Alcoholism II

Question 1

Outline the metabolism of alcohol

Answer 1

alcohol –(ADH)–> Acetaldehyde –(ALDH)–> Acetic Acid and Water

Question 2

Which beverages contain the most acetaldehyde?

Answer 2

fortified wines contain MOST acetaldehyde concentratsiions in its metabolic biproduct.

Lowest: beers, wines, spirits (highest). The higher concentrations of alcohol in the beverage, the higher the acetylaldehyde concentration as a byproduct

etOH has been shown to cause cardiomyopathy (heart muscle disease), liver cirrhosis, oral and pharyngeal cancer. most of this research focused on acetaldehyde as a molecule taht causes these problems because it is toxic and carcinogenic.

Question 3

how can disulfuram (antabuse) cause an individual to be sick when they drink etOH and act as a pharmacological treatment aid?

Answer 3

• causes an individual to be sick when they drink etOH by inhibiting aldehydedehydrogenase ALDH. Prevents acetaldehyde breakdown, and results in DOSE DEPENDENT build up and increase in acetaldehyde.
• this is a toxic reaction.Build up of toxin prevents/punishes further etOH consumption. It removes the reward of alcohol.

Question 4

explain the symptoms of the disulfuram-ethanol reaction (DER). pros and cons.

Answer 4

results in sick, flu-like symptoms. Flushed face, vomiting, increased HR, respiration.

pro: Used as a treatment aid for alcoholsim. Removes the reward of alcohol

cons: small amounts of etOH can caused DER. Some people are so sensitive that the alcohol in their aftershave can trigger adverse effects .
- can also cause DOSE-DEPENDENT-DEATH toxicity. If someone takes 5 shots immediately, the shock of acetaldehyde in the system can trigger adverse symptoms.
- therefore, disulfuram only works for pts who do NOT binge drink. They must be abstinent for weeks/months at a time.
- pt must be cognizant that they are alcoholics. Disulfuram uses avoidance tactics: works on punishment/avoidance learning models

Question 5

ideal candidates for disulfuram

Answer 5

• non binge drinker (or else can accidentally trigger dose dependent death.
• must be abstinent for weeks/months
• pt must be cognizant that they have a problem in order to use the conditioning aspects of disulfuram.

Question 6

antabuse may actually have reinforcing affects – doing the exact opposite of what it is used for. Explain a study and how this works.

Answer 6

if you drink a really really small amont of alcohol (smaller than what most people will drink in a normal drink), you may get reinforcing effects.
study: double blind subjects treated with antabuse or nothing. ech subject had alc/noalc, people in alc group had alc in g/kg. VERY SMALL AMOUNT. Physiological measures and indicators of euphoria were evaluated .

• subjects who received vodka and antabuse did not get sick– they were happy/euphoric. This is because they drank less than the threshold of alchol needed to induce sickness on antabuse.
• people with alcohol but NO antabuse were not as euphoric as people who drank alc WITH antabuse. Suggest that there is some reinforcing effect to acetaldehyde itself.

Question 7

mechanism behind potential acetaldehyde reinforcing effects

Answer 7

recall: mesolimbic DA is comprised of the VTA of the midbrain and its connection to the nucleus accumbens.
there is evidence for the role of acetaldehyde in motivational properties of etOH

Acetaldehyde increases VTA DA activity and therefore activates the mesolimbic DA system.
- this challenges the assumption that ALCOHOL solely mediates its own rewarding properties. Maybe its metabolites also contribute towards rewarding effects. These findings support the hypothesis that acetaldehyde is required for etOH-induced euphoria.

Question 8

ADH enzyme expression is controlled by ___ genes on chromosome #__

Answer 8

ADH enzyme expression is controlled by 7 genes on chromosome #4

Question 9

2 variants of the ADH enzyme

Answer 9

Beta1 ADH21 and Beta2 ADH22. they vary in their affinity and efficacy.

Question 10

differences between Beta1 ADH21 and Beta2 ADH22 ADH isoforms

Answer 10

ADH2*2 oxidizes etOH FASTER, whereas beta1 has low activity of ADH. Beta2 converts alcohol faster into acetaldehyde. Higher oxidation of etOH = increase acetaldehyde.

