Advances in experimental medicine and biology
January 1, 2024
Berend Olivier, Jocelien D A Olivier
11 citations
About 30% of people with major depressive disorder do not respond to first-line treatment, leading to treatment-resistant depression (TRD), for which no consensus definition exists. Recent research has focused on two types of psychedelics: serotonergic (psilocybin, ayahuasca) and atypical glutamatergic (ketamine, esketamine). Both produce fast and long-lasting antidepressant effects that persist beyond the drug's presence in the body, suggesting downstream signaling cascades. Clinical development of psilocybin and esketamine for TRD is described, highlighting challenges with placebo due to psychotomimetic or dissociative effects. Intranasal esketamine has been approved for TRD, and psilocybin shows positive results. Adverse effects are generally acceptable. This development represents a breakthrough in psychiatry.
Advances in experimental medicine and biology
January 1, 2024
Marie Drüge, Lisa Guthardt, Elisa Haller et al.
8 citations
Depressive disorders impose a heavy societal burden due to their high prevalence and impact on relationships, emotions, and motivation. Cognitive behavioral therapy (CBT) is the gold standard treatment for major depression, while mindfulness-based cognitive therapy (MBCT) effectively prevents relapse and can be integrated into individual therapy. Various delivery modes, including therapist-guided digital CBT, blended therapy, and digitalized MBIs, offer efficacious supplements to face-to-face therapy, improving accessibility. This chapter reviews the principles and evidence for CBT and MBCT and different delivery modes for depressive disorders in adults, discussing integration opportunities and challenges, along with practice implications and future research recommendations.
Advances in experimental medicine and biology
January 1, 2021
José Carlos Bouso, Genís Ona, Rafael G. Dos Santos et al.
6 citations
Research on psychedelic drugs for therapeutic use has grown, driven by the need for innovative psychiatric treatments. Clinical trials have assessed psilocybin and ayahuasca for mental disorders including major depression. This chapter reviews the history and terminology of psychedelic research, analyzes recent clinical trials administering these drugs to patients, describes neurobiological mechanisms that may underlie therapeutic effects, and notes that psychedelics are commonly used as adjuncts to psychotherapy. The chapter concludes by suggesting future challenges for this field.
Advances in experimental medicine and biology
January 1, 2026
Yunfei Tan, Kenji Hashimoto
1 citation
Treatment-resistant depression (TRD) affects about one-third of people with major depression, leading to higher suicide rates and impaired functioning. Originally defined as nonresponse to tricyclic antidepressants, TRD now includes inadequate response to multiple antidepressant classes, psychotherapy, and neuromodulation. Inconsistent criteria complicate prevalence estimates and diagnosis, with many presumed TRD cases actually involving bipolar depression or other disorders. Neurobiological research identifies glutamatergic dysregulation, default-mode network hyperactivity, impaired neuroplasticity, chronic inflammation, and epigenetic changes as markers. Clinically, patients experience persistent anhedonia, cognitive deficits, and sleep disturbances. Subtypes with distinct treatment responses have been identified, and biomarker-driven categories guide personalized care. Future work must standardize definitions and integrate multimodal biomarkers.
Advances in experimental medicine and biology
January 1, 2026
Alessandro Spiti, Daniela Caldirola, Giampaolo Perna
1 citation
Major depressive disorder (MDD) remains difficult to treat due to its varied symptoms. Antidepressant development began with electroconvulsive therapy, monoamine oxidase inhibitors, and tricyclic antidepressants, which targeted the monoaminergic system but had safety and efficacy limits. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors improved tolerability yet left unmet needs like treatment resistance. Research then expanded to new mechanisms: NMDA receptor antagonists such as ketamine and esketamine provide fast-acting effects through glutamatergic modulation; GABA modulation via neurosteroids like zuranolone offers a new approach for postpartum depression; kappa-opioid receptor antagonism is...
Advances in experimental medicine and biology
January 1, 2026
Berend Olivier, Jocelien D A Olivier
Major depressive disorder, including treatment-resistant depression, affects many people and carries high costs. About 30% of patients do not respond to first-line antidepressants like SSRIs and SNRIs. Research over the past two decades has produced two new drug classes: typical serotonergic psychedelics (psilocybin, ayahuasca) and atypical glutamatergic/NMDA psychedelics (ketamine, esketamine). Both provide fast, long-lasting antidepressant effects that outlast the drug's presence in the brain, though they cause short-lived side effects like psychotomimetic or dissociative symptoms. These developments represent a breakthrough, but the acute effects complicate blinded studies and placebo control. The field is now advancing new research methods and exploring underlying mechanisms.
Advances in experimental medicine and biology
January 1, 2023
Dimitrios Zagkas, Flora Bacopoulou, Dimitrios Vlachakis et al.
Meditation alters the operation of the Default Mode Network (DMN) and creates differences in functional connectivity between brain networks. A systematic review of 16 controlled trials involving 853 experienced and non-experienced meditators found that meditative interventions affect DMN activity. Practices examined included Mindfulness, Samatha, Raja Yoga, Transcendental Meditation, Vipassana, and Insight meditation from the Theravada tradition. Further research is needed to confirm meditation as an effective strategy for well-being.
Advances in experimental medicine and biology
January 1, 2021
Rafael G. Dos Santos, Jaime E. C. Hallak, José Alexandre S. Crippa
Cannabis contains over 400 compounds, including more than 100 phytocannabinoids, primarily THC and CBD. THC acts as a partial agonist at cannabinoid receptors, producing euphoria, relaxation, and altered perceptions, but also dysphoria, anxiety, and psychotic symptoms; it is used therapeutically for nausea, appetite stimulation, and chronic pain. CBD acts as a negative allosteric modulator of CB1 receptors, an inverse agonist of CB2, and inhibits anandamide reuptake; it also activates 5-HT1A and vanilloid receptors. CBD does not produce typical cannabis effects and has anxiolytic and antipsychotic properties; it is approved for treatment-resistant epilepsy. Common CBD adverse effects include diarrhea, somnolence, nausea, and transaminase elevations. The mechanisms underlying therapeutic and adverse effects are not fully understood and involve multiple targets beyond the endocannabinoid system.
Advances in experimental medicine and biology
January 1, 2019
Ruwan M Jayatunge, Mieczyslaw Pokorski
This review examines meditation as a therapy for posttraumatic stress disorder (PTSD), a complex psycho-physiological-behavioral condition. Meditation, a mind-to-body psychobehavioral therapy, is gaining popularity as an adjunct treatment in medicine and psychology. While not conclusive, available evidence suggests meditation is associated with overall reduction in PTSD symptoms and improves mental and somatic quality of life. The authors indicate that meditation techniques may be tried as an adjunct to pharmacotherapy or as standalone treatment in resistant cases.
Advances in experimental medicine and biology
January 1, 2018
Mieczyslaw Pokorski, Anna Suchorzynska
Two fundamentally different meditation techniques—Zazen (seated meditation) and Tai Chi (meditation in motion)—both significantly enhanced openness to experience, a personality dimension of the Big Five Model, in 48 healthy volunteers aged 39-50. The enhanced openness was associated with improved strategies for coping with stress, with meditators showing less avoidance-oriented approaches to perceived stress and improved mood compared to non-meditating controls. The findings suggest that enhanced openness to experience could shape one's desire to maintain a meditation regimen. Both types of meditation are conducive to mental health by improving general well-being, counteracting stress, and leading to better vigor of spirit, and may be considered a modest adjunct to psychotherapy.
Advances in experimental medicine and biology
January 1, 2011
Riccardo Manzotti
Machine consciousness will eventually need to confront the concept of free will, either to reject it or to implement it in machines. It is uncertain whether freedom and consciousness are separate features of the human mind or arise from the same underlying structure. This review examines literature on the link between determinism and freedom, typically discussed by compatibilists, and then sketches a preliminary model for machine free will.
Advances in experimental medicine and biology
January 1, 2011
Raúl Arrabales, Agapito Ledezma, Araceli Sanchis
Qualia, the subjective qualities of conscious experience, are difficult to study even in humans, but they can be investigated using artificial cognitive architectures. This work defines and models 'artificial qualia' within such systems and partially applies the model to generate visual qualia using the CERA-CRANIUM architecture, which is based on the global workspace theory of consciousness. Simple apparent motion effects serve as a testbed for simulating and analyzing synthetic visual experience. Unlike biological brains, the architecture's inner states can be directly inspected, enabling detailed analysis of percepts generated during visual stimulation. The observed states are used to discuss possible analogous mechanisms in human cognition.
Advances in experimental medicine and biology
January 1, 2010
Sulamita Frohlich, Carlos A Franco
A theoretical model of consciousness is presented, building on earlier work presented at a 2006 neuroscience congress. The model proposes that visual consciousness arises from interactions between cortical areas via feedforward sweep, recurrent, and wide-spread recurrent processes, linked to light entering the eyes. A reciprocal interaction model describes how the eye responds to light by regulating sleep-wake states through EEG synchronization, controlled by thalamic-cortical activity from brainstem nuclei. This yields an orthogonal graph representing all states of human consciousness, including emotional, unconscious, dreaming, and pre-conscious states, allowing observation without subjective experience. The Quantum Orch OR Model is applied to the graph, proposing that phenomenal conscious vision depends on quantum computation in microtubules, with the vertical axis representing a cholinergic-aminergic scale that triggers quantum mechanisms.
Advances in experimental medicine and biology
January 1, 2003
Sophie Erhardt, Lilly Schwieler, Göran Engberg
Schizophrenia may involve a glutamate deficiency, with the endogenous glutamate antagonist kynurenic acid (KYNA) playing a role. In anesthetized rats, pharmacologically elevated KYNA increased firing and burst activity of midbrain dopamine neurons, similar to effects of psychotomimetics PCP and ketamine. Cerebrospinal fluid KYNA was higher in 28 male first-episode schizophrenia patients (1.67 ± 0.27 nM) than in 17 male healthy controls (0.97 ± 0.07 nM). Elevated KYNA also reversed clozapine's excitatory effect on rat dopamine neurons to inhibition. The study suggests KYNA contributes to schizophrenia pathogenesis, linking dopamine and glutamate hypotheses.
Advances in experimental medicine and biology
January 1, 1990
J F MacDonald, M C Bartlett, I Mody et al.
Electropharmacological evidence suggests the PCP binding site is closely linked to the channel domain of the NMDA receptor, but it is too early to conclude the site lies deep within the NMDA channel pore. Determining the molecular details of the PCP site will require a complete kinetic analysis of NMDA single channel behavior. Additionally, hydrophobic receptor sites likely contribute to the blockade produced by some dissociative anesthetics.