Good Chemistry: Notes/References

good chemistry

Please note, this book was written pre-COVID 19. Any advice to hug, cuddle, copulate or gather needs to be re-evaluated in the new light of possible contagion of a potentially lethal virus.

P29 > people with PTSD show them faring better while using medicinal cannabis.

The study, recently published in Journal of Affective Disorders, shows cannabis reduced the severity of intrusions, returning thoughts of a traumatic event, by about 62%; flashbacks by 51%, irritability by 67%, and anxiety by 57%. The symptom reductions were not permanent, however.

P79 > human pheromones

Wyatt, T. D. (2020). Reproducible research into human chemical communication by cues and pheromones: learning from psychology's renaissance. Philosophical Transactions of the Royal Society B, 375(1800), 20190262.

Pause, B. M. (2017). Human chemosensory communication. In Springer Handbook of Odor (pp. 129-130). Springer, Cham.

P150 > The medicine seemed helpful...obsessive compulsive disorder.

Delgado, P. L., & Moreno, F. A. (1998). Hallucinogens, serotonin and obsessive-compulsive disorder. Journal of psychoactive drugs, 30(4), 359-366.

Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry, 67(11), 1735-1740.

Wilcox, J. A. (2014). Psilocybin and obsessive compulsive disorder. Journal of psychoactive drugs, 46(5), 393-395.

P256 > awe can reduce narcissism

van Mulukom, V., Patterson, R., & van Elk, M. (2020). Broadening Your Mind to Include Others - The relationship between serotonergic psychedelic experiences and maladaptive narcissism_PREPRINT. PsyArXiv. March, 10.

In short, what we found was that feelings of connectedness and vastness during significant serotonergic psychedelic trips of the past five years are associated with current feelings of empathy and connectedness, and lower levels of exploitative-entitled narcissism.

Px > both MDMA and psilocybin

Mithoefer, M. C., Grob, C. S., & Brewerton, T. D. (2016). Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. The Lancet Psychiatry, 3(5), 481-488.

https://www.sciencedirect.com/science/article/abs/pii/S2215036615005763

Here are several important MDMA references:

Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., ... & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 236(9), 2735-2745.

https://link.springer.com/article/10.1007/s00213-019-05249-5

Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J., ... & Doblin, R. (2018). 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry, 5(6), 486-497.

http://www.prati.org.il/wp-content/uploads/2019/01/23.pdf

Feduccia, A. A., Holland, J., & Mithoefer, M. C. (2018). Progress and promise for the MDMA drug development program. Psychopharmacology, 235(2), 561-571.

https://link.springer.com/article/10.1007/s00213-017-4779-2

Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T., MacAulay, R. K., Jerome, L., Yazar-Klosinski, B., & Doblin, R. (2017). Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. Journal of Psychopharmacology, 31(8), 967-974.

https://journals.sagepub.com/doi/pdf/10.1177/0269881117711712

Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., Martin, S. F., Yazar-Klosinski, B., ... & Doblin, R. (2013). Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3, 4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology, 27(1), 28-39.

https://journals.sagepub.com/doi/pdf/10.1177/0269881112456611?dom=icopyright&src=syn&

More MDMA papers:

Kamilar-Britt, P., & Bedi, G. (2015). The prosocial effects of 3, 4-methylenedioxymethamphetamine (MDMA): controlled studies in humans and laboratory animals. Neuroscience & Biobehavioral Reviews, 57, 433-446.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678620/

Bedi, G., Phan, K. L., Angstadt, M., & De Wit, H. (2009). Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology, 207(1), 73.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328967/

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910346/

Hysek, C. M., Domes, G., & Liechti, M. E. (2012). MDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions. Psychopharmacology, 222(2), 293-302.

https://doc.rero.ch/record/311302/files/213_2012_Article_2645.pdf

Bershad, A. K., Mayo, L. M., Van Hedger, K., McGlone, F., Walker, S. C., & de Wit, H. (2019). Effects of MDMA on attention to positive social cues and pleasantness of affective touch. Neuropsychopharmacology, 44(10), 1698-1705.

Ramos, L., Hicks, C., Caminer, A., Goodwin, J., & McGregor, I. S. (2015). Oxytocin and MDMA (‘Ecstasy’) enhance social reward in rats. Psychopharmacology, 232(14), 2631-2641.

https://d1wqtxts1xzle7.cloudfront.net

Psilocybin

Lots of data here:

https://beckleyfoundation.org/science/substances-methods/psilocybin/?fbclid=IwAR0tx8I3tb6RUjXYQfC3VOdVjDuftZScerGXsmvzC-i3ukJFmDYiyPIeyBk

See also:

Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., & Griffiths, R. R. (2020). Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific reports, 10(1), 1-14.

https://www.nature.com/articles/s41598-020-59282-y

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218(4), 649-665.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308357/?_escaped_fragment_=po=63.5135

MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology, 25(11), 1453-1461.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537171/

Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of general psychiatry, 68(1), 71-78.

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/210962

Pxii > I now notice that same terror of loneliness in the searching eyes of babies faced with the back of a cell phone.

Note: Until now, the undivided attention of the doting parents and community was the birthright of all babies. Now, they face stiff competition from our phones. For the first time in our evolution, babies have to compete with something more compelling than they are. And their loss will be a loss for our species.

Pxii > time spent on a screen can generate brain chemistry similar to infatuation and attachment,

Han, D. H., Lee, Y. S., Yang, K. C., Kim, E. Y., Lyoo, I. K., & Renshaw, P. F. (2007). Dopamine genes and reward dependence in adolescents with excessive internet video game play. Journal of addiction medicine, 1(3), 133-138.

Dong, G., Huang, J., & Du, X. (2011). Enhanced reward sensitivity and decreased loss sensitivity in Internet addicts: an fMRI study during a guessing task. Journal of psychiatric research, 45(11), 1525-1529.

Koepp, M. J., Gunn, R. N., Lawrence, A. D., Cunningham, V. J., Dagher, A., Jones, T., ... & Grasby, P. M. (1998). Evidence for striatal dopamine release during a video game. Nature, 393(6682), 266-268.

Pxiii > Heavy users of social media are more likely to be depressed and lonely

Twenge, J. M., Joiner, T. E., Rogers, M. L., & Martin, G. N. (2018). Increases in depressive symptoms, suicide-related outcomes, and suicide rates among US adolescents after 2010 and links to increased new media screen time. Clinical Psychological Science, 6(1), 3-17.

https://journals.sagepub.com/doi/full/10.1177/2167702617723376

Lin, L. Y., Sidani, J. E., Shensa, A., Radovic, A., Miller, E., Colditz, J. B., ... & Primack, B. A. (2016). Association between social media use and depression among US young adults. Depression and anxiety, 33(4), 323-331.

https://www.ncbi.nlm.nih.gov/pubmed/26783723

Primack, B. A., Shensa, A., Sidani, J. E., Whaite, E. O., yi Lin, L., Rosen, D., ... & Miller, E. (2017). Social media use and perceived social isolation among young adults in the US. American journal of preventive medicine, 53(1), 1-8.

https://www.ajpmonline.org/article/S0749-3797(17)30016-8/fulltext

Primack, B. A., Karim, S. A., Shensa, A., Bowman, N., Knight, J., & Sidani, J. E. (2019). Positive and negative experiences on social media and perceived social isolation. American Journal of Health Promotion, 0890117118824196.

https://journals.sagepub.com/doi/10.1177/0890117118824196

New research is suggesting that oxytocin itself may be involved in internet addiction:

Montag, C., Sindermann, C., Becker, B., & Panksepp, J. (2016). An affective neuroscience framework for the molecular study of Internet addiction. Frontiers in psychology, 7, 1906.

https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01906/full

Becker, B., & Montag, C. (2017). Opinion: real-time fMRI neurofeedback and the application of the neuropeptide oxytocin as promising new treatment approaches in internet addiction?. In Internet Addiction (pp. 311-321). Springer, Cham.

Pxiii > a recent study showed that decreasing your screen time by even thirty minutes a day can help you feel less lonely and depressed.

Hunt, M. G., Marx, R., Lipson, C., & Young, J. (2018). No more FOMO: Limiting social media decreases loneliness and depression. Journal of Social and Clinical Psychology, 37(10), 751-768.

https://guilfordjournals.com/doi/10.1521/jscp.2018.37.10.751

Pxiii > Nearly a quarter said they always or often felt lonely

DiJulio, B., Hamel, L., Muñana, C., & Brodie, M. (2018). Loneliness and Social Isolation in the United States, the United Kingdom, and Japan: An International Survey. The Economist & Kaiser Family Foundation.

https://www.kff.org/report-section/loneliness-and-social-isolation-in-the-united-states-the-united-kingdom-and-japan-an-international-survey-introduction/

Pxiii > Nearly one-half reported they often feel left out and don’t have meaningful connections with others

Polack, E. (2018). New Cigna Study Reveals Loneliness at Epidemic Levels in America. Business Wire.

For online versus in person bonding see references below. Pulled from this article:

Sherman, L. E., Michikyan, M., & Greenfield, P. M. (2013). The effects of text, audio, video, and in-person communication on bonding between friends. Cyberpsychology: Journal of psychosocial research on cyberspace, 7(2).

https://greenfieldlab.psych.ucla.edu/wp-content/uploads/sites/168/2019/06/41-Sherman-et-al.pdf

While some studies have shown that affinity or affection is stronger online than in-person among strangers (Antheunis et al., 2007, 2012; Bargh et al., 2002), evidence has not emerged to suggest that affection will also be higher in online environments for existing close relationships. Rather, one recent study (Seltzer, Prososki, Ziegler, & Pollak, 2012) examining oxytocin levels in daughters while they communicated with their mothers in person and through digital mediation found that IM, unlike face-to-face communication and audio-only communication, did not induce an increase in the bonding-related hormone oxytocin, a hormone that has also been found to correlate with affiliation cues when romantic couples communicate (Gonzaga et al., 2006). Another recent study found that emerging adults ranked friends with whom they communicated offline higher on measures of relationship quality and social attraction than friends with whom they communicated online only (Antheunis, Valkenburg, & Peter, 2012).

Antheunis, M. L., Schouten, A. P., Valkenburg, P. M., & Peter, J. (2012). Interactive uncertainty reduction strategies and verbal affection in computer-mediated communication. Communication Research, 39, 757-780.

Antheunis, M. L., Valkenburg, P. M., & Peter, J. (2012). The quality of online, offline, and mixed-mode friendships among users of a social networking site. Cyberpsychology: Journal of Psychosocial Research on Cyberspace, 6(3), article 1. Retrieved from http://www.cyberpsychology.eu/view.php?cisloclanku=2012120304

Antheunis, M. L., Valkenburg, P. M., & Peter, J. (2007). Computer-mediated communication and interpersonal attraction: An experimental test of two explanatory hypotheses. CyberPsychology & Behavior, 10, 831-836.

Bargh, J. A., McKenna, K. Y., & Fitzsimons, G. M. (2002). Can you see the real me? Activation and expression of the "true self" on the Internet. Journal of Social Issues, 58, 33-48.

Gonzaga, G. C., Turner, R. A., Keltner, D., Campos, B., & Altemus, M. (2006). Romantic love and sexual desire in close relationships. Emotion, 6, 163-179.

Seltzer, L.J., Prososki, A.R., Ziegler, T.E., and Pollak, S.D. (2012). Instant messages versus human speech: Hormones and why we still need to hear each another. Evolution and Human Behavior. 33, 42-45.

Also, oxytocin researcher Paul Zak, PhD (personal email communication 5/16/20):

In a preliminary study, Dr. Zak's lab showed that video conferencing causes oxytocin release about 80% of in-person interactions, while posting to social media and using email also result in an increase in oxytocin around 50% of the in-person change.

He also wrote this in a subsequent email:

“The study we did was on posting texts to social media (Tweets) that resulted in a 13% increase in oxytocin and a 11% decrease in cortisol. The change in oxytocin was therefore 12% of the average in-person increase.”

Pxiii “diseases of despair”

"mortality from drug overdose, suicide, and alcohol-related causes of death, which largely comprise a 'deaths of despair' category, increased and contributed to life expectancy reductions."

Elo, I. T., Hendi, A. S., Ho, J. Y., Vierboom, Y. C., & Preston, S. H. Trends in Non-Hispanic White Mortality in the United States by Metropolitan-Nonmetropolitan Status and Region, 1990–2016. Population and Development Review.

Note: Life expectancy overall in the United States fell for the second time in three years in 2017, driven largely by a surge in drug overdoses and suicide.

For many years, suicide among youths was relatively rare and its frequency relatively stable. But from 2007 to 2017, the number of suicides among people ages 10 to 24 suddenly increased 56 percent — from 6.8 deaths per 100,000 people to 10.6, the new report shows.

Suicide has become the second-most common cause of death among teenagers and young adults, overtaking homicides and outpaced only by accidents.

In the world, one person dies by suicide every forty seconds. There are generally 25 suicide attempts per completed suicide.

The three disease types are drug overdose (including alcohol overdose), suicide, and alcoholic liver disease.

According to the CDC, in 2016 alcohol abuse was linked to 88,000 deaths; more deaths than guns, opioids, or even HIV/AIDS at its peak. Drug-related deaths were at 63,500 (two-thirds of these involved opioids). And, almost 45,000 suicides were recorded. Increases in deaths due to diseases of despair are contributing to declining life expectancy in the U.S.

Pxiii > Social isolation has a lethality

Holt-Lunstad, J., & Smith, T. B. (2012). Social relationships and mortality. Social and Personality Psychology Compass, 6(1), 41-53.

Holt-Lunstad, J., Robles, T. F., & Sbarra, D. A. (2017). Advancing social connection as a public health priority in the United States. American Psychologist, 72(6), 517.

Pxiii > smoking about 15 cigarettes a day.

Holt-Lunstad, J., Smith, T. B., Baker, M., Harris, T., & Stephenson, D. (2015). Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspectives on psychological science, 10(2), 227-237.

Pxiii > our birth rate is in freefall

Hamilton, B. E., Martin, J. A., Osterman, M. J., & Rossen, L. M. (2019). Births: provisional data for 2018.

Pxxv > Left Nostril breathing: “You can check the notes on NaturalMood.com and read the studies, or you can just breathe through your left nostril and relax.”

Telles, S., Nagarathna, R., & Nagendra, H. R. (1994). Breathing through a particular nostril can alter metabolism and autonomic activities. Indian Journal of Physiology and Pharmacology, 38, 133-133.

https://www.ijpp.com/IJPP%20archives/1994_38_2/133-137.pdf

Pal, G. K., Agarwal, A., Karthik, S., Pal, P., & Nanda, N. (2014). Slow yogic breathing through right and left nostril influences sympathovagal balance, heart rate variability, and cardiovascular risks in young adults. North American journal of medical sciences, 6(3), 145.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978938/

Bhavanani, A. B., & Madanmohan, Z. S. (2012). Immediate effect of chandra nadi pranayama (left unilateral forced nostril breathing) on cardiovascular parameters in hypertensive patients. International journal of yoga, 5(2), 108.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410188/

Jella, S. A., & Shannahoff-Khalsa, D. S. (1993). The effects of unilateral forced nostril breathing on cognitive performance. International Journal of Neuroscience, 73(1-2), 61-68.

https://www.researchgate.net/profile/David_Shannahoff-Khalsa/publication/15067673_The_Effects_of_Unilateral_Forced_Nostril_Breathing_on_Cognitive_Performance/links/00b49525776b566a48000000.pdf

Pxiv > Loneliness also correlates with higher rates of cognitive decline and dementia.

