Addiction as an Intuitive Attempt for Homeostasis

There is an elementary misunderstanding about the nature of addiction (or the physiological and psychological cravings that tail after it), which has in turn essentially helped reinforce the idea that the disciplinary role of an individual, or rather the lack of it, is the driving force behind all of his/her shortcomings, cravings, addictions, vices, etc. It is generally understood that addiction, whether for food, drugs, entertainment, or erotica has consequences that, if left unaddressed, bear rotten fruit. The pleasurable side of addiction, the euphoria, sociability, or calmness that follows is oftentimes described as simply a feeling, without much investigative thought on what euphoria entails about the physiological state of the organism at that specific moment. I propose, as so have others, that what is defined as addiction is simply an attempt by an organism in relative metabolic distress to return to homeostasis, as it perceives a specific substance or activity as capable of producing temporary relief. A couple of anecdotes below illustrate this point:

1. A 61-year-old man is admitted to the ER department with visual hallucinations, paranoia, signs of dementia, and pain, believing that his landlady is conspiring against him and that “little people” are trying to invade his room. Upon questioning he is found to be “addicted” to caffeine (325-1300mgs daily) and aspirin (4-17g daily), having been using them since childhood to control “pain and stress.” (Golden et al., 2015).

2. “Dear Dr. Molner: You wrote not long ago that too much coffee is bad. Pappy turned 90 on January 8. His quota is 20 to 30 cups of coffee daily - with cream and sugar. He starts off at 5 am and the last cometh at 9 pm, his bedtime. When he hits the sack the house could burn down and he wouldn’t know it. When he was a mere youngster of 75 he had a prostate operation and sneaked out of the hospital the following morning because his nurse wouldn’t let him have coffee.” (newspaper excerpt from 1965)

Mainstream medicine labels the abovementioned cases as that of “addiction”, yet in both, large amounts of protective caffeine and aspirin acted to keep the men functional, staving off symptoms of degeneration and aging. In case #1, you can either view the hallucinations, dementia, and pain as symptoms of the addictive behavior OR as symptoms of underlying hypothyroidism which were successfully kept at bay for decades by the supposed addictive habit. In case #2, large amounts of coffee and sugar stabilized the system during deep aging, restored brain function, and acted as a proper sleep aid. At a dose of 25mg/kg (arguably physiological since caffeine metabolism differs between mice and humans), caffeine increases brain pregnenolone and progesterone concentrations by 109% and 183%, respectively (Concas et al., 2000).

The characteristic symptom of headaches that accompany people when they are trying to quit coffee is, I think, slightly more nuanced than the general explanation of it being a withdrawal symptom from a drug. Nitric oxide is widely used experimentally as a headache-inducing agent. Because nitric oxide increases during low thyroid function, caffeine is oftentimes the only available food used to lower it (experimentally it lowers NO by 10 to 20%).

I imagine when caffeine ingestion is stopped as thyroid function is normalized or more specifically NO is lowered, “withdrawal” headaches would cease.

Interestingly, and somewhat controversially, there is a similar and significant increase in the protective neurosteroids after masturbation (Purvis et al., 1976). As mentioned previously, I think it is a degenerate habit, however, it is important to paint the entire biological picture of behavior that in its excessiveness is often labeled as an addiction. The behavior itself will drop as soon as the metabolic rate is increased, progesterone’s calming and adrenal hormone antagonism being central to it.

Additionally, there is a 700% mean increase in salivary progesterone levels after chewing coca leaves (Vitzthum et al., 1993).

Continuing, there is a 30x increase in tissue pregnenolone levels after THC administration (Vallée et al., 2014).

Nicotine (as well as the other aromatase inhibitors present in tobacco) significantly lowers estrogen (Barbieri et al., 1986), as well as acts on the acetylcholine receptors to promote a sense of novel stimulation. It is not to say that smoking does not have its negatives (carbon monoxide from the smoke is estrogenic, and inhibits cholesterol’s conversion to pregnenolone), however, Broda described decades ago why smoking was unnecessarily vilified in causing heart disease.

“Although there is no doubt that statistics indicate that smokers have more heart attacks, the case is far from being open and shut. The smoker is often a tired person and smoking elevates the blood sugar a little and may provide a temporary lift. He may well be hypothyroid and that condition would make him more susceptible to atherosclerosis whether he smoked or not.” - Broda Barnes

I think at this point there is somewhat of a clearer view of why drugs like cocaine, marijuana, nicotine, alcohol, and caffeine are said to be addictive; they all act in some manner and capacity to temporarily increase the metabolic rate of the organism but tend to carry with themselves some serotonergic and estrogenic properties; alcohol is GABAergic but estrogenic, cocaine lowers estrogen but depletes thiamine and glucose, marijuana lowers brain estrogen but depletes cholesterol and is anti-androgenic and serotonergic with prolonged use, nicotine lowers aromatase but provides a false sense of stimulation. If glycogen stores are full, sweets for the most part aren’t appetizing. If the brain is saturated with youth-associated hormones and meaningfully stimulated, drugs that promise to temporarily increase them no longer seem attractive. With this thought in mind, a year or so ago I decided to take up smoking, to test out this theory and see if it’d “stick”. Ray described it as one of the hardest addictions to break, and since childhood, I had heard from parents about the strong psychological grip it tends to produce. As it turned out, being able to keep aromatase activity down and brain stimulation/novelty up, cravings for nicotine never developed and after a few packs I got bored and stopped. I have repeated this several times since, without the development of any sort of dependence (I don’t recommend people try this, however).

