Addiction Linked To High Stress Hormones

[haidut]

While the study only looked at "sex addiction" I think it has a broader message. Mainstream medicine claims that all addictions are caused by the same basic mechanism. So, it this is true then the findings can be expanded into all other "addictions" as well. Several decades ago, a smart scientist in Canada demonstrated in the famous "Rat Park" experiment that "addiction" is simply a desperate attempt to relieve stress by consuming a substance (or engaging in behavior) that make the organism feel better even if only temporarily. If you remove the stressor, the addiction behavior disappears, much to the chagrin of Big Pharma and to the detriment of their idiotic drugs targeting various "receptors" or genes thought to play a role in "addiction".
This study shows very convincingly that people with "sex addiction" have overactive HPA and thus low response to the dexamethasone suppression test. The same test is also used to diagnose Cushing syndrome, major depression, PTSD, etc. I wonder if the scientists will do a follow up test that would administer an anti-cortisol drug and see if the "addiction" disappears...One can only hope. I may actually email them and suggest they do this study with a more classic "addiction" example like alcohol or heroin.

http://www.psypost.org/2015/11/neurobio ... tems-38960

"...The study involved 67 men with hypersexual disorder and 39 healthy matched controls. The participants were carefully diagnosed for hypersexual disorder and any co-morbidity with depression or childhood trauma. The researchers gave them a low dose of dexamethasone on the evening before the test to inhibit their physiological stress response, and then in the morning measured their levels of stress hormones cortisol and ACTH. They found that patients with hypersexual disorder had higher levels of such hormones than the healthy controls, a difference that remained even after controlling for co-morbid depression and childhood trauma."

Corticotropin-releasing hormone antagonist - Wikipedia, the free encyclopedia
"...It's been shown that "the effect of footshock on reinstatement of alcohol seeking is block by systemic, ventricular, or intra-median raphe injections of CRF receptor antagonists."

Antalarmin - Wikipedia, the free encyclopedia
"...Antalarmin also showed positive effects in reducing withdrawal syndrome from chronic opioid use,[17] and significantly reduced self-administration of ethanol in ethanol-addicted rodents."

 

[Peata]

None of that surprises me, and seems to go along with what RP has said about "addictions". I know since I lowered my cortisol (going by symptoms not tests) my need for alcohol has gone. Even thought parts of my life used to have me under "learned helplessness" now those parts are not a big deal anymore even though they are still there. Something about my attitude toward them has changed and they don't really bother me.

 

[Nicholas]

this is interesting, because in a way it doesn't really reveal much. If stress hormones are behind addiction, there's something behind elevated stress hormones. Elevated cortisol is not something which just happens in isolation (well, i guess there could be specific disorders). And who is to say that the addiction itself does not also play a role in fueling the elevated stress hormones?

is it not common knowledge that removing the stressor removes the addiction?

 

[piotr_zarach]

"An even more challenging question is what is the proximal cause of the volume loss(brain). A usual suspect is the class of hormones called glucocorticoids (with the human version being cortisol). These steroids are secreted by the adrenal gland in response to stress, and decades of work have shown them to have a variety of adverse effects in the brain, centered in the hippocampus (which contains considerable quantities of receptors for glucocorticoids). The effects include retraction of dendritic processes, inhibition of neurogenesis, and neurotoxicity (reviewed in ref. 8). Moreover, hippocampal volume loss occurs in Cushing's syndrome (in which there is hypersecretion of cortisol, secondary to a tumor) (11). In addition, about half of individuals with major depression hypersecrete cortisol. Finally, the individuals in these studies demonstrating hippocampal atrophy were most likely to have suffered from the subtype of depression with the highest rates of hypercortisolism (2, 3). Thus, considerable correlative evidence implicates glucocorticoids. Nonetheless, no study has yet demonstrated that such atrophy only occurs, or even is more likely to occur, among depressives who are hypercortisolemic."

"A final set of questions swirl around the complex issue of causal links among the correlates uncovered. Which factors contribute to and which are consequences of depression? A number of scenarios can be constructed. In the first (Fig. ​(Fig.11A), an array of interacting factors involving stress and a biological vulnerability give rise to a depression and its associated affective symptoms (arrow 1). Hypercortisolism occurs in approximately half of subjects. An extensive literature demonstrates that such hypercortisolism can be both a response to the stressors preceding depression (arrow 2) and to depression itself (arrow 3), and can, in turn, contribute to the affective symptomology (arrow 4) (20). In this model, these symptoms give rise to the hippocampal abnormalities (arrow 5), which then contribute to the cognitive deficits of sustained depression (arrow 6)."