Luchetti, M., Terracciano, A., Aschwanden, D., Lee, J. H., Stephan, Y., & Sutin, A. R. (2020). Loneliness is associated with risk of cognitive impairment in the Survey of Health, Ageing and Retirement in Europe. International Journal of Geriatric Psychiatry.

https://pubmed.ncbi.nlm.nih.gov/32250480/

Pxvi > In animal studies, opiates very effectively relieve separation distress.

Panksepp, J., Herman, B., Conner, R., Bishop, P., & Scott, J. P. (1978). The biology of social attachments: opiates alleviate separation distress. Biological psychiatry.

Pxvi > many of my patients have begun to use cannabis

In a July 2019 Gallup poll, 12% of U.S. adults said they smoke marijuana, a percentage that is essentially unchanged since 2015.

https://news.gallup.com/poll/284135/percentage-americans-smoke-marijuana.aspx?utm_source=twitterbutton&utm_medium=twitter&utm_campaign=sharing

Pxvii > the menu of medications in the psychiatric tool kit now includes a handful of psychedelic drugs.

“Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.”

Reiff, Collin M., et al. "Psychedelics and psychedelic-assisted psychotherapy." American Journal of Psychiatry 177.5 (2020): 391-410.

https://adaa.org/sites/default/files/Psychedelics%20and%20Psychedelic-Assisted%20Psychotherapy%20AJP%202020.pdf

See also:

Serotonergic psychedelics are partial agonists at frontal and limbic 5-HT2A receptors.

Controlled trials with these drugs report anxiolytic and antidepressant effects.

Open-label trials report anti-addictive effects.

Biological mechanisms include neuroplasticity and fronto-limbic activation.

Psychological mechanisms include enhanced social cognition and openness to experience.

The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity.

dos Santos, R. G., & Hallak, J. E. C. (2019). Therapeutic use of serotonergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neuroscience & Biobehavioral Reviews.

https://www.sciencedirect.com/science/article/pii/S0149763419309649

Pxvii > even transformative

Forstmann, M., Yudkin, D. A., Prosser, A. M., Heller, S. M., & Crockett, M. J. (2020). Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings. Proceedings of the National Academy of Sciences.

https://www.pnas.org/content/early/2020/01/14/1918477117

Chirico, A., & Yaden, D. B. (2018). Awe: a self-transcendent and sometimes transformative emotion. In The function of emotions (pp. 221-233). Springer, Cham.

https://www.researchgate.net/profile/David_Yaden2/publication/324651280_Awe_A_Self-Transcendent_and_Sometimes_Transformative_Emotion/links/5adf8b950f7e9b285945da6d/Awe-A-Self-Transcendent-and-Sometimes-Transformative-Emotion.pdf

Pxxvii > We’ll see how awe can enable learning

Rudd, M., Hildebrand, C., & Vohs, K. D. (2018). Inspired to create: Awe enhances openness to learning and the desire for experiential creation. Journal of Marketing Research, 55(5), 766-781.

Anderson, C. L., Dixson, D. D., Monroy, M., & Keltner, D. (2019). Are awe-prone people more curious? The relationship between dispositional awe, curiosity, and academic outcomes. Journal of personality.

Valdesolo, P., Shtulman, A., & Baron, A. S. (2017). Science is awe-some: The emotional antecedents of science learning. Emotion Review, 9(3), 215-221.

NOTES FOR CHAPTER ONE

P1 > Paul Simon song reference is to “the only living boy in new york”

https://www.youtube.com/watch?v=5biEjyXNa2o

P4 > When you listen to someone talking, your motor areas specialized for speech start firing. It’s like you quietly mimic them and what they’re saying, as you’re hearing it.

Wilson, S. M., Saygin, A. P., Sereno, M. I., & Iacoboni, M. (2004). Listening to speech activates motor areas involved in speech production. Nature neuroscience, 7(7), 701.

https://www.nature.com/articles/nn1263

P4 > Neural mirroring facilitates social behavior by helping us to understand the minds of others, making intersubjectivity possible.

Iacoboni, M. (2009). Imitation, empathy, and mirror neurons. Annual review of psychology, 60, 653-670.

https://www.annualreviews.org/doi/abs/10.1146/annurev.psych.60.110707.163604

P4 > A reason why you should forgo Botox

Dent, J. (2015). The botox dilemma. Ethics Quarterly, (99), 8.

Murphy, Kate New York Times 4/18/19 “Can Botox and Cosmetic Surgery Chill Our Relationships with Others?”

P7> In 2015, Johann Hari published “Chasing the Scream: The First and Last Days of the War on Drugs,”

Hari, J. (2015). Chasing the scream: The first and last days of the war on drugs. Bloomsbury Publishing USA.

P7 >The Globalization of Addiction: A Study in Poverty of the Spirit

A review of Bruce Alexander’s book is here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717062/

P8 > Please just remember that oxytocin is a pain-reliever, literally

Rash, J. A., Aguirre-Camacho, A., & Campbell, T. S. (2014). Oxytocin and pain: a systematic review and synthesis of findings. The Clinical journal of pain, 30(5), 453-462.

https://www.ncbi.nlm.nih.gov/pubmed/23887343

Wang, Y. L., Yuan, Y., Yang, J., Wang, C. H., Pan, Y. J., Lu, L., ... & Xue, L. (2013). The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides, 47(2), 93-97.

http://www.tahomaclinic.com/Private/Articles1/Oxytocin/Wang%202013%20-%20oxytocin%20and%20pain%20modulation%20in%20headache%20patients.pdf

P11 > leading to violent behavior.

Metzl, J. M., & MacLeish, K. T. (2015). Mental illness, mass shootings, and the politics of American firearms. American journal of public health, 105(2), 240-249.

Tung, E. L., Hawkley, L. C., Cagney, K. A., & Peek, M. E. (2019). Social isolation, loneliness, and violence exposure in urban adults. Health Affairs, 38(10), 1670-1678.

Niño, M., Ignatow, G., & Cai, T. (2017). Social isolation, strain, and youth violence. Youth violence and juvenile justice, 15(3), 299-313.

P15 > a microdose is

For general information on microdosing:

https://www.thecut.com/2018/05/microdosing-guide-and-explainer.html

Two videos:

James Fadiman, PhD giving a lecture

https://www.youtube.com/watch?v=6AfFM8pfy4s

WIRED magazine 7 minute video “does microdosing make you smarter?”

https://www.youtube.com/watch?v=0pcqV3JgGlo

See also:

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems amongst microdosers. Frontiers in psychiatry, 10, 672.

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00672/full

Odds ratio showed that Self Rated Efficacy of Microdosing psychedelics was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, Self Rated Efficacy of Microdosing psychedelics was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown.

P 17 > the default mode network

We used fMRI to examine brain activity during autobiographical remembering, prospection, and theory-of-mind reasoning. Using multivariate analyses, we found a common pattern of neural activation underlying all three processes in the DMN. In addition, autobiographical remembering and prospection engaged midline DMN structures to a greater degree and theory-of-mind reasoning engaged lateral DMN areas.

Spreng, R. N., & Grady, C. L. (2010). Patterns of brain activity supporting autobiographical memory, prospection, and theory of mind, and their relationship to the default mode network. Journal of cognitive neuroscience, 22(6), 1112-1123.

https://www.mitpressjournals.org/doi/full/10.1162/jocn.2009.21282

Also see:

“These results indicate that the DMN is indispensable in the social understanding of others.”

Li, W., Mai, X., & Liu, C. (2014). The default mode network and social understanding of others: what do brain connectivity studies tell us. Frontiers in human neuroscience, 8, 74.

https://www.frontiersin.org/articles/10.3389/fnhum.2014.00074/full

P18 > Many things can trigger neuroplasticity,

Long list:

Valkanova, V., Rodriguez, R. E., & Ebmeier, K. P. (2014). Mind over matter–what do we know about neuroplasticity in adults?. International Psychogeriatrics, 26(6), 891-909.

https://psilosybiini.info/paperit/Mind%20over%20matter%20-%20what%20do%20we%20know%20about%20neuroplasticity%20in%20adults%20 (Valkanova%20et%20al.,%202014).pdf

Exercise:

Knaepen, K., Goekint, M., Heyman, E. M., & Meeusen, R. (2010). Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor. Sports medicine, 40(9), 765-801.

http://www.searlneuropsychology.com/uploads/5/1/2/1/5121658/kristel_et_al_2010_neuroplasticity_-_exercise-induced_response_of_peripheral_bdnf.pdf

Reinsberger, C. (2015). Of running mice and exercising humans-the quest for mechanisms and biomarkers of exercise induced neurogenesis and plasticity. German Journal of Sports Medicine/Deutsche Zeitschrift fur Sportmedizin, 66(2).

https://www.germanjournalsportsmedicine.com/fileadmin/content/archiv2015/Heft_2/DZSM_2015-02_WEB_Reinsberger_Quest_For_Mechanisms.pdf

Environmental enrichment:

Kempermann, G., Gast, D., & Gage, F. H. (2002). Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Annals of neurology, 52(2), 135-143.

P18 > we know that this capacity for structural reorganization, which underlies learning and memory, can happen throughout our lifetimes.

Kheirbek, M. A., & Hen, R. (2013). (Radio) active neurogenesis in the human hippocampus. Cell, 153(6), 1183-1184.

P24 > A study of blood flow (which indirectly measures brain activity) in people given THC showed increased flow

Note: THC increased perfusion in the anterior cingulate cortex, superior frontal cortex, and insula, and reduced perfusion in the post-central and occipital gyrus.

van Hell, H. H., Bossong, M. G., Jager, G., Kristo, G., van Osch, M. J., Zelaya, F., ... & Ramsey, N. F. (2011). Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study. International Journal of Neuropsychopharmacology, 14(10), 1377-1388.

https://academic.oup.com/ijnp/article/14/10/1377/753434

P27 > Cannabis... helps to put the body in ‘para.’

These and other data presented are consistent with the picture of reduced sympathetic and enhanced parasympathetic activity described in animals on THC.

Benowitz, N. L., & Jones, R. T. (1977). Prolonged delta-9-tetrahydrocannabinol ingestion; Effects of sympathomimetic amines and autonomic blockades. Clinical Pharmacology & Therapeutics, 21(3), 336-342.

https://www.ncbi.nlm.nih.gov/pubmed/837652

P27 > CBD is non intoxicating

Cristino, L., Bisogno, T., & Di Marzo, V. (2019). Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nature Reviews Neurology, 1-21.

https://www.nature.com/articles/s41582-019-0284-z

P27 > CBD does not diminish memory

Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018). Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Frontiers in immunology, 9.

P 28 > This may be because CBD alters the shape of the cannabinoid receptor, where THC docks, weakening its ability to bind together.

Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British journal of pharmacology, 172(20), 4790-4805.

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13250

P29 > Research shows that THC acts on receptors in brain areas involved in memory (hippocampus) and fear (amygdala) processing.

Raymundi, A. M., da Silva, T. R., Zampronio, A. R., Guimarães, F. D. S., Bertoglio, L. J., & Stern, C. A. (2019). A time-dependent contribution of hippocampal CB1, CB2, and PPARγ receptors to cannabidiol-induced disruption of fear memory consolidation. British journal of pharmacology.

https://www.ncbi.nlm.nih.gov/pubmed/31648363

Katona, I., Rancz, E. A., Acsády, L., Ledent, C., Mackie, K., Hájos, N., & Freund, T. F. (2001). Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. Journal of Neuroscience, 21(23), 9506-9518.

https://www.jneurosci.org/content/jneuro/21/23/9506.full.pdf

P29 > without altering normal sleep patterns

Linares, I. M., Guimaraes, F. S., Eckeli, A., Crippa, A., Zuardi, A. W., Souza, J. D., ... & Crippa, J. A. (2018). No acute effects of cannabidiol on the sleep-wake cycle of healthy subjects: a randomized, double-blind, placebo-controlled, crossover study. Frontiers in pharmacology, 9, 315.

https://www.frontiersin.org/articles/10.3389/fphar.2018.00315/full

P30 > some people respond more to CBD alone

Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects

https://pubmed.ncbi.nlm.nih.gov/32456572/

P 29 > clinical studies have been tricky to do in the United States due to the quality of allowable study drug.

Note: Our government seems to run the only farm in America that can’t turn out good cannabis.

Sue Sisley and her team of lawyers including Matthew Zorn are in the process of suing the US

See here:

https://www.marijuanamoment.net/scientists-and-veterans-file-lawsuit-challenging-deas-marijuana-rescheduling-denials/

And here

https://www.marijuanamoment.net/scientists-sue-dea-over-alleged-secret-document-that-delayed-marijuana-research-expansion/

And here

https://www.nbcnews.com/news/us-news/one-doctor-vs-dea-inside-battle-study-marijuana-america-n1195436

See also:

FDA's regulatory uncertainty on hemp is stunting the industry

https://reason.com/2020/05/30/the-fda-is-stunting-the-growth-of-americas-nascent-legal-hemp-industry/

P 29 > rapid and sustained antidepressant effects,

Sales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. (2019). Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Molecular neurobiology, 56(2), 1070-1081.

https://www.drperlmutter.com/wp-content/uploads/2018/12/CBD-BDNF.pdf

P29 > A recent study of PTSD patients linked cannabis use with milder episodes of depression and fewer suicidal thoughts than non-users

Lake, S., Kerr, T., Buxton, J., Walsh, Z., Marshall, B., Wood, E., & Milloy, M. J. (2019). Does cannabis use modify the effect of post-traumatic stress disorder on severe depression and suicidal ideation? Evidence from a population-based cross-sectional study of Canadians. Journal of Psychopharmacology, 0269881119882806.

https://www.ncbi.nlm.nih.gov/pubmed/31684805

See also:

According to data from 404 medical cannabis users in the US, who self-identified as having post-traumatic stress disorder cannabis effectively reduced symptoms by more than 50%. Data were obtained from a medical cannabis app that patients use to track changes in symptoms as a function of different strains and doses of cannabis across time. The participants used the app 11,797 times over 31 months to evaluate the symptoms (intrusive thoughts, flashbacks, irritability, and/or anxiety) immediately before and after inhaling cannabis.

All symptoms were reduced by more than 50% immediately after cannabis intake. Time predicted larger decreases in intrusions and irritability, with later cannabis use sessions predicting greater symptom relief than earlier sessions. Higher doses of cannabis predicted larger reductions in intrusions and anxiety, and dose used to treat anxiety increased over time. Baseline severity of all symptoms remained constant across time. Authors from the Washington State University, who conducted the study, noted limitations, that are self-selection of the sample, self-identification as having post-traumatic stress disorder and no control group using a placebo.

LaFrance EM, Glodosky NC, Bonn-Miller M, Cuttler C. Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. J Affect Disord. 2020;274:298-304.

And

In a placebo-controlled study study with 71 participants, consisting of 3 groups (25 healthy controls, 27 trauma-exposed adults without post-traumatic stress disorder, and 19 patients with post-traumatic stress disorder) low doses of THC lowered threat-related reactivity in a certain brain region, the so-called amygdala. After intake of placebo or THC all participants underwent a well-established threat processing procedure during functional magnetic resonance imaging (fMRI). The study involved researchers from different departments Wayne State University in Detroit, USA.

