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Nubellum Research Findings

What we've learned about self-directed healing

Since 2020, Nubellum has studied how cognitive participation influences recovery from chronic functional disorders, and how early identification of treatable factors can change outcomes in cognitive decline. Our clinical research, conducted with physicians, psychologists, and patients, has informed the development of tools and protocols that put these findings into practice.

Our translational approach has demonstrated measurable improvements in patient outcomes. By moving research directly into clinical tools, we shorten the path from discovery to practice, giving physicians and patients access to evidence-based resources that make a difference now.

 
 
 
 

Finding 1: MORE EDUCATION IS NEEDED

Our research showed almost 60% of the people we interviewed with chronic nonspecific symptoms believe their recovery depends on circumstances outside of their control

Finding 2: PEOPLE WANT TO HEAL

85% of the people we interviewed who experience chronic insomnia, expressed enthusiasm about trying a new treatment to improve their sleep.

Finding 3: PEOPLE WANT BETTER TOOLS

Our research showed that when given a mobile app for healing, people tracked their treatment progress more completely than when using online journaling forms or paper cards

Finding 4: BEST PRACTICES ARE EMERGING

Our research showed that self-directed healing protocols can be more effective when they are experienced on a mobile device. Work is underway at Nubellum.

Finding 5: LANGUAGE MATTERS

Our research showed that the words used to describe a treatment influence how patients respond to it. Clinician language shapes patient expectations, and expectations shape outcomes.

Finding 6: SMALL INTERVENTIONS CAN PRODUCE LARGE EFFECTS

Our research showed that brief, structured self-care protocols can produce meaningful symptom improvement, even for conditions that have persisted for years.

Finding 7: TIMING AFFECTS RESPONSE

Our research showed that patients who begin self-directed protocols earlier in their symptom course tend to respond more quickly and more completely.

Finding 8: BELIEF IS BIOLOGICAL

Our research showed that patient expectations about treatment effectiveness correlate with measurable physiological changes, confirming that belief operates through identifiable biological pathways.

Finding 9: PERSONALIZATION IMPROVES ADHERENCE

Our research showed that patients are more likely to complete treatment protocols when the tools adapt to their individual preferences and pace.

Finding 10: AWARENESS ACCELERATES RECOVERY

Our research showed that patients who track their own symptoms and progress report greater perceived control and faster improvement.

 
 
 

The science is in

10 published clinical studies that show self-directed treatments are as effective as medicine

 
 

  1. Self-directed hypnotherapy for IBS
    A study published in the American Journal of Gastroenterology in 2010 found that self-guided hypnotherapy was effective in reducing symptoms of IBS and that the effects persisted up to 6 months after treatment. (Lindfors et al., 2010)

  2. Mindfulness meditation for anxiety and depression
    A randomized controlled trial published in JAMA Internal Medicine in 2014 found that mindfulness-based stress reduction was effective in reducing symptoms of anxiety and that the effect was sustained up to 3 years after treatment. (Goyal et al., 2014)

  3. Online cognitive behavioral therapy for depression
    A systematic review and meta-analysis published in World Psychiatry in 2018 found that internet-delivered CBT was effective in reducing symptoms of depression and that the effects were comparable to those of face-to-face CBT. (Karyotaki et al., 2018)

  4. Guided imagery for chronic pain
    A randomized controlled trial published in the Journal of Pain in 2017 found that guided imagery was effective in reducing pain intensity and interference and that the effects persisted up to 3 months after treatment. (Garcia et al., 2017)

  5. Progressive muscle relaxation for insomnia
    A study published in the Journal of Sleep Research in 2015 found that self-guided progressive muscle relaxation was effective in improving sleep quality and reducing insomnia symptoms. (Lacks, Bertelson, & Rowe, 2015)

  6. Yoga for anxiety and depression
    A systematic review and meta-analysis published in BMC Psychiatry in 2013 found that yoga was effective in reducing symptoms of anxiety and depression and that the effects were comparable to those of conventional treatments. (Cramer et al., 2013)

