Transcript Quintin T. Chipley, M.A., M.D.   This presenter has no funding from any institution, corporation, or agency regarding the content of this presentation. Although.

Quintin T. Chipley, M.A., M.D.


This presenter has no funding from any
institution, corporation, or agency
regarding the content of this presentation.
Although he loves his work at the University
of Louisville as the Counseling Coordinator
for the Health Sciences Center students,
that institution should in no way be held
responsible for the content of this
presentation.

Even Acute Conditions often require months,
and post-acute condidtions may need years
to remit after substance cessation
Clinical Case example: Parkinsonian
syndrome secondary to Nicorette gum abuse
(proposed mechanism: The over-triggered
ACH neurons cause the dopamine producing
neurons to constantly exhaust their supply,
finally leading to dopamine depletion.)

Co-Morbid conditions are sometimes the
abuse of a substance (perhaps leading to
addiction) in an effort to self-medicate
Clinical Case example: Tobacco use in
Chronic Schizophrenia (Proposed
mechanism: the micro-jolts of dopamine
released after nicotine acts on ACH neurons
gives the patient a “micro respite” from
confused thoughts)

Increase Psychotic Disorders, even among
people without a genetic predisposition:
One study indicates an extra 1 in 1400 people will develop
chronic psychosis.
The intereaction effect with a genetic predisposition becomes
much larger

Depressive and anxiety disorders are
probably even more prevalent and with
greater social and financial burden
 Dose
 Age
dependent
dependent: the younger
the abuser, the greater the risk
D9-THC
here
Cannabidiol
here


THC is the active agent in the “mind
expanding” hallucinatory-type experiences.
These include distortions in perception of
time an space. (A metabolite produce in the
liver may also be responsible for increased
heart rate, anxiety. a.k.a sympathomemetic.)
Cannabidiol produces sedation and even
reduces distortions
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
D9-THC dose-response curve keeps on
rising: The greater the dose, the greater the
response
Cannabidiol has a dose-response curve that
tends to “flatten” out: after a certain plasma
level is reach, an increase in plasma level
does not create more effect


In Cannabis sativa the ratio of D9-THC:
Cannabidiol is high even before horticultural
selection
In Cannabis indica the ratio of D9–THC :
Cannabidiol is not nearly as high

By the time we consider individual differences
in human physiology (liver function:
acytelation and cytochrome p450 actions),
differences in genetic predispositions for
psychotic, mood, and anxiety disorders, and
differences in relative concentrations of the
major psychoactive components of Cannabis
as acquired on the streets and in
“pharmacies” we are looking at a crap-shoot
regarding the outcome.
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
If you remember, it did not take long for
major tobacco companies to learn how to use
post-harvest chemistry (essentially freebasing tobacco) to make the nicotine more
bioavailable , rendering the product more
popular.
How long do you think it will be before
research shows a way to close the ring in
Cannabidiol so that it becomes D9-THC?
D9-THC
here
Cannabidiol
here
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Obviously, substance use abstinence is first
Should an anti-psychotic medication be used in
the presentation of psychosis secondary to
Cannabis use?
Frankly, there is not enough evidence –based
material in the literature to say.
If you follow the theory-based notion that the
longer a person stays in a psychotic state, the
more permanent is the neuronal architecture
change, then aggressive treatment is warranted.
But anti-psychotic meds have considerable risks.


Greater than for other substituted
amphetamines (MDMA, for example) and
non-substituted amphetamines (substituted
refers to the addiction of side groups, such as
methyl groups, onto the basic molecule)
Cognitive deficits (memory, concentration),
social intelligence deficits (loss of attention to
subtle social signals) , motor deficits

Causes irreparable harm to the mid section of
the neuronal axon that prevents recovered
adumbration of the dendrites and butons
(Think of pruning back a bush or tree so
severely that the plant loses ability to create
new sprouts; or trimming the root-ball so
severely that new absorptive ends cannot
grow.)

Mechanisms of why the chemical cause the
cellular pathophysiology are not clearly
understood.
Perhaps related to chronic intracranial
hyperthermia (YES! The amphetamine
dysregulates metabolic control so that
proteins “cook!”), but other stimulants have
similar temperature increases without the
same chronic damage

Definitely compromises the tight-junctions of
the endothelial cells of the cerebral
vasculature, which weakens the blood-brain
barrier and allows leukocytes to cross; if HIV
infection is present, these leukocytes take the
virus into the neuronal matrix and accelerates
HIV-related dementia
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Substance use abstinence
No distinct pharmacological remedy is
suggested in the literature
Talk-Therapy and group therapy to amplify
as much as is possible social-feedback

Nutrition related

Non-nutrition related


Thiamine deficiency (lack in diet or poor
absorption due to gut-lining inflammation)
causes certain neurons that rapidly
metabolize glucose to be unable to balance
osmotic pressures across the membrane
except by swelling, thus killing the neuron.
Basically:
low thiame + carbohydrate = cell death
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
Wernicke’s is the acute phase, with ataxia,
slurring of speech, and confusion; all of which
sounds like acute intoxication and therefore is
easily missed when you are looking at a chronic
alcoholic
Korsakoffs is the persistent condition.
Characterized by confabulation: the act of
unconsciously manufacturing narratives to
“replace” lost content so that an inner-sense of
congruence is maintained even if it does not
relate to external reality.
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Prevention: the “VA cocktail” that is rich in
thiamine
Intervention: if a patient has missed the
chance for preventative dosing with thiamine,
and if the first signs of Wernicke’s
encephalopathy are noted, an intra-muscular
dose of thiamine might help
Patience for the patient: Once Korsakoff’s is
present, there really is no known cure. When
they confabulate, they are not “lying.”


Alcohol Related Dementia seems to be the
new term of choice; some say it is the leading
cause of dementia; some say second leading
cause
Studies that scan brains show diminished
blood flow to both the cortical tissue (i.e.top, thin layer of the brain) and subcortical
structures when compared to age-matched
healthy normals


The mechanism seems to be different than
for non-alcohol related Vascular Dementia
Pathophysiology is poorly understood. A
strong hypothesis is that chronic oxidative
damage to the cells that line the blood
vessels is the cause.


When you graph dose vs benefit, a “J” curve
emerges: This means that “no consumption”
people have greater risk of dementia than “low
consumption” people,” but “high consumption
people” have dementia risks greater than either
of the others. Since the notion of “low
consumption” is absurd for the person with the
disease of alcoholism, it is pretty easy to see
where they end up on the curve.
TAKE HOME MESSAGE: “Earth people” (normals)
may get a benefit; alcoholics cannot.

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I only found one case-report from Europe
using memantine
I found no reports regarding use of classic
anti-dementia drugs (Arricept, etc)
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