THC lowered threat-related amygdala reactivity. Authors concluded that “these preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

Rabinak, C. A., Blanchette, A., Zabik, N. L., Peters, C., Marusak, H. A., Iadipaolo, A., & Elrahal, F. (2020). Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology, 1-14.

https://link.springer.com/article/10.1007/s00213-020-05499-8#citeas

P29 > which may be a result of increases in BDNF (brain-derived neurotrophic factor) levels, a powerful protein that encourages synaptic growth—new brain cells and connections—and improves short-term memory.

Note : “These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.”

https://www.drperlmutter.com/wp-content/uploads/2018/12/CBD-BDNF.pdf

P30 > CBD has also been shown to attenuate the aggressive behavior that can be induced by social isolation.

Hartmann, A., Lisboa, S. F., Sonego, A. B., Coutinho, D., Gomes, F. V., & Guimarães, F. S. (2019). Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 94, 109637.

P30 > CBD can have a role in treating both schizophrenia and psychosis in general.

Davies, C., & Bhattacharyya, S. (2019). Cannabidiol as a potential treatment for psychosis. Therapeutic Advances in Psychopharmacology, 9, 2045125319881916.

https://journals.sagepub.com/doi/full/10.1177/2045125319881916#articleShareContainer

Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., ... & Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational psychiatry, 2(3), e94.

https://www.nature.com/articles/tp201215.pdf?origin=ppub

Zuardi, A. W., Hallak, J. E., Dursun, S. M., Morais, S. L., Sanches, R. F., Musty, R. E., & Crippa, J. A. S. (2006). Cannabidiol monotherapy for treatment-resistant schizophrenia. Journal of Psychopharmacology, 20(5), 683-686.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1024.3957&rep=rep1&type=pdf

Gururajan, A., & Malone, D. T. (2016). Does cannabidiol have a role in the treatment of schizophrenia?. Schizophrenia Research, 176(2-3), 281-290.

P31 > Recent studies show that the more people have access to cannabis, the fewer pursue illegal opiates and die from overdoses

Lake, S., Socías, M. E., & Milloy, M. J. (2019). RE: Medical cannabis: Strengthening evidence in the face of hype and public pressure.

Flexon, J. L., Stolzenberg, L., & D'Alessio, S. J. (2019). The effect of cannabis laws on opioid use. International Journal of Drug Policy, 74, 152-159.

Also,

States with active medical marijuana laws saw certain opioid prescription rates drop nearly 20 percent compared to prohibition states, a first-of-its-kind study out of Columbia University’s Irving Medical Center has found. Authors said the findings underscore the importance of providing patients with pain management alternatives, such as cannabis, in efforts to reduce opioid use.

“State MCLs were associated with a statistically significant reduction in aggregate opioid prescribing of 144,000 daily doses (19.7% reduction) annually,” the study, published this month in the Journal of the American Academy of Orthopaedic Surgeons, says. Medical cannabis laws “were associated with a statistically significant reduction of 72,000 daily doses of hydrocodone annually.”

https://journals.lww.com/jaaos/Abstract/9000/State_Medical_Cannabis_Laws_Associated_With.99112.aspx

Lopez, C. D., Boddapati, V., Jobin, C. M., & Hickernell, T. R. (2020). State Medical Cannabis Laws Associated With Reduction in Opioid Prescriptions by Orthopaedic Surgeons in Medicare Part D Cohort. The Journal of the American Academy of Orthopaedic Surgeons.

P31 > Recent studies are showing that the more people have access to cannabis...the fewer die from opioid overdoses.

Chan, N. W., Burkhardt, J., & Flyr, M. (2019). The effects of recreational marijuana legalization and dispensing on opioid mortality. Economic Inquiry.

Note: More access to cannabis means less use of illicit opiates in general:

Stephanie Lake, Zach Walsh, Thomas Kerr, Ziva D. Cooper, Jane Buxton, Evan Wood, Mark A. Ware, M. J. Milloy. Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis. PLOS Medicine, 2019; 16 (11): e1002967 DOI: 10.1371/journal.pmed.1002967

Analysis of the interval pre (2007-2012) versus post (2013-2017) cannabis legalization revealed statistically significant decreases for Colorado and Maryland, but not Utah, for pain medications. There was a larger reduction from 2012 to 2017 in Colorado (-31.5%) than the other states (-14.2% to -23.5%). Colorado had a significantly greater decrease in codeine and oxymorphone than the comparison states. The most prevalent opioids by morphine equivalents were oxycodone and methadone.

Kropp Lopez AK, Nichols SD, Chung DY, Kaufman DE, McCall KL, Piper BJ. Prescription Opioid Distribution after the Legalization of Recreational Marijuana in Colorado. Int J Environ Res Public Health. 2020;17(9).

P31 > cannabis use reduces binge drinking

Alley, Z. M., Kerr, D. C., & Bae, H. (2019). Trends in college students’ alcohol, nicotine, prescription opioid and other drug use after recreational marijuana legalization: 2008-2018. Addictive behaviors, 106212.

https://www.sciencedirect.com/science/article/abs/pii/S030646031930783X

This study reported large reduction of alcohol consumption after implementation of medical cannabis laws

Andreyeva, E., & Ukert, B. (2019, October). The impact of medical marijuana laws and dispensaries on self-reported health. In Forum for Health Economics and Policy. De Gruyter.

P31> long term observational study of people with lower back pain

In a long-term study with 61 patients with low back pain, who used opioids, about half of them were able to stop all opioid usage after initiating cannabis use, which took several years. This observational study was conducted at a single site, the medical practice of Jeffrey Y. Hergenrather. Cannabis recommendations were provided to patients as a way to mitigate their low back pain.

Authors found that 50.8% were able to stop all opioid usage, which took a median of 6.4 years after excluding two patients. For those 29 patients (47.5%) who did not stop opioids, 9 (31%) were able to reduce opioid use, 3 (10%) held the same baseline, and 17 (59%) increased their usage. Authors concluded that in “this long-term observational study, cannabis use worked as an alternative to prescription opioids in just over half of patients with low back pain and as an adjunct to diminish use in some chronic opioid users.”

Takakuwa, K. M., Hergenrather, J. Y., Shofer, F. S., & Schears, R. M. (2020). The Impact of Medical Cannabis on Intermittent and Chronic Opioid Users with Back Pain: How Cannabis Diminished Prescription Opioid Usage. Cannabis and Cannabinoid Research.

https://www.liebertpub.com/doi/abs/10.1089/can.2019.0039

P31 > Studies from researchers like Dr. Yasmin Hurd and Julia Arnsten

Bachhuber, M., Arnsten, J. H., & Wurm, G. (2019). Use of cannabis to relieve pain and promote sleep by customers at an adult use dispensary. Journal of psychoactive drugs, 51(5), 400-404.

https://www.tandfonline.com/doi/abs/10.1080/02791072.2019.1626953?journalCode=ujpd20

Hurd, Y. L. (2020). Leading the next CBD wave—safety and efficacy. JAMA psychiatry, 77(4), 341-342.

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2758326

Hurd, Y. L., Spriggs, S., Alishayev, J., Winkel, G., Gurgov, K., Kudrich, C., ... & Salsitz, E. (2019). Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. American Journal of Psychiatry, 176(11), 911-922.

https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2019.18101191?journalCode=ajp

P33 > If oxytocin tamps down the amygdala, the fear center

Viviani, D., Charlet, A., van den Burg, E., Robinet, C., Hurni, N., Abatis, M., ... & Stoop, R. (2011). Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. science, 333(6038), 104-107.

https://www.ncbi.nlm.nih.gov/pubmed/21719680

Paloyelis, Y., Krahé, C., Maltezos, S., Williams, S. C., Howard, M. A., & Fotopoulou, A. (2016). The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials. Journal of neuroendocrinology, 28(4).

https://onlinelibrary.wiley.com/doi/full/10.1111/jne.12347

P33 > In animal studies, oxytocin has been shown to inhibit the development of tolerance to alcohol and opioids and to reduce drug-seeking behaviors, reward, and craving with cocaine, methamphetamine (speed) and cannabis . Oxytocin can attenuate the withdrawal symptoms from addiction to morphine.

Kovács, G. L., Sarnyai, Z., & Szabó, G. (1998). Oxytocin and addiction: a review. Psychoneuroendocrinology, 23(8), 945-962.

https://www.researchgate.net/profile/Zoltan_Sarnyai/publication/13363967_Oxytocin_and_addiction_A_review/links/59efbbfcaca272a250012f48/Oxytocin-and-addiction-A-review.pdf

McGregor, I. S., & Bowen, M. T. (2012). Breaking the loop: oxytocin as a potential treatment for drug addiction. Hormones and behavior, 61(3), 331-339.

http://ivmedicalcenter.com/wp-content/uploads/2018/10/Breaking-the-loop-Oxytocin-as-a-potential-treatment-for-drug-addiction.pdf

Sarnyai, Z., & Kovács, G. L. (2014). Oxytocin in learning and addiction: from early discoveries to the present. Pharmacology Biochemistry and Behavior, 119, 3-9.

https://www.researchgate.net/profile/Zoltan_Sarnyai/publication/259095928_Oxytocin_in_learning_and_addiction_From_early_discoveries_to_the_present/links/59dc41d0a6fdcc1ec89fb4ee/Oxytocin-in-learning-and-addiction-From-early-discoveries-to-the-present.pdf

Carson, D. S., Cornish, J. L., Guastella, A. J., Hunt, G. E., & McGregor, I. S. (2010). Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats. Neuropharmacology, 58(1), 38-43.

McRae-Clark, A. L., Baker, N. L., Moran-Santa Maria, M., & Brady, K. T. (2013). Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study. Psychopharmacology, 228(4), 623-631.

P36 > many of the classical psychedelics are potent anti-inflammatory molecules.

Particularly DOI, a less well known psychedelic:

Flanagan, T. W., & Nichols, C. D. (2018). Psychedelics as anti-inflammatory agents. International Review of Psychiatry, 30(4), 363-375.

http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Therapeutic%20Effects%20of%20Psychedelics%2019/Flanagan%20Nichols%2018%20IntRevPsychiatry%20Psychedelics%20as%20anti-inflammatory%20agents.pdf

Nichols, C. D., Sebastian, M., & Flanagan, T. (2017). Psychedelics As A New Anti-Inflammatory Therapeutic For Atherosclerosis. The FASEB Journal, 31(1_supplement), 825-3.

Szabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E. (2014). Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PloS one, 9(8), e106533.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106533

Uthaug, M. V., Lancelotta, R., Szabo, A., Davis, A. K., Riba, J., & Ramaekers, J. G. (2019). Prospective examination of synthetic 5-methoxy-N, N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology, 1-13.

https://link.springer.com/article/10.1007/s00213-019-05414-w

P37 > MDMA therapy has been getting positive results

Meta-analysis of MDMA data:

Bahji, A., Forsyth, A., Groll, D., & Hawken, E. R. (2020). Efficacy of 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 96, 109735.

https://www.sciencedirect.com/science/article/pii/S0278584619301484

P38 > called “the repository of truth” in a well-loved book, The Biology of Love.

Janov, A. (2010). The biology of love. Prometheus Books, p 66.

P49 > ayahuasca (a psychedelic tea)

There will be more specific references to ayahuasca in further chapters. For general information, see:

Labate, B. C., & MacRae, E. (2016). Ayahuasca, ritual and religion in Brazil. Routledge.

http://www.bialabate.net/wp-content/uploads/2008/09/Ayahuasca_Ritual_Religion_Brazil_2010.pdf

And:

Sánchez, C., & Bouso, J. C. (2015). Ayahuasca: From the Amazon to the global village. Transnational Institute.

http://fileserver.idpc.net/library/Ayahuasca_from_the_Amazon_to_the_Global_Village_Report.pdf

P52 > make art.

Lower cortisol reported after 45 minutes of art-making

Girija Kaimal, Kendra Ray, Juan Muniz. Reduction of Cortisol Levels and Participants' Responses Following Art Making. Art Therapy, 2016; 33 (2): 74 DOI: 10.1080/07421656.2016.1166832

P52 > You know what else is good? Silence. Beris, R. (2013). Science Says Silence is Much More Important to Our Brains than We Think. Geraadpleegd van

http://www.lifehack.org/377243/science-says-silence-much-moreimportant-our-brains-than-thought.

See for a review:

WHAT HAPPENS TO OUR BRAIN WHEN WE EXPERIENCE COMPLETE SILENCE & PEACE OF MIND

https://www.furilia.com/what-happens-to-our-brain-when-we-experience-complete-silence-peace-of-mind/?fbclid=IwAR1Uf9OhNooZ3td4gFWopu2GwTdMthOI13xS63O7ejgwdmhlPgzxrbnpVm4

NOTES FOR CHAPTER TWO

P57 > some of us (myself included) are genetically predisposed to be both prosocial and also more sensitive to social slights and exclusions, owing to differences in our oxytocin receptors.

McQuaid, R. J., McInnis, O. A., Matheson, K., & Anisman, H. (2015). Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to social exclusion. Social cognitive and affective neuroscience, 10(8), 1153-1159.

https://www.ncbi.nlm.nih.gov/pubmed/25564674

Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR) gene single nucleotide polymorphism (SNP), rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism, and trust. In the current study among university students (N = 288), it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e., in the case of early-life abuse or neglect) may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity.

McQuaid, R. J., McInnis, O. A., Stead, J. D., Matheson, K., & Anisman, H. (2013). A paradoxical association of an oxytocin receptor gene polymorphism: early-life adversity and vulnerability to depression. Frontiers in neuroscience, 7, 128.

https://www.frontiersin.org/articles/10.3389/fnins.2013.00128/full

P58 > shows that this change in psychological flexibility is what mediating the relationship between the acute psychedelic effects

Davis, A. K., Barrett, F. S., & Griffiths, R. R. (2020). Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science, 15, 39-45.

https://www.sciencedirect.com/science/article/pii/S2212144719301206

The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of ‘loosened cognition’ in the mid to long term that is conducive to improved psychological wellbeing.

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., ... & Nutt, D. J. (2016). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological medicine, 46(7), 1379-1390.

https://www.gwern.net/docs/nootropics/2016-carhart-harris.pdf

P58 > An increase in openness, a key personality fixture that was once thought immutable, is at least one of the reasons why their psilocybin patients are getting better, or staying better.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537171/

Lebedev, A. V., Kaelen, M., Lövdén, M., Nilsson, J., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). LSD-induced entropic brain activity predicts subsequent personality change. Human brain mapping, 37(9), 3203-3213.

P58 > Each partner has the blueprint for the others’ growth.

Hendrix, H. (2007). Getting the love you want: A guide for couples. St. Martin's Griffin.

See also:

https://imagorelationships.org/

P59 > We know that psychedelics can initiate moments of massive ego disintegration

Lebedev AV, Lövdén M, Rosenthal G, Feilding A, Nutt DJ, Carhart-harris RL. Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin. Hum Brain Mapp. 2015;36(8):3137-53. doi:10.1002/hbm.22833

Nour MM, Evans L, Nutt D, Carhart-harris RL. Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). Front Hum Neurosci. 2016;10:269. doi:10.3389/fnhum.2016.00269

For recent pharmacological theory on this which does not limit itself to 5HT2A stimulation:

“Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution.”

Mason, N. L., Kuypers, K. P. C., Müller, F., Reckweg, J., Tse, D. H. Y., Toennes, S. W., ... & Ramaekers, J. G. (2020). Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology, 1-11.

https://www.nature.com/articles/s41386-020-0718-8

P67 > a genetic variant that affects the oxytocin receptor which can mute the MDMA experience.)

These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers.

