Research on psychedelic therapy has shown promising results for mental health conditions such as depression, anxiety, post-traumatic stress disorder (PTSD), and substance use disorders. Furthermore, given the mind-altering effects of these substances, can they also help in the treatment of Alzheimer’s disease and related dementias?
Read on to learn about the latest in this area of research.
What is Alzheimer’s Disease?
Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects the brain. As a result, the disease leads to a decline in cognitive function, memory, thinking skills, and language.
It is the most common cause of dementia. Dementia is a term used to describe a group of symptoms associated with a decline in memory and thinking skills severe enough to interfere with daily life.
Current Statistics
Alzheimer’s disease and related dementias (ADRD) represent a significant and growing global health challenge. According to the World Health Organization, over 55 million people worldwide have dementia; it is estimated that there are 10 million new cases every year.
In 2023, Alzheimer’s disease affected over 6 million individuals in the United States. As the population ages, the prevalence of ADRD is expected to rise, posing substantial social, economic, and healthcare challenges.
Pathology and Risk Factors
The pathology of Alzheimer’s disease involves the accumulation of abnormal protein deposits in the brain, including beta-amyloid plaques and tau tangles. This disrupts the normal functioning of nerve cells and leads to degeneration and the subsequent loss of communication between brain cells.
Therefore, these changes cause impairment in speech, object recognition, memory, cognitive function, language, problem-solving, and visuospatial processing-related executive functions.
While age is a significant risk factor, Alzheimer’s disease is not a normal part of aging. Although the majority of individuals affected are over 65 years of age, it can also occur in those who are younger. This is referred to as early-onset Alzheimer’s.
The exact cause of Alzheimer’s disease is not fully understood. Several risk factors increase the likelihood of developing Alzheimer’s disease, including age, family history, genetics, environmental, and certain lifestyle factors.
Prevention strategies for Alzheimer’s disease often emphasize lifestyle modifications. It’s important to note that while these measures may reduce the risk, they do not guarantee prevention. These include the following:
- Maintaining a healthy weight
- Quitting smoking
- Getting sufficient sleep
- Managing blood sugar
- Engaging in regular physical activity
- Managing cardiovascular risk factors (such as high blood pressure and high cholesterol)
- Staying mentally active
- Fostering social connections
- Drinking in moderation
Signs and Symptoms
Alzheimer’s disease typically advances slowly, with symptoms worsening over time. Therefore, in the early stages, individuals may experience mild memory loss and confusion, which can be overlooked or attributed to normal aging. The Centers for Disease Control and Prevention published the following 10 Warning Signs of Alzheimer’s:
- Memory loss that disrupts daily life, such as getting lost in a familiar place or repeating questions.
- Challenges in planning and/or solving problems such as handling money and paying bills.
- Confusion with time or place, such as losing track of dates.
- New problems with words in speaking, writing, or following a conversation.
- Difficulty completing familiar tasks at home, at work, or for leisure.
- Decreased or poor judgment.
- Misplacing things and being unable to retrace steps to find them.
- Changes in mood, personality, or behavior.
- Withdrawal from work or social activities
As the disease progresses, individuals may experience challenges in communication, disorientation, and issues with coordination and motor functions. The cognitive decline becomes more noticeable, affecting a person’s ability to function independently. In the later stages, individuals may require full-time care with daily activities.
Treatment Options
There is currently no cure for Alzheimer’s disease. That said, there are various treatment options aimed at managing symptoms and improving the quality of life for affected individuals. Medications such as cholinesterase inhibitors and memantine are commonly prescribed to help alleviate or control cognitive symptoms.
Research into Alzheimer’s disease continues, with ongoing efforts to understand its underlying mechanisms, identify potential biomarkers for early detection, and develop innovative therapeutic approaches. The ultimate goal is to find effective interventions that can modify the course of the disease or prevent its onset.
This is where psychedelics may have a role in supporting the treatment of ADRD. It may offer hope for individuals and families affected by this devastating condition. Currently, there is a lack of clinical trials that have specifically investigated this approach within this population and published their findings. However, leading researchers have written articles in support of their therapeutic potential. Here is a summary of their proposed mechanisms.
Neuroplasticity
Psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), are known to have a unique impact on the brain’s neuroplasticity. Neuroplasticity refers to the brain’s ability to reorganize itself by forming new neural connections throughout life. This process is crucial for learning, memory, and adapting to new experiences.
