“Low-dose long-term administration of cannabis compound reverses brain aging”
It’s the mechanism that is of interest to this group. From the abstract:
“Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions.”
That does not sound good.
And:
“In the brain, Δ9-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet. Thus, long-term Δ9-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery. Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.”
I’d be interested in any reactions to this apparently new finding.
In general I avoid reading into broad sweeping statements like those unless there are very specific articles that are cited (and many of them, which then should lead to very highly cited review papers).
“We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats.”
“we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR.”
Below is a mini-review from 2022 on the effects of rapamycin on cognition and neurogenesis in mice and humans.
Source: Culig L, Chu X, Bohr VA. Neurogenesis in aging and age-related neurodegenerative diseases. Ageing Res Rev . 2022;78:101636. doi:10.1016/j.arr.2022.101636. (Link below)
Excerpt from full text:
“Treatment with rapamycin has been associated with improvements in learning and memory in both young and old animals. In 8-month-old male mice, chronic rapamycin treatment (16 weeks) was able to enhance spatial learning and memory, as well as reduce anxiety- and depression-like behaviors (Halloran et al., 2012). The same study observed that 40 weeks of treatment improved recall of an aversive event in older mice (25 months of age), suggesting that even when started late in life, chronic rapamycin treatment was able to delay cognitive decline associated with aging (Halloran et al., 2012). Similarly, lifelong rapamycin administration in mice (started at 2 months of age) was able to improve learning and memory when tested at 18 months of age, but shorter rapamycin administration in adult mice (12 weeks; started at 15 months of age) wasn’t able to improve cognition in animals with pre-existing, age-dependent learning and memory deficit (Majumder et al., 2012). Finally, chronic treatment (15 months) with rapamycin was able to ameliorate deficits in learning and memory in aged (34-month old) rats (Van Skike et al., 2020). Hence, it is yet to be determined which dosing and duration at which age are optimal for exerting improvements in cognitive function. Interestingly, 12 weeks of rapamycin administration in 22-month old mice resulted in increased abundance of activated NSCs in the SVZ (Leeman et al., 2018). However, different results were obtained in a study where rapamycin (i.p.) significantly reduced the number of proliferating cells in the adult hippocampus of 3-month old mice (Romine et al., 2015). It is difficult to compare these results as (1) the experiments were carried out in different age groups, (2) the method and duration of rapamycin administration was different and (3) as they focus on different neurogenic niches. Hence, further experiments are necessary to determine the effects of rapamycin on neurogenesis - especially in the DG of healthy mice after prolonged administration. In humans, a small study in heart transplant recipients found that short-term (4 weeks) immunosuppression with a rapamycin analogue everolimus was associated with improvements in memory performance and mood (Lang et al., 2009). However, a randomized controlled trial in healthy older adults (25 subjects) revealed no improvements in cognition after 8 weeks of rapamycin treatment, noting that longer trials with larger sample sizes may be warranted (Kraig et al., 2018). A clinical trial exploring the effects of rapamycin in older adults with MCI on cognition is currently active (NCT04200911).”