Bershad, A. K., Weafer, J. J., Kirkpatrick, M. G., Wardle, M. C., Miller, M. A., & de Wit, H. (2016). Oxytocin receptor gene variation predicts subjective responses to MDMA. Social neuroscience, 11(6), 592-599.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988944/

P67 > the promise of the drug for treating alcoholism

Bogenschutz, M. P., & Johnson, M. W. (2016). Classic hallucinogens in the treatment of addictions. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 250-258.

https://newrootsibogaine.com/wp-content/uploads/2018/05/Bogenschutz_2016_Classic-hallucinogens-in-the-treatment-of-addictions.pdf

Krebs, T. S., & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994-1002.https://www.ncbi.nlm.nih.gov/books/NBK99377/

Dyck, E. (2006). ‘Hitting highs at rock bottom’: LSD treatment for alcoholism, 1950–1970. Social History of Medicine, 19(2), 313-329.

https://www.researchgate.net/profile/Erika_Dyck/publication/31220427_%27Hitting_Highs_at_Rock_Bottom%27_LSD_Treatment_for_Alcoholism_1950-1970/links/551166940cf29a3bb71db8c4/Hitting-Highs-at-Rock-Bottom-LSD-Treatment-for-Alcoholism-1950-1970.pdf

Kurland, A., Savage, C., Pahnke, W. N., Grof, S., & Olsson, J. E. (1971). LSD in the treatment of alcoholics. Pharmacopsychiatry, 4(02), 83-94.

NOTES FOR CHAPTER THREE

P101 > the massive ongoing rewiring that helps lay the foundation for all the new behaviors of motherhood Craig Howard Kinsley, “The Neuroplastic Maternal Brain,” Hormones and Behavior 54, no. 1 (2008): 1–4;

Cindy K. Barha and Liisa A. M. Galea, “Influence of Different Estrogens on Neuroplasticity and Cognition in the Hippocampus,” Biochimica et Biophysica Acta (BBA)—General Subjects 1800, no. 10 (2010): 1056–67.

P102 > emotionally significant experiences, various stresses,

Opendak, M., & Gould, E. (2015). Adult neurogenesis: a substrate for experience-dependent change. Trends in cognitive sciences, 19(3), 151-161.

P102 > But estrogen is also a key player in the neuroplasticity of pregnancy.

BDNF, is the brain “fertilizer” that helps you make new brain cells and underlies learning and memory. Animal studies show that if you have high estrogen levels, you have more BDNF and therefore more neuroplasticity in the brain. In women, estrogen increases BDNF levels in the brain’s learning and memory areas. This may be one reason why estrogen replacement therapy in the menopausal years may forestall or prevent dementia.

Barha, C. K., & Galea, L. A. (2010). Influence of different estrogens on neuroplasticity and cognition in the hippocampus. Biochimica et Biophysica Acta (BBA)-General Subjects, 1800(10), 1056-1067.

Catenaccio, E., Mu, W., & Lipton, M. L. (2016). Estrogen-and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging. Brain Structure and Function, 221(8), 3845-3867.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679703/

P105 > parenting styles do correlate with different oxytocin receptor gene types,

Feldman, R., Zagoory-Sharon, O., Weisman, O., Schneiderman, I., Gordon, I., Maoz, R., ... & Ebstein, R. P. (2012). Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes. Biological psychiatry, 72(3), 175-181.

https://ruthfeldmanlab.com/wp-content/uploads/2019/06/OT-sensitive-parenting-and-genes.BPS2012.pdf

Bradley, B., Davis, T. A., Wingo, A. P., Mercer, K. B., & Ressler, K. J. (2013). Family environment and adult resilience: contributions of positive parenting and the oxytocin receptor gene. European journal of psychotraumatology, 4(1), 21659.

https://www.tandfonline.com/doi/full/10.3402/ejpt.v4i0.21659

For parenting and oxytocin receptor, see also:

Keebaugh, A. C., Barrett, C. E., Laprairie, J. L., Jenkins, J. J., & Young, L. J. (2015). RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles. Social neuroscience, 10(5), 561-570.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618772/

Keebaugh, A. C., & Young, L. J. (2011). Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Hormones and behavior, 60(5), 498-504.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210320/

See also:

Michalska, K. J., Decety, J., Liu, C., Chen, Q., Martz, M. E., Jacob, S., ... & Lahey, B. B. (2014). Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting. Frontiers in Behavioral Neuroscience, 8, 21.

https://www.frontiersin.org/articles/10.3389/fnbeh.2014.00021/full

Monin, J. K., Goktas, S. O., Kershaw, T., & DeWan, A. (2019). Associations between spouses’ oxytocin receptor gene polymorphism, attachment security, and marital satisfaction. PloS one, 14(2), e0213083.

G carriers were more emotionally sensitive (lower self-esteem) in response to social ostracism promoted through an on-line ball tossing game (Cyberball). Furthermore, GG individuals also exhibited altered blood pressure and cortisol levels following rejection, effects not apparent among A carriers. The data support the view that the presence of the G allele not only promotes prosocial behaviors but also favors sensitivity to a negative social stressor.

P106 > The CDC recently issued (Childhood trauma)

Merrick, M. T., Ford, D. C., Ports, K. A., Guinn, A. S., Chen, J., Klevens, J., ... & Ottley, P. (2019). Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention—25 States, 2015–2017. Morbidity and Mortality Weekly Report, 68(44), 999.

https://www.cdc.gov/mmwr/volumes/68/wr/mm6844e1.htm?s_cid=mm6844e1

P106-107 > Imaging studies of people with depression, anxiety, or PTSD

Janiri, D., Moser, D. A., Doucet, G. E., Luber, M. J., Rasgon, A., Lee, W. H., ... & Frangou, S. (2019). Shared Neural Phenotypes for Mood and Anxiety Disorders: A Meta-analysis of 226 Task-Related Functional Imaging Studies. JAMA psychiatry, 1-8.

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2753513

P107 > Conversely, when you have multiple social supports, your ability to dampen a stress response greatly increases

“social relationships can dampen HPA axis stress responses and protect individuals from maladaptive psychological and physical disease states.”

Hostinar, C. E., & Gunnar, M. R. (2013). Future directions in the study of social relationships as regulators of the HPA axis across development. Journal of Clinical Child & Adolescent Psychology, 42(4), 564-575.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161011/

P109 > that social smile triggers

Wörmann, V., Holodynski, M., Kärtner, J., & Keller, H. (2012). A cross-cultural comparison of the development of the social smile: A longitudinal study of maternal and infant imitation in 6-and 12-week-old infants. Infant Behavior and Development, 35(3), 335-347.

P 115 > Receptors for oxytocin and vasopressin are abundant in areas of the nervous system that regulate emotional and social behaviors, and the reward process that molds them.

Carter, C. S. (2017). The oxytocin–vasopressin pathway in the context of love and fear. Frontiers in endocrinology, 8, 356.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743651/#B17

Caldwell, H. K. (2017). Oxytocin and vasopressin: powerful regulators of social behavior. The Neuroscientist, 23(5), 517-528.

http://www.neuroplaybrasil.com/arquivos/Oxytocin_and_Vasopressin_Powerful_Regulators_of_Social_Behavior.pdf

Caldwell, H. K., & Albers, H. E. (2015). Oxytocin, vasopressin, and the motivational forces that drive social behaviors. In Behavioral neuroscience of motivation (pp. 51-103). Springer, Cham.

P115 > oxytocin-vasopressin pathway

Note: regarding oxytocin and vasopressin: each can trigger the others’ receptors, and each can form what are called heterodimers. This means their receptors can form bonds with other receptors, changing the configuration of what chemicals will trigger a response in the new receptor complex.

Cottet, M., Albizu, L., Perkovska, S., Jean-Alphonse, F., Rahmeh, R., Orcel, H., ... & Durroux, T. (2010). Past, present and future of vasopressin and oxytocin receptor oligomers, prototypical GPCR models to study dimerization processes. Current opinion in pharmacology, 10(1), 59-66.

P120 > Yes, oxytocin works on fathers

Gordon, I., Zagoory-Sharon, O., Leckman, J. F., & Feldman, R. (2010). Prolactin, Oxytocin, and the development of paternal behavior across the first six months of fatherhood. Hormones and Behavior, 58(3), 513–518. http://doi.org/10.1016/j.yhbeh.2010.04.007

P107 > in favor of breastfeeding

Rabin, Roni Caryn “Breast-Feeding Is Good for the Mother, and Not Just the Baby” New York Times 10/26/18

P121 > A study where they gave women intranasal oxytocin showed that it enhanced the salience of infant laughter. Meaning it made it more important

Riem, M. M., Van Ijzendoorn, M. H., Tops, M., Boksem, M. A., Rombouts, S. A., & Bakermans-Kranenburg, M. J. (2012). No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter. Neuropsychopharmacology, 37(5), 1257.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306887/

P124 > unpaid emotional labor

Hochschild, A. R. (2012). The managed heart: Commercialization of human feeling. Univ of California Press.

Steinberg, R. J., & Figart, D. M. (1999). Emotional labor since: The managed heart. The Annals of the American Academy of Political and Social Science, 561(1), 8-26.

Arlie R. Hochschild, with A. Machung, The Second Shift: Working Parents and the Revolution at Home (Berkeley: University of California Press, 1989)

See also the “stalled gender revolution”

(even as women’s societal roles have evolved, women’s position in the family has lagged behind)

https://www.universityofcalifornia.edu/news/who-stalled-gender-revolution

https://sociologicalscience.com/articles-v6-13-321/

There is also the “pleasure gap”

https://bookshop.org/books/the-pleasure-gap-american-women-and-the-unfinished-sexual-revolution/9781580058360

P126> There is a version of this in the animal kingdom called predator inspection

Natterson-Horowitz, B., & Bowers, K. (2019). Wildhood: The Epic Journey from Adolescence to Adulthood in Humans and Other Animals. Scribner.

P126 > that risk-taking behavior increases when adolescents are with their peers

Chein, J., Albert, D., O’Brien, L., Uckert, K., & Steinberg, L. (2011). Peers increase adolescent risk taking by enhancing activity in the brain’s reward circuitry. Developmental science, 14(2), F1-F10.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075496/

Logue, S., Chein, J., Gould, T., Holliday, E., & Steinberg, L. (2014). Adolescent mice, unlike adults, consume more alcohol in the presence of peers than alone. Developmental science, 17(1), 79-85.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/desc.12101?referrer_access_token=xg0y-SveONblf4u-Y3ixSota6bR2k8jH0KrdpFOxC64kktbSXBXm40r4YNhbPMSwEKgBiFW1Qm_MXxJMyuJawLVyUl9qiqVAqyDJPmHs867eh0-HA7soLFK1Tc-G4FoWkI-HT6jR9RCwAmRD-uHoXg%3D%3D

P126 > just knowing there were other teens watching, prompted the driver to act more carelessly.

Chein, J., Albert, D., O’Brien, L., Uckert, K., & Steinberg, L. (2011). Peers increase adolescent risk taking by enhancing activity in the brain’s reward circuitry. Developmental science, 14(2), F1-F10.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075496/

P126> better to be the helicopter pad

Reynolds Sil and Reynolds Liza, Mothering and Daughtering: Keeping Your Bond Strong Through the Teen Years 2013, Sounds True Inc.

P126 >: teach your child to ... play music.

Hennessy, S. L., Sachs, M. E., Ilari, B. S., & Habibi, A. (2019). Effects of Music Training on Inhibitory Control and Associated Neural Networks in School-Aged Children: A Longitudinal Study. Frontiers in neuroscience, 13, 1080.

https://www.frontiersin.org/articles/10.3389/fnins.2019.01080/full

P126 > Those glowing devices are screwing up kids’ neural development

A study that scanned the brains of three to five year-olds found in those whose use exceeded American Academy of Pediatrics guidelines (more than one hour a day without parental involvement) had less developed white matter tracts in areas key to the development of language, literacy and cognitive skills. In this cross-sectional study of 47 healthy prekindergarten children, screen use greater than that recommended by the American Academy of Pediatrics guidelines was associated with (1) lower measures of microstructural organization and myelination of brain white matter tracts that support language and emergent literacy skills and (2) corresponding cognitive assessments.

Hutton, J. S., Dudley, J., Horowitz-Kraus, T., DeWitt, T., & Holland, S. K. (2019). Associations Between Screen-Based Media Use and Brain White Matter Integrity in Preschool-Aged Children. JAMA pediatrics, e193869-e193869.

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2754101?guestAccessKey=56c4b22b-ee5f-4594-bb23-c3813c9cccb1&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=110419

P127 > psychedelic parenting

https://www.vice.com/en_us/article/gv5pyy/psychedelic-parenting-is-about-more-than-just-drugs

https://merryjane.com/news/psychedelic-parenting-is-now-a-thing-but-does-it-actually-work

https://www.insider.com/how-psychedelics-like-mushrooms-lsd-help-parents-relate-to-kids-2019-10

P127 > In a recent study, every additional hour spent engaged in social media

Boers, E., Afzali, M. H., Newton, N., & Conrod, P. (2019). Association of screen time and depression in adolescence. JAMA pediatrics, 173(9), 853-859.

https://jamanetwork.com/journals/jamapediatrics/article-abstract/2737909

See also:

Twenge, J. M., Spitzberg, B. H., & Campbell, W. K. (2019). Less in-person social interaction with peers among US adolescents in the 21st century and links to loneliness. Journal of Social and Personal Relationships, 36(6), 1892-1913.

P129 > and the crucial reopening of critical learning periods

Nardou, R., Lewis, E. M., Rothhaas, R., Xu, R., Yang, A., Boyden, E., & Dölen, G. (2019). Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature, 569(7754), 116-120.

https://www.nature.com/articles/s41586-019-1075-9

P133 > One is called magnocellular

Actually it’s all more complicated than I’ve made it out to be here. Not exactly just two cell types with distinctly defined roles. see:

Eliava, M., Melchior, M., Knobloch-Bollmann, H. S., Wahis, J., da Silva Gouveia, M., Tang, Y., ... & Chavant, V. (2016). A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron, 89(6), 1291-1304.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679079/

Althammer, F., & Grinevich, V. (2018). Diversity of oxytocin neurones: Beyond magno-and parvocellular cell types?. Journal of neuroendocrinology, 30(8), e12549.

https://pubmed.ncbi.nlm.nih.gov/29024187/

P134 > And even though we may think of the default mode network as completely self-absorbed, it is indispensable in the social understanding of others.

Li, W., Mai, X., & Liu, C. (2014). The default mode network and social understanding of others: what do brain connectivity studies tell us. Frontiers in human neuroscience, 8, 74.

P135 > nucleus Accumbens

There is a nucleus accumbens in each hemisphere; it is situated between the caudate and putamen. The nucleus accumbens is considered part of the basal ganglia and also is the main component of the ventral striatum. The nucleus accumbens itself is separated into two anatomical components: the shell and the core.

Salamone, J. D., & Correa, M. (2012). The mysterious motivational functions of mesolimbic dopamine. Neuron, 76(3), 470-485.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450094/

The nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning (e.g., Pavlovian-instrumental transfer);^[4]^[7]^[8]^[9]^[10] hence, it has a significant role in addiction.^[4]^[8]

See also

The caudate nucleus plays a vital role in how the brain learns, specifically the storing and processing of memories. It works as a feedback processor, which means it uses information from past experiences to influence future actions and decisions.

Nucleus accumbens is thought to play an important role in reward, laughter, pleasure, addiction, fear, and the placebo effect.^[1]^[2]

The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.^[3]

P136 > But one lab run by Robert Levenson at UC Berkeley, has proposed

Note: 5-HTTLPR (serotonin-transporter-linked polymorphic region) is located on chromosome 17.

