Paolo Cassano

Massachusetts General Hospital | MGH · Department of Psychiatry

Biophotons is the very weak light generated by cells. This light has been shown to change with different states of cell activity and/or cell health. Although their precise significance is still not clear, biophotons are thought to function as a means of cell-to-cell communication and cell repair. In this narrative review, we consider first, the cur...

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm², medium: 300 mW/cm², high: 850 mW/cm²) and a sham treatment. The low and medium doses were administere...

Bipolar disorder (BD) is a debilitating psychiatric disorder characterized by mood disturbances and executive function deficits. Impairments in executive function, including impulsivity, significantly impact the daily lives of individuals with BD. Transcranial photobiomodulation (t-PBM) with near-infrared light offers a promising noninvasive neuros...

Down syndrome (DS) is the leading genetic cause of intellectual disability globally, affecting about 1 in every 800 births. Individuals with DS often face various neuropsychiatric conditions alongside intellectual disabilities due to altered brain development. Despite the diverse phenotypic expressions of DS, typical physical characteristics freque...

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neurop...

Introduction Neuropathic pain (NP) significantly impacts quality of life and often coexists with affective disorders such as anxiety and depression. Addressing both NP and its psychiatric manifestations requires a comprehensive understanding of therapeutic options. This study aimed to review the main pharmacological and non‐pharmacological treatmen...

Traumatic brain injury (TBI) is a common cause of neurologic morbidity for which few effective therapies exist, especially during the chronic stage. A potential therapy for chronic TBI is transcranial photobiomodulation (tPBM). tPBM is a noninvasive neuromodulation technique that uses light to stimulate the cortex and increase blood flow and metabo...

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments , many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with th...

Transcranial photobiomodulation (t-PBM) is an innovative, non-invasive treatment for depression. This study aimed to investigate the changes in individual depressive symptoms during t-PBM treatment and identify the symptoms that improved in those who responded to treatment. The research analyzed data from two trials, the Evaluation of Light-emittin...

Objective: To evaluate feasibility, acceptability, and preliminary efficacy of heated yoga to treat moderate-to-severe depression. Design: An 8-week randomized controlled trial (RCT) of heated yoga versus waitlist control was conducted from March 2017 to August 2019. Methods: Participants in the yoga condition were asked to attend heated yoga class...

This chapter explores the potential of photobiomodulation (PBM) therapy for Parkinson's disease, providing an overview of the condition, discussing relevant animal models, and examining the therapeutic approach in both animal studies and human clinical trials. Section 10.1 introduces Parkinson's disease, a neurodegenerative disorder characterized b...

This chapter examines the potential of photobiomodulation (PBM) for enhancing brain function in healthy young and aging adults, focusing on cognitive boosting and the effects of PBM on healthy animals and human volunteers. Section 1 discusses cognitive boosting in healthy young and aged adults, highlighting the potential of PBM as a non-invasive in...

This chapter delves into the biophysical principles and safety concerns associated with the use of photobiomodulation (PBM) for brain applications. It provides a comprehensive understanding of the different components involved in designing and implementing PBM treatments. Section 2.1 discusses various light sources used in PBM, including lasers, LE...

This chapter delves into the potential of photobiomodulation (PBM) therapy for stroke, providing an overview of the condition, discussing relevant animal models, and examining the therapeutic approach in both animal studies and human clinical trials. Section 1 introduces stroke, a leading cause of death and disability worldwide. The chapter discuss...

This chapter explores the potential of photobiomodulation (PBM) therapy for traumatic brain injury (TBI), providing an overview of the condition, discussing relevant animal models, and examining the therapeutic approach in both animal studies and human clinical trials. Section 1 introduces traumatic brain injury, a significant cause of death and di...

Non-invasive delivery of photons from an external light source to the head and thence into the brain tissue is generally referred to as transcranial photobiomodulation (PBM). In this approach, light must pass through several types of tissue, such as the scalp, skull, periosteal, meningeal, subdural space, arachnoid mater, subarachnoid space, and pi...

This final chapter synthesizes the key findings and insights presented throughout the book on photobiomodulation (PBM) and its potential applications for brain-related disorders and cognitive enhancement in healthy individuals. It emphasizes the importance of understanding the underlying mechanisms of PBM, including its impact on cellular and molec...

This chapter delves into the application of photobiomodulation (PBM) in neuronal cell cultures, focusing on the importance of in vitro studies and the various cellular mechanisms affected by this treatment approach. Section 1 discusses the importance of in vitro studies, highlighting their value in providing controlled environments for the investig...

This chapter explores the concept of preconditioning with photobiomodulation (PBM) in the context of neuronal cells and the brain, focusing on its potential to enhance resilience against various stressors and promote neuroprotection. Section 1 introduces the idea of preconditioning, explaining its significance in the field of PBM and how it can be...