Question 11

How does Beta1 ADH21 and Beta2 ADH22 ADH isoforms change with demographic?

Answer 11

95% of caucasions have beta1 form. Slow metabolism of etOH. higher rates of alcohlism because you feel the pleasureable effects of alcohol longer than the toxic effects of Acetaldehyde

90% of asians have beta2 form. this means they have fast metabolism and faster oxidation rates. people with this isoform of ADH feel the toxic effect of acetaldehyde faster.

Question 12

in addition to ADH isoforms, what differences in ALDH are seen?

Answer 12

there is a variant form of ALDH called ALDH2*2. Low activity, therefore, SLOW acetaldehyde oxidation/metabolism. results in acetaldehyde buildup because of its slow activity (low affinity for acetaldehyde). causes further toxic effects

Question 13

What isoform for ALDH is seen in Asians?

Answer 13

asians have a high prevalence for ALDH22 on top of ADH22. This ALDH22 results in the Asian Flush Response. Some may be homozygous for ALDH22 and have virtually no capacity to metabolize acetaldehyde. Being heterozygous for this isoform may result in decreased activity of the enzyme and reduced ability to breakdown acetaldehyde.

Question 14

presence of ____ isoform for alcohol dehydrogenase and ___ isoform for acetaldehyde dehydrogenase is considered protective against alcoholism. Provokes the aversive, less rewarding reaction

Answer 14

presence of ADH22 isoform for alcohol dehydrogenase and ALDH22 isoform for acetaldehyde dehydrogenase is considered protective against alcoholism. Provokes the aversive, less rewarding reaction.

• acetaldehyde stays in the system longer. Aversive side effects. Asians are less vulnerable to alcoholism.

Question 15

recall, increased 5HT in system results in less alcohol consumption. What receptor is actually causing this?

Answer 15

5HT2c receptor activation result in depression of DA mesolimbic reward system. it specifically affects DA neuronal firing in the VTA.

Fluoxetine/SSRI = increase 5HT = increased 5HT2C receptor activation = DECREASED DA-VTA firing in the mesolimbic system

therefore, 5HT2c AGONISTS may reduce addiction behaviour because it depresses the reward system. `

Question 16

it is seen that low doses of alcohol in women can result in oral, pharyngeal, esophagus, stoach, liver, lung, cervix, endometrium, renal cell carcinoma cancers. However, what is the type of cancer that alcohol may actually reduce the chance of?

Answer 16

there has been studies that show the statistical difference in reductions for NON HODGKINS LYMPHOMA and thyroid cancers.

Question 17

alcohol is seen to cause cancers, possibly due to oxygen radicals. What is another reason?

Answer 17

etOH may contribute to upper level digestive tract cancers if the person also smokes. More etOH is positively correlated with more smoking. etOH acts as a solvent for tobacco. Tobacco may hae worse affects on smokers.

Question 18

explain how ACOAs have higher risk of developing alcoholism

Answer 18

• FH+ individuals were matched with FH- on all their demographics besides their family history. Looked at both males and females.
• FH+ showed a reduced response to aversive alcohol effects.
• more recent studies found that they were more sensitive to alcohol during the RISING blood alcohol curve and LESS sensitive when LOWERING blood alcohol curve.
  ie/ greater euphoria and less dysphoria

these ACOAs therefore have more POSITIVE than NEGATIVE drinking effects.

• results in the tendency to drink more
• ACOAs would have elevated levels of alc and acetaldehyde
• ACOAs have significantly increased risk to develop alcoholism.

Question 19

According to the neurochemical theory/mechanism of alcoholism:

Answer 19

TIQs (tetrahydroisoquinolines) may be the neurochemical basis of addiction because they are structurally similar to endogenous opiates. These new “rogue” transmitters may interfere with normal transmission, as they can act as NTs or neuromodulators

It is suggested that a person will drink to maintain these new chemicals. Evidence: animals given TIQs directly in the brain = increased alcohol consumption.

• also possible that TIQs bind to opioate receptors and provide reward.

