The “Adaptogen” Concept
Once Selye conceived the theoretical basis for a drug that increased resistance to stressor agents,
researchers began looking for these substances. One such researcher was the Russian
pharmacologist NV Lazarev. In 1947 Lazarev began experimenting with the French drug
dibazole (2?benzylbenzamidazole). Lazarev discovered that when dibazole was administered,
animals had an increased ability to resist stressors such as cold, toxins, bacteria, etc. (1) For ten
years he worked with dibazole and related compounds in the aim of better understanding drugs
that augmented the GAS.
In 1959, Lazarev published his landmark findings which introduced a new concept that he
termed the “state of non?specifically increased resistance”(SNIR). The state was “non?specific” in
the sense that resistance was raised to any and all systemic stressors. Lazarev studied chemically
synthesised compounds, specifically benzamidazole derivatives, for their ability to generate the
SNIR. (2,3) He observed that certain chemicals could be used to induce the same state of super
resistance initiated in the Counter?shock phase of the Alarm Reaction. (6) Lazarev called these
substances “adaptogens” because of their ability to increase resistance to stressors or to cause
II Brekhman was a student and loyal disciple of Lazarev. Whereas Lazarev looked for adaptogens
amongst chemical compounds, Brekhman looked for them from within the plant kingdom.
Brekhman suspected the drugs labelled ?tonic? by traditional medical systems probably acted as
adaptogens. The fact they had been used for thousands of years to increase vitality and promote
well being strongly suggested this was the case. Through experiments with lab animals and
humans, he observed that several tonic plants of traditional medicine systems did cause a SNIR
and act as adaptogens. (4,5) As a consequence, Brekhman parted company with his teacher to
focus on adaptogens of botanical origin.
Brekhman spent ten years researching botanical adaptogens. In 1969 he published two articles in
English detailing his observations about botanical adaptogens during this period of intensive
study. “New substances of plant origin which increase non?specific resistance” appeared in the
Annual Review of Pharmacology (5) and “Pharmacological Investigation of Glycosides from
Ginseng and Eleutherococcus” in Lloydia. (7)
The papers revealed that Brekhman began his work surveying Eastern medical traditions for
drugs labelled tonic by traditional healers. Through this survey he isolated tonic plants as
potential adaptogens worthy of further investigation including members of the Araliaceae family
(Acanthopanax sessiflorum, Aralia manshurica, Aralia cordata, Aralia schmidtii, Kalopanax
septumlobum, Echinopanax elatum, Eleutherococcus senticosus, Panax ginseng), members of the
Compositae family (Raponticum carthamoides, Carlina biebersteinii), members of the
Crassulaceae family (Rhodiola rosea), and members of the Schizandraceae family (Schizandra
Brekhman then created a criterion to isolate adaptogens from traditionally used tonic drugs.
Brekhman’s criterion was as follows:
1. An “adaptogen” should be completely innocuous to the body, should have a wide range of therapeutic
activity, cause minimal alteration of bodily functions or not cause them at all, and should manifest its
adaptogenic action only against a corresponding challenge to the system.
2. An adaptogen’s action should be non?specific, as defined as its capacity to increase resistance to the
harmful influences of an extremely wide spectrum of physical, chemical, and biological factors.
3. An “adaptogen” should have a normalising action irrespective of the direction of the foregoing
pathological changes. (5)
When the collection of traditionally used tonic plants were subjected to this criterion, Brekhman
found the following:
• Some of the tonics were low in toxicity. Research revealed that doses of these tonics, large
enough to increase non?specific resistance, did not cause significant disorders in normal
function of the organism. (5)
• Some of the tonics increased organism resistance to radiation, alloxan?induced diabetes,
tumorgenesis, carcinogenesis, metastasis, narcotics, hypertension, catabolism, and
physical and mental strain. (5)
• Some of the tonics normalised abnormal function including adrenal hypertrophy and
hypotrophy, thyroid hypertrophy and hypotrophy, hyperglycaemia and hypoglycaemia,
hypo?leukocytosis and neutropenia, hyper?erythrocytosis and erythropenia. (5)
Applying his criterion, Brekhman concluded four tonics were adaptogens. Eleutherococcus
senticosus was observed to have the strongest “adaptogen” activity of those isolated. The other
adaptogens, listed in order of their strength, were Panax ginseng, Raponticum carthamoides, and
Rhodiola rosea. (5)
Brekhman studied these new adaptogens and found that:
• The crude drugs altered biochemical and anatomical manifestations of the Alarm
Reaction phase of stress. The organ damage usually associated with the AR did not occur
when the adaptogens were administered. (5)
• Though the adaptogens prevented organ damage, they did not reduce the general
resistance associated with the AR. In fact, non?specific resistance to stressors was
increased when the adaptogens were administered. In other words, adaptogens of
botanical origin were found to offer organisms “super resistance” as well as a reduction
of the usual physiological damage associated with the AR. (5)
• The adaptogenic effect only became apparent when the organism was taxed with extra
demands. In normal, unstressed organisms the adaptogens had no effect on the organs
associated with stress. (5)
• The adaptogens worked on a cellular level as well as on a gross physiological level. For
example, Erythrocytes, treated with adaptogens, did not experience the anticipated
damage from radiation. Cells treated with adaptogens experienced increased protein
synthesis and DNA replication. Additionally, the adaptogens acted as anti?oxidants. (5)
• The adaptogens contained saponins. (5)
• The adaptogenic effect of Eleutherococcus senticosus and Panax ginseng was, at least in
part, due to the saponins found in the plants (eleutherosides and panaxosides).
