Dopamine in Extreme Environments: Dopamine Control, Part Two // Melanie Boling, Harvard University.

Dopamine in Extreme Environments: Dopamine Control, Part Two.

The Hypothalamic-Pituitary-Adrenal axis or HPA axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis.

During childhood, abnormal development of the HPA axis can result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery.

These ingredients together create the perfect storm to affect an individual later on in life. These changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood and in some cases develop during childhood or alter biomarkers, which act as early warning systems, permanently.

The primary function of the HPA axis is to regulate your stress response.

(2-Minute Neuroscience: HPA Axis - YouTube, n.d.)

Activation of the HPA axis results in widespread hormonal, neurochemical and physiological alterations. Inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the brain’s Basal Ganglia (responsible for motor control, executive functions, behavior, and emotions). Dysfunction of neurotransmitters and their receptors can lead to dopamine-relevant corticostriatal reward circuitry.

Findings have included inflammation-associated reductions in ventral striatal responses to reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine. The ventral striatum is the striatal region most closely associated with reward.

Dopamine response exhibits increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. There has been mounting interest regarding the role of cytokines in behavioral alterations and the development and progression of neuropsychiatric disorders. This means that inflammatory response derived from stress-response drives both brain and behavior changes, among many other types of physiological dysfunction.

Cytokines from peripheral immune cells can access the Central Nervous System (CNS) by several mechanisms including:

1) Passage through leaky regions in the blood-brain-barrier such as the circumventricular organs.

2) Activation of endothelial cells and perivascular macrophages in the cerebral vasculature to produce local inflammatory mediators such as cytokines, chemokines, prostaglandins, and nitric oxide.

3) Carrier-mediated transport of cytokines across the blood-brain-barrier.

4) Local activation of peripheral nerve afferents which then relay cytokine signals to relevant brain regions, including the nucleus of the solitary tract and hypothalamus.

5) Recruitment of activated immune cells such as monocytes/macrophages and T cells from the periphery to the brain, where these cells can, in turn, produce cytokines.

“Under physiologic conditions, cytokines such as Tumor Necrosis Factor or TNF-alpha and IL-1 have been shown to be involved in a number of essential brain processes such as synaptic remodeling, neurogenesis, and long-term potentiation. However, in excess, inflammatory cytokines can act in the brain to affect monoamine neurotransmitter systems and behavior, and recent evidence indicates that dopamine function in the basal ganglia may be a primary target in this regard. The basal ganglia are key subcortical structures that regulate motivation and motor activity, and dopamine plays an essential modulatory role in basal ganglia function. The effect of inflammatory cytokines on basal ganglia dopamine may be especially relevant to depression and fatigue as well as psychomotor disturbances and the development of neurodegenerative disorders” (Felger & Miller, 2012).

Chronic inflammation and exposure to inflammatory cytokines lead to changes in the basal ganglia and dopamine function which result in very specific behaviors to include anhedonia (inability to feel pleasure), fatigue, and psychomotor slowing. The reduction of neural responses to hedonic reward (pleasure), decreased dopamine metabolites in CSF or cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been reported.

Peripheral inflammatory cytokines or activated immune cells can dramatically influence local inflammatory networks and drive neuroinflammation (inflammatory response of brain and spinal cord) by activating local production of cytokines and inflammatory signaling pathways.

Inflammatory cytokines and their receptors are expressed in the brain at low levels during non-pathological states and are found to be fairly ubiquitous, yet this cytokine network in the brain can be rapidly mobilized in response to inflammatory stimuli. Examples of inflammatory stimuli could be what you consume; your environment; a run-in with the wrong person; a memory. These are all examples of inflammatory stimulus which would trigger an inflammatory response leading to an uptick in inflammatory cytokines released into the brain and into the body, more specifically the central nervous system.

Cytokines in the brain are produced primarily by microglia, but can also be produced by astrocytes and to some extent by neurons and oligodendrocytes. Endothelial cells and perivascular macrophages respond to circulating cytokines to induce expression of prostaglandin-producing enzymes cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PGES).

Following acute inflammatory stimulus, increased central nervous system inflammation signal a protection response to the brain, and acute changes in neurotransmitter metabolism, including increases in monoamines such as serotonin and norepinephrine in the hypothalamus, can contribute to the induction of fever, activation of the HPA axis, and transition from an anabolic to a catabolic state.

Changes in monoamine metabolism promote behavioral alterations including reduced locomotor activity and anhedonia that allow for shunting of energy and metabolic resources to combat infection and/or facilitate wound healing. Cytokine signals from the periphery alert the central nervous system of immune insult in order to prepare and protect an organism during times of sickness and injury.