Question 20

TIQs can act as ___ or ____

Answer 20

NTs or Neuromodulators

Question 21

TIQ is an endogenous ____ that looks like an opiate, and is derived via ___ of ____ and ____ to form a salsolinol

Answer 21

endogenous ALKALOID compound derived via CONDENSATION of CATECHOLAMINE (DA/NE) AND ACETALDEHYDE TO FORM A SALSOLINOL.

Question 22

Recall: Lateral hypothalamus (LH) stimulation in rats induced more DA/NE in the system. This suggests a role of CA in the mediation of the positive reinforcing effects of etOH because etOH intake is increased during LH stimulation and after lH stimulation.

How does this play into the Neurochemical Theory of Alcoholism?

Answer 22

LH stimulation causes an increase in catecholamines. Increase Da and Ne in system results in increased exploration and consumption of alcohol and therefore the rats have more acetaldehyde in the system. The acetaldehyde and the elevated levels of catecholamines form heightened amounts of TIQs, which are suggested to have reinforcing effects in and of itself as being an opiate mimicker. It can also act as an NT or neuromodulator to interfere with normal transmission.

• the formation of TIQs explains the observation that alc intake in LH stimulated rats continued to be elevated long after stimulation ended. Rats would continually self-administer acetaldehyde directly into their brains; acetaldhyde is reinforcing probably cause it can form more TIQs.
• after LH stimulation and initial alcohol consumption, the TIQ metabolites as a result of acetaldhyde+ DA remains in the system to act as neuromodulators/rogue NTs/endogenous opiate mimickers to provide continuous reward.

Question 23

TIQs are involved with ____ ____ regulation by the Inhibition of enzymes. They may also be engaged in ____ biosynthesis.

Answer 23

TIQs are involved with BIOGENIC AMINE regulation by the Inhibition of enzymes. They may also be engaged in MONOAMINE biosynthesis.

Question 24

How can the finding that ACOAs have higher risk for alcoholism (because they experience more positive effects and less negative effects) help explain the neurochemical theory of alcoholism?

Answer 24

ACOAs may drink more over shorter periods of time = increased levels of acetaldehyde, and thus high probability of forming TIQs. The ACOA may become dependent on TIQs, and continue to drink to maintain levels of TIQ.

Question 25

Problems with TIQs

Answer 25

TIQs are structurally similar to endogenous opiates and may exert rewarding effects by binding to opiate receptors, or by altering the normal brain transmission because it can act as an NT or neuromodulator.

TIQs are actually neurotoxins. They are found in high levels in parkinson patients, and may contribute to the degeneration of DA neurons through oxidative DNA damage, since it is altering metabolism and thus cell activity through activation of DA and Opiate reward system and by acting as a NT

Question 26

Reward deficiency hypothesis of alcoholism

Answer 26

the idea that specific genetic anomalies may be associated with alcohlism and other neurochemical disorders by altering the receptor isoforms that are involved in the brain pathways afflicted by the disorder.

the reward deficiency hypothesis specifically looked at genetic anomalies of dopamine receptors.

Question 27

explain the alleles involved (the genetic anomalies) that produce different isoforms of dopamine receptors (according to the reward deficiency hypothesis)

Answer 27

A1 allele of D2 receptor gene results in the reduced density (30% reduction) of D2 receptors, compared to the A2 allele.

A1 allele reduced the expression of the D2 receptor.
Fewer number of D2 receptors as a result of holding the A1 allele = reduced DA activity. This means there is an alteration in the ability to process reward.

Question 28

explain how the D2 receptor alteration as a result of genetic anomalies (A1 vs A2) cause a change in the reward cascade

Answer 28

Fewer D2 receptors = reduced DA Activity. therefore, there is an alteration in the ability to process reward. The person may not find normal experiences pleasureable, or they may be in a state of constant slight depression.

• when DA is released an interactis with D2 receptors, other NTs are affected, and a reward cascade occurs. DA is considered a LYNCHPIN: can affect other NT systems –> For example: DA is not the only NT involved in alcoholism/addiction. This cascade may involve the release of 5HT which may interact with GABA and ultimately DA.
• in a normal person, these NTs work together in a cascade of excitation or inhibition which leads to feelings of wellbeing. A disruption of these intercellular interactions result in negative feelings. the person may require a rush, or engage in impulsive behavior, in order to feel pleasure that a normal person would feel doing normal tasks because of their reduced DA receptors.