http://www.ncbi.nlm.nih.gov/pubmed/12502009



"When an organism is under stress, or perceives itself under stress, the hypothalamus secretes corticotropin-releasing hormone/factor (CRH/CRF). CRH/CRF in turn increases secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. ACTH in turn stimulates the release of glucocorticoids from the adrenal cortex. Persistent, uncontrolled physical and psychosocial stress causes excess cortisol secretion from the adrenal glands. Excess cortisol causes dendritic shrinkage in the hippocampus and a contrasting growth of dendrites in the lateral amygdala. These stress-induced changes tend to lower mood; they can cause clinical depression in the genetically vulnerable. Current evidence suggests that tianeptine acts to prevent and even reverse stress-induced neural damage, promoting both neuronal survival and synaptic plasticity. Sustained use of tianeptine tends to "normalise" the hypothalamic-pituitary-adrenal (HPA) system. Tianeptine reduces basal and stress-evoked activity of the HPA, helping its users cope in a stressful environment. Treatment with tianeptine inhibits corticosterone-induced gene transcription. Stress-induced increases in plasma ACTH, and corticosterone levels are diminished. So too is basal activity of corticotropin-releasing factor (CRF) neurons and their sensitivity to stress. Prolonged tianeptine use also reduces some forms of stress-induced apoptosis ("programmed cell-death"), notably in the temporal cortex and dentate gyrus of the hippocampus. At the molecular level, tianeptine exerts profound effects on the glutamate system. The amino acid glutamate serves as the main excitatory neurotransmitter in the brain. Its excitatory action is mediated by via multiple receptor subtypes. The three main subtypes of glutamate-gated ion channel are kainate, ampa, and N-methyl-D-aspartate (NMDA). Tianeptine prevents overstimulation of AMPA/kainate type glutamate receptors in the hippocampus that regulate Ca2+ entry into the nerve cell; excess Ca2+ entry into nerve cells is toxic. Tianeptine also modulates the NMDA glutamate receptors. NMDA receptors for glutamate play a critical role in mediating the functional and intracellular effects of stress. Tianeptine reportedly targets the phosphorylation-state of glutamate receptors in the hippocampus, "normalising" stress-induced changes in the amplitude ratio NMDA glutamate receptor to AMPA/kainate glutamate receptor-mediated excitatory post-synaptic currents. Selective glutamate receptor antagonists, including sub-anaesthetic doses of the dissociative anaesthetic ketamine, can act as analgesics and neuroprotective antidepressants, despite dose-limiting side-effects. Their mind-altering properties deter wider clinical psychiatric use. Tianeptine, on the other hand, is an analgesic and antidepressant that lacks psychotomimetic side-effects at any sensible dose."

http://www.tianeptine.com/

 

[Peata]

is it not common knowledge that removing the stressor removes the addiction?

No, I had never heard that my whole life before Ray Peat. Once you were "hooked" on something, it was likely to be a lifelong battle to get off/stay off.

 

[tara]

HALT
Hungry, Angry, Lonely Tired
12 steppers talk about these as common triggers for resuming addictive practice when in recovery.

 

[DaveFoster]

The researchers gave them a low dose of dexamethasone on the evening before the test to inhibit their physiological stress response, and then in the morning measured their levels of stress hormones cortisol and ACTH. They found that patients with hypersexual disorder had higher levels of such hormones than the healthy controls, a difference that remained even after controlling for co-morbid depression and childhood trauma."

Astounding. This explains the hypersexuality I get from high caffeine doses.

Besides cyproheptadine and L-theanine, do you know any ways to lower ACTH and cortisol?

 

[DaveFoster]

this is interesting, because in a way it doesn't really reveal much. If stress hormones are behind addiction, there's something behind elevated stress hormones. ?

Pufa Stimulates Cortisol Production Even In The Absense Of Acth | Ray Peat Forum

 

[haidut]

Astounding. This explains the hypersexuality I get from high caffeine doses.

Besides cyproheptadine and L-theanine, do you know any ways to lower ACTH and cortisol?

I posted studies recently, showing glycine can also lower it and pretty much any other agent like taurine, niacinamide, magnesium, etc will probably also do. GABA agonists are used for Cushing syndrome. Apigenine and Naringenin are well known herbal GABA agonists used for anxiety and have been shown to lower cortisol as well. Extract from Magnolia bark known as Relora has been shown to lower cortisol in humans. Pretty much anyting sedating will lower cortisol at least temporarily. This is one of the reasons people under extreme stress abuse alcohol and opioids. Both are heavily sedating.

 

[Kasper]

This seems to be true for me.