Under conditions of chronic inflammation such as during chronic medical illnesses, extreme stress, or operating in an extreme environment, central nervous system inflammation can exert profound and protracted changes in neurotransmitter systems, neurotrophic factors, and neuronal integrity that can have negative and even detrimental outcomes on behavior.

Dopamine Control provided by the directives of psychological field kits intervene in the inflammatory response, which results in the return to homeostasis. Personalized psychological field kits reduce HPA axis activation or mitigate dysfunction by allowing the body to return to baseline even at times of extreme stress, for example during high-stress mission operations or crises within an extreme environment.

“Dopamine” by Italian Artisi, Maria Elena Buemi (Dopamine (Molecola Della Creatività) Painting by Maria Elena Buemi | Saatchi Art, n.d.).

Dopamine in Extreme Environments: Dopamine Control, Part Three, coming soon.

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References

Bamford, N. S., Wightman, R. M., & Sulzer, D. (2018). Dopamine’s effects on corticostriatal synapses during reward-based behaviors. Neuron, 97(3), 494–510. https://doi.org/10.1016/j.neuron.2018.01.006

Cools, R., & Roberts, A. C. (2004). The Role of Dopamine in Cognition: Insights from Neuropsychological Studies in Humans and Non-Human Primates. In S. Otani (Ed.), Prefrontal Cortex: From Synaptic Plasticity to Cognition (pp. 219–243). Springer US. https://doi.org/10.1007/1-4020-7949-4_10

Chromium May Help Treat Depression Naturally and Curb Carb Cravings. (2020, May 4). University Health News. https://universityhealthnews.com/daily/depression/beating-depression-naturally-while-simultaneously-curing-your-carb-cravings-yes/

Dopamine (molecola della Creatività) Painting by maria elena buemi | Saatchi Art. (n.d.). Retrieved January 13, 2022, from https://www.saatchiart.com/art/Painting-Dopamine-molecola-della-Creativit/683742/3362178/view

Felger, J. C., & Miller, A. H. (2012). Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise. Frontiers in Neuroendocrinology, 33(3), 315—327. https://doi.org/10.1016/j.yfrne.2012.09.003

Felger, J. C. (2017). The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications. Current Topics in Behavioral Neurosciences, 31, 199–219. https://doi.org/10.1007/7854_2016_13

Foo, C., Lozada, A., Aljadeff, J., Li, Y., Wang, J. W., Slesinger, P. A., & Kleinfeld, D. (2021). Reinforcement learning links spontaneous cortical dopamine impulses to reward. Current Biology, 31(18), 4111-4119.e4. https://doi.org/10.1016/j.cub.2021.06.069

Keltikangas-Järvinen, L., & Salo, J. (2009). Dopamine and serotonin systems modify environmental effects on human behavior: A review. Scandinavian Journal of Psychology, 50(6), 574–582. https://doi.org/10.1111/j.1467-9450.2009.00785

Lieberman, D., & Long, M. (2018). The Molecule of More: How a Single Chemical in Your Brain Drives Love, Sex, and Creativity--and Will Determine the Fate of the Human Race. Faculty Bookshelf. https://hsrc.himmelfarb.gwu.edu/books/249

Oct. 20th, P. M. | published & 2021. (n.d.). Rise and Grind. Reporter. Retrieved October 27, 2021, from https://reporter.rit.edu/views/rise-and-grin

Nordgreen, J., Edwards, S. A., Boyle, L. A., Bolhuis, J. E., Veit, C., Sayyari, A., Marin, D. E., Dimitrov, I., Janczak, A. M., & Valros, A. (2020). A Proposed Role for Pro-Inflammatory Cytokines in Damaging Behavior in Pigs. Frontiers in Veterinary Science, 7, 646. https://doi.org/10.3389/fvets.2020.00646

Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012). Neurobiology of resilience. Nature Neuroscience, 15(11), 1475–1484. https://doi.org/10.1038/nn.3234

Sudevan, S., Muto, K., Higashitani, N., Hashizume, T., Higashibata, A., Ellwood, R. A., Deane, C. S., Rahman, M., Vanapalli, S. A., Etheridge, T., Szewczyk, N. J., & Higashitani, A. (2021). Loss of Contact in Space Alters Dopamine System in C. elegans (SSRN Scholarly Paper ID 3919931). Social Science Research Network. https://doi.org/10.2139/ssrn.3919931

2-Minute Neuroscience: HPA Axis—YouTube. (n.d.). Retrieved January 13, 2022, from https://www.youtube.com/watch?v=QAeBKRaNri0

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About the author:

Melanie began attending Harvard in 2020 to complete a Graduate Certificate in Human Behavior with a specialization in Neuropsychology. Boling’s research has examined extreme environments and how they can have a potential negative impact on humans operating in the extreme environment. During her time at Harvard, she has built a mental wellness tool called a psychological field kit. Implementing these tools will allow an individual to thrive in an extreme environment while mitigating negative variables such as abnormal human behavior which can play a role in team degradation.

