Memory Revival: Psychedelics & Alzheimer’s

This article reviews current research on evidence for synthetic and natural psychedelics in treating causes and symptoms of Alzheimer’s disease.

We’ve previously discussed what a review article is and how they differ from other types of articles, such as research articles.

Brief recap – a review article attempts to summarize the current state of scientific understanding of a topic. This typically includes discussing a current understanding of a condition’s pathophysiology (what we believe causes a disease), the current state of treatments, and where future research appears to be heading.

Review articles analyze published research to give a “snapshot” of the current state of knowledge on a topic. Review articles are considered secondary sources. The author is giving a “secondhand” account of research conducted by other people. It is not reviewing original research the authors themselves conducted.

 

What is Alzheimer’s Disease? And Why Psychedelics?

Alzheimer’s Disease (AD) is a progressive, neurodegenerative disease. Over time, it destroys cognitive skills – remembering, thinking, and reasoning – as well as the ability to communicate and, in later stages, the ability to carry out simple tasks of everyday living. It’s currently the 7th-leading cause of death in the United States.

Amongst individual cases of AD, a variety of different functions may be preserved (such as the ability for a carpenter to continue producing work, despite an inability to function in most other areas of life) and each individual experiences differences in disease progression. This suggests the possibility for a neuroplastic response. Plasticity is “ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions, or connections”. In other words – plasticity refers to your brain’s ability to rewire itself in response to stimuli – such as learning to cook or ride a bicycle. It explains how the brain changes with learning.

Dementia, including AD, may involve a loss of plasticity. It may also involve cell death within the brain due to long-term, high levels of neuroinflammation. Research suggests abnormalities with neurotransmission, including a loss of inhibitory GABA functioning, plays a role in development of dementia, including AD.

 

How Psychedelics May Treat Dementia

A proposed key mechanism for treating AD is the plastogenic effect of psychedelics. It’s believed that certain psychedelics have the ability to cause neuroplasticity within brain circuits, and slow, possibly even reverse, brain atrophy caused by AD.

Research in animals reveals that the serotonin system appears relevant to AD through several proposed mechanisms, namely:

• regulating learning and memory functions, and

• helping solve the selective loss of neurons in serotonin pathways, as well as lowered activity within serotonergic synapses, demonstrated in AD patients

What are the proposed mechanisms? Let’s touch on a few:

Modulate glutamate neurotransmission and facilitate synaptic plasticity

Glutamate is the most abundant neurotransmitter in your brain. It plays a role in numerous functions. Relevant to today’s discussion is glutamate’s effect on memory consolidation, which drives our ability to learn and retain information. Glutamate reinforces activity within neurons – it can even recruit resting neurons into action! Thus, glutamate acts as a driving force for neuroplasticity – and in a brain affected by AD, this can help recruit neurons to re-establish connections destroyed by the AD disease process.

Upregulate neurotrophic factors which promote neuron survival and glutamate-driven neuroplasticity

Neurotrophic factors are molecules that help your neurons survive, grow, and replicate. As we’ve discussed, the AD disease process causes neuronal loss. Logically, we see why promoting neuron survival in this situation is good. And we just discussed glutamate’s role in driving neuroplasticity. One exciting aspect of psychedelics for addressing AD is that psychedelic treatments could address both symptoms of AD and the disease process itself. Remember, AD is a progressive disease – without treatment, it is going to get worse with time. And we currently don’t have a treatment that stops this progression. Current treatments are frequently inadequate for managing symptoms. Imagine a treatment that both addressed current symptoms, AND slowed or even prevented further disease progression. Serotonergic psychedelics have this potential, in large part due to their ability to drive neuroplasticity.

Reduces neurotoxicity driven by the AD disease process by modulating GABAAR

γ-aminobutyric acid type A receptors (GABAARs) are receptors in your brain which play a major role in inhibiting processes within the brain. (In this instance, don’t view “inhibition” as “bad”.)

We won’t go into a full dive on GABAARs. Just know that they play essential functions in regulating our cognition, behavior, and consciousness. Issues with GABAARs functioning are associated with conditions including AD, autism, schizophrenia, and postpartum depression, among others.

Activate mammalian target of rapamycin (mTOR) pathways within brain regions atrophied by AD

mTOR is a protein responsible for regulating our cell growth, reproduction, and survival. It is essential for proper function of human metabolism and physiology. Activating mTOR within these brain region pathways contributes to production of brain-derived neurotrophic factor (BDNF), and neuroplasticity in the prefrontal cortex (PFC) region of the brain.

 

Current and future research

“…(the) potential for psychedelic compounds to influence and enhance functional neuronal connectivity, stimulate neurogenesis, restore brain plasticity, reduce inflammation and enhance cognition provides a new therapeutic target and compelling argument for further investigation of the potential for psychedelics as a disease modifying compound in conditions where currently none exists.”
– Vann Jones and O’Kelly, 2020.

There is a current trial underway evaluating psilocybin for treating depression in patients with mild Alzheimer’s disease.

But, as usual in my writing, I now have to complain about the Schedule I status of psychedelics and how this stymies further research. I’m running out of ways to say the War on Drugs is bad. We’ll continue to see individual patients do their own research, and n = 1 studies do have value. But in order to fully evaluate the ability for psychedelics to address AD symptoms and disease progression, psychedelics must be rescheduled.

 

Conclusions

Psychedelics are a promising possibility for treating AD and other dementias, in large part due to their ability to drive neuroplasticity. It’s hoped that neuroplasticity could halt the progressive nature of AD, and possibly even restore lost functionality.

We’re a long way from knowing whether psychedelics actually work to treat AD as proposed. The field of medicine is full of treatments hailed as game-changers which turned out to be duds. Lab research does not always translate to real-life differences in real-life patients.

That said – there’s real promise in a treatment that can restore neuron functionality and drive growth in the brain. I’ll be following the research closely, with hopes that one day patient cases like my grandfather are no longer the norm. Maybe one day, psychedelics will help turn AD into a bad memory.

 

References:

Alzheimer’s and dementia (no date) National Institute on Aging. Available at: https://www.nia.nih.gov/health/alzheimers-and-dementia (Accessed: 26 December 2023).

Author links open overlay panelMichael James Winkelman a et al. (2023) The potential of psychedelics for the treatment of alzheimer’s disease and related dementias, European Neuropsychopharmacology. Available at: https://www.sciencedirect.com/science/article/pii/S0924977X23001347 (Accessed: 26 December 2023).

Garcia-Romeu, A. et al. (1AD) Psychedelics as novel therapeutics in alzheimer’s disease: Rationale and potential mechanisms, SpringerLink. Available at: https://link.springer.com/chapter/10.1007/7854_2021_267 (Accessed: 26 December 2023).

Mateos-Aparicio, P. and Rodríguez-Moreno, A. (2019) The impact of studying brain plasticity, Frontiers in cellular neuroscience. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400842/ (Accessed: 26 December 2023).

Vann Jones, S.A. and O’Kelly, A. (2020a) Psychedelics as a treatment for alzheimer’s disease dementia, Frontiers. Available at: https://www.frontiersin.org/articles/10.3389/fnsyn.2020.00034/full (Accessed: 26 December 2023).

Vann Jones, S.A. and O’Kelly, A. (2020b) Psychedelics as a treatment for alzheimer’s disease dementia, Frontiers. Available at: https://www.frontiersin.org/articles/10.3389/fnsyn.2020.00034/full (Accessed: 26 December 2023).