Alzheimer’s disease (AD) is a devastating neurodegenerative disorder that affects millions of people worldwide. The hallmark features of AD include neuroinflammation, dendritic atrophy, and loss of synapse density in cortical regions controlling cognition, memory, and mood. Recent research has pointed to a potentially groundbreaking therapy using psilocybin, a naturally occurring compound found in certain mushrooms known for its hallucinogenic properties. While some current treatments carry significant risk for adverse side effects, psilocybin and other psychedelics are relatively low risk. This blog discusses the emerging evidence suggesting that psilocybin may hold promise as a treatment for AD due to its ability to promote neuronal growth and modulate neuroinflammation.
Recent studies have demonstrated that psychedelics like psilocybin can stimulate 5-HT2A receptors, promoting cortical neuron growth, activation of neuronal survival mechanisms, and modulation of the immune system. Activation of these receptors induces the expression of immediate early genes (IEGs), which are known to be involved in neuroplasticity. Moreover, psychedelics have been shown to activate signaling pathways that promote neurotrophic factor release, particularly brain-derived neurotrophic factor (BDNF), which plays a crucial role in neuronal growth and survival. BDNF is often reduced in AD, contributing to the progressive loss of spines and synapses associated with dementia. In both human and animal studies, psychedelics like psilocybin increased BDNF expression in the cortex, increasing neuronal growth. These structural changes are accompanied by functional changes, such as an increase in spontaneous excitatory postsynaptic currents (sEPSCs), which indicate improved synaptic activity.
Neuroinflammation is increasingly recognized as a critical component of AD pathophysiology. Psychedelics have shown potential in modulating the immune system and reducing inflammation. By promoting cortical neuron growth and modulating neuroinflammation, psilocybin may have the potential to simultaneously address two significant components of AD pathophysiology.
One of the most promising aspects of psychedelic medicine is the long-lasting therapeutic effects observed after a single administration. Clinical trials and preclinical studies have demonstrated that psychedelic-assisted therapy can elicit therapeutic responses lasting for months. In some cases, this effect has been associated with increased neuroplasticity. In addition to promoting neuronal growth and modulating neuroinflammation, using psilocybin to activate 5-HT2A receptors has been shown to improve mitochondrial function. Mitochondrial dysfunction and oxidative stress are common features of neurodegenerative diseases like AD. By enhancing mitochondrial function, psilocybin may further contribute to its therapeutic potential for AD.
While the evidence supporting the use of psilocybin for treating neurodegenerative disorders like AD is still limited, the emerging research is promising. The unique ability of psychedelics to promote both structural and functional neuroplasticity through the activation of 5-HT2A receptors makes them an intriguing candidate for further exploration as a potential treatment for AD. As we continue to investigate the therapeutic potential of psychedelics, it is crucial to conduct further research to better understand their mechanisms of action and assess their safety and efficacy for treating neurodegenerative diseases. Collaborative efforts between researchers, medical professionals, and therapeutic facilitators will be essential to unlock the full potential of psychedelic medicine and offer hope to those affected by devastating neurological disorders like AD.
Reference: Saeger, H. N., & Olson, D. E. (2022). Psychedelic-inspired approaches for treating neurodegenerative disorders. Journal of Neurochemistry, 162, 109–127.