Question 29

Use the rockman wheel to explain the reward deficiency hypothesis and the reward cascade.

Answer 29

GABA, 5HT, Glut, Opiate, CBR, and NE systems are all affected by DA systems. WHen the wheel is balanced, reward and feeling of well being is processed normally. When unbalance, the person experiences in inability to experience reward properly.

• person will seek out a way to “fill the void” (ie/ drugs, behaviours etc)>
• all these NTs may be involved in the system and should be working in harmony. All these NTs erly on the lynch pin DA for proper expression. If DA is not really prsent because of a lack of activity of dopaminergic neuron, the Rockman wheel may “wobble” and become off balance, throwing off the other “spokes” of the wheel and thus throwing off GABA, 5HT, Opiate etc systems. Problems with the inherent DA system = difficulties processing reward.

Question 30

discuss the prevalence of the A1/A2 D2 receptor alleles in alcoholics and addicts

Answer 30

in alcohlics, it was found that 69% had the A1 allele, indicating that they do not have as many D2 receptors. Their rockman wheel was thrown off.

in cocaine addicts with a FH+ for alcoholism, 87% had A1 allele.

in obese alcoholic drug abusers, 82% had the A1 allele.

The A1 allele and thus the decreased D2 receptor density alters these peoples reward systems by preventing them feeling normal pleasures in life. the disordered DA system throws off other NT systems according to the rockman wheel, and they often resort to “rush” behaviour to exhibit the pleasure and regain the balance.

Question 31

discuss the study conducted by Berman et al 2003 who looked at the relationship between harm avoidance (HA) and A1 allele in COAS (children of alcoholics)

Answer 31

• COAs had LOWER HAs– they were more likely to engage in harmful behaviour. they were more uninhibited, carefree, energetic, great risk takers etc.
• found significant prevalence of the A1 allele in these subjects
• possible reason for having LOW HA is to feel the pleasure/stimulate their more depressed reward system.
• these children have LESS TOLERANCE FOR EXPERIENCING NEGATIVE AFFECTS BECAUSE THEY ARE ALREADY AT A LOWERED LEVEL OF PLEASURE/HAPPINESS THAN NORMAL PEOPLE. They do not have normal coping strategies because these strategies (ex/ gardening, reading a book, relaxing) often do not do much to increase their pleasure since they have less D2 receptors. They develop coping mechanisms to fill the void.

Question 32

discuss the study conducted by Conner et al. 2005 who investigated D2 A1+ and A1- allele in 48 COA boys.

Answer 32

• there was no history of chemical dependence in these subjects.
• boys wiht A1+ show greater substance use severity and were more likely to have tried more substances by adolesencts. Supports the hypothesis that boys with A1+ allele are at higher risk for developing etOH /drug problems.
• A1 allele may be involved in COMORBID antisocial personality disorder symptoms and higher novelty seeking.

Question 33

studies that show how A1 alleles can place a person at higher risk of developing SEVERE substance use disorders.

Answer 33

in a study that divided 450 mexican americans who were alcoholics and non alcoholics, and then further divided the alcohlics into early and late onset alcoholism, 70% of early-onset alcoholics had an A1 gene. 40% had the A1 gene in late onset.

this indicates A1 gene plays a role in SEVERE substance use because people with this gene have a higher risk of developing alcoholic traits early in life.

Question 34

anhedonia

Answer 34

a condition that leads to the loss of the ability to experience pleasure. linked to natural reinforcers like food, sex etc.

-anhedonia is linked with RDS (reward deficiency hypothesis: brain dopaminergic system). If you have a compromised DA system because of down regulation of D2 receptors, you will have anhedonia. (decreased pleasure)

Question 35

How is anhedonia linked to the reward deficinecy hypothesis

Answer 35

-anhedonia is linked with RDS (reward deficiency hypothesis: brain dopaminergic system). If you have a compromised DA system because of down regulation of D2 receptors, you will have anhedonia. (decreased pleasure)

Question 36

treatment to reduce anhhedonia in terms of reward deficinecy hypothesis

Answer 36

treatment to reduce anhedonia would include the natural acivation of DA receptors which would increase DA sensitivity.