After 2 weeks of using taurine (2 up to 8 gram a day), gelatin (40 gram a day), theanine (600mg-1000mg a day), I think all my previously addictive behaviour has gone.

 

[Soren]

While the study only looked at "sex addiction" I think it has a broader message. Mainstream medicine claims that all addictions are caused by the same basic mechanism. So, it this is true then the findings can be expanded into all other "addictions" as well. Several decades ago, a smart scientist in Canada demonstrated in the famous "Rat Park" experiment that "addiction" is simply a desperate attempt to relieve stress by consuming a substance (or engaging in behavior) that make the organism feel better even if only temporarily. If you remove the stressor, the addiction behavior disappears, much to the chagrin of Big Pharma and to the detriment of their idiotic drugs targeting various "receptors" or genes thought to play a role in "addiction".
This study shows very convincingly that people with "sex addiction" have overactive HPA and thus low response to the dexamethasone suppression test. The same test is also used to diagnose Cushing syndrome, major depression, PTSD, etc. I wonder if the scientists will do a follow up test that would administer an anti-cortisol drug and see if the "addiction" disappears...One can only hope. I may actually email them and suggest they do this study with a more classic "addiction" example like alcohol or heroin.

Hey Georgi,

Question about withdrawal symptoms with regards to Opioids.

I have listened to all your podcasts with Danny and I have found them all to be fascinating and enlightening. One of particular interest to me is the podcast you did on addiction. I completely agree with the premise's you put forth in that podcast, especially with regards to learned helplessness and how the environment can lead to chronically elevated stress levels, which then can lead to someone being addicted to certain substances that temporarily lower these stress levels. It seems obvious to me based on the evidence, that to presuppose that addiction is the result of an 'addiction gene' is just absurd on its face.

Do you have any thoughts, when it comes to treatments/supplements to help with with-drawl symptoms for addiction? I have some relatives who have struggled with addiction now and in the past, and I am currently putting together a comprehensive theory for them to help with their addiction. This includes, explaining what are the underlying causes (environment, chronically elevated stress hormones etc), the chain of events that can lead to these causes, supplements and lifestyle choices that will help reduce these causes, explaining why they work and how best to implement them.

On this site I have found a wealth of information to help me in this regard, especially from the studies you post. However, the one aspect of addiction that I have struggled to find information on is a comprehensive explanation of withdrawal.

My thought process has been that things that lower the stress hormones, (cortisol, estrogen, prolactin etc), will help with withdrawal and getting out of the state of learned helplessness. However, i'm trying to get a better understanding of what causes the withdrawal symptoms, so that I can better know how to address them. I roughly understand that high serotonin can be responsible for some of the withdrawal symptoms and I know targeting estrogen, cortisol and prolactin with various treatments can help to lower serotonin.

However, I don't feel I have a sufficient level of knowledge on withdrawal. I want to be able to make recommendations as to what I think will help with withdrawal symptoms, but when I recommend something to a friend or family member on anything regarding health, I endeavour to have as thorough an understanding as I can about what it is I am recommending. I want to know why and how it works. I know from my own health journey that simply having a casual level of knowledge is not sufficient when it comes to health. Many of the things that I used to consider healthy because I read them on some paleo or fitness blog quickly fell apart when I did some of my own research and increased my own knowledge and understanding rather than simply trusting the "health gurus" of this world.

I would greatly appreciate your thoughts on the best way to treat withdrawal symptoms as well as any studies, forums, articles, papers or other resources you would recommend in this regard.

Thanks

 

[haidut]

Hey Georgi,

Question about withdrawal symptoms with regards to Opioids.

I have listened to all your podcasts with Danny and I have found them all to be fascinating and enlightening. One of particular interest to me is the podcast you did on addiction. I completely agree with the premise's you put forth in that podcast, especially with regards to learned helplessness and how the environment can lead to chronically elevated stress levels, which then can lead to someone being addicted to certain substances that temporarily lower these stress levels. It seems obvious to me based on the evidence, that to presuppose that addiction is the result of an 'addiction gene' is just absurd on its face.

Do you have any thoughts, when it comes to treatments/supplements to help with with-drawl symptoms for addiction? I have some relatives who have struggled with addiction now and in the past, and I am currently putting together a comprehensive theory for them to help with their addiction. This includes, explaining what are the underlying causes (environment, chronically elevated stress hormones etc), the chain of events that can lead to these causes, supplements and lifestyle choices that will help reduce these causes, explaining why they work and how best to implement them.

On this site I have found a wealth of information to help me in this regard, especially from the studies you post. However, the one aspect of addiction that I have struggled to find information on is a comprehensive explanation of withdrawal.

