Where are drugs stored in the body?

Mary* was feeling great! She was no longer taking medications which made her feel emotionally numb and clouded. She felt clear-headed and stable, something she had not felt for a long time.

The Truehope program was really working!

She felt energized and motivated, so she began to go jogging. She wanted to improve her health and lose some of the weight she had gained over the last year. All at once her symptoms began to backslide.

When Mary called Truehope, her support person helped her to look up the side effects of her previous medications. Sure enough, those were the symptoms she was feeling.

Mary’s experience is not unique.

We have often remarked that some psychiatric drugs must store in the body in some way, otherwise we would not observe some of the long term side-effects or reactions that we do see. If someone has used medications, experience has taught us not to recommend cleanses, massages, or vigorous exercise, among other things.

We have seen these activities bring on adverse symptoms. We also know these are drug related because we don’t see these issues in those who have never used medications. As we began to search for answers, this is what we found.

Doctors look at drugs in the body using a mathematical model. Mathematically, this model explains the behaviour of the drug in the body in terms of the dosing, blood levels, and elimination or excretion.

The current concept used to describe how drugs move in the body is a two compartment model. The first area is called the central compartment and is typically the blood and well perfused organs like the liver and kidneys. The second area is called the peripheral compartment and is typically poorly perfused tissues like fat and lean tissues like muscle.

Very few drugs show simple direct distribution and equilibrium through the body. Sometimes, it may take 2 or 3 (or more) doses of a drug before that drug shows up in the blood at a level that might be expected with the first dose. This means that a portion of the drug goes to other areas of the body and gets “removed” from circulation.

In the bloodstream, drugs are transported partly in solution as free (unbound) drug and partly as reversibly bound to blood components (eg, plasma proteins, blood cells). The extent of drug distribution into tissues depends on the extent of plasma protein and tissue binding.1

Tissue binding is a mechanism by which a drug is removed from circulation and stored in tissue such as a hair, bone, teeth, and adipose tissue. This mechanism can result in storage of significant quantities of a drug, because tissue storage sites may need to be saturated before there is sufficient free drug to be effective at receptor sites.2

Only unbound drug is thought to be available for passive diffusion to extravascular or tissue sites where the pharmacologic effects of the drug can occur. Therefore, the unbound drug concentration in systemic circulation typically determines drug concentration at the active site and thus efficacy.1,3

Some lipid-soluble drugs (e.g., caffeine, diazepam, thiopental) have a longer half-life in the pregnant woman, whereas polar drugs (e.g., oxazepam, ampicillin) tend to have a shorter half-life. The volume of distribution for lipophilic drugs is increased during pregnancy because of the accumulation of fat, which may serve as a reservoir for some drugs via tissue binding.

When the drug is discontinued, tissue deposits may give up their stores slowly, resulting in persistent drug effects. Because lipid-soluble drugs are stored in adipose tissue, the increased adipose tissue during pregnancy can lead to a slight decrease in the amount of the free lipid-soluble drugs, such as sedatives and hypnotics, and persistence of drug effects (“hangover”) after the drug has been discontinued.”2

The fat or adipose tissue is a “highly sluggish reservoir due to lesser blood flow; but if body fat starts depleting, as occurs during starvation, the stored drug may be mobilized and toxicity may occur.”2 Thus, storage in fat initially shortens the drug’s effect but then prolongs it.1

Some drugs accumulate within cells because they bind with proteins, phospholipids, or nucleic acids. For example, chloroquine concentrations in white blood cells and liver cells can be thousands of times higher than those in plasma. Phencyclidine, or PCP, is one example of a drug that remains in fat tissue for over three weeks after a single injection.4 THC, the active chemical in marijuana, is detectable in adipose tissue for up to four weeks after last use.5 Very sensitive test methods can detect THC in blood and urine for as much as two months following discontinued use.6,7

The reality is that drug storage is real and this may be why some people experience persistent effects even after having stopped their prescribed medication for some time. As we continue to look for answers we know we will find solutions that will help ease drug effects on the Truehope Program. We have already found some; free form amino acids and protein isolate provide some relief. Vitamin C shows some promise also.

Sharing your experiences of what works and what doesn’t will help us fit the pieces of the puzzle together so that in the future Mary and others can be free of the negative effects of medications.

*Mary is representative of many participants on the Truehope program.


  1. The Merck Manual Online
  2. Blackburn S.T. Maternal, Fetal, & Neonatal Physiology: A Clinical Perspective. Third Edition. Elsevier Health Sciences. St. Louis. 2007.
  3. Beers, M.H. Berkow, R. (Ed.) The Merck Manual of Diagnosis and Therapy. 17th Edition. Merck Research Laboratories. New Jersy. 1999.
  4. Misra AL, Pontani RB, Bartolomeo J. Persistence of phencyclidine (PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioural effects. Research Communications in Chemical Pathology and Pharmacology. 1979 Jun; 24(3):431–45.
  5. Johansson E, Norén K, Sjövall J, Halldin MM. Determination of delta 1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomedical Chromatography. 1989 Jan; 3(1):35–8.
  6. Dackis CA, Pottash AL, Annitto W, Gold MS. Persistence of urinary marijuana levels after supervised abstinence. American Journal of Psychiatry. 1982 Sep; 139(9):1196–8.
  7. Harvey DJ, Leuschner JT, Paton WD. Gas chromatographic and mass spectrometric  studies on the metabolism and pharmacokinetics of delta 1-tetrahydrocannabinol in the rabbit. Journal of Chromatography. 1982 Apr 30; 239:243–50.