Psychedelic-Assisted Neuroplasticity for the Treatment of Mental Health Disorders PMC

Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders. In the last decade, evidence has mounted that psychedelic drugs can have positive physiological effects. It didn’t take long for the discovery of the anti-inflammatory effects of 5HT-2A agonists15 to inspire researchers to examine psychedelic compounds as potential medicines against neurodegeneration. As of 2021, there are two ongoing studies probing the potential of psychedelics in AD and in cases of mild cognitive impairment.

• Even MDMA requires another large clinical trial to address lingering concerns, van Elk says.
• Mean accuracy values of 0.87 ± 0.04 and recall values of 0.89 ± 0.04 were demonstrated, respectively.
• In contrast with many other classes of psychoactive substances (ketamine being a possible exception 92, 93), psychedelics do not lead to addiction or dependence 25, 94, and some respondents with SUDs remarked on these notable differences 79, 83.
• The results of memory and executive function tests, conducted in isolation or as part of standardized neuropsychological batteries, correlate with pathological changes in the medulla as well as with the patient’s overall level of maladjustment.
• Everybody figures it out,” says Balázs Szigeti, a clinical data scientist in the Translational Psychedelic Research program at the University of California, San Francisco, who studies this issue.

Corresponding authors

The number of publications on the applications of machine learning (right) and deep learning (left) to diagnostics of Parkinson’s disease (yellow graph) and Alzheimer’s disease (purple graph) by year (reproduced from 4). Robert A. Schoevers received a research grant from the Netherlands Organization Health Research and Development for a clinical study on oral esketamine, and is the co-investigator of a clinical study on psilocybin funded by Compass Pathways. He has also received an educational grant from Janssen, Pharmaceutical Companies of Johnson and Johnson, and honorarium from Clexio Biosciences.

The authors analyzed several works on the assessment of anxiety and depression based on written texts, voice recordings, data from MRI scans, survey methods, and their combinations. The paper noted that different algorithms were better suited for different types of data (they examined gradient boosting, random forest, and neural networks), but the average accuracy of the best-performing algorithms did not exceed 80%. The authors attribute the low results both to the small amount of data and to incomplete or imbalanced training datasets. Chen et al. 75 also noted the need to use additional data channels, including voice, activity, sleep, questionnaire, and instrumental methods (e.g., MRI) to potentially improve the accuracy of diagnosis. Additional data channels can also represent different aspects of everyday activity to add behavioral patterns into the data.

The relevance of behavior to human mental disorders varies with the innate properties of rodents. The diverse etiologies of mental disorders can affect the efficiency of individual differences, and mimicking the psychiatric symptoms of humans is often obstructed by orthologous differences. The renaissance of research into psychedelics class ofdrugs hasrenewed interest for a possible psychedelic clinical therapy for treatingpsychiatric conditions such as treatment-resistant depression, majordepressive-disorder, post-traumatic stress disorder, and other neuropsychiatricdiseases. Psychedelics are known to stimulate neurogenesis and gliogenesis,reduce inflammation, and ameliorate oxidative stress, which makesthem promising candidates for therapeutics in psychiatric, neurodegenerative,and movement disorders. The patent highlight showcase methods fortreating mental health disorders and promoting neural plasticity. The effectiveness of a given therapy in slowing down the progression of neurodegenerative disorders depends on their timely detection.

Will psychedelics ever live up to their hype?

The use of data augmentation in training deep neural networks can reduce the effect of overfitting and improve accuracy and stability. EEG data augmentation uses sliding window data sampling, data from generative models, noise addition (generally Gaussian noise is used), sampling, segment recombination, and Fourier transform 86. The architectures of neural networks and the achieved accuracy of depression detection according to EEG data are presented in Table 3. In addition, the possibility of using genetic data with instrumental and sociodemographic variables is attracting more and more attention 41.

Neuroplasticity for the Treatment

Unlike traditional medications that mainly manage symptoms, psychedelics may offer a pathway to disease modification through mechanisms like enhanced neuroplasticity (the brain’s ability to adapt and reorganize itself), reduction of neuroinflammation, and promotion of cellular regeneration. These effects could be crucial in counteracting underlying disease causes, such as neuron loss and cognitive decline. Psilocybin was designated a breakthrough therapy designation by the Food and Drug Administration (FDA) in 2018, 2019, and 2024 owing to its potency for monotherapy or combination treatment.107 Several types of psilocybin‐assisted therapies are currently in clinical trials. To overcome the current limitations in using and investigating psychedelics, researchers have attempted to visualize the brain or retrospectively study mental disorders before and after therapy.