In regions of Peru where food is scarce and the diet is lacking in nutrients and protein (the latter aids the liver in estrogen detoxification for example), the rate of coca leaf chewing is notably high. When these nutritional deficiencies are addressed, "addicts" voluntarily give up coca use (Zapata-Ortiz, 1970). Ray mentioned at some point that estrogen dominance is a “prerequisite” for developing cocaine addiction, and several studies have successfully employed progesterone as a treatment. From what I gather, progesterone and pregnenolone both seem to be powerful agents in treating various sorts of addictions by returning an organism to something resembling euthyroidism. Feeling uncomfortable in your skin is a characteristic psychological symptom of high cortisol, and I imagine acts to drive experimentation with a variety of drugs; a misplaced attempt at trying to feel normal.

“For example, a man who had been unhappy with his work and had struggled with ‘alcoholism’ for 13 years, gave me the impression of someone lacking the basic hormone precursor, pregnenolone. A few minutes after he took 100 mg. of pregnenolone, his depression and anxiety disappeared. Later, he said ‘That's the feeling I've been trying to get from alcohol, but it never worked.’” - Ray

Both P4 and P5 powerfully lower cortisol, reduce the excitotoxic obsessiveness that comes with estrogen and bring forth a sort of effortless control of cravings that tend to develop with the use of drugs. A study did indeed confirm that pregnenolone works to lower cravings for alcohol (Milivojevic et al., 2023). Another meta-analysis study found that “the female sex hormone, progesterone, attenuates the craving for and the euphoric effects of drugs of abuse [cocaine, nicotine]…exogenous progesterone and, its metabolite allopregnanolone, demonstrated preliminary efficacy as a treatment for substance use in both men and women.” (Peltier et al., 2018). Cyproheptadine doesn't get talked about very much in the context of addiction, however is a powerful serotonin antagonist, and has been shown to terminate morphine-induced withdrawal symptoms (loose stools, chattering of teeth, weight loss, etc) (Opitz et al., 1973). Sweets, by the way, are one of the easiest ways to blunt the cortisol response (chocolate is currently hailed as the most craved and addictive food, on account of its sugar, saturated fat, magnesium, and dopaminergic action) as both cortisol and cravings increase during stress and depression (Willner et al., 1998).

I think there is a tendency to make the judgment of addiction based on the perception of “too much”, without addressing the question of just how much of a drug, substance, activity, or food is needed not just to sustain basic function and mere mindless reproduction, but to thrive and create and explore through an ever-developing physiology surrounded by an ever-changing environment. Most importantly, in a culture of boomer “bootstraps” advice and self-induced discipline psychosis, placing the blame on laziness simply uncovers the inability of the average Gogginshead to grasp basic biology and the motivations behind human desire.

References

Barbieri RL, Gochberg J, Ryan KJ. Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro. J Clin Invest. 1986 Jun;77(6):1727-33. doi: 10.1172/JCI112494.

Concas, A., Porcu, P., Sogliano, C., Serra, M., Purdy, R. H., & Biggio, G. (2000). Caffeine-Induced Increases in the Brain and Plasma Concentrations of Neuroactive Steroids in the Rat. Pharmacology Biochemistry and Behavior, 66(1), 39–45. doi:10.1016/s0091-3057(00)00237-9

Golden, L. E., Sassoon, P., & Cáceda, R. (2015). A case report of late onset psychosis with dementia and aspirin and caffeine addiction. Schizophrenia Research, 168(1-2), 591–592. doi:10.1016/j.schres.2015.08.021 

Milivojevic V, Sullivan L, Tiber J, Fogelman N, Simpson C, Hermes G, Sinha R. Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder. Psychopharmacology (Berl). 2023 Jan;240(1):101-114. doi: 10.1007/s00213-022-06278-3.

Opitz, K., & Reimann, I. (1973). Suppression of the drug-induced morphine withdrawal syndrome by cyproheptadine. Psychopharmacologia, 28(2), 165–170. doi:10.1007/bf00421401 

Peltier MR, Sofuoglu M. Role of Exogenous Progesterone in the Treatment of Men and Women with Substance Use Disorders: A Narrative Review. CNS Drugs. 2018 May;32(5):421-435. doi: 10.1007/s40263-018-0525-5.

Purvis, K., Landberg, B.-M., Cekan, Z., & Diczfalusy, E. (1976). Endocrine Effects of Masturbation in Men. Journal of Endocrinology, 70(3), 439–444. doi:10.1677/joe.0.0700439 

Vallée, M., Vitiello, S., Bellocchio, L., Hébert-Chatelain, E., Monlezun, S., Martin-Garcia, E., … Piazza, P. V. (2014). Pregnenolone Can Protect the Brain from Cannabis Intoxication. Science, 343(6166), 94–98. doi:10.1126/science.1243985

Vitzthum, V. J., Von Dornum, M., & Ellison, P. T. (1993). Effect of coca-leaf chewing on salivary progesterone assays. American Journal of Physical Anthropology, 92(4), 539–544. doi:10.1002/ajpa.1330920410

Willner, P., Benton, D., Brown, E., Cheeta, S., Davies, G., Morgan, J., & Morgan, M. (1998). “Depression” increases “craving” for sweet rewards in animal and human models of depression and craving. Psychopharmacology, 136(3), 272–283. doi:10.1007/s002130050566 

Zapata-Ortiz, V. (1970). The Chewing of Coca Leaves in Peru. International Journal of the Addictions, 5(2), 287–294. doi:10.3109/10826087009056996