Stigmatized natural chemicals – time to reconsider

Dr. Weeks’ Comment:  If we agree with French physiologist Claude Bernard  that “Poison is a matter of dosage.”  (“Tout est poison, rien n’est poison, tout est une question de dose.”  or  in English: “Everything is poisonous, nothing is poisonous, it is all a matter of dose.”)  then, it follows logically that there are no toxic substances, per se!  

Yet our government stigmatizes various chemicals and prevents them from being use as medicines.  My mentor, Abram Hoffer, Ph.D., M.D. was a pioneer in the therapeutic use of LSD which is only now, after 50 year hiatus, coming back into fashion. For years I was duped by the rabid foes of medical marijuana but the science describing its benefits is irrefutable.   GHB, the “date rape” drug,  was stigmatized because predators can abuse it, but the substance itself  (now available by prescription as sodium oxybate or  “Xyrem”)  remains a tremendously beneficial treatment  for those suffering with sleep disorders (narcolepsy, cataplexy, insomnia),  mood disorders (depression, anxiety) psychotic disorders (manic depression with psychosis) inflammatory disorders (fibromyalgia), addictions  (reduces alcohol craving and allows for safe detoxification) as well as stroke prevention (GHB reduces cerebral oxygen requirements).  

Now, ketamine, long demonized as party drug, has been shown for years to be a safe and effective anti-depressant yet rare are the doctors able and willing to prescribe this natural chemical even for “treatment resistant major depression”. 

“…treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine…”


Neural Correlates of Rapid Antidepressant Response to Ketamine in

Treatment-Resistant Unipolar Depression: A Preliminary Positron

Emission Tomography Study


Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown.


In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response.


Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex.


Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine’s rapid antidepressant effects.



Leave a Comment

Your email address will not be published. Required fields are marked *