Gyurak, A., Haase, C. M., Sze, J., Goodkind, M. S., Coppola, G., Lane, J., ... & Levenson, R. W. (2013). The effect of the serotonin transporter polymorphism (5-HTTLPR) on empathic and self-conscious emotional reactivity. Emotion, 13(1), 25.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553251/

NOTES FOR CHAPTER FOUR

P143 > Brian Anderson, who worked with long-term HIV/AIDS survivors,

Anderson, B., Danforth, A., Daroff, R., Stauffer, C., Dilley, J., Mitchell, J., & Woolley, J. (2019). T137. Psilocybin-Assisted Group Therapy for Demoralization in Long-Term AIDS Survivors. Biological Psychiatry, 85(10), S182.

https://www.clinicaltrials.gov/ProvidedDocs/67/NCT02950467/Prot_SAP_000.pdf

P147 > Even when people read stories that reflect their personal values, this default mode circuitry becomes active.

Kaplan, J. T., Gimbel, S. I., Dehghani, M., Immordino-Yang, M. H., Sagae, K., Wong, J. D., ... & Damasio, A. (2016). Processing narratives concerning protected values: A cross-cultural investigation of neural correlates. Cerebral Cortex, 27(2), 1428-1438.

https://academic.oup.com/cercor/article/27/2/1428/3056299

P147 > There’s a classic film of a black cat having its amygdala stimulated.

https://link.springer.com/article/10.1007/BF01124389

P147 > Interestingly, it is the people who are most resistant to changing their minds, rigid in their beliefs, that show the biggest amygdala threat response.

Ine one study by Jonas Kaplan, the participants who were able to change their mind when evaluating counterevidence showed lower signaling coming from the fearful amygdala.

Kaplan, J. T., Gimbel, S. I., & Harris, S. (2016). Neural correlates of maintaining one’s political beliefs in the face of counterevidence. Scientific reports, 6, 39589.

https://www.nature.com/articles/srep39589

P148 > These sentencing, or healing, circles

Lilles, H. (2001). Circle sentencing: Part of the restorative justice continuum (pp. 161-179). Hart Publishing.

http://www.courts.ca.gov/documents/SentencingCircles.pdf

http://restorativejustice.org/restorative-justice/about-restorative-justice/tutorial-intro-to-restorative-justice/lesson-3-programs/circles/#sthash.oTYpE00v.dpbs

P148 > reparations

To the native people whose land we stole, to the descendants whose ancestors were stolen from their land, to the victims of drug wars and inequality everywhere. Directly investing into communities that need it is one answer of many:

Chicago suburb to use recreational marijuana sales tax to fund reparations program: report

https://thehill.com/homenews/state-watch/472450-chicago-suburb-to-use-recreational-marijuana-sales-tax-to-fund

Lawmakers in a Chicago suburb have approved using sales tax revenue made from recreational marijuana purchases to establish a reparations program in the area

Ald. Robin Rue Simmons, who proposed the reparations bill, told the Press that the move will “directly invest in black Evanston,” and the money will be invested in the community that the “war on drugs ... unfairly policed and damaged.”

P148 > Dr. Monica Williams is an expert on racial trauma

Williams, M. T. (2020). Microaggressions: Clarification, evidence, and impact. Perspectives on Psychological Science, 15(1), 3-26.

https://psycharchives.org/bitstream/20.500.12034/2130/1/Williams_MicroaggressionsPPS-inpress.pdf

Williams, M. T., Chapman, L. K., Wong, J., & Turkheimer, E. (2012). The role of ethnic identity in symptoms of anxiety and depression in African Americans. Psychiatry research, 199(1), 31-36.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445759/

Williams, M., Powers, M., Yun, Y. G., & Foa, E. (2010). Minority participation in randomized controlled trials for obsessive–compulsive disorder. Journal of anxiety disorders, 24(2), 171.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431431/

on how MDMA might help treat the trauma of racism in Double Blind, a magazine devoted to the culture and science of psychedelics. (Shelby Hartman and Madison Margolin, co-founders)

https://doubleblindmag.com/mdma-racial-trauma-monnica-williams/

On a call for a more inclusive psychedelic research community (amen to that. More than 80% of participants in psychedelic trials going back to 1993 have been white.)

George, J. R., Michaels, T. I., Sevelius, J., & Williams, M. T. (2020). The psychedelic renaissance and the limitations of a White-dominant medical framework: A call for indigenous and ethnic minority inclusion. Journal of Psychedelic Studies, 4(1), 4-15.

https://akjournals.com/view/journals/2054/4/1/article-p4.xml

P149 > integrating students of different social classes and races can not only improve test scores in children, but can also help develop empathy

Weathers, E. S., Fahle, E. M., Jang, H., & Kalogrides, D. Is Separate Still Unequal? New Evidence on School Segregation and Racial Academic Achievement Gaps.

P149 > being part of a diverse community can decrease anxiety

Levin, S., Van Laar, C., & Sidanius, J. (2003). The effects of ingroup and outgroup friendships on ethnic attitudes in college: A longitudinal study. Group Processes & Intergroup Relations, 6(1), 76-92.

https://www.researchgate.net/profile/Jim_Sidanius/publication/247720617_The_effects_of_ingroup_and_outgroup_friendships_on_ethnic_attitudes_in_college_A_longitudinal_study/links/53e0e05a0cf2235f35270d59/The-effects-of-ingroup-and-outgroup-friendships-on-ethnic-attitudes-in-college-A-longitudinal-study.pdf

For effects of integration see also:

Linda Tropp and Suchi Saxena, “Re-weaving the Social Fabric through Integrated Schools: How Intergroup Contact Prepares Youth to Thrive in a Multicultural Society,” May 2018

https://school-diversity.org/wp-content/uploads/2018/05/NCSD_Brief13.pdf

https://tcf.org/content/facts/the-benefits-of-socioeconomically-and-racially-integrated-schools-and-classrooms/?session=1

https://www.nytimes.com/2019/11/21/learning/is-racial-and-economic-diversity-in-schools-important.html

P149 > So does something called loving-kindness (or metta) meditation

Kristeller, J. L., & Johnson, T. (2005). Cultivating loving kindness: A two-stage model of the effects of meditation on empathy, compassion, and altruism. Zygon®, 40(2), 391-408.

http://www.metanexus.net/archive/conference2003/pdf/WOLPaper_Kristeller_Jean.pdf

P150 > anorexia

MAPS is helping to support Dr. Adele LaFrance on a study exploring MDMA-assisted psychotherapy for the treatment of treatment-resistant anorexia nervosa and binge eating disorder. This will be a multi-center trial, with one location in the US and two locations in Canada, with an fMRI substudy. The study is expected to begin in 2021.

P155 > kambo

Keppel Hesselink, J. M. (2018). Kambô: A ritualistic healing substance from an Amazonian frog and a source of new treatments. Open Journal of Pain Medicine, 2(1), 004-006.

Hesselink, J. M. K. (2018). Kambo and its Multitude of Biological Effects: Adverse Events or Pharmacological Effects. Int Arch Clin Pharmacol, 4, 017.

https://kambotree.com/wp-content/uploads/2020/01/Kambo_and_its_Multitude_of_Biological_Effects_Adve.pdf

P156 > This type of therapy promotes psychological flexibility,

The objective of Acceptance and Commitment Therapy is not elimination of difficult feelings, but rather to be present with what life brings us, and to move toward valued behavior. ACT is about breaking free from old habits, and from “ego.”

Watts, R., & Luoma, J. (2019). The use of the psychological flexibility model to support psychedelic assisted therapy. Journal of Contextual Behavioral Science.

https://www.sciencedirect.com/science/article/pii/S2212144719301140?fbclid=IwAR3r4LBp9m1ovgPqryQhJ6AQ9noAAwH4dYz_OGOO2WMx3d9Tr1wFGZopkQI#!

Hulbert-Williams, N. J., Storey, L., & Wilson, K. G. (2015). Psychological interventions for patients with cancer: psychological flexibility and the potential utility of Acceptance and Commitment Therapy. European journal of cancer care, 24(1), 15-27.

https://www.semanticscholar.org/paper/Psychological-interventions-for-patients-with-and-Hulbert-Williams-Storey/6bf1bbb5dca740520846e20daadcb5f37aee1c55

The Acceptance and Action Questionnaire measures psychological flexibility as conceptualized within the Acceptance and Commitment Therapy framework.

Levin, M. E., Luoma, J. B., Lillis, J., Hayes, S. C., & Vilardaga, R. (2014). The Acceptance and Action Questionnaire–Stigma (AAQ-S): Developing a measure of psychological flexibility with stigmatizing thoughts. Journal of contextual behavioral science, 3(1), 21-26.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255270/

Levin, M. E., Hildebrandt, M. J., Lillis, J., & Hayes, S. C. (2012). The impact of treatment components suggested by the psychological flexibility model: A meta-analysis of laboratory-based component studies. Behavior therapy, 43(4), 741-756.

https://www.researchgate.net/profile/Michael_Levin6/publication/232224816_The_Impact_of_Treatment_Components_Suggested_by_the_Psychological_Flexibility_Model_A_Meta-Analysis_of_Laboratory-Based_Component_Studies/links/53dfcb680cf2a768e49be0d9.pdf

Bond, F. W., Hayes, S. C., & Barnes-Holmes, D. (2006). Psychological flexibility, ACT, and organizational behavior. Journal of Organizational Behavior Management, 26(1-2), 25-54.

http://research.gold.ac.uk/23/1/bond_jobm2006_preprint_GRO.pdf

P157 > MDMA enhances emotional empathy and prosocial behavior.

Hysek, C. M., Schmid, Y., Simmler, L. D., Domes, G., Heinrichs, M., Eisenegger, C., ... & Liechti, M. E. (2013). MDMA enhances emotional empathy and prosocial behavior. Social cognitive and affective neuroscience, 9(11), 1645-1652.

https://academic.oup.com/scan/article/9/11/1645/1681238

P164 > ibogaine

Mash, D. C., Kovera, C. A., Pablo, J., Tyndale, R. F., Ervin, F. D., Williams, I. C., ... & Mayor, M. (2000). Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Annals of the New York Academy of Sciences, 914(1), 394-401.

Farrow, S. C., Kamileen, M. O., Caputi, L., Bussey, K., Mundy, J. E., McAtee, R. C., ... & O’Connor, S. E. (2019). Biosynthesis of an anti-addiction agent from the iboga plant. Journal of the American Chemical Society, 141(33), 12979-12983.

P164> can reverse opioid dependence

Mash, D. C., Kovera, C. A., Pablo, J., Tyndale, R., Ervin, F. R., Kamlet, J. D., & Hearn, W. L. (2001). Ibogaine in the treatment of heroin withdrawal.

Brown, T. K., & Alper, K. (2018). Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse, 44(1), 24-36.

Sweetnam, P. M., Lancaster, J., Snowman, A., Collins, J. L., Perschke, S., Bauer, C., & Ferkany, J. (1995). Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity. Psychopharmacology, 118(4), 369-376.

These studies show fewer withdrawal symptoms:

Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in withdrawal and craving scores in participants undergoing opioid detoxification utilizing ibogaine. Journal of psychoactive drugs, 50(3), 256-265.

https://experienceibogaine.com/wp-content/uploads/2018/10/Changes-in-Withdrawal-and-Craving-Scores.pdf

Mojeiko, V., Brown, T. K., Gargour, K., & Jordan, M. (2010). Observational study of the long-term efficacy of ibogaine-assisted treatment in participants with opiate addiction. Multidisciplinary Association for Psychedelic Studies.

https://maps.org/research-archive/presentations/Brown_GITA_Vancouver_Oct2012_iboga_comm_rev.pdf

P165 > practitioners like Dr. Peter Gasser have revived the practice of psychedelic group sessions

Here is a recent group therapy meta analysis:

Trope, A., Anderson, B. T., Hooker, A. R., Glick, G., Stauffer, C., & Woolley, J. D. (2019). Psychedelic-assisted group therapy: a systematic review. Journal of Psychoactive Drugs, 51(2), 174-188.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650145/

This is Peter Gasser’s discussion of his wish to do group therapy research

https://maps.org/news/bulletin/articles/420-bulletin-spring-2017/6622-research-update-psychedelic-group-therapy-in-switzerland

And here is a published paper of Gasser’s work with individuals

“All research with LSD-assisted psychotherapy in the 1950s and the 1960s came to a halt by the early 1970s. Our study, the first in more than 40 years to evaluate safety and efficacy of LSD as an adjunct to psychotherapy, was conducted in participants with anxiety after being diagnosed with a life-threatening illness. In contrast to the shortcomings of older studies, we used a controlled, randomized, and blinded study design to meet contemporary research standards. LSD was given in a psychotherapeutic context to facilitate a deep psychedelic state, allowing the participant to encounter his/her own inner realities during an emotionally intensified dream-like “journey.”

“In our study, using appropriate inclusion/exclusion criteria, detailed participant preparation, and a carefully supervised experience in a supportive psychotherapeutic setting, psychological side effects were mild and limited. There were no AEs often attributed to LSD such as prolonged anxiety (“bad trip”) or lasting psychotic or perceptional disorders (flashbacks). Congruent with studies in the past (Hintzen and Passie, 2010), the few mild somatic effects of LSD such as changes in heart rate and blood pressure were of no clinical significance.”

Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of nervous and mental disease, 202(7), 513.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086777/

P166 > having social relationships can dampen the stress response,

“social relationships can dampen HPA axis stress responses and protect individuals from maladaptive psychological and physical disease states.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161011/

P173 > that listening to music is good for your physical and mental health

For review of music’s effects on health see:

MacDonald, R. A. (2013). Music, health, and well-being: A review. International journal of qualitative studies on health and well-being, 8(1), 20635.

https://www.tandfonline.com/doi/pdf/10.3402/qhw.v8i0.20635

P173 > attending live concerts can help overall health and happiness

It pains me to type this, as large public gatherings like concerts will have to wait for now. But:

Those who attended concerts felt a 21% increase in well-being – compared to 10% for yoga and 7% for dog-walking – with a 25% increased feeling of self-worth, a 25% increased feeling of closeness to others, and 75% increased mental stimulation.

Those who attend live concerts once a fortnight and more were the most likely to score their happiness, contentment, productivity and self-esteem at the highest level (10/10), suggesting that regularly experiencing live music is the key to building a long-standing improvement to wellbeing.

Please note this is not study results, but only a press release:

https://news.o2.co.uk/press-release/science-says-gig-going-can-help-you-live-longer-and-increases-wellbeing/

P 173 > listening to music is good for your physical and mental health,

Weinberg, M. K., & Joseph, D. (2017). If you’re happy and you know it: Music engagement and subjective wellbeing. Psychology of Music, 45(2), 257-267.

https://journals.sagepub.com/doi/abs/10.1177/0305735616659552

P174 > Intensely pleasurable responses to music can trigger activity in the same brain regions that are responsible for reward, motivation, emotion, and arousal.