Conclusions and Recommendations: Amazonian Entheogen Therapy for the treatment of U.S. Military Veterans. // Melanie Boling, Graduate Student of Neuropsychology, Harvard University.

Conclusions and Recommendations

“Ayahuasca brew consists of the ayahuasca vine or Banisteriopsis caapi and an admixture like the chacruna leaves or Psychotria viridis. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors.”

Many veterans are trapped in their trauma and plant medicine has provided the means for releasing trauma during their psychedelic experience (Veterans Are Turning to Ayahuasca for PTSD Relief, n.d.).

A small shamanic ceremony would also allow for facilitators and shamans alike to stay true to their culture. Plant Medicine Healing Centers and Clinics allow shamans; tribal members; and facilitators to continue practicing the traditions of their culture and making a living while doing so; all the while preserving and safeguarding a living history allows for more generations to learn the way of the rainforest through plant medicine.

Healing centers lower the dependent variable of a tribe from going extinct; or moving further away from traditional ways that are not successfully being passed onto the younger generations (Plotkin, 2021).

Melanie Boling and Expeditionary Service Dog River Roux with the healers of a Shibipo Tribe Healing Center in the Andes Mountains of Peru (Imagery Beyond Borders, January 2021).

“Benefits obtained from the brew intake, such as mind healing, increased self-knowledge, improved memory and persistently elevated mood. It has gained recent traction with U.S. Military Veterans for seeking healing from treatment-resistant mental illness such as Anxiety, Obsessive-Compulsive Disorder and Depression.”

Amazonian Entheogens or Psychedelic Plant Medicine hold great potential for the treatment of U.S. Military Veterans, and applying this through small group indigenous shamanic ceremonies, holds space to guide survivors into a journey within themselves for those seeking therapeutic healing for specific treatment-resistant illnesses such as Complex-Post-traumatic Stress Disorder or C-PTSD; Military Sexual Trauma or MST; and Traumatic Brain Injury or TBI. 

Trust and safety are the key components to the overall success of Psychedelic Plant Medicine.

“The most important tool used by shamans is the icaro. These traditional songs sung or whistled by shamans before, during, and after an ayahuasca ceremony not only comprise the setting of the experience, they also positively influence the internal landscape of a person’s psyche. While we’re still trying to understand icaros in therapeutic terms, there’s no doubt that these songs play a vital role in the healing aspects of ayahuasca.”

I feel that the answers to all of the world’s problems lie within the world’s rainforests, specifically the Amazon Rainforest. There is much more to learn about Psychedelic Plant Medicine and questions to be answered used for the healing of the United States Military Veteran Community.

Some questions that I have for the scientific community that has yet to be researched are:

1. If different parts of the same ayahuasca plant are said to cause different experiences with the same user; could these different parts of the same plant be used to treat different illnesses? 

2. Would cultivation and/or harvesting of the ayahuasca vine at different periods of the plant’s growth cause a different experience for the user or could it be used to treat different illnesses? IE. CBD vs CBG?

3. Does adding the ayahuasca vine with various admixtures beyond the charunca leaf be used to treat other specific illnesses? IE. Cancer, or Stroke.

4. Can different lineages of the ayahuasca vine be used to treat more specific illnesses? IE. Alzheimer’s, or Parkinson’s Disease.

5. Will the consumption of ayahuasca brew in an “extreme environment” such as “high-altitude environments” cause a warp-speed healing event in patients/users such as someone with a traumatic brain injury or brain damage caused by stroke? (I already know the answer to this, to be revealed at a later time).

6. If ayahuasca, psilocybin mushrooms, and San Pedro Cactus or “huacuma” were to be administered in a clinical setting, even as a microdose; then combined with a “simulated extreme environment”, such as Hyper-Baric Oxygen Therapy or HBOT which is used to promote neurogenesis in the brain after TBI; could these variables also play a role in the “warp-speed” healing of neurogenesis on the brain and body?

Ayahuasca inhibits various parts of the brain associated with cognitive flexibility. It produces structural changes within the brain that are responsible for activity within 24 hours of ayahuasca consumption which leads to positive increases in cognitive flexibility. Results show that mindfulness is beneficial and lasting to the first-time or experienced ayahuasca user. Ayahuasca’s use allows the loosening of one’s cognitive grip which helps alleviate the feeling of being stuck and the depression associated with similar behavioral patterns (Murphy-Beiner & Soar, 2020). 

