The biggest obstacle to the acceptance of cannabis as a therapeutic tool against brain aging may not be scientific, but cultural. The fear of “getting high” keeps many patients and even healthcare professionals away. But microdoses of the substance can escape the zone of psychoactivity while still providing benefits. This could open the door to new formulations focused on prevention, particularly in more vulnerable populations, such as older adults with mild cognitive impairment or a family history of dementia.
As the world’s population ages, the number of people with dementia, such as Alzheimer’s disease, also increases. Faced with the absence of curative treatments and the limited effectiveness of available drugs, interest in new therapeutic approaches is growing. And among them, cannabinoids from the Cannabis plant.
A new Brazilian study recently published in the international journal _Journal of Alzheimer’s Disease_ studied the effects of microdoses of cannabis extract in patients with a mild form of Alzheimer’s. The results are discreet, but they carry a promising message: perhaps the future of medical cannabis lies in invisible doses, and not in the psychoactive effects that still frighten many patients and doctors.
The study led by Professor Francisney Nascimento and colleagues from the Federal University of Latin American Integration (UNILA) recruited elderly patients diagnosed with a mild form of Alzheimer’s and evaluated the effects of daily use of a cannabis extract containing THC and CBD at extremely low concentrations. Subpsychoactive doses, which do not cause the famous “high” associated with recreational use of the plant and pose no health risk. In fact, many would wonder if this dose causes any effect, since it works in what we would call a “microdose,” to use a term often associated with psychedelics.
The choice of this approach did not come out of nowhere. In 2017, the group of Andras Zimmer and Andras Bilkei-Gorzo had already demonstrated that very low doses of THC restored cognition in aged mice, reversing gene expression patterns and synaptic density in the hippocampus to levels similar to those in young animals.
Subsequently, other studies confirmed that the endocannabinoid system, important for neuronal homeostasis and plasticity, undergoes a natural decline during aging.
Inspired by these results, as well as a case report published in 2022 by the same Brazilian group showing clinical improvement after 22 months of microdoses in a patient with Alzheimer’s disease, the authors decided to move forward with a randomized, double-blind, placebo-controlled clinical trial in human volunteers.
The primary outcome measure was the ADAS-Cog, a scale widely used to assess cognitive function in patients with dementia. After 24 weeks of treatment, the group that received the extract with THC showed stabilization of scores, while the placebo group showed worsening. This is a difference limited to only one of the subscales evaluated and observed only at long-term follow-up, but it nevertheless remains statistically significant.
In other words, the impact was modest, but relevant. In patients with preserved or moderately compromised cognitive function, it may be unrealistic to expect major changes within a few weeks. The study’s real contribution may lie elsewhere: It suggests that microdoses may have a preventative role, functioning almost like a supplement that protects the brain from age-related decline.
This hypothesis is echoed in another Brazilian study, published by me in 2022 in Translational Psychiatry, which demonstrated the reduction of lipoxin A4 (LXA4) in the aging brain – a pro-inflammation mediator that acts, among other mechanisms, through stimulation of the endocannabinoid system.
A new paradigm: cannabis without the “high”
The biggest obstacle to the acceptance of cannabis as a therapeutic tool against brain aging may not be scientific, but cultural. The fear of getting “high” keeps many patients and even healthcare professionals away. But studies like this show that there are ways to overcome this problem, such as using doses so low that they don’t cause noticeable changes in consciousness, but can still modulate important biological systems, such as inflammation and neuroplasticity.
Microdoses of cannabis can escape the zone of psychoactivity while still providing benefits. This could open the door to new formulations focused on prevention, particularly in more vulnerable populations, such as older adults with mild cognitive impairment or a family history of dementia.
Despite its potential, the study also has important limitations: the sample size is small and the effects were limited to a single dimension of the cognitive scale. However, this work represents an unprecedented step: it is the first clinical trial to successfully test the microdosing approach in patients with Alzheimer’s disease. This is a new way to approach this plant in the treatment of important diseases.
To move forward, new studies will be needed with a larger number of participants, a longer follow-up time and a combination with biological markers (such as neuroimaging and inflammatory biomarkers). Only then will it be possible to answer the fundamental question: can cannabis prevent Alzheimer’s disease? We have taken an important step towards this understanding, it seems, but for now the question remains unanswered.
* Fabricio Pamplona holds a PhD in Pharmacology from the Federal University of Santa Catarina (UFSC)
*This article is republished from The Conversation under a Creative Commons license. Read the original.
About The Author
