A study published in the journal BioMed Central has shown how the psychedelic N, N-Dimethyltryptamine (DMT) could be used as a medicine to prevent the onset of the neurodegenerative condition Alzheimer’s disease (AD).
According to the NHS, Alzheimer’s disease is the most common cause of dementia in the UK. Symptoms of Azheimer’s range from minor memory problems such as forgetting about recent conversations or names to confusion, disorientation and problems with speech and language. In the UK, Alzheimer’s affects an estimated 1 in 14 people over the age of 65.
In the study, scientists associated with different Chinese state institutions including The University of Hong Kong-Shenzhen Hospital examined two groups of mice to determine the role DMT might have in the treatment and prevention of AD.
The first group contained 3×TG-AD transgenic mice, bred to develop cognitive decline from a young age. The second group, wild mice with no symptoms of AD, were used as a control group.
Both groups were injected with 2mg of DMT per kg of the weight of the mouse, or the same volume of saline solution every day for three weeks, then put through numerous tests.
In one of the tests, mice were placed into a water maze in which they had to find a target area marked by a slightly submerged platform, the time it took them to swim to the target was recorded by scientists and the results were used to determine if there was a change in memory and cognitive function.
The mice were trained twice a day for five days to find a target area. On the sixth day, they were given a final test in which they had to swim to the target area but without the platform as guidance.
“Water maze test is a valid behavioural paradigm for the study of spatial learning and memory. There were 8 mice with equal number of male and female mice per group in the test. The test was performed at the end of 3 weeks treatment in mice as our previous description. Briefly, during the 5-day training phase, the platform was placed in the centre of the target quadrant and submerged under 1 cm of the water surface. The escape latency of mice to find the hidden platform was recorded after being released from the randomly selected quadrant,” the study author explained.
The maze test results showed mice who had been given DMT were much better at finding the target area, improving the time it took them to do so after training, than the group who were administered saline solution.
“These results suggested that chronic DMT treatment was sufficient to suppress cognitive decline of AD,” the study said.
Alongside the maze evaluation (after administration of DMT), scientists tested the mouse brains to determine the abundance of Sig-1r receptors, the functionality of neuronal ER-mitochondria crosstalk, and importantly, the level of amyloid accumulation.
In the brains of people with Alzheimer’s, abnormal levels of amyloid clump together to form plaques that disrupt cell function. The build-up of amyloid plaque in the brain is thought to cause the onset of AD. Amyloid does this by clogging up the signalling routes known as ER-mitochondria that connect mitochondria in brain cells to a part of the brain called the endoplasmic reticulum (ER).
These signalling routes are believed to clog up with amyloid due to a reduction in Sig-1r receptor activity. One job of the Sig-1r receptors job is to regulate amyloid. This is why scientists have focused their attention on the ability of DMT to affect Sig-1r receptors and ER-mitochondria.
“DMT could serve [as] a novel preventive and therapeutic agent against AD.”
The results of the Sig-1r tests showed DMT to bring activation levels of the receptor in the 3×TG-AD transgenic mice up to that of the levels of the wild mice, this indicates that DMT could be useful in reducing the cognitive decline associated with AD.
“Our findings indicated that low-dose chronic treatment with DMT increased Sig-1r levels in in vivo models of AD. These results were consistent with other previous studies, which found that the agonist of Sig-1r increased the expression of Sig-1r protein and mRNA,“ study authors wrote.
The test performed to assess the functionality of neuronal ER-mitochondria crosstalk showed again that the group of mice exposed to DMT had benefited, as the results were positive compared to those of the control group.
“The presence of DMT greatly increased the number of PLA dots in the cells exposed to Aβ [amyloid], but did not show great effects in the control cells…These results suggested that DMT improved the ER-mitochondrial crosstalk under pathological conditions,” the study said.
Finally, the test to determine the buildup of amyloid involved examining the hippocampus and prefrontal cortex areas of brains in the mouse control groups, with the DMT group having substantially diminished amyloid levels compared to the control group. Results of this test indicate that DMT was effective at degrading amyloid build-up.
“DMT treatment significantly facilitated the degradation of Aβ plaques in these two regions.”
Concluding the study, the authors summarised the mechanisms they think enabled DMT to be a beneficial medicine in the fight against AD: “Taken together, the current study demonstrated that the anti-AD effects of DMT are associated with its restoration of neuronal ER-mitochondria crosstalk via the Sig-1r activation. Sig-1r was identified as a target for maintenance of mitochondrial calcium homeostasis and restoration of mitochondrial function, particularly mitochondrial calcium uptake. It then improved mitochondrial OXPHOS capacity and ATP production. DMT could serve a novel preventive and therapeutic agent against AD.”
Correction: This article has been amended to confirm that mice in the study were administered a dose of 2mg/kg, not 2ml/kg.