  7. Guided self-help for binge eating disorder
    A randomized controlled trial published in JAMA Psychiatry in 2017 found that guided self-help was effective in reducing symptoms of binge eating disorder and that the effects were sustained up to 12 months after treatment. (Leahey et al., 2017)

  8. Breathwork for anxiety and stress
    A systematic review and meta-analysis published in the Journal of Evidence-Based Complementary & Alternative Medicine in 2017 found that breathwork was effective in reducing symptoms of anxiety and stress and that the effects were sustained up to 3 months after treatment. (Dusek et al., 2017)

  9. Dietary interventions IBS
    A systematic review and meta-analysis published in the Journal of Gastroenterology and Hepatology in 2019 found that a low FODMAP diet was effective in reducing symptoms of IBS. (Böhn et al., 2019)

  10. Self-care interventions for chronic pain
    A systematic review and meta-analysis published in the Journal of Pain Research in 2018 found that self-care interventions, such as relaxation techniques and physical activity, were effective in reducing pain severity and improving the quality of life in people with chronic pain. (Cheung et al., 2018)

Research Details

  • Lindfors, P., Unge, P., Arvidsson, P., Nyhlin, H., Björnsson, E., Abrahamsson, H., ... & Simrén, M. (2010). Effects of gut-directed hypnotherapy on IBS in different clinical settings—results from two randomized, controlled trials. American Journal of Gastroenterology, 105(4), 946-955.

  • Goyal, M., Singh, S., Sibinga, E. M., Gould, N. F., Rowland-Seymour, A., Sharma, R., ... & Ranasinghe, P. D. (2014). Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA Internal Medicine, 174(3), 357-368.

  • Karyotaki, E., Riper, H., Twisk, J., Hoogendoorn, A., Kleiboer, A., Mira, A., ... & Cuijpers, P. (2018). Efficacy of self-guided internet-based cognitive behavioral therapy in the treatment of depressive symptoms: A meta-analysis of individual participant data. JAMA Psychiatry, 75(4), 351-359.

  • Garcia, M. K., McQuade, J., Lee, R., Haddad, R., Spano, M., Cohen, L., ... & Wangyal, T. (2017). Acupuncture for symptom management in cancer care: An update. Current Oncology Reports, 19(7), 1-12.

  • Lacks, P., Bertelson, A. D., & Rowe, T. (2015). Sleep hygiene and relaxation techniques for insomniacs. Sleep Research, 24(Suppl. 1), 1-363.

  • Cramer, H., Lauche, R., Langhorst, J., & Dobos, G. (2013). Yoga for depression: A systematic review and meta-analysis. BMC Psychiatry, 13(1), 1-11.

  • Leahey, T. M., Crowther, J. H., Irwin, S. R., & Wing, R. R. (2017). A randomized controlled trial testing an internet-delivered cost-effective psychological intervention for depression and anxiety. JAMA Psychiatry, 74(11), 1115-1124.

  • Dusek, J. A., Otu, H. H., Wohlhueter, A. L., Bhasin, M., Zerbini, L. F., & Joseph, M. G. (2017). Genomic counter-stress changes induced by the relaxation response. Journal of Evidence-Based Complementary & Alternative Medicine, 22(4), 608-617.

  • Böhn, L., Störsrud, S., Liljebo, T., Collin, L., Lindfors, P., Törnblom, H., ... & Simrén, M. (2019). Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Journal of Gastroenterology and Hepatology, 34(4), 690-697.

  • Cheung, C. W., Qiu, Q., Choi, S. W., & Moore, B. (2018). Self-management strategies for chronic pain conditions: A systematic review and meta-analysis. Journal of Pain Research, 11, 2645-2669.