• other data suggsts that diet, exercise, and other manipulations that normalize the DA system would be helpful.
• aka using natural reinforcers, less dramatic than drugs. these are considered MINOR CORRECTIONS.

Question 37

Why might DA agonist not be good treatment for reward deficiency syndrome?

Answer 37

because of hedonistic homeostatic dysregulation.

Question 38

basic components/understanding of hedonistic homeostatic dysregulation

Answer 38

hedonistic homeostatic dysregulation is used to describe the theory of drug addiction. integrates basic neuroscince with psychology. Describes a CYCLE OF DYSREGULATION of the brain reward systems that PROGRESSIVELY INCREASES, resulting in compulsive drug use and a loss of control over drug taking.

• implicates DA (specifically DA D2 receptors) in mediating reward.
• the wheel is imbalanced. Ex/ person doesn’t have as many D2 receptors because of A1 allele. Results in decreased DA activity. You take DA agonist to “rebalance” the wheel, but without it, you remain imbalanced. pathological, compulsive disorder designed to AVOID THE NEGATIVE WITHDRAWAL phase of dopamine replacement therapy. ( seen in parkinsons)

Question 39

Hedonic Homeostatic Dysregulation core symptoms

Answer 39

• impairment in social and occupational behaviour
• pathological gamlbing
• hypersexuality
• repetitive motor acts
• walking great distances aimlessly
• alteractions in appetite
• drug hoarding
• addiction to DA (compulsive use of dopamine replacement therapy drugs)

Question 40

explain the relationship between genetics and addictive effects of DRT

Answer 40

there is research that suggests that there is a genetic predisposition to the addictive effects of drug replacement therapy, as well as genetic predisposition to addiction.
- recent papers have highlighted that there is pathological gambling disorders as a consequence of DRT. This gambling behaviour does not respond to usual treatment. Only reduction in DA seems to be successful in treatment.

Question 41

factors that affect the severity of withdrawal symptoms

Answer 41

1) individual differences in liver enzymes and general sensitivities
2) amount of etOH consumed
3) time period
4) periods of abstnences
5) liver function

• drug withdrawal reaction is always on a continuum

Question 42

typical withdrawal symptoms

Answer 42

• tremors
• craving
• insomnia
• loss of appetite
• headache
• vivid dreams
• anxiety
• hypervigilance
• nausea
• sweating.
• agitation
• irritability
• seizures
• vomiting.

Question 43

T/F Benzos are good for treating alcohol withdrawal because it decreases the time it takes to detox from alcohol

Answer 43

false. benzos help with withdrawal symptoms like anxiety and agitation, but it doesn’stop withdrawl or speed up the detox process.

Question 44

Example of a long acting benzo used for alcohol addiction withdrawal

Answer 44

Lithium (chlorodiazepoxide). most frequently used. Long half life. ideal for out and in patient use.

Question 45

example of a short acting benzo used for alcohl addiction withdrawal

Answer 45

Lorazepam. Short acting. Good for in patient withdrawal but bad for out patient withdrawal because if can result in breakthrough seizures: even though a benzo is on board a persons system, because there is a short half life, it is more likely that withdrawal side effects are still displayed after taking it.

Question 46

example of a short acting benzo used for alcohol addiction withdrawal

Answer 46

Lorazepam. Short acting. Good for in patient withdrawal but bad for out patient withdrawal because if can result in breakthrough seizures: even though a benzo is on board a persons system, because there is a short half life, it is more likely that withdrawal side effects are still displayed after taking it.

Benzos are also controversial to use for alcohol withdrawal in general because it has abuse potential.

Question 47

In addition to benzodiazepines, what is another class of medication used to offset withdrawal symptoms of alcohol

Answer 47

anticonvulsants. there is a lack of abuse potential. No CNS depression when combined with alcohol.