Neuroplasticity becomes particularly relevant in Alzheimer’s because the condition is characterized by the degeneration of neural connections and the loss of neurons. The accumulation of beta-amyloid plaques and tau tangles disrupts normal neural functioning and leads to cognitive decline.
Psychedelics appear to enhance neuroplasticity through their action on serotonin receptors. Serotonin is a neurotransmitter that plays a key role in mood regulation, and psychedelics influence the serotonin system. Studies suggest that psychedelics can promote the growth of new neurons (neurogenesis) and increase the density of dendritic spines, which are crucial for synaptic connections.
Therefore, by enhancing neuroplasticity, psychedelics may potentially contribute to the regeneration of neural pathways and the restoration of cognitive function.
Improve Glucose Metabolism
It’s been shown that there is a decrease in glucose metabolism in certain brain regions of individuals with Alzheimer’s. This effect can be detected using imaging techniques like positron emission tomography (PET scans). The brain uses glucose as its main source of energy, and an abnormal glucose metabolic rate would negatively impact brain functioning. It has been shown that this decline in glucose metabolism is associated with the accumulation of beta-amyloid and tau tangles, which are characteristics of Alzheimer’s pathology.
A literature review was conducted to explore the role that psychedelic therapy—specifically psilocybin and LSD—could play in the prevention and treatment of Alzheimer’s disease.
The search included meta-analyses, systematic reviews, and randomized control trials. A total of 75 articles met the initial criteria, and 8 articles were selected for the review. Neuroplastic changes were measured by positron emission testing and functional magnetic resonance imaging to determine the efficacy of psychedelic therapy.
The results showed that psychedelic therapy is associated with anti-inflammatory properties, increased brain glucose metabolism, neurogenesis, and neuroprotective properties. The authors concluded that their findings are “consistent with the hypothesis that psychedelic therapy can not only help symptomatic treatment of Alzheimer’s Disease but may also have a role in disease modification.”
Reduce Inflammation
When our body experiences an injury or infection, inflammation is a natural immune response. However, inflammation can contribute to various diseases, such as Alzheimer’s, when it becomes chronic or dysregulated.
Alzheimer’s is associated with the accumulation of abnormal protein aggregates in the brain. The immune system recognizes these aggregates as foreign or harmful. As a result, it triggers an inflammatory response to clear them. However, in Alzheimer’s, this response becomes chronic and contributes to neuronal damage.
Microglia are the immune cells of the brain that play a role in learning debris. Microglia become chronically activated and release pro-inflammatory substances in Alzheimer’s. Their overactivation can lead to the release of harmful substances that contribute to neuroinflammation and neuronal damage.
One of the therapeutic areas of focus for psychedelics is their role as anti-inflammatory agents. Here are some suggested mechanisms:
Serotonin Receptor Modulation
Psychedelics, such as psilocybin and LSD, primarily interact with serotonin receptors in the brain. The serotonin system not only regulates mood but also has complex interactions with the immune system.
Some studies suggest that serotonin receptors, particularly the 5-HT2A receptor, play a role in modulating inflammatory responses. Therefore, activation of these receptors may have anti-inflammatory effects, but the exact mechanisms are still under investigation.
Microglial Modulation
There is some evidence that psychedelics may modulate microglial activity. Studies have shown anti-inflammatory effects associated with psychedelic use. That said, the specific impact on microglia in the context of Alzheimer’s is an area that requires more research.
Manage Behavioral and Neuropsychiatric Symptoms
The quality of life of individuals with Alzheimer’s and their caregivers is significantly impacted due to behavioral and psychological symptoms such as apathy, mood changes, depression, aggression, anxiety, and sleep problems.
The conventional treatment for these symptoms, such as antidepressants, anti-anxiety drugs, anticonvulsant drugs (to treat aggression), and antipsychotics (to treat paranoia, hallucinations, and agitation), only manage symptoms temporarily. They also lead to unpleasant side effects such as dizziness which can put the individual at risk of a fall.
Numerous clinical trials have shown the promising effects of psychedelics in reducing depression symptoms, decreasing anxiety in patients with life-threatening illnesses, and treating PTSD. There is research looking at how psychedelics influence sleep.