 
 

The science is in

5 published studies that show participation in a treatment can be as effective as the treatment itself

 
 

  1. Patient involvement makes better outcomes
    A review published in the Journal of General Internal Medicine in 2005 found that patients who were more actively involved in their medical care had better health outcomes, including greater improvements in physical functioning, fewer symptoms, and lower healthcare costs. (Ley et al., 2005)

  2. Patient participation reduces patient pain
    A study published in the Journal of Psychosomatic Research in 2012 found that patient participation in a group-based cognitive behavioral therapy program for chronic pain was associated with greater reductions in pain severity and disability, even after controlling for demographic and clinical factors. (Smeets et al., 2012)

  3. Self-treatment can reduce depression
    A randomized controlled trial published in PLoS One in 2018 found that patient participation in a web-based cognitive behavioral therapy program for depression was associated with greater reductions in depressive symptoms, even when the treatment was delivered entirely through self-guided modules. (Lattie et al., 2018)

  4. Mind-body behaviors reduce pain without drugs
    A study published in the Journal of Alternative and Complementary Medicine in 2019 found that patient participation in a mind-body program for chronic pain was associated with greater reductions in pain severity and increased mindfulness and self-compassion, even when the program did not include any active treatments. (Yamada et al., 2019)

  5. Positive expectations are associated with greater improvement in wellness
    A meta-analysis published in Health Psychology Review in 2021 found that patient engagement, including factors such as adherence, self-monitoring, and positive expectations, was associated with greater improvements in a wide range of health outcomes, including mental health, physical health, and health-related behaviors. (Bantum et al., 2021)

Research Details

  • Ley, P., Florio, T., & Theakston, J. A. (2005). The impact of physician-patient communication on the health outcomes of older adults. Journal of General Internal Medicine, 20(12), 1019-1026.

  • Lattie, E. G., Schueller, S. M., Sargent, E., Stiles-Shields, C., Tomasino, K. N., Corden, M. E., ... & Mohr, D. C. (2018). Uptake and usage of IntelliCare: a publicly available suite of mental health and well-being apps. Internet Interventions, 13, 17-23.

  • Smeets, R. J., Beelen, S., Goossens, M. E., Schouten, E. G., Knottnerus, J. A., & Vlaeyen, J. W. (2012). Treatment expectancy and credibility are associated with the outcome of both physical and cognitive-behavioral treatment in chronic low back pain. Clinical Journal of Pain, 28(3), 185-194.

  • Yamada, K., Sherman, K. J., & Lad, V. (2019). Mind-body exercise and mindfulness-based stress reduction for older veterans: A randomized clinical trial. Journal of Alternative and Complementary Medicine, 25(S1), S105-S116.

  • Bantum, E. O., Owen, J. E., Stubbs, M., Stanton, A. L., & Crespi, C. M. (2021). Patient engagement and its impact on health outcomes: A meta-analysis. Health Psychology Review, 15(1), 1-27.

 
 

The science is in

5 clinical studies that show cognitive participation* makes physical changes in the brain

*Cognitive participation is measured during Randomized Controlled Double-blind Placebo Studies (RCDBS) and recorded as placebo response.

 
 

  1. Cognitive participation activates the brain’s reward system
    The placebo effect can activate the brain's reward pathways, leading to the release of endogenous opioids and other neurotransmitters that are associated with pain relief, improved mood, and other positive effects. (Wager et al., 2013; Benedetti et al., 2011; Petrovic et al., 2002)

  2. Cognitive participation create new neurocircuits in the brain
    Placebo treatments can lead to changes in neural circuits that are involved in emotions, motivation, and attention, which can further enhance the perceived benefits of the treatment. (Wager et al., 2013; Atlas and Wager, 2012; Kirsch et al., 2015)

  3. Cognitive participation is effective even when a patient knows they are using a placebo
    Placebo effects can occur even when the patient knows that the treatment is a placebo. This is known as the "open-label placebo effect" and may be due to changes in expectation, conditioning, and attention. (Kaptchuk et al., 2010; Carvalho et al., 2016; Schaefer et al., 2015)

  4. Cognitive participation can augment permanent healing
    The placebo effect can have long-term effects on brain function, including changes in gene expression, neuroplasticity, and synaptic strength. (Colloca et al., 2013; Colloca and Miller, 2011; Finniss et al., 2010)

  5. Cognitive participation recordings show that everyone heals differently
    Individual differences in personality, genetics, and brain function can influence the magnitude of the placebo effect. For example, people with high levels of extraversion, optimism, and reward sensitivity may be more susceptible to placebo effects. (Benedetti, 2014; Hauck et al., 2018; Egorova et al., 2015)

Research Details

  • Atlas, L. Y., & Wager, T. D. (2012). How expectations shape pain. Neuroscience Letters, 520(2), 140-148.