This chapter explores the potential of photobiomodulation (PBM) therapy for various psychiatric disorders, providing an overview of each condition and examining the therapeutic approach in both animal studies and human clinical trials. Section 13.1 focuses on depression, discussing the problem of depression (13.1.1) and relevant animal models (13.1...

This chapter delves into the molecular, cellular, and neurobiological mechanisms underlying photobiomodulation's (PBM) effects on neuronal cells and the brain. It discusses the various pathways and processes influenced by PBM, providing a comprehensive understanding of its therapeutic potential. Section 1 covers the molecular and cellular mechanism...

This chapter investigates the potential of photobiomodulation (PBM) therapy for various other brain-related disorders, providing an overview of each condition and examining the therapeutic approach in both animal studies and human clinical trials. Section 14.1 focuses on disorders of consciousness and vegetative state, introducing the topic (14.1.1...

This chapter explores the application of photobiomodulation (PBM) therapy for dementia, providing an overview of various types of dementia and discussing the potential benefits and limitations of PBM in both animal models and human studies. Section 1 introduces the concept of dementia, discussing its various forms, including mild cognitive impairme...

This chapter examines the biphasic dose-response phenomenon in photobiomodulation (PBM) of neuronal cells and the brain, a critical aspect of understanding and optimizing treatment parameters. The discussion is divided into in vitro and in vivo studies, further exploring the biphasic response in terms of power or irradiance, time or fluence, and tr...

This chapter explores the critical aspect of light penetration into the brain, which is essential for understanding the therapeutic potential of photobiomodulation (PBM). It discusses the absorption features of biological tissue components, the penetration profiles of scalp, skull, and brain tissues, and concludes with remarks on penetration depth....

Background: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary...

Incompletely treated major depressive disorder (MDD) poses an enormous global health burden. Conventional treatment for MDD consists of pharmacotherapy and psychotherapy, though a significant number of patients do not achieve remission with such treatments. Transcranial photobiomodulation (t-PBM) is a promising novel therapy that uses extracranial...

Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy...

We report on the rationale and design of an ongoing National Institute of Mental Health (NIMH) sponsored R61-R33 project in major depressive disorder (MDD). Current treatments for MDD have significant limitations in efficacy and side effect burden. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and...

Introduction Executive function (EF) deficits are often associated with Autism Spectrum Disorder (ASD), even in the absence of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis. To date, no approved medication treatments exist for EF deficits associated with ASD. Objectives To assess the efficacy of transcranial photobiomodulation (tPBM) o...

Abstract: Major depressive disorder (MDD) is a prevalent mental health condition and a leading cause of global disability. Despite the availability of first-line interventions, they often come with limitations related to tolerability, side effects, time commitment, and cost. Somatic therapies such as electroconvulsive therapy (ECT) and repetitive...

Introduction: Mood and anxiety disorders are a prevalent and significant leading cause of years lived with a disability worldwide. Existing antidepressants drugs are only partially effective, having burdensome side effects. One-third of patients do not achieve remission after several adequate antidepressant trials, and relapses of depression are fr...

Sexual dysfunction (SD) is frequently encountered in patients suffering from depression. There is a bidirectional relationship between various types of SD and depression, so the presence or treatment of one condition may exacerbate or improve the other condition. The most frequent sexual problem in untreated depressed patients is declining sexual d...

Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD. Methods: A 2...

Objective: To assess the efficacy and safety of transcranial photobiomodulation (tPBM) in adults with autism spectrum disorder (ASD). Methods: Adults with high-functioning-ASD, between 18 and 59 years of age, were enrolled to receive twice a week tPBM for 8 weeks in an open-label single group design. ASD symptom severity was assessed at baseline, m...

Background: Transcranial photobiomodulation (t-PBM) with near�-infrared (NIR) light penetrates into the cerebral cortex and is absorbed by the mitochondrial enzyme cytochrome c oxidase (CCO), stimulating the mitochondrial respiratory chain. t-PBM also significantly increases cerebral blood flow (CBF) and oxygenation. Small studies have reported tha...

Background: Transcranial photobiomodulation (t-PBM) with near infrared (NIR) light penetrates into the cerebral cortex and is absorbed by the mitochondrial enzyme cytochrome c oxidase (CCO), stimulating the mitochondrial respiratory chain. t-PBM also significantly increases cerebral blood flow (CBF) and oxygenation. Small studies have reported that...

Background: Major depressive disorder (MDD) is prevalent and has significant impact on individuals and society. Cognitive symptoms are frequent in MDD and insufficiently treated by antidepressant medications. Transcranial photobiomodulation (t-PBM) is a novel device therapy which shows promise as an antidepressant and pro-cognitive treatment. To d...

Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcran...

Background Evidence-based pharmacological treatments for PTSD are few and of limited efficacy. Prior work suggest that angiotensin type 1 receptor (AT1R) inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the AT1R antagonist losartan, an antihypertensive drug, repurposed for the...

BACKGROUND Telehealth provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition in-person clinical trials to remote implementation during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studie...

