Chronic psychiatric and neurological conditions secondary to substance abuse and addiction

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.

DISCLOSURES:

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.)

Acute and Post-Acute Conditions

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)

Co-Morbid conditions

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

Chronic Conditions secondary to Cannabis Abuse and Addiction

Dose dependent

Age dependent: the younger the abuser, the greater the risk

How Does Cannabis Do This?

Possible Mechanism for Cannabis:Comparing D9-THC and Cannabidiol

D9-THC

Cannabidiol

here

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

Comparing D9-THC and Cannabidiol – Cont.

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

Comparing “Dose-Response” for D9-THC and Cannabidiol

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

Comparing “Dose-Response” for D9-THC and Cannabidiol

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.

What’s the point???

If you remember, it did not take long for major tobacco companies to learn how to use post-harvest chemistry (essentially free-basing 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?

What might be on the horizon???

PAY ATTENTION TO THE POSSIBILITIES.

D9-THC

Cannabidiol

here

here

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.

Treatment?

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

Methamphetamine sequaelae

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.)

Methamphetamine: Cont.

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

Methamphetamine: cont.

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

Methamphetamine: cont.

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

Treatment

Nutrition related

Non-nutrition related

Chronic Conditions secondary to Ethanol abuse and addiction

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

Nutrition Related Problems

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.

Nutrition Related Problems- Cont.

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.”

Treatment

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

Non-nutrition related

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.

Pathophysiology

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.

What about “Wine protects against dementia” reports?

I only found one case-report from Europe using memantine

I found no reports regarding use of classic anti-dementia drugs (Arricept, etc)

Treatment

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