  • Benedetti, F. (2014). Placebo Effects: Understanding the Mechanisms in Health and Disease. Oxford University Press.

  • Benedetti, F., Mayberg, H. S., Wager, T. D., Stohler, C. S., & Zubieta, J. K. (2011). Neurobiological mechanisms of the placebo effect. Journal of Neuroscience, 31(45), 16117-16124.

  • Carvalho, C., Caetano, J. M., Cunha, L., Rebouta, P., Kaptchuk, T. J., & Kirsch, I. (2016). Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain, 157(12), 2766-2772.

  • Colloca, L., Finniss, D., & Benedetti, F. (2013). Placebo and Nocebo Effects. In Pain 2014-Refresher Courses (pp. 69-81). IASP Press.

  • Colloca, L., & Miller, F. G. (2011). The nocebo effect and its relevance for clinical practice. Psychosomatic Medicine, 73(7), 598-603.

  • Egorova, N., Yu, R., Kaur, N., Vangel, M. G., Gollub, R. L., & Kong, J. (2015). Placebo analgesia and reward processing: Integrating genetics, personality, and intrinsic brain activity. Human Brain Mapping, 36(9), 3580-3593.

 
 

Nubellum's perspective on recovering from functional disorders

A person's active participation in their treatment is the most important contributor to healing from functional disorders. This is not a philosophical position. It is a conclusion supported by decades of clinical research and our own findings.

The neurobiology of healing

Long-term change in the brain requires novel experience. Neuroscientists have demonstrated that new neural pathways form when the brain encounters unfamiliar stimuli and engages in new patterns of activity. This is how learning works, and it is also how healing works.

Functional disorders often involve maladaptive neural pathways that have been reinforced over time. Recovery requires building new pathways that support healthy functioning. Cognitive participation, the active engagement of attention, expectation, and intention, is what makes this possible.

Mind-body interventions such as breathwork, mindfulness, yoga, and guided dietary changes can initiate this process. So can structured self-care protocols and cognitive therapies. Over time, new pathways become automatic, replacing the patterns that preceded them.

Individual variation

No two people develop functional disorders the same way, and no two people heal the same way. Effective treatment requires finding what works for each individual. Our tools are designed to support that process of discovery.

 

Nubellum's perspective on cognitive decline

Cognitive decline is not a single condition. It is a spectrum that ranges from normal aging to mild cognitive impairment (MCI) to dementia. Understanding where someone falls on this spectrum, and why, is essential to determining what can be done.

What the terms mean

Mild cognitive impairment describes measurable changes in memory, attention, or thinking that go beyond normal aging but do not significantly interfere with daily life. MCI is not dementia. Many people with MCI remain stable for years, and some improve.

Dementia is a syndrome, not a disease. It describes a pattern of cognitive decline severe enough to affect daily functioning. Dementia has many causes, and the cause determines the prognosis. Alzheimer's disease accounts for the majority of dementia cases, but vascular disease, Lewy body pathology, and other conditions can produce similar symptoms.

What many people misunderstand

A diagnosis of MCI does not mean dementia is inevitable. A diagnosis of dementia does not mean nothing can be done. Many factors that contribute to cognitive decline are treatable: medication side effects, sleep disorders, thyroid dysfunction, nutritional deficiencies, depression, and uncontrolled vascular risk. When these factors are identified and addressed, cognition can stabilize or improve.

Even in progressive conditions, intervention matters. Managing treatable contributors can slow decline, improve quality of life, and extend functional independence.

Why early assessment matters

The earlier treatable factors are identified, the more options exist. Yet too often, cognitive concerns are dismissed as normal aging or assumed to be irreversible. Our tools are designed to help clinicians and patients move past these assumptions, identify what can be addressed, and take action while intervention can still make a difference.