Background Telehealth has provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition from in-person to remote clinical trials during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studies have...

Major depressive disorder (MDD) is associated with prefrontal hypometabolism and mitochondrial dysfunction. Photobiomodulation (PBM) is a novel treatment under development for MDD. PBM uses near-infrared (NIR) or red light to modulate metabolism and functioning of different tissues and organs, including the brain. NIR and red light are nonionizing...

Objective: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function...

Objective: Nonresponse to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment is common in patients with major depressive disorder (MDD), particularly in women, occurring in about 70% of patients despite adequate dosing. Well-tolerated augmentation strategies are needed, particularly ones that do not cau...

Significance: Major depressive disorder (MDD) affects over 40 million U.S. adults in their lifetime. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for head and brain anatomical changes due to aging. Aim: We study effective t-PBM dosage and its variations acr...

Significance Major depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging. Aim We study effective t-PBM dosage and its variations acros...

We performed 3-D Monte Carlo simulations to investigate the light dosage of transcranial photobiomodulation (t-PBM) across lifespan. An overall decrease in energy deposition was found as a result of increasing thicknesses of the extra-cerebral tissues.

Objective Our objective was to assess whether transcranial photobiomodulation (tPBM) with near-infrared light (NIR) shows modulatory effects on cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Background tPBM has emerged as a novel intervention for several neuropsychiatric conditions due to its neuropr...

Background and objective: Photobiomodulation (PBM) therapy is a promising and non-invasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM parameters is important to maximize effectiveness and tolerability. Several studies have reported on the penetration of visible-to-near-infrared (NIR) light through vari...

Background: Transcranial photobiomodulation (t-PBM) is a noninvasive modality that may improve cognitive function in both healthy and diseased subjects. Objective: This systematic review and meta-analysis addresses the question of whether t-PBM improves cognitive function in healthy adults. Methods: We searched MEDLINE using PubMed, EMBASE, SCOPUS...

Background: Transcranial photobiomodulation (t-PBM) consists in the delivery of near-infrared light (NIR) to the scalp, directed to cortical areas of the brain. NIR t-PBM recently emerged as a potential therapy for depression, although safety of repeated treatments has not been adequately explored. Objective: This study assessed incidence of side...

Objective: Our aim was to test the anxiolytic effect of transcranial photobiomodulation (t-PBM) with near-infrared light (NIR) in subjects suffering from generalized anxiety disorder (GAD). Background: t-PBM with NIR is an experimental, noninvasive treatment for mood and anxiety disorders. Preliminary evidence indicates a potential anxiolytic effe...

The application of photobiomodulation therapy (PBMT) for neuronal stimulation has been studied in different animal models and in humans, and has been shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and...

The transcranial photobiomodulation (t-PBM) technique is a promising approach for the treatment of a wide range of neuropsychiatric disorders, including disorders characterized by poor regulation of emotion such as major depressive disorder (MDD). We examine various approaches to deliver red and near-infrared light to the dorsolateral prefrontal co...

Photobiomodulation (PBM) is a novel device-based treatment for major depressive disorder (MDD). PBM delivers near-infrared (NIR) or red light transcranially or systemically, aiming to modulate mitochondrial bioenergetics metabolism via the delivery of energy to the cytochrome c oxidase (CCO) enzyme. This primary action on mitochondria can lead to s...

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide range of neurological and psychiatric disorders, and memory enhancement in age-related cognitive decline and neurodegenerative diseases. We describe a laboratory protocol for transcranial photobiomod...

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplast...

This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (8...

Objectives Transcranial photobiomodulation (t‐PBM) consists of the delivery of near‐infrared (NIR) or red light to the scalp designed to penetrate to subjacent cortical areas of the brain. NIR t‐PBM has recently emerged as a potential therapy for brain disorders. This study assessed the efficacy of repeated sessions of NIR t‐PBM on sexual dysfuncti...

Background: Photobiomodulation (PBM) with red and near-infrared light (NIR) -also known as Low-Level Light Therapy-is a low risk, inexpensive treatment-based on non-retinal exposure-under study for several neuropsychiatric conditions. The aim of this paper is to discuss the proposed mechanism of action and to perform a systematic review of pre-cli...

Background: Heavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emo...

Background: This study examined whether a culturally focused psychiatric consultation program (CFP) for Latino Americans was equally effective in reducing depressive symptoms in English-speaking and Spanish-speaking patients. Methods: The CFP utilizes the Engagement Interview Protocol (EIP), a semi-standardized protocol eliciting patient narrati...

Background: Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-related diseases, including heart disease, diabetes, and cancer. A link has also been suggested between shortened LTL and major depressive disorder (MDD), suggesting that MDD may be a disease of accelerated aging. This prospective, longitud...

transcranial photobiomodulation with near-infrared and red radiation for the treatment of psychiatric conditions is reviewed. While still experimental, preliminary data on the use of both laser and LED devices for brain disorders are promising.

Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjec...

Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-...

We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclini...