Drug residues store in the body following cessation of use: Impacts on neuroendocrine balance and behavior – Use of the Hubbard sauna regimen to remove toxins and restore health☆
Introduction
Research now reveals detectible levels of human-manufactured toxins in all individuals. One study alone found 167 different contaminants in volunteers who did not work with chemicals or near industrial facilities [1].
Accumulations of chemicals in body tissues are increasingly associated with patterns of adverse health including suppressed or inappropriate/hyperreactive immune function (autoimmunity, asthma, allergies), cancers, cognitive deficits, mood changes, neurological illnesses, changes in libido, reproductive dysfunction, and glucose dysregulation [2], [3]. There is even concern that pregnant women exposed to toxins can pass disorders on to their children – even for several succeeding generations [4].
While policy initiatives such as the European REACH (the name REACH refers to its three key steps: Registration, Evaluation and Authorization of Chemicals) appropriately trigger an authorization process to regulate environmental chemicals exhibiting certain hazardous characteristics considered of “very high concern” – such as persistent bioaccumulative toxics and endocrine-disrupting chemicals – it is noteworthy that chemicals classified as “pharmaceuticals” have many similar characteristics but are not addressed with the same caution as environmental chemicals. Environmental chemicals with bioaccumaltive tendencies are avoided for their potential to cause adverse health, while the use of nonbiological drugs that may have comparable persistence is generally encouraged.
Although these categories of compounds are given different names and are differentially regulated by law, are they really so different? Perhaps, emerging research argues, addictive and avoidant individual behaviors are simply different responses to the same underlying mechanism [5].
Within the spectrum of these chemicals, the key to their similarity is lipophilicity – the tendency of a compound to diffuse into lipid-rich spaces. Many of these substances are poorly soluble in water and quite soluble in fat, including the white adipose tissue and all cellular membranes – thereby giving them relatively free access to the cells of all organs, body wide. Hence, long-term storage, both within adipose and elsewhere, and the possibility that these chemicals may contribute to a cumulative toxic burden, are important issues.
Tests to determine chemical safety and consequent health impacts do not take into account combinations of contaminants; thus, effects are largely underestimated or potentially unobserved. A single perturbation may not appear to shift the dynamic system, but with each additional perturbation an instability is added, capable at some point of tipping the balance between states described as “health” and “illness.”
There are many mechanisms by which retention in the body can negatively impact health.
Many drugs and toxins mimic substances naturally found in the body and may directly affect normal trans-cellular chemical communication by hormones and cytokines1 – such structural mimetics often causing effects quite dissimilar or even opposite to those of the endogenous substance (for example blockage of a receptor normally accessible to a hormone). This may occur locally within a tissue (paracrinely), or endocrinely as drugs/toxins are released from body tissues back into circulation. Further, circulating drugs and toxins may occupy sites on plasma transport proteins thereby subtly interfering with the equilibria kinetics that govern plasma transport of nutrients and hormones, for example.
Retention of toxins in key organs may directly impair organ health and function by a number of intracellular mechanisms, including disruption of the sophisticated networks that regulate situational gene expression or the delicate feedbacks by which the intermediates and products of constitutive metabolic chains regulate the activity of key metabolic enzymes.
Eliminating toxins requires certain endogenous substances; for example, catabolism of retinol is accelerated during drug metabolization by the microsomal pathway, thereby contributing to hepatic vitamin A depletion [6]. Nutrients used during metabolic processes of detoxification are concomitantly or subsequently not available for other metabolic processes, thus creating local deficiencies. Chronic exposure may result in systemic deficiencies.
Adipose tissue is a very intricate organ and not merely involved in storing excess calories and “unwanted” compounds. Recent research reveals that hormones released by adipose tissue regulate many bodily functions including emotional state, energy level and body metabolism, hunger and cravings, inflammatory response, and also modulate immune function. Not surprisingly, symptoms associated with disruption of these systems are common in those exposed to environmental chemicals and also in substance abusers [5].
Section snippets
Hypothesis
The 1960s and 1970s were largely focused on the question of whether a diverse collection of synthetic compounds could act as carcinogens, hence, largely ignoring the potential impact of these substances, acting at low levels, to impact other aspects of health, including cognitive behavior and reproductive function [1].
Coincident with new research that reveals accumulations of chemicals in the fat of a very high percentage of human populations [7], the range of adverse effects has expanded
Evidence for drug storage in adipose
As is the case with environmental contaminants, drugs and/or their metabolites – both pharmaceutical and illicit – have the potential to remain in the body for an extended time, contributing to the ongoing accrual of complex mixtures of synthetic compounds [14], [15], [16]. The case of LSD is illustrative in this respect, its long-term adipose accumulation were demonstrated in very early investigations [17]. Research has also shown that cocaine rapidly distributes into the fat tissues following
Drugs impact adipose functions: influence on addictive behaviors
In addition to the possibility that re-release of psychoactive chemicals from adipose may be directly responsible for adverse behavioral and physical health, the potential for adipose-stored chemicals to alter the normal endocrine function of white fat is cause for significant concern. The view of fat as a “storage depot” for the body’s disposition of extra calories – and a “sink” where drugs no longer in circulation are sequestered – changed dramatically in 1994 with the discovery that
Discussion
Various metabolic processes allow organisms to accommodate low doses of foreign compounds. While inherent detoxification pathways result in elimination via the liver and kidneys, and binding proteins effectively remove drugs and toxics from the circulation, these systems do not efficiently eliminate certain compounds and their retention in fat, possibly long-term, is of utmost concern.
There is not a great deal of research that clearly indicates how long drugs and their metabolites remain stored
Conclusions
The contribution of drugs and their metabolites to total toxic burden and resulting adverse health effects cannot be ignored. Simply assessing direct impacts of a drug on a specific unwanted symptom, may overestimate the compound’s real therapeutic index because indirect side-effects, including effects of longer-term adipose-tissue storage are rarely, if ever, assessed. This is akin to the broader economic assessment of environmental impacts of substances such as high-nitrogen fertilizers,
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This manuscript was prepared under the support of private donations to the Foundation for Advancements in Science and Education a 501(c)3 public benefit corporation.