Blood AJ, Zatorre RJ. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci U S A. 2001;98(20):11818–23.

https://www.pnas.org/content/98/20/11818

P174 > autonomous sensory meridian response

Guhn, M., Hamm, A., & Zentner, M. (2007). Physiological and musico-acoustic correlates of the chill response. Music Perception: An Interdisciplinary Journal, 24(5), 473-484.

https://mp.ucpress.edu/content/24/5/473.abstract

Note: estimates of percent of the population who have the capacity to experience these chills ranges between 55 and 86%.

https://psycnet.apa.org/psycinfo/2007-02644-005

http://mp.ucpress.edu/content/13/2/171.abstract

P174 > Made up by Jennifer Allen

https://www.nytimes.com/2019/04/04/magazine/how-asmr-videos-became-a-sensation-youtube.html

For more info on ASMR:

Barratt, E. L., & Davis, N. J. (2015). Autonomous Sensory Meridian Response (ASMR): a flow-like mental state. PeerJ, 3, e851.

https://peerj.com/articles/851/

Website run by Dr. Craig Richard, author of Brain Tingles

https://asmruniversity.com/

For neuroimaging of ASMR:

Note: areas that ‘lit up’ for ASMR fMRI: medial prefrontal cortex, nucleus accumbens, insula/inferior frontal gyrus, supplementary motor areas, dorsal anterior cingulate cortex, secondary somatosensory cortex

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209833/

P174 > Some of us can get this particular head tingle,

Barratt, E. L., & Davis, N. J. (2015). Autonomous Sensory Meridian Response (ASMR): a flow-like mental state. PeerJ, 3, e851.

https://peerj.com/articles/851/

P175 > people who experience frisson with music score higher on the personality trait called “openness to experience.”

Colver, M. C., & El-Alayli, A. (2016). Getting aesthetic chills from music: The connection between openness to experience and frisson. Psychology of Music, 44(3), 413-427.

https://journals.sagepub.com/doi/abs/10.1177/0305735615572358

P175 > So do people who experience ASMR

Fredborg, B., Clark, J., & Smith, S. D. (2017). An examination of personality traits associated with Autonomous Sensory Meridian Response (ASMR). Frontiers in psychology, 8, 247.

https://www.frontiersin.org/articles/10.3389/fpsyg.2017.00247/full

P175 > the fMRI activity shows similar patterns when looking at all three: ASMR, musical frisson, and prosocial affiliative behaviors.

Lochte, B. C., Guillory, S. A., Richard, C. A., & Kelley, W. M. (2018). An fMRI investigation of the neural correlates underlying the autonomous sensory meridian response (ASMR). BioImpacts: BI, 8(4), 295.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209833/

P175 > The default mode network in people who are able to experience ASMR is less cohesive, or has less functional connectivity than in people who don’t have this sensation.

Smith, S. D., Katherine Fredborg, B., & Kornelsen, J. (2017). An examination of the default mode network in individuals with autonomous sensory meridian response (ASMR). Social neuroscience, 12(4), 361-365.

https://www.tandfonline.com/doi/full/10.1080/17470919.2016.1188851?scroll=top&needAccess=true&-

P175 > Mirror neurons, the brain cells that help us mimic others or have a theory of mind about them, are highly active during music-mediated empathy

Bergland, Christopher Empathy, Music Listening, and Mirror Neurons Are Intertwined Marco Iacoboni shares personal insights on his “mirroring” research.

https://www.psychologytoday.com/intl/blog/the-athletes-way/201806/empathy-music-listening-and-mirror-neurons-are-intertwined

See also

Molnar-Szakacs, I., & Overy, K. (2006). Music and mirror neurons: from motion to’e’motion. Social cognitive and affective neuroscience, 1(3), 235-241.

P175 > Musicologist Zachary Wallmark conducted an fMRI based study which found that high empathy people use their social cognitive circuitry to process music.

Wallmark, Z., Deblieck, C., & Iacoboni, M. (2018). Neurophysiological effects of trait empathy in music listening. Frontiers in Behavioral Neuroscience, 12, 66.

https://www.frontiersin.org/articles/10.3389/fnbeh.2018.00066/full

P175 > as Mendel Kaelen calls it in his paper showing music’s central therapeutic function in psychedelic therapy.

Kaelen, M., Giribaldi, B., Raine, J., Evans, L., Timmerman, C., Rodriguez, N., ... & Carhart-Harris, R. (2018). The hidden therapist: evidence for a central role of music in psychedelic therapy. Psychopharmacology, 235(2), 505-519.

https://link.springer.com/article/10.1007/s00213-017-4820-5

P176 > There was a great gathering of singers after the final day of Ramadan in June of 2018,

https://www.sunnyskyz.com/happy-videos/7399/1-000-Strangers-Christians-Jews-And-Muslims-Sing-039-One-Love-039-By-Bob-Marley?fbclid=IwAR02oSNourCVjvY8vEnrlo7dv3kpLmK7pBfv8D8yV5pqhnOL8SYTP6mszuk

P176 > The organizer of the event, Koolulam, is a social-musical initiative,

https://www.koolulam.com/

P176 > music can increase acts of altruism,

Fukui, H., & Toyoshima, K. (2014). Music increase altruism through regulating the secretion of steroid hormones and peptides. Medical hypotheses, 83(6), 706-708.

https://www.sciencedirect.com/science/article/abs/pii/S030698771400348X

P178 > music can decrease stress by lowering cortisol section,

Ooishi, Y., Mukai, H., Watanabe, K., Kawato, S., & Kashino, M. (2017). Increase in salivary oxytocin and decrease in salivary cortisol after listening to relaxing slow-tempo and exciting fast-tempo music. PloS one, 12(12), e0189075.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189075

P178 > and increase acts of altruism through regulating the secretion of oxytocin.

De Dreu, C. K., Greer, L. L., Handgraaf, M. J., Shalvi, S., Van Kleef, G. A., Baas, M., ... & Feith, S. W. (2010). The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science, 328(5984), 1408-1411.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.395.4829&rep=rep1&type=pdf

P178 > There is a unique brain-to-brain coupling that is specific to the experience of shared intentionality.

Fishburn, F. A., Murty, V. P., Hlukowsky, C. O., MacGillivray, C., Bemis, L. M., Murphy, M. E., ... & Perlman, S. B. (2018). Putting our Heads Together: Interpersonal Neural Synchronization as a Biological Mechanism for Shared Intentionality. Social Cognitive and Affective Neuroscience, 1, 9.

https://academic.oup.com/scan/article/13/8/841/5061228

P178 > there is something called musical entrainment

Trost, W. J., Labbé, C., & Grandjean, D. (2017). Rhythmic entrainment as a musical affect induction mechanism. Neuropsychologia, 96, 96-110.

P179 religious rites and ceremonies

Chen, Y., Koh, H. K., Kawachi, I., Botticelli, M., & Vanderweele, T. J. (2020). Religious service attendance and deaths related to drugs, alcohol, and suicide among US health care professionals. JAMA psychiatry.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203669/

P181 > Oxytocin function helps explain the connection between prosocial behavior and health.

Poulin, M. J., & Holman, E. A. (2013). Helping hands, healthy body? Oxytocin receptor gene and prosocial behavior interact to buffer the association between stress and physical health. Hormones and behavior, 63(3), 510-517.

https://www.sciencedirect.com/science/article/abs/pii/S0018506X13000202

P182 > the reward from charity is no exception

Harbaugh, W. T., Mayr, U., & Burghart, D. R. (2007). Neural responses to taxation and voluntary giving reveal motives for charitable donations. Science, 316(5831), 1622-1625.

https://www.wisebrain.org/papers/NeuralAltruism.pdf

Note:

Consistent with pure altruism, we find that even mandatory, tax-like transfers to a charity elicit neural activity in areas linked to reward processing. Moreover, neural responses to the charity's financial gains predict voluntary giving. However, consistent with warm glow, neural activity further increases when people make transfers voluntarily. Both pure altruism and warm-glow motives appear to determine the hedonic consequences of financial transfers to the public good.

First, these transfers are associated with neural activation similar to that which comes

from receiving money for oneself. The fact that mandatory transfers to a charity elicit activity in

reward-related areas suggests that even mandatory taxation can produce satisfaction for taxpayers. Charity and paying taxes both elicit reward circuitry. First, these transfers are associated with neural activation similar to that which comes from receiving money for oneself. The fact that mandatory transfers to a charity elicit activity in reward-related areas suggests that even mandatory taxation can produce satisfaction for taxpayers. In summary, we find that three very different things—monetary payoffs to oneself, observing a charity get money, and a warm-glow effect related to free choice—all activate similar neural substrates. This result supports arguments for a common “neural currency” of reward .

P182 > social reward requires a coordination of oxytocin and serotonin

Note: These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of OT and 5-HT in the NAc, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.

Dölen, G., Darvishzadeh, A., Huang, K. W., & Malenka, R. C. (2013). Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature, 501(7466), 179.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091761/

See also

Dölen, G., & Malenka, R. C. (2014). The emerging role of nucleus accumbens oxytocin in social cognition. Biological psychiatry, 76(5), 354-355.

http://neuroscience.jhu.edu/files2/dolen_malenka_biological_psychiatry.pdf

Note: her lab has come up with a clever acronym for the project - Psychedelic Healing: Adjunct Therapy Harnessing Opened Malleability (www.phathomproject.com)"

P182 consumptive pleasures

Benson, A. L. (2006). New perspectives on compulsive buying: Its roots, measurement and physiology. ACR North American Advances.

Mela, D. J. (2006). Eating for pleasure or just wanting to eat? Reconsidering sensory hedonic responses as a driver of obesity. Appetite, 47(1), 10-17.

Fancourt, D., & Steptoe, A. (2020). The longitudinal relationship between changes in wellbeing and inflammatory markers: Are associations independent of depression?. Brain, behavior, and immunity, 83, 146-152.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928572/

P183 > a recent MDMA study using the classic game of the prisoner’s dilemma,

Gabay, A. S., Kempton, M. J., Gilleen, J., & Mehta, M. A. (2019). MDMA increases cooperation and recruitment of social brain areas when playing trustworthy players in an iterated Prisoner's Dilemma. Journal of Neuroscience, 39(2), 307-320.

https://www.jneurosci.org/content/jneuro/39/2/307.full.pdf

P183> At a time of great hostility and mistrust

Heifets, B. D., & Malenka, R. C. (2016). MDMA as a probe and treatment for social behaviors. Cell, 166(2), 269-272.

https://www.sciencedirect.com/science/article/pii/S0092867416308534#!

P184 > as Arthur Janov says in his seminal book The Biology of Love, that “ideas cannot change feelings.”

Janov, A. (2010). The biology of love. Prometheus Books, page 23

P185> When reviewing research involving liberals and conservatives, the results paint a particular picture.

Oxley, D. R., Smith, K. B., Alford, J. R., Hibbing, M. V., Miller, J. L., Scalora, M., ... & Hibbing, J. R. (2008). Political attitudes vary with physiological traits. science, 321(5896), 1667-1670.

https://www.ncbi.nlm.nih.gov/pubmed/18801995

Hasson, Y., Tamir, M., Brahms, K. S., Cohrs, J. C., & Halperin, E. (2018). Are liberals and conservatives equally motivated to feel empathy toward others?. Personality and Social Psychology Bulletin, 44(10), 1449-1459.

https://www.researchgate.net/profile/Yossi_Hasson/publication/325045483_Are_Liberals_and_Conservatives_Equally_Motivated_to_Feel_Empathy_Toward_Others/links/5b966dc3a6fdccfd543a429f/Are-Liberals-and-Conservatives-Equally-Motivated-to-Feel-Empathy-Toward-Others.pdf

P185 > bias toward paying attention to negative stimuli

Dodd, M. D., Balzer, A., Jacobs, C. M., Gruszczynski, M. W., Smith, K. B., & Hibbing, J. R. (2012). The political left rolls with the good and the political right confronts the bad: connecting physiology and cognition to preferences. Philosophical Transactions of the Royal Society B: Biological Sciences, 367(1589), 640-649.

https://royalsocietypublishing.org/doi/full/10.1098/rstb.2011.0268#aff-1

P185 > They also have a stronger physiological response to startling noises and images

Oxley, D. R., Smith, K. B., Alford, J. R., Hibbing, M. V., Miller, J. L., Scalora, M., ... & Hibbing, J. R. (2008). Political attitudes vary with physiological traits. science, 321(5896), 1667-1670.

https://www.ncbi.nlm.nih.gov/pubmed/18801995

There is also data showing that people who hold conservative beliefs have larger amygdalae

Kanai, R., Feilden, T., Firth, C., & Rees, G. (2011). Political orientations are correlated with brain structure in young adults. Current biology, 21(8), 677-680.

https://www.cell.com/current-biology/fulltext/S0960-9822(11)00289-2

P185-186 > liberals express empathy toward larger social circles, with conservatives expressing it toward smaller circles.

Waytz, A., Iyer, R., Young, L., & Graham, J. (2016). Ideological differences in the expanse of empathy. Social psychology of political polarization, 61-77.

https://moralitylab.bc.edu/wp-content/uploads/2011/10/WIYG.circle_chapter_draft.pdf

P186 > My friend and colleague Doug Rushkoff argues that our digital ecosystem is designed to exploit and divide us rather than enhance and unite us.

https://www.fastcompany.com/90295374/how-to-reclaim-our-humanity-in-a-world-of-machines-douglas-rushkoff-team-human

NOTES FOR CHAPTER FIVE

P189 > face the fact that we’re in an abusive relationship with our planet:

Leiserowitz, A., Maibach, E., Roser-Renouf, C., & Smith, N. (2010). Climate change in the American mind: Americans’ global warming beliefs and attitudes in January 2010. Yale and George Mason University. Yale Project on Climate Change.

https://climatecommunication.yale.edu/wp-content/uploads/2019/01/Climate-Change-American-Mind-December-2018.pdf

Fountain, Henry “Climate Change Is Accelerating, Bringing the World ‘Dangerously Close’ to Irreversible Change.” New York Times 12/4/19

https://www.nytimes.com/2019/12/04/climate/climate-change-acceleration.html?nl=todaysheadlines&emc=edit_th_191205?campaign_id=2&instance_id=14225&segment_id=19306&user_id=c0d1206bf9d2940e543f361805601330&regi_id=393317081205

Re: mass extinction, see:

https://www.nytimes.com/2020/06/01/science/mass-extinctions-are-accelerating-scientists-report.html

P190 > When you’re dangling off a cliff, your physiological state is not para, I can assure you.

Note: There is a Zen koan about a man dangling off a cliff who manages to reach out and pluck a berry from a bush growing there, able to savor life’s pleasures even despite his desperate position, but for most of us, this equanimity with dying is evasive.

P190 > In Braiding Sweetgrass,

Kimmerer, R. (2013). Braiding sweetgrass: Indigenous wisdom, scientific knowledge and the teachings of plants. Milkweed Editions.

P191 > She understands the “deep ecological grief” many feel currently. “Grief is a measure of how much we love. And so I honor that grief.”

Tuttle, Kate “Braiding Sweetgrass’ author Robin Wall Kimmerer on restoring a relationship with the land.” Boston Globe 11/20/19.

https://www.bostonglobe.com/2019/11/20/arts/braiding-sweetgrass-author-robin-wall-kimmerer-restoring-relationship-with-land/

P193 > Kids who grow up surrounded by nature become happier adults,

Engemann, K., Pedersen, C. B., Arge, L., Tsirogiannis, C., Mortensen, P. B., & Svenning, J. C. (2019). Residential green space in childhood is associated with lower risk of psychiatric disorders from adolescence into adulthood. Proceedings of the National Academy of Sciences, 116(11), 5188-5193.

https://www.pnas.org/content/116/11/5188

P193 > natural views out of the windows of surgery patients had a restorative effect on their recovery

Ulrich, R. (1984). View through a window may influence recovery. Science, 224(4647), 224-225.

https://is.muni.cz/el/1423/jaro2014/HEN597/um/47510652/Ulrich_1984.pdf

P193 > Other brain areas that become more active when subjects view nature scenes are the insula (empathy, intuition) and the anterior cingulate (also empathy, and impulse control, emotion, and decision-making).

