This post is dedicated to these two great medical researchers. The fathers of homeostatic cannabinoid based medicine:
Lumír Ondřej Hanuš, discoverer of the endogenous ligand, anandamide, from the brain (1992) and Raphael Mechoulam, discoverer of the psychoactive compound, THC, from Cannabis sativa (1964). Both compounds bind to the CB1 and 2 cannabinoid receptors in the brain.
These two men need to be nominated and awarded the Nobel Prize in medicine for discovering the healing potential of cannabis. Their discoveries will save the human race a great deal of suffering. Thank you for your gift to humanity, gentlemen.
The “cannabinoid homeostatic healing perspective” has quietly been gathering evidence over the last 10 years which overwhelmingly supports the need for human trials to test the use of medical marijuana as a psychiatric treatment. The 75 years of (mis)information we have been fed is now being shown to be unequivocally untrue.
Yes, Big Pharma pushes drugs on us, but is there a large, legitimate need for an agent to heal our modern anxieties? Is this really a problem? Yes! The need for newer, second generation, nontoxic psychiatric medicines clearly exists, as seen in these health stories.
“One in Five American Adults Takes Psychiatric Drugs” (Wall Street Journal)
“Epidemic? Half of US teens ‘meet criteria for mental disorder'” (Raw Story)
“Drugs Found Ineffective for Veterans stress” (New York Times)
“Medical marijuana: medical necessity versus political agenda” (Medical Science Monitor)
“After reviewing relevant scientific data and grounding the issue in ethical principles like beneficence and nonmaleficence, there is a strong argument for allowing physicians to prescribe marijuana. Patients have a right to all beneficial treatments and to deny them this right violates their basic human rights.”
Government prejudice and bias aside, here is what the latest research has concluded…
From “The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants”
Trends in Pharmacological Sciences/2009 – Laboratory of Neuroendocrinology, The Rockefeller University, New York
“Within preclinical models, facilitation of endocannabinoid neurotransmission evokes both antidepressant and anxiolytic effects. Similar to the actions of conventional antidepressants, enhancement of endocannabinoid signaling can enhance serotonergic and noradrenergic transmission; increase cellular plasticity and neurotrophin expression (brain growth factor) within the hippocampus; and dampen activity within the neuroendocrine stress axis.”“Furthermore, limbic endocannabinoid activity is increased by both pharmacological and somatic treatments for depression, and, in turn, appears to contribute to some of the neuroadaptive alterations elicited by these treatments.” (Read = cannabinoids heal the brain)
“These preclinical findings support the rationale for the clinical development of agents which inhibit the cellular uptake and/or metabolism of endocannabinoids in the treatment of mood disorders.”
From “Endocannabinoids and stress”
Stress: The International Journal on the Biology of Stress / July 2011 – Max Planck Institute of Psychiatry Munich, Germany
“Endocannabinoid (eCB) signaling serves to maintain HPA-axis homeostasis, by buffering basal activity as well as by mediating glucocorticoid fast feedback mechanisms. Following chronic stressor exposure”…
“Investigation into the role of the endocannabinoid system in allostatic states and recovery processes may give insight into possible therapeutic manipulations of the system in treating chronic stress-related conditions in humans.”Conclusions from “Endocannabinoid-mediated modulation of stress responses: physiological and pathophysiological significance”
Immunobiology / August 2010
“The endogenous cannabinoid (endocannabinoid) system has emerged as an important lipid signaling system playing a key role in mediating and/or modulating behavioural, neurochemical, neuroendocrine, neuroimmune and molecular responses to stress.”
“…The goal now should be to exploit our understanding of the role of the endocannabinoid system in fundamental stress physiology and pathophysiological processes to better understand and treat a range of stress-related disorders including anxiety, depression and pain.”
And beyond healing the brain, can cannabinoid therapy, through plasticity, create optimal human emotional wellness by stimulating flow, and peak experiences which lead to personal self-actualization?
First, some health background.
Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change.
In addition, it is a process of reestablishing homeostasis. This theory suggests that both homeostasis and allostasis are endogenous systems responsible for maintaining the internal stability of an organism.
Allostatic load is defined as the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrine response that results from repeated or chronic stress.
This term is used to explain how frequent activation of the body’s stress response, essential for managing acute threats, can in fact damage the body in the long run. Allostatic load is generally measured through a composite index of indicators (stressors) of cumulative strain on several organs and tissues, but especially on the cardiovascular system (HPA) and immune system.The biological organism that you are has an internal environment necessary for life that must find a homeostatic relationship with the outside environment. When these two environments are in balance, so are you.
Because these two environments are moving targets, maintaining this synchronization is constant work. There are many things you must do on a daily basis to maintain your health: being a human is very high maintenance!
The daily physical, emotional, and cognitive energy one must generate to maintain this balanced allostatic load is the very definition of health.
Humans experience stress, or perceive things as threatening, when they do not believe that their resources for coping with obstacles (stimuli, people, situations, etc.) are enough for what the circumstances demand. Remember, attitude is everything.