My thought process has been that things that lower the stress hormones, (cortisol, estrogen, prolactin etc), will help with withdrawal and getting out of the state of learned helplessness. However, i'm trying to get a better understanding of what causes the withdrawal symptoms, so that I can better know how to address them. I roughly understand that high serotonin can be responsible for some of the withdrawal symptoms and I know targeting estrogen, cortisol and prolactin with various treatments can help to lower serotonin.

However, I don't feel I have a sufficient level of knowledge on withdrawal. I want to be able to make recommendations as to what I think will help with withdrawal symptoms, but when I recommend something to a friend or family member on anything regarding health, I endeavour to have as thorough an understanding as I can about what it is I am recommending. I want to know why and how it works. I know from my own health journey that simply having a casual level of knowledge is not sufficient when it comes to health. Many of the things that I used to consider healthy because I read them on some paleo or fitness blog quickly fell apart when I did some of my own research and increased my own knowledge and understanding rather than simply trusting the "health gurus" of this world.

I would greatly appreciate your thoughts on the best way to treat withdrawal symptoms as well as any studies, forums, articles, papers or other resources you would recommend in this regard.

Thanks

I is fairly well established, even in mainstream medicine, that withdrawal symptoms are manifested through the serotonergic system so anti-serotonin drugs can help immensely. Pregnenolone, as well as vitamin B1/B2/B3, thyroid, theanine, etc have all been found to stop cravings for any substance of abuse. The studies are in animals but two studies pregnenolone studies have been replicated in humans - on craving weed and alcohol. I don't see why the same process would not work for all addictions. Coincidentally, both pregnenolone and anti-serotonin drug tend to lower not only serotonin but cortisol as well.

 

[Koveras]

I is fairly well established, even in mainstream medicine, that withdrawal symptoms are manifested through the serotonergic system so anti-serotonin drugs can help immensely. Pregnenolone, as well as vitamin B1/B2/B3, thyroid, theanine, etc have all been found to stop cravings for any substance of abuse. The studies are in animals but two studies pregnenolone studies have been replicated in humans - on craving weed and alcohol. I don't see why the same process would not work for all addictions. Coincidentally, both pregnenolone and anti-serotonin drug tend to lower not only serotonin but cortisol as well.

Thought this 1968 study was interesting as well and consistent with your comment on theanine (Also in regards to anti-serotonin drugs I suppose, although my initial thought there was to the receptor blockers).

"Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated."

Alcohol preference in the rat: reduction following depletion of brain serotonin. - PubMed - NCBI

 

[haidut]

Thought this 1968 study was interesting as well and consistent with your comment on theanine (Also in regards to anti-serotonin drugs I suppose, although my initial thought there was to the receptor blockers).

"Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated."

Alcohol preference in the rat: reduction following depletion of brain serotonin. - PubMed - NCBI

Thanks. Also given that pregnenolone reduces stress hormones, the fact that it reduces alcohol preference as well is yet another point for "addiction" being tied to stress.
Pregnenolone and ganaxolone reduce operant ethanol self-administration in alcohol-preferring p rats. - PubMed - NCBI
Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-t... - PubMed - NCBI

 

[docall18]

this is interesting, because in a way it doesn't really reveal much. If stress hormones are behind addiction, there's something behind elevated stress hormones. Elevated cortisol is not something which just happens in isolation (well, i guess there could be specific disorders). And who is to say that the addiction itself does not also play a role in fueling the elevated stress hormones?

is it not common knowledge that removing the stressor removes the addiction?

I often wonder what is the root cause of people's issues. Is it all down to poor blood sugar regulation, pufa's, genetics?

What is the cause of one person who has eaten quite well (lots of milk, fruit etc) their whole life having poor metabolism and cortisol issues, and another person who eats fast food being relatively healthy?

I dont do well on drugs such as cypro, theanine, clonidine, bromo etc because I dont have a deficiency in them. They fix one issue only to push something else out of balance.

 

[lindsay]

I was recently listening to a podcast on RadioLab about addiction - with a focus on Alcoholism and slightly on cocaine. It was very interesting - about a French man who cured his extreme alcoholism by taking higher doses of Baclofen. It worked for another man who was addicted cocaine - he just began self medicating with Baclofen and noticed that his need for cocaine stopped entirely.

Later in the interview, they interviewed a young man in his late 20's or early 30's who had struggled with extreme alcoholism for many years - he drank something like 20 - 25 drinks per day from the time he woke up until the time he went to sleep. Anyhow, he had been through multiple rehabs and always relapsed when he came out of rehab. The interesting part of the interview was that, he took a different drug from Baclofen, but in the same family, and was able to stop drinking so much - more what people would consider a moderate amount. But he said that he didn't like how he felt - that he didn't feel like himself - because he associated all of the best moments of his life with when he started drinking, since it relaxed him and allowed him to function socially.