Brekhman observed they too had the adaptogenic effect. (7)
• The adaptogenic saponins found in Eleutherococcus senticosus and Panax ginseng had
different degrees of adaptogenic activity. Some were more adaptogenic than others were.
Brekhman created an animal model for testing adaptogens that involved opposing forms of
stress: work and immobility. These two tests, conducted on a given “adaptogen,” became
fundamental in Brekhman’s process.
On the work side, animals were first treated with an “adaptogen.” Rats or mice were then put
onto an endless rope in a cage with an electrified floor. The time it took for the animals to reach
complete exhaustion, i.e. drop to the electrified floor and remain on it despite the electrical
current, was timed. An untreated group of animals acted as the control.
On the immobility side, animals were first treated with an “adaptogen.” The animals were then
immobilised either by fixation on their backs or by hanging them up for twenty?four hours. Blood
and urine were examined for stress markers including blood sugar levels and urinary 7?
ketosteroid excretion. In addition, ascorbic acid and cholesterol levels of the adrenal glands and
liver glycogen stores were monitored. The animals were then sacrificed and examined for gross
physiological signs of stress including changes in the adrenals, thymus, spleen, and thyroid. An
untreated control was subject to the same hardship and post?mortem examination.
Further study of identified adaptogens
Brekhman observed that Acanthopanax sessiliflorum, Aralia cordata, Aralia manshurica, Aralia
schmidtii, Carlina biebersteinii, Echinopanax elatus, Eleutherococcus senticosus, Kalopanax
septumlobum, Raponticum carthamoides, Rhodiola rosea, and Schizandra chinensis caused a
State of Non?specifically Increased Resistance. He suggested that the research community
investigate these drugs to confirm his findings that they displayed the adaptogenic effect.
Elucidation of the mode of action
Brekhman studied the mode of action of drugs displaying the adaptogenic effect and suggested
other researchers do the same.
Identification of other botanical drugs
Brekhman identified a handful of botanical drugs displaying the adaptogenic effect. He also
created a criterion with which additional drugs displaying this effect could be identified and
suggested other researchers undertake this work.
1. Lazarev, NV. VII Vsesojuzniy s’ezd fiziologox, biokhimikov I farmakologov 1947 (7th all
union congress of physiology, biochemistry, pharmacology). P. 579. Medgiz, Moscow.
2. Lazarev, NV. Farmacol.Toxicol (1958) 21, 3, 81–86.
3. Lazarev NV, Ljublina E, Rozin M. Patol.Fiziol.Eksperim.Terapia (1959). 3, 4, 16–21.
4. Brekhman, II. Man and Biologically Active Substances. Acad.Sci.USSR. Leningrad. (1966)
Man and Biologically Active Substances. The Effect of Drugs, Diet and Pollution on
Health. Pergamon Press. New York. 1980. P. 58.
5. Brekhman, II and Dardymov, IV. New substances of plant origin which increase nonspecific
resistance. Annual Review of Pharmacology. 1969.Volume 9. P. 410–426.
6. Selye, Hans. The Physiology and Pathology of Exposure to Stress. A treatise based on the
concepts of the General Adaptation Syndrome and the Disease of Adaptation. Acta Inc.
Medical Publishers. 1950. P. 55–60.
7. Brekhman, II and Dardymov, IV. Pharmacological Investigation of Glycosides from
Ginseng and Eleutherococcus. II Lloydia, March 1969. Volume 32, Number 1. P. 46–51.