My wish is that with my own scientific field research I can solve problems; provide the answers to some of these scientific questions; and do my part in guiding others within my own United States Military Veteran Community and the world, to realize the full potential of Entheogen Therapy or Psychedelic Plant Medicine from the Amazon Rainforest.

United States Air Force Operation Enduring Freedom and Operation Iraqi Freedom Combat Veteran Melanie Boling in the Peruvian Andes as part of her scientific research for Harvard University, where she is pursuing a Masters Degree in Neuropsychology; and Graduate Certificate in Environmental Policy and International Development. Boling is an Extreme (ICE) Environments Behavioural Ecologist for her NGO, Peer Wild (Imagery Beyond Borders, January 2021).

Would you like to know more?

Be sure to read back on all of our articles about Entheogen Therapy or Psychedelic Plant Medicine derived from the scientific paper, “Reported results of Amazonian Entheogens for treatment of Complex-Post-Traumatic Stress Disorder (C-PTSD); Military Sexual Trauma (MST); and Traumatic Brain Injury (TBI) among U.S. Military Veterans and the benefits of application through small group indigenous shamanic ceremonies.”

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References:

Boling, Melanie. (2021). Melanie Noelani Boling. Imagery Beyond Borders. https://imagerybeyondborders.org

Boling, Melanie (2021). Reported results of Amazonian Entheogens for treatment of Complex-Post-Traumatic Stress Disorder (C-PTSD); Military Sexual Trauma (MST); and Traumatic Brain Injury (TBI) among U.S. Military Veterans and the benefits of application through small group indigenous shamanic ceremonies. The Amazon Rainforest: From Conservation to Climate Change-research. Harvard Summer School, August 9, 2021.

Murphy-Beiner, A, and K Soar. “Ayahuasca’s ‘Afterglow’: Improved Mindfulness and Cognitive Flexibility in Ayahuasca Drinkers.” Psychopharmacology 237, no. 4 (April 2020): 1161–69. https://doi.org/10.1007/s00213-019-05445-3.

Plotkin, M. J. (2021). The Amazon: What everyone needs to know. Chapter 8 seminar. Lecture notes The Amazon Rainforest: From Conservation to Climate Change- seminar. Harvard Summer School. Delivered 3 August 2021.

“Veterans Are Turning to Ayahuasca for PTSD Relief.” Accessed July 15, 2021. https://www.vice.com/en/article/a3kaye/veterans-are-turning-to-ayahuasca-for-ptsd-relief.

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About the author:

Melanie began attending Harvard in 2020 to complete a Graduate Certificate in Human Behavior with a specialization in Neuropsychology. Boling’s research has examined extreme environments and how they can have a potential negative impact on humans operating in the extreme environment. During her time at Harvard, she has built a mental wellness tool called a psychological field kit. Implementing these tools will allow an individual to thrive in an extreme environment while mitigating negative variables such as abnormal human behavior which can play a role in team degradation.

Melanie Boling, Extreme (ICE) Environments Behavioural Ecologist, Peer Wild and Graduate Student of Neuropsychology, Harvard University.

Small Shamanic Ceremonies stay true to the culture and provide space for healing U.S. Military Veterans. // Melanie Boling, Harvard University.

Small Shamanic Ceremonies stay true to the culture and provide space for healing. 

Melanie Boling, Extreme (ICE) Environments Behavioural Ecologist and Graduate Student of Neuropsychology, Harvard University in the Peruvian Andes (Imagery Beyond Borders, January 2021).

The human condition beyond the understanding of the United States Healthcare System and even academia seems to be the path that some United States Military Veterans are on in order to find relief for themselves (Plotkin, 2021).

If the ‘psychedelic renaissance’ continues to proliferate in the United States at the pace it is currently at, this could mean that more avenues of care will be readily available to civilians and veterans, alike.

However, until the United States Government deems these plant medicines legal, people will continue to seek refuge outside of the bubble of the United States or find other ways to be treated by plant medicine that strays from the more traditional methods used by shamans and other facilitators/practitioners of the Amazon Rainforest healing. 

Shamanic Healing is said to “free the soul from the body in order to communicate with the spirit realm” (Plotkin, 2021). These “consultations” with the spirit world through traditional plant medicine healing techniques such as consuming the ayahuasca brew that stimulates the brain and body are often accompanied by a magic song; or in the Shipibo culture “The Icaros”. It is said that consuming ayahuasca makes you dizzy, and the dizziness brings about the magic song. 