Therefore, psychedelics may play a role in managing symptoms and reducing the comorbidities of Alzheimer’s, allowing individuals to feel more comfortable while providing support and easing stress both for themselves and for their caregivers.
A literature review was conducted to focus on psychedelics and neuropsychiatric symptoms (NPS) of Alzheimer’s disease. The search included randomized controlled trials, clinical trials, and case reports using the keywords “psychedelics”, “neuropsychiatric symptoms,” and “Alzheimer’s Disease”.
Unfortunately, the results showed that there were no studies that looked at the treatment of NPSs of dementia with classical psychedelics. The authors conclude that although there appears to be potential for psychedelics in the treatment of Alzheimer’s, they are cautiously optimistic. Specifically, rigorous research with conclusive evidence needs to be conducted to address issues including dosage schedules, contraindications, and most effective compounds.
Therefore, research into the potential benefits of psychedelics on the quality of life for individuals with Alzheimer’s disease is limited, and no specific conclusions can be drawn.
Ethical Considerations
There is a growing interest in researching psychedelic medicine to treat individuals with ADRD. However, there are ethical and moral implications to consider, given the nature of the disease and its effect on the person’s mental well-being.
A paper examined the ethics of psychedelic medicine and research involving persons living with ADRD. It offered preliminary analyses of six ethical issues:
- Impact of psychedelics on autonomy and consent
- Impact of “ego dissolution” on persons experiencing a pathology of self
- How psychedelics might impact caregiving
- Potential exploitation of patient desperation
- Institutional review boards’ orientation to psychedelic research
- Methods to mitigate inequity
Current Research
Findings from Johns Hopkins University
The Center for Psychedelic & Consciousness Research at Johns Hopkins University is looking at psilocybin as a potential aid for depression in early Alzheimer’s disease.
Albert Garcia-Romeu, PhD, one of the principal investigators, shared specific details about the trial with Penn Memory Center at the Penn Neuroscience Center in March 2023.
“In some patient populations, psilocybin is very helpful in reducing depression, reducing anxiety, and improving quality of life…those types of benefits could be really useful in a population with Alzheimer’s,” explained Dr. Garcia-Romeu.
The study is looking for participants who have recently been diagnosed with Alzheimer’s Disease and are feeling depressed. It begins with a screening process that includes a six-hour session to assess the participant’s physiology and mental health history. Subsequently, if the criteria are met, the baseline psychosocial symptoms would be measured through various tests.
If the person qualifies, their baseline psychosocial symptoms, such as anxiety and depression, would be measured through a series of cognitive tests. The next phase takes about three to four weeks and involves counseling and weekly meetings with study facilitators.
Emerging Insights and Considerations
The third phase would include administration of psilocybin. This includes a first dose of roughly 15mg of psilocybin in a capsule and a second dose of 25mg in another session.
Then the integration phase would occur. The process takes approximately two to three months to complete, with a six-month follow-up to assess the symptoms and quality of life of the subjects.
Learn more about this clinical trial on Alzheimer’s and psilocybin.
Be sure to read about five things to know before enrolling in a psilocybin clinical trial.
Therefore, the potential use of psychedelics in treating Alzheimer’s disease and related dementias disease is an area of emerging research. While early findings are promising, it’s important to note that further studies are needed to fully understand their efficacy, safety, and long-term effects in this context.
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What is Alzheimer’s Disease?