Stress is defined as anything that causes an organism to change or adapt to a new challenge from one or both of these environments.
Two major systems controlled by the ECS are the reaction to stress and control of your immune system. These two systems function in tandem.
The multitude of events changing around you and to which you must adapt every day are called stressors. Evidence shows that prolonged, unrelieved stress down-regulates the ECS over time.
Long-term, unresolved stress and anxiety leads to depression, represented by exhaustion in the chart.
On the day you can no longer maintain ongoing homeostasis with the environment you start to decline in overall health and, over time, die.
Researchers are starting to use the phrase CB1/CB2 “tone” to describe how well this retro-grade feedback loop “anandamide-FAAH- CB1-CB2 receptor pathway” is doing its job.
The “tone” of the CB1 and CB2 receptors is controlled by a naturally named molecule called anandamide. The endocannabinoid system (ECS) controls every major body system. It is a major feedback master control system whose job it is to bring homeostasis to individual systems and to all body systems together/ It’s that important.The medical evidence that has gathered in the last 10 years points strongly to a new treatment paradigm in which medical cannabinoids heal the brain by strengthening the tone of CB1 and CB2 receptors; it is perhaps the boost in this retrograde signal strength that shuts down anxiety and depression and resets the system.
Will plant-based cannabinoids become front-line medications to treat mood disorders, anxiety, and PTSD in the near future? Clearly, the evidence supports cannabinoid-based medicines as the new second generation psychiatric medications.
Big Phama thinks so, too, and is already positioning itself to step in. By the way, just how many sprays of Sativex under your tongue do you think it will take to relieve anxiety and depression?
The job of the endocannabinoid system has now been firmly established as that of a “gatekeeper” that maintains homeostasis in every major body system.
It has now been verified that CB2 receptors are widely distributed throughout the brain.
“We demonstrated that CB2 receptors and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse.”CB1 and CB2 receptors found at the synaptic cleft monitor electrical traffic being transmitted along the axon of the neuron and send a “retrograde” or backwards signal to dampen down impulses that would overload the system. It has been described as a neural circuit breaker “by buffering basal activity as well as by mediating glucocorticoid fast feedback mechanisms.”
From “Functional interactions between stress and the endocannabinoid system: from synaptic signaling to behavioral output”
The Journal of Neuroscience / November 2010 Laboratory of Neuroendocrinology, the Rockefeller University, New York.
(Please note the six researchers and the universities who authored this article on the link above!)
“Endocannabinoid signaling is distributed throughout the brain, regulating synaptic release of both excitatory and inhibitory neurotransmitters.”
“The evidence reviewed here demonstrates that endocannabinoid signaling is involved in both repeated stress and activating and terminating the hypothalamic-pituitary-adrenal axis (below) response to both acute and repeated stress.”
“In addition to neuroendocrine function, however, endocannabinoid signaling is also recruited by stress and glucocorticoid hormones to modulate cognitive and emotional processes such as memory consolidation and extinction.” (Important for PTSD)
“Collectively, these data demonstrate the importance of endocannabinoid signaling at multiple levels as both a regulator and an effector of the stress response.”In the example above, cannabinoids acting though the ECS dampen down glutamate, which excites cells in your muscle to contract when alarmed. The flight or flight reaction is correctly called the “general adaptive syndrome.”
Cannabis’s safety profile is unparalleled. Its use has caused zero deaths since they have been keeping records! It should be the medicine all others are measured against for producing harm.
Again, for the US government to block research and deny free access to medical marijuana is a violation of basic human rights. To ignore empirically based medical proof in order to protect special interests and to play politics with people’s lives is the very definition of ignorance.
Marijuana Wellness: Flow, Peak Experience and Self-Actualization
(The High is the Cure!)
Pain in life is inevitable, but suffering is optional. Right view! Right view!
Every day is a ganja day! Maintain ~ Ron
Need to de-stress tonight? Check out http://www.youtube.com/watch?v=LIqTDJNMr4Y
Further reading for extra credit:
“The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives”
Journal of Psychopharmacology / British Association for Psychopharmacology 
“The endocannabinoid system in anxiety, fear memory and habituation”
Journal of Psychopharmacology / British Association for Psychopharmacology 
“Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects”
Frontiers in Behavioral Neuroscience 
“Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report”
Pharmacopsychiatry / March 2008
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Editor’s note: Ron Marczyk is a retired high school health eduation teacher who taught Wellness and Disease Prevention, Drug and Sex Ed, and AIDS education to teens aged 13-17.
He also taught a high school International Baccalaureate psychology course. He taught in a New York City public school as a Drug Prevention Specialist.
He is a Registered Nurse with six years of ER/Critical Care experience in NYC hospitals, earned an M.S. in cardiac rehabilitation and exercise physiology, and worked as a New York City police officer for two years.
Currently he is focused on how evolutionary psychology explains human behavior.
To see all of Ron Marczyk’s “Worth Repeating” articles for Toke Signals, click here.