Kim, G. W., Jeong, G. W., Kim, T. H., Baek, H. S., Oh, S. K., Kang, H. K., ... & Song, J. K. (2010). Functional neuroanatomy associated with natural and urban scenic views in the human brain: 3.0 T functional MR imaging. Korean Journal of Radiology, 11(5), 507-513.

https://synapse.koreamed.org/search.php?where=aview&id=10.3348/kjr.2010.11.5.507&code=0068KJR&vmode=FULL

P193 > Neuroeconomist Nik Sawe conducted early fMRI data that showed that when people view iconic natural images, their reward circuitry lights up as if they’ve eaten food or had sex.

Sawe, N. (2017). Using neuroeconomics to understand environmental valuation. Ecological Economics, 135, 1-9.

P193> Pleasant nature scenes also activate the reward system and an area rich in opiate receptors,

Yue, X., Vessel, E. A., & Biederman, I. (2007). The neural basis of scene preferences. Neuroreport, 18(6), 525-529.

http://cvcl.mit.edu/SUNSeminar/VesselBiederman_scene_PreferenceNR07.pdf

P194 > One study conducted in Scotland found that access to green space

Mitchell, R., & Popham, F. (2008). Effect of exposure to natural environment on health inequalities: an observational population study. The lancet, 372(9650), 1655-1660.

https://www.sciencedirect.com/science/article/pii/S014067360861689X

P194 > the effect of income inequality on health outcomes.

Income inequality drives mental illness and drug use/addiction

Income inequality is associated with terrible health and social outcomes. Period.

Stiglitz, Joseph E. 2015. “When Inequality Kills.” Project Syndicate, December 7. https://www.project-syndicate.org/commentary/lower-life-expectancy-white-americans-byjoseph-e--stiglitz-2015-12?barrier=accessreg.

Ribeiro, W. S., Bauer, A., Andrade, M. C. R., York-Smith, M., Pan, P. M., Pingani, L., ... & Evans-Lacko, S. (2017). Income inequality and mental illness-related morbidity and resilience: a systematic review and meta-analysis. The Lancet Psychiatry, 4(7), 554-562.

http://eprints.lse.ac.uk/79968/1/Bauer_Income%20inequality_2017.pdf

Halfon, N., Larson, K., Son, J., Lu, M., & Bethell, C. (2017). Income inequality and the differential effect of adverse childhood experiences in US children. Academic Pediatrics, 17(7), S70-S78.

https://www.academicpedsjnl.net/article/S1876-2859(16)30497-1/fulltext

Parker, N., Wong, A. P. Y., Leonard, G., Perron, M., Pike, B., Richer, L., ... & Paus, T. (2017). Income inequality, gene expression, and brain maturation during adolescence. Scientific reports, 7(1), 1-11.

https://www.nature.com/articles/s41598-017-07735-2

Dasgupta, N., Beletsky, L., & Ciccarone, D. (2018). Opioid crisis: no easy fix to its social and economic determinants. American journal of public health, 108(2), 182-186.

https://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.2017.304187

Pierce, Justin R., and Peter K. Schott. 2016. “Trade Liberalization and Mortality: Evidence from U.S. Counties.” NBER Working Paper Series. National Bureau of Economic Research Working Paper 22849. doi:10.5860/CHOICE.41Sup-0414.

P196 > bacteria in dirt is often good for your body and your mood,

Note From Moody Bitches, page 276: Allowing exposure to bacteria in nature can make us smarter, happier, and calmer. Mycobacte- rium vaccae improves levels of serotonin and norepinephrine in the brain after exposure, and it stimulates growth of some brain cells, result- ing in decreased levels of anxiety. Mice given live M. vaccae navigate a maze in half the time and with fewer anxiety behaviors than control mice. Bacteria also play a role in regulating the stress response. In laboratory animals and healthy human subjects, administering Lactobacillus helveticus and Bifidobacterium longum for two weeks significantly reduces anxiety-like behavior and negative emotionality. Some studies have found that certain bacteria are essential for normal social develop- ment in mice, whose autistic-like behavior improves when given the bacteria Bacteroides fragilis.

Christopher A. Lowry et al., “Identification of an Immune-Responsive Mesolimbocortical Serotonergic System: Potential Role in Regulation of Emotional Behavior,” Neuroscience 146, no. 2 (2007): 756–72.

T. G. Dinan and J. F. Cryan, “Regulation of the Stress Response by the Gut Microbiota: Implications for Psychoneuroendocrinology,” Psychoneuroendocrinology 37 (2012): 1369–78.

M. Messaoudi et al., “Assessment of Psychotropic- like Properties of a Probiotic Formulation (Lactobacillus Helveticus R0052 and Bifidobacterium Longum R0175) in Rats and Human Subjects,” British Journal of Nutrition 105 (2011): 755–64.

L. Desbonnet et al., “Microbiota is Essential for Social Development in the Mouse,” Molecular Psychiatry 19, no. 2 (2014):

Elaine Y. Hsiao et al., “Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders,” Cell 155, no. 7 (2013): 1451–63.

P197 > In nature nothing exists alone.

Carson, Rachel Silent spring. 1962. Houghton Mifflin, New York.

P 197 > the entourage effect, where the sum of a plant’s effects is greater than its parts

Ribeiro, S. (2018). Whole organisms or pure compounds? Entourage effect versus drug specificity. In Plant Medicines, Healing and Psychedelic Science (pp. 133-149). Springer, Cham.

https://repositorio.ufrn.br/jspui/bitstream/123456789/25464/1/SidartaRibeiro_ICe_Whole%20organisms_2018.pdf

See also:

Experience with classic psychedelics uniquely predicted self-reported engagement in pro-environmental behaviors, and that this relationship was statistically explained by people's degree of self-identification with nature.

Forstmann, M., & Sagioglou, C. (2017). Lifetime experience with (classic) psychedelics predicts pro-environmental behavior through an increase in nature relatedness. Journal of Psychopharmacology, 31(8), 975-988.

https://www.semanticscholar.org/paper/Lifetime-experience-with-(classic)-psychedelics-an-Forstmann-Sagioglou/1d2e76f52f3cb3ae762fb79c0b785491a096462a

P199 > In a paper titled, “From Egoism to Ecoism,”

The frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience.

Kettner, H., Gandy, S., Haijen, E. C., & Carhart-Harris, R. L. (2019). From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner. International Journal of Environmental Research and Public Health, 16(24), 5147.

https://www.mdpi.com/1660-4601/16/24/5147

P200 > Dr. Roland Griffiths’s now landmark study on psilocybin

Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268-283.

https://www.researchgate.net/profile/Roland_Griffiths/publication/235984074_Psilocybin_Can_Occasion_Mystical-Type_Experiences_Having_Substantial_and_Sustained_Personal_Meaning_and_Spiritual_Significance/links/0c96051dc66a9d4465000000.pdf

P202 > David Luke Huichol paper

https://www.researchgate.net/publication/278302650_Wixaritari_The_world's_oldest_psychedelic_tribe_and_their_fight_to_save_their_spiritual_ecology_Invited_Talk

P207 > although there is research suggesting that cats, too, are capable of attachment behaviors.

117 cats and their owners were put in a “strange situation” test. They enter an unfamiliar room together. After 2 minutes, the owner walks out. Two minutes later, they return. Two-thirds of the cats went back to greet their owners, the securely attached cats. One third showed insecure attachment, shunning their owners or clinging to them when they returned.

Studies of dogs and infants yield similar results: 65% infants, 58% dogs, show secure attachment to caregivers.

Vitale, K. R., Behnke, A. C., & Udell, M. A. (2019). Attachment bonds between domestic cats and humans. Current Biology, 29(18), R864-R865.

https://pictures-of-cats.org/wp-content/uploads/2019/09/Study-into-how-attached-domestic-cats-are-to-us.pdf

P207 > a service called “cuddle clones”

Cuddleclones.com

P208 > There is a company I often recommend for CBD products and they have a great line for pets,

BluebirdBotanicals.com

P208 > they increase oxytocin concentrations in their owners as a “manifestation of attachment behavior.”

Nagasawa, M., Kikusui, T., Onaka, T., & Ohta, M. (2009). Dog's gaze at its owner increases owner's urinary oxytocin during social interaction. Hormones and Behavior, 55(3), 434-441.

http://library.allanschore.com/docs/DogHumanNasagawa09.pdf

See also

Nagasawa, M., Mitsui, S., En, S., Ohtani, N., Ohta, M., Sakuma, Y., ... & Kikusui, T. (2015). Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Science, 348(6232), 333-336.

And

Miller, S. C., Kennedy, C. C., DeVoe, D. C., Hickey, M., Nelson, T., & Kogan, L. (2009). An examination of changes in oxytocin levels in men and women before and after interaction with a bonded dog. Anthrozoös, 22(1), 31-42.

https://www.researchgate.net/profile/Lori_Kogan/publication/233581989_An_Examination_of_Changes_in_Oxytocin_Levels_in_Men_and_Women_Before_and_After_Interaction_with_a_Bonded_Dog/links/5559f01608ae6fd2d82818d8.pdf

P208 > There is one particular levator muscle above the inner eyebrow

Kaminski, J., Waller, B. M., Diogo, R., Hartstone-Rose, A., & Burrows, A. M. (2019). Evolution of facial muscle anatomy in dogs. Proceedings of the National Academy of Sciences, 201820653.

https://www.pnas.org/content/pnas/early/2019/06/11/1820653116.full.pdf

P209 > One study showed that new dog owners felt less lonely and had fewer negative emotions (like nervousness or distress) often within three months of getting a dog.

Powell, L., Edwards, K. M., McGreevy, P., Bauman, A., Podberscek, A., Neilly, B., ... & Stamatakis, E. (2019). Companion dog acquisition and mental well-being: a community-based three-arm controlled study. BMC Public Health, 19(1), 1428.

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7770-5

See also:

Powell, L., Guastella, A. J., McGreevy, P., Bauman, A., Edwards, K. M., & Stamatakis, E. (2019). The physiological function of oxytocin in humans and its acute response to human-dog interactions: A review of the literature. Journal of veterinary behavior, 30, 25-32.

https://pubag.nal.usda.gov/?page=1301&per_page=100&search_field=all...

P209> Another study showed that exposure to a dog at any time in childhood reduced the risk of schizophrenia by twenty-four percent.

“We don’t know the mechanism,” said the lead author, Dr. Robert H. Yolken, a professor of pediatrics at Johns Hopkins University in Baltimore, though he noted that the microbiome, or collection of gut bacteria, of people with schizophrenia is different from that of controls.

“One possibility is that having a dog in the house causes a different microbiome and changes the likelihood of developing a psychiatric disorder,” he said.

Yolken, R., Stallings, C., Origoni, A., Katsafanas, E., Sweeney, K., Squire, A., & Dickerson, F. (2019). Exposure to household pet cats and dogs in childhood and risk of subsequent diagnosis of schizophrenia or bipolar disorder. PloS one, 14(12).

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225320

P209> Other research shows that dogs decrease blood pressure, cortisol levels and heart rate in stressful situations in their owners

Note:

All participants completed the Trier Social Stress Test and provided cortisol, HR, and State-Trait Anxiety Inventory measures. For participants paired with a dog, overall cortisol levels were attenuated throughout the experimental procedure, and HR was attenuated during the Trier Social Stress Test. For all groups, state anxiety increased after the Trier Social Stress Test, and HR during the Trier Social Stress Test was a predictor of cortisol. These results suggest that short-term exposure to a novel dog in an unfamiliar setting can be beneficial. They also suggest a possible mechanism for the beneficial effect associated with affiliation with pets.

Polheber, J. P., & Matchock, R. L. (2014). The presence of a dog attenuates cortisol and heart rate in the Trier Social Stress Test compared to human friends. Journal of behavioral medicine, 37(5), 860-867.

https://link.springer.com/article/10.1007%2Fs10865-013-9546-1

P209 > One scientist put dogs in MRIs to discover that the part of the dog’s brain that lights up when they hear their owners’ voices is the same part of the human brain that lights up when we are fond of someone, implying that dogs can love people, at least neurologically, as we do.

Berns, G. (2013). How dogs love us: A neuroscientist and his adopted dog decode the canine brain. Houghton Mifflin Harcourt.

P209 > Dog researcher Clive Wynne doesn’t think that dogs have a unique ability to understand and communicate with humans, but rather a unique capacity for interspecies love.

https://www.nytimes.com/2019/11/22/science/dogs-love-evolution.html

P209 > interspecies love

Beetz, A., Uvnäs-Moberg, K., Julius, H., & Kotrschal, K. (2012). Psychosocial and Psychophysiological Effects of Human-Animal Interactions: The Possible Role of Oxytocin. Frontiers in Psychology, 3, 234. http://doi.org/10.3389/fpsyg.2012.00234

P210 > psychedelics are “spiritual tools”

Here is the Stan Grof quote in its entirety:

They [psychedelics] are spiritual tools. If they are properly used, they open spiritual awareness. They also engender ecological sensitivity, reverence for life, and capacity for peaceful cooperation with other people and other species. I think, in the kind of world we have today, transformation of humanity into this direction might well be our only real hope for survival. I believe that it is essential for our planetary future to develop tools that can change the consciousness which has created the crisis we are in.

Dr. Stanislav Grof, interviewing Dr. Albert Hofmann at Esalen, 1984; first published in MAPS vol. XI., number 2, fall 2001

http://www.maps.org/news-letters/v11n2/11222gro.html

P211 > decoupling between the default-mode network and the medial temporal lobes, an area involved in cognitive and emotional functions, which are normally significantly coupled.

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., ... & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in human neuroscience, 8, 20.

https://www.frontiersin.org/articles/10.3389/fnhum.2014.00020/full#h8

P211 > His paper in the International Review of Psychiatry that came out of that research, “Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy,”

Hendricks, P. S. (2018). Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. International Review of Psychiatry, 30(4), 331-342.

https://www.ncbi.nlm.nih.gov/pubmed/30260256

P211 > intriguing work done a few years earlier by Paul Piff, showing that experiencing awe made people feel smaller and less self-important.

Piff, P. K., Dietze, P., Feinberg, M., Stancato, D. M., & Keltner, D. (2015). Awe, the small self, and prosocial behavior. Journal of personality and social psychology, 108(6), 883.

https://www.apa.org/pubs/journals/releases/psp-pspi0000018.pdf

P211-212 > It reduced self-serving, narcissistic behaviors and also led to increased prosocial behaviors

Perlin, J. D., & Li, L. (2020). Why Does Awe Have Prosocial Effects? New Perspectives on Awe and the Small Self. Perspectives on Psychological Science, 1745691619886006.

Grof quote with Hofman found here

https://maps.org/news-letters/v11n2/11222gro.html

P214 > Nature relatedness, or how connected you are to nature, has a direct correlation with happiness.

Zelenski, J. M., & Nisbet, E. K. (2014). Happiness and feeling connected: The distinct role of nature relatedness. Environment and behavior, 46(1), 3-23.

http://shinrin-yokusweden.se/wp-content/uploads/2016/08/happiness_and_feeling_connected-2014-zelenski-3-23.pdf

P214 > They showed people were happier outdoors in nature than when in an urban environment.