“The most important tool used by shamans is the icaro. These traditional songs sung or whistled by shamans before, during, and after an ayahuasca ceremony not only comprise the setting of the experience, they also positively influence the internal landscape of a person’s psyche. While we’re still trying to understand icaros in therapeutic terms, there’s no doubt that these songs play a vital role in the healing aspects of ayahuasca” (Imagery Beyond Borders, January 2021). 

My scientific theory is that the icaro magic song sung by the shaman directly penetrates the vagus nerve which is the main component of the Human Parasympathetic Nervous System; one of the direct connections that allow your brain and your gut to communicate with one another. The vagus nerve controls mood; immune response; digestion; and even your heart rate. All bodily functions are directly affected by the consumption of ayahuasca and throughout the duration of the ayahuasca ceremony. During the singing of the icaro the vagus nerve is stimulated, creating a more euphoric experience for some, and for others an uptick in purging for the ayahuasca consumer; and in some cases bystanders who only are present for the ceremony itself. This is the power of ayahuasca. 

Traditional Ayahuasca Healing Centers around the world are springing up from India to Costa Rica promising the patients a week or more of services that often come with a hefty price tag.

Plant medicine healing centers or clinics allow shamans; tribal members; and facilitators to continue practicing the traditions of their culture and making a living while doing so (Plotkin, 2021). Thus, preserving and safeguarding a living history allows for more generations to learn the way of the rainforest through plant medicine.

In Sacred Valley of the Andes Mountains just outside of Cusco, Peru, Ayahuasca Healing Centers allow tribes to continue practicing the traditions of their culture and making a living while doing so (Imagery Beyond Borders, January 2021).

These healing centers lower the dependent variable of a tribe from going extinct; or moving further away from traditional ways that are not successfully being passed onto the younger generations (Plotkin, 2021). 

With certain types of emotional trauma, like Complex-Post-Traumatic Stress Disorder or C-PTSD and Military Sexual Trauma or MST, small shamanic ceremonies would be the venue or “set and setting” of choice for those suffering from these types of mental illness. Largely, due to the extrinsic factors that play a centralized role in long-term post-traumatic stress or sexual abuse, assault, or trauma.

The idea of holding a small shamanic ceremony would also allow for facilitators and shamans alike to stay true to their culture while holding space to guide these survivors into a journey within themselves.

Nobody’s healing is more important than the other, and keeping a circle small would promote community, while also providing the participants to be on the same level with one another.

With regard to United States Military Veterans, offering the same level of understanding through these profound psychedelic experiences could promote a sense of unity and purpose. Being a part of something bigger than oneself is a core value instilled in those who have served their country in the military forces.

Larger groups at healing retreats can often breed chaos as well as trauma-bonding, which would potentially push certain at-risk veterans to get lost in the shuffle. In turn, this would be repeating the same patterns that of the Veterans Affairs Healthcare System, ultimately potentially providing a short-term band-aid that would later fail the veteran with long-term relief.

Would you like to know more?

Be sure to read back on all of our articles about Entheogen Therapy or Psychedelic Plant Medicine derived from the scientific paper, “Reported results of Amazonian Entheogens for treatment of Complex-Post-Traumatic Stress Disorder (C-PTSD); Military Sexual Trauma (MST); and Traumatic Brain Injury (TBI) among U.S. Military Veterans and the benefits of application through small group indigenous shamanic ceremonies”.

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References:

Boling, Melanie (2021). Reported results of Amazonian Entheogens for treatment of Complex-Post-Traumatic Stress Disorder (C-PTSD); Military Sexual Trauma (MST); and Traumatic Brain Injury (TBI) among U.S. Military Veterans and the benefits of application through small group indigenous shamanic ceremonies. The Amazon Rainforest: From Conservation to Climate Change-research. Harvard Summer School, August 9, 2021.

Plotkin, M. J. (2021). The Amazon: What everyone needs to know. Chapter 8 seminar. Lecture notes The Amazon Rainforest: From Conservation to Climate Change- seminar. Harvard Summer School. Delivered 3 August 2021.

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About the author.

Melanie began attending Harvard in 2020 to complete a Graduate Certificate in Human Behavior with a specialization in Neuropsychology. Boling’s research has examined extreme environments and how they can have a potential negative impact on humans operating in the extreme environment. During her time at Harvard, she has built a mental wellness tool called a psychological field kit. Implementing these tools will allow an individual to thrive in an extreme environment while mitigating negative variables such as abnormal human behavior which can play a role in team degradation.

Melanie Boling, Extreme (ICE) Environments Behavioural Ecologist, Peer Wild; and Graduate Student of Neuropsychology, Harvard University.