But this research says no neuroplasticity occurs. Ask your competent? doctor to clarify.
ROBUST METHODS FOR QUANTIFYING NEURONAL
MORPHOLOGY AND MOLECULAR SIGNALING REVEAL THAT
PSYCHEDELICS DO NOT INDUCE NEUROPLASTICITY
March 2024
The latest here:
The Fascinating Link between Psychedelics and Neuroplasticity
In recent years, the scientific community has started to unveil one of the most intriguing possibilities of treatment of modern times: the use of psychedelics to induce or promote neuroplasticity for therapeutic purposes. This exploration is not a mere revisiting of the countercultural relics of the 1960s; rather, it aims at reappraising a journey into the depth of human mind to seek answers to some of the most pressing mental health challenges [1]. Psychedelics, such as lysergic acid diethylamide, mescaline, psilocybin (found in magic mushrooms), and N-dimethyltryptamine (DMT) (present in ayahuasca), are known for their relevant effects on perception, thought, and emotion, often leading to mystical experiences. Once sidelined their detrimental effects, however, these compounds are increasingly recognized for their potential to rewire the brain, especially when it is resistant to traditional treatments [2].
From a neurobiological perspective, these substances are linked to the well-documented hallucinogenic effects, mostly involving the activity of the fronto-cortical network. Recent insights, however, suggest that psychedelics may also promote structural plasticity and neuronal growth within the fronto-cortical-limbic circuits, likely through an increased levels of the Brain-Derived Neurotrophic Factor (BDNF) [3], a vital protein for neuronal growth and survival. This effect, known as “psychoplastogen”, fosters neuroplastic changes that are pivotal for synaptic, structural, and behavioral adaptations, both in normal and pathological conditions. Neuroplasticity, i.e., the brain’s ability to reorganize itself by generating new neural connections, is vital for learning, memory, and sleep, among others, as well as for the recovery from different types of brain injury. Apart from pure motor tasks, indeed, neural plasticity plays a crucial role also in cognitive functioning and mental health [4]. Accordingly, impaired or maladaptive neuroplasticity has been linked to several neurological and neuropsychiatric disorders, such as depression and age-related cognitive decline [5]. Psychedelics might mitigate synaptic deficit, neuronal degeneration, and the loss of network connectivity, which are all linked to chronic stress, sustained neuroinflammation, depression, and treatment resistance [6]. This potential for neuroplasticity and recovery is one of the reasons underlying the exploration of psychedelics as new treatments for mental and cognitive disorders.
Pharmacologically, psychedelics act on the serotonin 5-HT2A receptor (5-HT2AR), which are pivotal in regulating mood, cognition, and perception. This activation leads to specific changes in neurotransmitter signaling, particularly within the serotoninergic system, which is involved not only in mood regulation but also in cognition. Accordingly, it is known that some of the key cognitive functions where serotonin exerts a crucial role include short-term and long-term memory, decision making, attention, and executive function, as well as learning and social behavior [3]. However, the exact mechanism through which the 5-HT2AR activation influences neuronal growth remains largely unclear. In this scenario, the neuroplastic effects of psychedelics are believed to be mediated by several signaling pathways, including the tropomyosin receptor kinase B (TrkB), the mammalian target of rapamycin (mTOR), and the
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor glutamate signaling. Overall, these pathways coordinate the rapid and sustained enhancement of synaptic and structural neuronal remodeling, which seems to contribute to the clinical effect of psychedelics in mental health disorders, probably through the counteract of synaptic deficit and neuronal loss [3, 7].
Interestingly, human research using neuroimaging and post-mortem studies, as well as some animal models, have revealed that psychedelics can exert an anti-apoptotic effect on neurons in the prefrontal cortex (PFC) [8, 9, 10, 11, 12, 13]. This degeneration is typically exacerbated by stress, suggesting that psychedelics might counteract such detrimental effects through their neuroplastic properties. Furthermore, these substances stimulate the growth of new neural connections and enhance communication across different brain regions [7]. The activation of this pathway also initiates a cascade of neurobiological events eventually leading, among others, to an increased expression of BNDF. In particular, DMT has been associated with an increase in peripheral BDNF levels, highlighting a clear impact of psychedelics on this important neurotrophic factor [6, 14].
The downstream effect of psychedelics involves the upregulation of transcription and translation of synaptic proteins within the PFC and the hippocampus. Notably, these substances are able to induce long-lasting alterations in synaptic function and morphology also at the level of pyramidal neurons. As such, psychedelics have been linked to a temporary rise in cortical glutamate release and prolonged activation of excitatory neurotransmission in pyramidal neurons, primarily within the PFC [6], thus suggesting a role also at premotor and motor level.
Finally, psychedelics significantly impact brain connectivity, enhancing overall brain interactions and linking regions that normally would not communicate directly. This increased connectivity can lead to unique experiences, such as synesthesia, where senses overlap (e.g., seeing sounds), and intense perceptions (more than normal). Specifically, psychedelics reduce the activity in the Default Mode Network (DMN), which is associated with self-referential thoughts and the ego awareness; these changes can also include disruptions in thalamo-cortical connectivity, thus reducing the filtering of sensory inputs and intensifying sensory experiences. These alterations in functional connectivity are of particular interest for therapeutic applications, offering potential benefits for treating specific mental health issues, such as depression, post-traumatic stress disorder, and addiction disorders, by “resetting” dysfunctional brain networks [9]. The ongoing research into these effects holds promise for new insights into consciousness and mental health treatment [3]. A schematic summary of perspectives/strenghts and challenges/limitations associated with psychedelic therapy are detailed in the below-reported table (see Table 1).
| Aspect to be considered | Perspectives/Strenghts | Challenges/Limitations |
|---|---|---|
| Mental Health | Potential to treat resistant mental health disorders including depression, post-traumatic stress disorders, and addiction. | Variability in individual responses; potential for adverse psychological effects. |
| Neuroplasticity and Brain Connectivity | Promotes structural plasticity, neuronal growth, and enhances brain interactions, potentially leading to improved cognitive and emotional processing. | Mechanisms of action are not fully understood; changes in connectivity might lead to unpredictable outcomes. |
| Regulatory and Safety | Growing interest may lead to the development of new therapeutic protocols and guidelines/consensus statements. | Lack of comprehensive regulatory frameworks; safety concerns due to powerful and possibly unpredictable effects. |
| Research and Clinical Trials | Ongoing research holds promises for new insights and treatments. | Need for more rigorous and extensive clinical trials to establish efficacy and safety profiles. |
| Socio-cultural Acceptance | Increased acceptance may integrate psychedelics into mainstream therapeutic options. | Socio-cultural stigma and legal barriers still present may significantly limit a widespread acceptance and a diffuse adoption. |
Concluding, the exploration of the complex but intriguing connections between psychedelics and neuroplasticity opens innovative avenues of research in the understanding and potentials of these molecules in mental health disorders. Although preliminary data seem to be promising, further research is needed to fully disentangle the mechanisms of action, optimize therapeutic protocols, and ensure a safe use of these substances [15]. Currently, however, integrating psychedelics into mainstream therapy faces significant clinical and socio-cultural challenges. Of course, safety always comes first, since the powerful nature of these substances are able to induce profound changes which, in the absence of solid scientific evidence and proper therapeutic guidance, might lead to adverse events and undesiderable outcomes. Comprehensive regulatory frameworks, rigorous clinical trials, and accurate training for operators are essential steps of this challenging but also fascinating path of modern neuropsychiatry.
No comments:
Post a Comment