mg/kg per day for 4 weeks lead to a reduction in Aß plaques and preservation of neurons.
One research group has recently shown that THC has anti- Aß properties in vitro . Namely, they found that incubation of cells that produce Aß with THC resulted in a time- and dose-dependent arrest of Aß production. The authors also underlined that the amount of THC used to treat the cells corresponds to very low doses of THC, and in fact were a thousand times lower compared to the doses of THC that have been shown to cause cognitive impairments in rat studies. Moreover, they found no cytotoxic side effects of this dose of THC in cells, suggesting that likely this treatment would be safe and effective in the pre-clinical studies that would transpire from this data.
Further studies are needed to find out if changing CB1 activity can have the same benefit for humans with Trisomy 21. If if does, then cannabis will be an excellent therapy to help manage cognitive impairment.