MacKerron, G., & Mourato, S. (2013). Happiness is greater in natural environments. Global environmental change, 23(5), 992-1000.

https://eprints.lse.ac.uk/49376/1/Mourato_Happiness_greater_natural_2013.pdf

P1215 > Double Blind, a magazine devoted to psychedelic culture and science...this pull line spoke to me: “Awe over the natural world is what’s needed to disrupt apathy towards climate change.”

Zachary Slobig “The Function of Awe” Double Blind issue 1, 2019.

NOTES FOR CHAPTER SIX

P213 > and a sense of gratitude (which can combat depressive thinking

Caputo, A. (2015). The relationship between gratitude and loneliness: The potential benefits of gratitude for promoting social bonds. Europe's Journal of Psychology, 11(2), 323.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873114/

“The Science of Gratitude” White paper.

https://ggsc.berkeley.edu/images/uploads/GGSC-JTF_White_Paper-Gratitude-FINAL.pdf

Wood, A. M., Joseph, S., & Maltby, J. (2008). Gratitude uniquely predicts satisfaction with life: Incremental validity above the domains and facets of the five factor model. Personality and individual differences, 45(1), 49-54.

https://www.psykologifabriken.se/wp-content/uploads/2011/04/gratitude-and-life-satisfaction2.pdf

P231 > a hyperconnection of nearly every other area of the brain

https://www.sciencedirect.com/science/article/pii/S0149763419309649

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2019). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 116462.

<https://www.sciencedirect.com/science/article/pii/S1053811919310535?via%3Dihub

“We observe a general decrease in directed functional connectivity for all three psychedelics, [LSD, psilocybin and low-dose ketamine], the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence.”

P231 > in part because they’re meaning makers.

Cannabis is a also a meaning maker.

Besides 5HT2A, both Cannabis and psychedelics like LSD, psilocin 5MeODMT also interact with the serotonin receptor 5HT1A.

da Silva, N. R., Gomes, F. V., Sonego, A. B., da Silva, N. R., & Guimarães, F. S. (2020). Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors. Pharmacological Research, 104749.

https://www.sciencedirect.com/science/article/abs/pii/S1043661819315439

For psychopharmacology of psychedelics, here are some articles to get you started:

McKenna DJ, Repke DB, Lo L, Peroutka SJ. Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology. 1990;29(3):193-198. doi:10.1016/0028-3908(90)90001-8

Blair JB, Kurrasch-Orbaugh D, Marona-Lewicka D, et al. Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines. J Med Chem. 2000;43(24):4701-4710. doi:10.1021/jm000339w

De Vivo M, Maayani S. Characterization of the 5-hydroxytryptamine1a receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther. 1986;238(1):248-253. http://jpet.aspetjournals.org/content/238/1/248. Accessed March 19, 2020.

LSD is a full agonist at 5HT1A and also activates the Dopamine D2 receptor

Marona-Lewicka D, Thisted RA, Nichols DE. Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis. Psychopharmacology. 2005;180(3):427-435. doi:10.1007/s00213-005-2183-9

DMT and 5HT1A and 5HT2

http://jpet.aspetjournals.org/content/238/1/248

Deliganis AV, Pierce PA, Peroutka SJ. Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors. Biochemical Pharmacology. 1991;41(11):1739-1744. doi:10.1016/0006-2952(91)90178-8

So:

“5-HT2B is the best hit for thirteen drugs.”

“5-HT1A is the best hit for nine drugs.”

“Five of the top six psychedelic receptors are 5-HT1 and 5-HT2”

psychedelics interact with a large number of receptors (forty-two out of the forty-nine sites at which most of the drugs were assayed)

Ray TS. Psychedelics and the Human Receptorome. PLoS ONE. 2010;5(2). doi:10.1371/journal.pone.0009019

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814854/

HOWEVER: new research is suggesting that glutamate is definitely involved as well:

https://www.nature.com/articles/s41386-020-0718-8

P232 > When examined through the lens of positive psychology,

Jungaberle, H., Thal, S., Zeuch, A., Rougemont-Bücking, A., von Heyden, M., Aicher, H., & Scheidegger, M. (2018). Positive psychology in the investigation of psychedelics and entactogens: A critical review. Neuropharmacology, 142, 179-199.

https://www.sciencedirect.com/science/article/abs/pii/S0028390818303368#!

P232 and long-term effects on many of the parameters that enrich our lives: mood, cognitive flexibility

Afterglow and cognitive flexibility with ayahuasca

Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9.

https://link.springer.com/article/10.1007%2Fs00213-019-05445-3

P232 > mindfulness

Madsen, M. K., Fisher, P. M., Stenbæk, D. S., Kristiansen, S., Burmester, D., Lehel, S., ... & Knudsen, G. M. (2020). A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding. European Neuropsychopharmacology.

https://www.sciencedirect.com/science/article/abs/pii/S0924977X20300602?via%3Dihub&fbclid=IwAR0niBbdES0q_DPF51QkTM0I7bFQFZ_Ildw6GO2rEZrcTwuv9vNohCg-DVY

P232 > DMT

DMT sometimes occasions profound "ontological shock" experiences — experiences so discontinuous from conventional reality that they prompt a reconsideration of the very nature of reality.

Winstock, A. R., Kaar, S., & Borschmann, R. (2014). Dimethyltryptamine (DMT): Prevalence, user characteristics and abuse liability in a large global sample. Journal of Psychopharmacology, 28(1), 49-54.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.828.2959&rep=rep1&type=pdf

Fontanilla, D., Johannessen, M., Hajipour, A. R., Cozzi, N. V., Jackson, M. B., & Ruoho, A. E. (2009). The hallucinogen N, N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science, 323(5916), 934-937.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/?source=post_page

Deliganis, A. V., Pierce, P. A., & Peroutka, S. J. (1991). Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors. Biochemical pharmacology, 41(11), 1739-1744.

Peinkhofer, C., Dreier, J. P., & Kondziella, D. (2019). Semiology and mechanisms of near-death experiences. Current neurology and neuroscience reports, 19(9), 62.

For more on near death experiences:

https://www.wired.co.uk/article/near-death-experiences-psychedelic-religious?fbclid=IwAR0GYOkTqFxJKDMhXHbf9quGeryoWEbgzy7bXSeSjJCPrkX0N3zFA7EmyMc

DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component.

Timmermann, C., Roseman, L., Schartner, M., Milliere, R., Williams, L., Erritzoe, D., ... & Turton, S. (2019). Neural correlates of the DMT experience as assessed via multivariate EEG. bioRxiv, 706283.

https://www.nature.com/articles/s41598-019-51974-4?fbclid=IwAR1QOx0Dwzm8XXLYhJAj6vI4_SD_zfULw6SDUfFAQY0OuzNj-ma13ZAokDc

Please see also 5MeO-DMT

Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2019). 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American journal of drug and alcohol abuse, 45(2), 161-169.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430661/

P232 > I consider cannabis to be a psychedelic is that high enough doses of THC will trigger the 5HT2A receptor.

Ibarra-Lecue, I., Mollinedo-Gajate, I., Meana, J. J., Callado, L. F., Diez-Alarcia, R., & Urigüen, L. (2018). Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway. Neuropsychopharmacology, 43(10), 2028-2035.

https://www.nature.com/articles/s41386-018-0076-y

CBD, like LSD, also affects 5HT1A:

https://www.sciencedirect.com/science/article/abs/pii/S1043661819315439

P233 > Harriet Schellekens, away from work on maternity leave with her third child, emailed me a rough draft of the abstract for her new paper

Note: TheThe OTR-5HTR2A heteroreceptor complexes were identified in limbic regions (interalia hippocampus, cingulate cortex, and nucleus accumbens), key regions associated with cognition and social-related behaviors... Overall, these results constitute a novel mechanism of specific interaction between the OT and 5-HT neurotransmitters via OTR-5HTR2A heteroreceptor formation and provide potential new therapeutic strategies in the treatment of social and cognition-related diseases.

Chruścicka, B., Wallace Fitzsimons, S. E., Borroto-Escuela, D. O., Druelle, C., Stamou, P., Nally, K., ... & Schellekens, H. (2019). Attenuation of Oxytocin and Serotonin 2A Receptor Signalling through Novel Heteroreceptor Formation. ACS Chem. Neurosci. 2019, 10, 7, 3225-3240

P234 > Not only do oxytocin and the 5HT2A receptor create a dimer, but the cannabinoid receptor CB1 also dimerizes with 5HT2A.

Heteromers between CB1 and 5ht2A

Viñals, X., Moreno, E., Lanfumey, L., Cordomí, A., Pastor, A., de La Torre, R., ... & Lluís, C. (2015). Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB₁ and serotonin 5-HT2A receptors. PLoS biology.

https://psycnet.apa.org/record/2015-36499-001

Galindo Guarín, L., Moreno, E., López-Armenta, F., Guinart, D., Cuenca Royo, A. M., Izquierdo Serra, M., ... & Benítez-King, G. (2018). Cannabis users show enhanced expression of CB1-5HT2A receptor heteromers in olfactory neuroepithelium cells.

https://repositori.upf.edu/bitstream/handle/10230/35804/galindo-mon-cann.pdf?sequence=1&isAllowed=y

Mato, S., Aso, E., Castro, E., Martín, M., Valverde, O., Maldonado, R., & Pazos, Á. (2007). CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. Journal of neurochemistry, 103(5), 2111-2120.

P234 > Acceptance Commitment Therapy

Sloshower, J., Guss, J., Krause, R., Wallace, R. M., Williams, M. T., Reed, S., & Skinta, M. D. (2020). Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame. Journal of Contextual Behavioral Science, 15, 12-19.

https://www.sciencedirect.com/science/article/pii/S2212144719301218?via%3Dihub

P241 > after Denver in May of that year

https://www.cnn.com/2019/05/08/us/denver-magic-mushrooms-approved-trnd/index.html

P246 > taking psychedelics now, at the end of life

https://www.opendemocracy.net/en/transformation/trip-beyond-fear-psychedelics-and-end-life/?fbclid=IwAR3VCnW2rZSuY1RvoED2zrY5mOdULOKDiT5nQFLyFDctfgLidsDgskwtG6U

EPILOGUE

P241 > Oakland...decriminalized

Decriminalize Nature Oakland, Decriminalize California, and the Denver Psilocybin Initiative.

Activists in nearly 100 U.S. cities are working on local measures to decriminalize psychedelics such as psilocybin.

https://www.marijuanamoment.net/nearly-100-cities-are-considering-decriminalizing-psychedelics-map-shows/?fbclid=IwAR02DOXo8OWBeN-LB-B_IlOy_KIXfl_HGLgAEUZv_wyVlboF2nJevTrWbyU

See also

Jane Philpott: "Decriminalization sounds radical but it’s the sensible approach. After all, addiction is not a crime. It is not weakness or moral failure. It’s a health issue. Problematic drug use is driven by poverty, trauma, stigma, isolation and abandonment. We can’t solve a health and social issue by criminalizing those who suffer. That effort has been a complete failure."

https://www.macleans.ca/opinion/decriminalization-is-not-a-radical-solution-to-the-opioid-crisis-and-it-would-work/

P256> The life expectancy statistics are just starting to improve.

American Life Expectancy Rises for First Time in Four Years By Sabrina Tavernise and Abby Goodnough New York Times 1/30/20

https://www.nytimes.com/2020/01/30/us/us-life-expectancy.html?nl=todaysheadlines&emc=edit_th_200130&campaign_id=2&instance_id=15408&segment_id=20795&user_id=c0d1206bf9d2940e543f361805601330&regi_id=393317080130

P257> This creativity enabled by psychedelics stems from increased connectivity in the brain,

we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine,...These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence.

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2019). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 116462.

https://www.sciencedirect.com/science/article/pii/S1053811919310535?via%3Dihub

Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.

Preller, K. H., Duerler, P., Burt, J. B., Ji, J. L., Adkinson, B., Stämpfli, P., ... & Anticevic, A. (2020). Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity. Biological Psychiatry.

https://www.sciencedirect.com/science/article/abs/pii/S0006322320300056

P252 > repair includes reparations. To the native people whose land we stole, to the descendants whose ancestors were stolen from their land, to the victims of drug wars and inequality everywhere. Directly investing into communities that need it is one answer.

Chicago suburb to use recreational marijuana sales tax to fund reparations program: report

https://thehill.com/homenews/state-watch/472450-chicago-suburb-to-use-recreational-marijuana-sales-tax-to-fund

Lawmakers in a Chicago suburb have approved using sales tax revenue made from recreational marijuana purchases to establish a reparations program in the area

P256 > planetary PTSD

https://maps.org/news/bulletin/articles/435-maps-bulletin-winter-2018-vol-28-no-3/7520-united-to-cure-planetary-ptsd-winter-2019#:~:text=What%20is%20planetary%20post%2Dtraumatic,warfare%2C%20patriarchy%2C%20and%20homophobia.

P256 > #ThankYouPlantMedicine

A nonprofit called Thank You Plant Medicine. The goal of the campaign is to bring people together in a mass wave of gratitude starting Thursday, February 20, 2020. The idea is for people to share their personal stories of healing and transformation with plant medicine and other psychedelics that day using the hashtag #Thankyouplantmedicine. (ThankYouPlantMedicine.com)

P256> decriminalizing mushrooms and other psychedelic plants.

Denver, Oakland, Santa Cruz, Chicago so far. There is a push to make Oregon a medical psilocybin state. Stay tuned as things progress quickly. Please see: Decriminalize Nature Oakland, Decriminalize California, and the Denver Psilocybin Initiative.

Activists in nearly 100 U.S. cities are working on local measures to decriminalize psychedelics such as psilocybin.

https://www.marijuanamoment.net/nearly-100-cities-are-considering-decriminalizing-psychedelics-map-shows/?fbclid=IwAR02DOXo8OWBeN-LB-B_IlOy_KIXfl_HGLgAEUZv_wyVlboF2nJevTrWbyU

P256 > MDMA in its promise to treat PTSD,

https://link.springer.com/article/10.1007/s00213-019-05249-5

http://www.prati.org.il/wp-content/uploads/2019/01/23.pdf

Gorman, I., Belser, A. B., Jerome, L., Hennigan, C., Shechet, B., Hamilton, S., ... & Feduccia, A. A. (2020). Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. Journal of Traumatic Stress.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jts.22479

P257 > MDMA is also being studied to treat alcoholism

Sessa, B., Sakal, C., O’Brien, S., & Nutt, D. (2019). First study of safety and tolerability of 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants. BMJ Case Reports CP, 12(7), e230109.

Sessa, B. (2018). Why MDMA therapy for alcohol use disorder? And why now?. Neuropharmacology, 142, 83-88.

P256 > and autism are sharing their stories of healing

See Aaron Paul Orsini’s book Autism on Acid

https://www.amazon.com/Autism-Acid-Helped-Bridge-Neurotypical-Autistic-ebook/dp/B07T3JS2NG

See also:

Sigafoos, J., Green, V. A., Edrisinha, C., & Lancioni, G. E. (2007). Flashback to the 1960s: LSD in the treatment of autism. Developmental Neurorehabilitation, 10(1), 75-81.

https://www.ncbi.nlm.nih.gov/pubmed/17608329

https://psychedelictimes.com/psychedelics-autistic-woman/?fbclid=IwAR24bvatT_fVFXIYg5RpvUzoCVmBs7zoIt3ouSS4e1U8U8ko2vKMvDdIUf0

https://www.vice.com/en_us/article/pa58xy/what-one-man-learned-when-he-treated-his-autism-symptoms-with-shrooms

dr. holland