CDC. (2020, October 26). Alzheimer’s Disease and Related Dementias. CDC; CDC. https://www.cdc.gov/aging/aginginfo/alzheimers.htm
Current Statistics
World Health Organization. (2023, March 15). Dementia. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/dementia
Alzheimer’s Disease Facts and Figures. (2023). Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/facts-figures
Pathology and Risk Factors
Hill, N. L., Kolanowski, A. M., & Gill, D. J. (2011). Plasticity in Early Alzheimer’s Disease: An Opportunity for Intervention. Topics in Geriatric Rehabilitation, 27(4), 257. https://doi.org/10.1097/tgr.0b013e31821e588e
What is Alzheimer’s Disease? (n.d.). Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-alzheimers
Alzheimer’s disease. (2023, August 30). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447
Healthy Body, Healthier Brain. (2020, May 29). Centers for Disease Control and Prevention. https://www.cdc.gov/aging/publications/features/healthy-body-brain.html
Signs and Symptoms
10 Warning Signs of Alzheimer’s. (2019, December 13). Centers for Disease Control and Prevention. https://www.cdc.gov/aging/healthybrain/ten-warning-signs.html
Treatment Options
Alzheimer’s Disease Fact Sheet. (2023, April 5). National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-and-dementia/alzheimers-disease-fact-sheet
How Is Alzheimer’s Disease Treated? (2023, September 12). National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers-disease-treated
Neuroplasticity
Pilozzi, A., Foster, S., Mischoulon, D., Fava, M., & Huang, X. (2022). A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression. International Journal of Molecular Sciences, 24(15), 12513. https://doi.org/10.3390/ijms241512513
Improve Glucose Metabolism
Dewanjee, S., Chakraborty, P., Bhattacharya, H., Chacko, L., Singh, B., Chaudhary, A., Javvaji, K., Pradhan, S. R., Vallamkondu, J., Dey, A., Kalra, R. S., Jha, N. K., Jha, S. K., Reddy, P. H., & Kandimalla, R. (2022). Altered glucose metabolism in Alzheimer’s disease: Role of mitochondrial dysfunction and oxidative stress. Free Radical Biology and Medicine, 193, 134–157. https://doi.org/10.1016/j.freeradbiomed.2022.09.032
Jones, M. (2023). The Potential Role of Psychedelic Therapy in Alzheimer’s Dementia. Summer Interdisciplinary Research Symposium. https://scholar.valpo.edu/sires/171/
Vann Jones, S. A., & O’Kelly, A. (2020). Psychedelics as a Treatment for Alzheimer’s Disease Dementia. Frontiers in Synaptic Neuroscience, 12. https://doi.org/10.3389/fnsyn.2020.00034
Reduce Inflammation
Novoa, C., Salazar, P., Cisternas, P., Gherardelli, C., Vera-Salazar, R., Zolezzi, J. M., & Inestrosa, N. C. (2022). Inflammation context in Alzheimer’s disease, a relationship intricate to define. Biological Research, 55(1). https://doi.org/10.1186/s40659-022-00404-3
Augusto-Oliveira, M., Arrifano, G. P., Lopes-Araújo, A., Santos-Sacramento, L., Takeda, P. Y., Anthony, D. C., Malva, J. O., & Crespo-Lopez, M. E. (2019). What Do Microglia Really Do in Healthy Adult Brain? Cells, 8(10). https://doi.org/10.3390/cells8101293
Flanagan, T. W., & Nichols, C. D. (2018). Psychedelics as anti-inflammatory agents. International Review of Psychiatry, 30(4), 363–375. https://doi.org/10.1080/09540261.2018.1481827
Winkelman, M. J., Szabo, A., & Frecska, E. (2023). The potential of psychedelics for the treatment of Alzheimer’s disease and related dementias. European Neuropsychopharmacology, 76, 3–16. https://doi.org/10.1016/j.euroneuro.2023.07.003
Garcia-Romeu, A., Darcy, S., Jackson, H., White, T., & Rosenberg, P. (2021). Psychedelics as Novel Therapeutics in Alzheimer’s Disease: Rationale and Potential Mechanisms. Current Topics in Behavioral Neurosciences. https://doi.org/10.1007/7854_2021_267
Manage Behavioral and Neuropsychiatric Symptoms
Treatments for Behavior. (n.d.). Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/treatments/treatments-for-behavior
Alzheimer’s Disease. (2022, December 10). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/9164-alzheimers-disease
Sarangi, A., & Akinkunmi, O. (2023). Psychedelics for the Neuropsychiatric Symptoms of Alzheimer’s disease. The American Journal of Geriatric Psychiatry, 31(3), S44–S45. https://doi.org/10.1016/j.jagp.2022.12.201
Ethical Considerations
Peterson, A., Largent, E. A., Lynch, H. F., Karlawish, J., & Sisti, D. (2022). Journeying to Ixtlan: Ethics of Psychedelic Medicine and Research for Alzheimer’s Disease and Related Dementias. AJOB Neuroscience, 1–17. https://doi.org/10.1080/21507740.2022.2148771
Current Research
McCarthy, M. (2023, April 19). Can psychedelics help patients with dementia? Penn Memory Center. https://pennmemorycenter.org/psychedelics-dementia/