This I found really fascinating. There was a mother who came on at the end of the episode and mentioned that she had lost her son to alcoholism and drug overdose and that she said he was such a great person, but just couldn't function in society. Another researcher stated that most people who are prone to addictive behaviors are some of the fittest in evolutionary terms - very motivated and sensitive and focused on the promise of rewards - but being in a society where there's no need to work for these rewards any longer (finding food, sex, etc.) and some people just can't function. This kind of fits my understanding of addiction, because some of the most interesting people I know have suffered (or still suffer) with addictive behaviors and are usually more intelligent (or at least more interesting) than most people you will meet.

Anyhow, the episode is called, "The Fix." It was really interesting. I think the biggest issue is that society just eliminates certain groups of people because they don't fit the spectrum of "normal." And then they become bored - RP talks about how boredom is a terrible horrible stressor, and it can be seen with many young people in school environments, etc.

 

[Simonsays]

It starts in childhood (stressful unempathic care) , produces permanent high cortisol, substance abuse starting in teenage years, later leading to adult addiction. Addiction to exercise/work/shopping is often overlooked. Many addicts also "cross addict" . As in the gym is full of junkies.

I know a few ex drinkers who are now exercise addicts!

Family under the microscope

Dont put your children in daycare at a young age

"The effect appears to be lasting. When cortisol is measured at age 15, the longer a child was in daycare when small, the higher its levels. As high cortisol has been shown many times to be a correlate of all manner of problems, this is bad news."

Severe stress hurts children's brains, changes hippocampus, study shows

NB The study (2007) still clinging to the belief that there is some kind of "genetic predisposition"

 

[NathanK]

This I found really fascinating. There was a mother who came on at the end of the episode and mentioned that she had lost her son to alcoholism and drug overdose and that she said he was such a great person, but just couldn't function in society. Another researcher stated that most people who are prone to addictive behaviors are some of the fittest in evolutionary terms - very motivated and sensitive and focused on the promise of rewards - but being in a society where there's no need to work for these rewards any longer (finding food, sex, etc.) and some people just can't function. This kind of fits my understanding of addiction, because some of the most interesting people I know have suffered (or still suffer) with addictive behaviors and are usually more intelligent (or at least more interesting) than most people you will meet.

Anyhow, the episode is called, "The Fix." It was really interesting. I think the biggest issue is that society just eliminates certain groups of people because they don't fit the spectrum of "normal." And then they become bored - RP talks about how boredom is a terrible horrible stressor, and it can be seen with many young people in school environments, etc.

This is all pretty interesting. I spent most of my life feeling almost painfully bored... and ive lived, what most would think, a pretty exciting life. A bit of an adrenaline junkie.

The joke between a lot of my family is that we have "addictive personalities". We really have to watch what we indulge in because we find it harder to say no the deeper we go. Luckily, we all stayed away from hard drugs.

I think youre right about societal selection and elimination of diverse people. People who thrive in reduntant repetitive jobs seem to make up the masses. Maybe that plays a part in the increase in autism spectrum disorders.

 

[DaveFoster]

If stress hormones are behind addiction, there's something behind elevated stress hormones. Elevated cortisol is not something which just happens in isolation

Social isolation elevates glucocorticoids; the sensitivity likely varies based on the individual.

Social isolation and stress-related cardiovascular, lipid, and cortisol responses. - PubMed - NCBI

 

[Regina]

It starts in childhood (stressful unempathic care) , produces permanent high cortisol, substance abuse starting in teenage years, later leading to adult addiction. Addiction to exercise/work/shopping is often overlooked. Many addicts also "cross addict" . As in the gym is full of junkies.

I know a few ex drinkers who are now exercise addicts!

Family under the microscope

Dont put your children in daycare at a young age

"The effect appears to be lasting. When cortisol is measured at age 15, the longer a child was in daycare when small, the higher its levels. As high cortisol has been shown many times to be a correlate of all manner of problems, this is bad news."

Severe stress hurts children's brains, changes hippocampus, study shows

NB The study (2007) still clinging to the belief that there is some kind of "genetic predisposition"

Do we know if the "volume" of hippocampus can restore to "normal" when the stressors resolve (through reduction of cortisol/stress chemicals and therapy?)? Haidut has also mentioned damaged serotonergic system. Early childhood neglect and abuse can leave a child with "reactive attachment disorder."
There is a very creepy video of how a child in this condition behaves:
[warning: creepy]

Can we really undue this? I mean, I hope so.