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. He led longitudinal studies of children at risk for anxiety disorders and depression, which examined behavioral differences, risk factors, longitudinal outcomes, treatment, genetics and brain structure and function of children of parents with mood and anxiety disorders. The famous German toxicologist Louis Lewin used the name phantastica earlier in this century, and as we shall see later, such a descriptor is not so farfetched. The most popular names—hallucinogen, psychotomimetic, and psychedelic („mind manifesting”)—have often been used interchangeably.

When will psychedelics be legal?

Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Beyond the serotonergic system, other neurotransmitter systems-including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems-also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.

Researchers are now investigating whether psychedelic therapies can be administered more broadly, treating not only mood disorders but also neurodegenerative conditions like dementia and Alzheimer’s disease. Will psychedelics usher in a more hopeful era for patients with neurodegenerative conditions? There are only two ongoing studies exploring the use of psychedelics for the treatment of Alzheimer’s disease, and this article reviews the rationale behind them.

Authors and Affiliations

These may in turn better tailor future psychedelic treatments: transforming mental health and neurodegenerative disease research research as well as inform and improve therapeutic effectiveness. Qualitative inquiry can also complement quantitative research by generating, rather than validating, hypotheses, which can be tested using quantitative instruments. A newly popularised way of looking at AD, as well as other neurodegenerative diseases such as Parkinson’s or multiple sclerosis, is a disease driven by chronic inflammation. In the last decade, it has become clear that the brains of AD patients exhibit a sustained inflammatory response.9 The main agents of this response are microglia. These are the brain’s mobile “cleaner” cells that constantly scavenge the brain for any sign of damaged cells, infectious agents, or indeed plaques such as the ones formed by Aß.

14. Prevention of the Associated Psychological Problems

• Along with well-established instrumental methods, such as MRI, fMRI, and EEG, it became possible to automatize the use of several auxiliary diagnostics indicators.
• Thus, the term entheogen, derived from the Greek word entheos, which means „god within”, was introduced by Ruck et al. and has seen increasing use.
• In recent decades, pre-clinical assessment has become a major focus of research into neurodegenerative disorders 5,6.
• His current clinical passion is psychedelic-assisted psychotherapy, which he mentors interested doctors in providing.
• While some qualitative research efforts have been directed at exploring the role of the subjective psychedelic experience in the treatment of mental disorders, to date no systematic review exists.
• Typical EEG patterns used in screening have been described in the scientific and practical literature 20.

The 5‐hydroxytryptamine 2A receptor (5‐HT2AR) has a species‐specific residue 242 between human (serine) and mouse (alanine) residues in the binding pocket, as well as seven variations (p.S12N, p.T25N, p.D48N, p.I197N, p.A230T, p.A447N, p.H452Y) in human 5‐HT2AR. These changes may modify the pharmacological interactions between receptors and psychedelic drugs. Nonconserved structures may confer distinct pharmacological action across 5‐HT isoform‐dependently, where psychedelics interact. B) Rodents employed to assess the effectiveness of psychedelic drugs behaviorally and biochemically need the prerequisite induction of psychiatric symptoms in multiple ways.

Psychedelics, a diverse group of psychoactive compounds, including LSD, psilocybin, DMT, MDMA, and ketamine, have shown potential in modulating neurologic and psychiatric disorders due to several mechanisms. This review investigates the therapeutic potential of psychedelics in both neurologic and neuropsychiatric disorders due to their several mechanisms such as anti-inflammatory, anti-oxidative, and biological properties. This study was conducted across major databases, such as PubMed, Scopus, Web of Science, Google Scholar, and Medline, due to the systematically searched literature including clinical, preclinical, and in vitro studies. Psychedelic compounds such as psilocybin, LSD, and MDMA have demonstrated beneficial effects across various models of neuropsychiatric and neurologic disorders, including depression, PTSD, Alzheimer’s disease, and Parkinson’s disease. Additionally, psychedelics modulate key neurotransmitter systems, notably increasing synaptic levels of serotonin and dopamine, which are critically involved in mood regulation and cognitive function. Compared to conventional treatments, psychedelics offer faster onset, durable effects, and possible disease-modifying properties, making them promising candidates for future neurotherapeutics.

He has also published numerous articles about his research on (CBD) in mental health. He lectures all over the world to professional groups interested in a deeper look at mental health issues, safer tools, and a paradigm-shifting perspective about transformative care. Dr. Guss is interested in the integration of psychedelic therapies with contemporary psychoanalytic theory and has published in Studies in Gender and Sexuality and Psychoanalysis, Culture and Society.