Question 48

examples of anticonvulsant medication

Answer 48

1) valproate
2) carbamazeprine

• **3) gabapentin: shown effective in animal studies by reducing convulsive and anxiety related aspects of etOH withdrawlal.
• since its NOT metabolized by the liver, it may be a preferred treatment for alcohlics with compromised liver function.

Question 49

4 main drug classes for relapse prevention

Answer 49

1) disulfuram
2) serotonergic agents (SSRIS)
3) opiate antagonists
4) Acamprosate.

Question 50

how does disulfuram help with relapse prevention

Answer 50

• it is an inhibitor of aldehyde dehydrogenase. When a person drinks again (after being sober for a while), it maintain acetaldehyde in the system and elicits noxious effects.

Question 51

T/F SSRIs can help reduce etOH consumption in humans

Answer 51

false. SSRIS initially were shown to reduce etOH consumption in animals. Wasn’t really effective in human trials in reducing etOH consumption. BUT. it may be helpful with obsessive craving.

Question 52

Obsessive craving.

Answer 52

lack of control over intrusive thoughts about drinking. SSRIs seem to help with this.

• related to 5HT dysregulation and consquently mood dysregulation. Evidenced by lack of control over the regulation of behavioural impulses, mood and cognitive attentional processes.

Question 53

Examples of opiate antagonists

Answer 53

naloxone, naltrexone, nalmefene.

Question 54

opiate system contributes to the ____ ____ properties of alcohol through the interaction with DA systems (see rockman wheel)

Answer 54

opiate system contributes to the POSITIVE REINFORCING properties of alcohol through the interaction with DA systems (see rockman wheel)

Question 55

How do opiate antagonists prevent relapse

Answer 55

opiate antagonists may act by blokcing the effects of endogenous opioids released after etOH consumption or during exposure to the environmental cues associated with etOH.

• also may reduce DA activity: craving for the + rewarding effects of etOH or “reward craving” may be reduced by these drugs. Heps to prevent relapse to heavy drinking by reducing the rewarding effects of etOH id initial drinking does occur.
• these drugs are better than placebo.

Notes: opioid antagonists involve a dopaminergic/opiodergic dysregulation or a personality style characterized by reward seeking (prob biologicall controlled ie/ DA D2 receptor deficiencies)

Question 56

Acamprosate is a relapse prevention tool and is structurally similar to ___

Answer 56

GABA.

therapeutic effects of acamprosate thought to be related to the modulation of the excitatory glutamate AA system (NMDA RECEPTOR)

Question 57

Alcohol withdrawal results in a ___ GABA and ___ Glutamate activity.

Answer 57

Alcohol withdrawal results in a DECREASED GABA and INCREASED Glutamate activity. (due to upregulation of NMDA Rs).

• acamprosate can alleviate withdrawal symptoms by acting as a GABA mimicker.

Question 58

withdrawal stress may lead to relapse– called ___ ____ and works by ____ reinforcement.

Answer 58

withdrawal stress may lead to relapse– called RELIEF CRAVING and works by NEGATIVE reinforcement.

• relief craving or the desire for the reduction or tension or arousal.

Question 59

conditions in which acamprosate is used

Answer 59

used early post-withdrawal to prevent relapse.

when pts try to reduce drinking, their brains are left in a state of hyperexcitability and negative affect. Many return to drinking to avoid these negative experiences (negative reinforcement). Acomprosate seems to modulate the glutamate system and promote abstinence by resetting the balance between GABA and NMDA receptors.

Question 60

repeated/chronic etOH exposure induces a downregulation of ___ and upregulation of ____ via ___ changes.

Answer 60

repeated/chronic etOH exposure induces a downregulation (increased inhibition) of GABA and upregulation of glutamate (increased excitation) via ADAPTIVE changes.

Question 61

There is no “go to “ drug for alcohlism. But some studies have seem the effect of Naltrexone. Under what conditions.

Answer 61

there is some effect of naltrexone (opiate antagonist), but only if alcoholics with LOW LEVELS of clinical depressions take it.

Question 62

T/F acomprosate is very promising treatment in alcohol relapse prevention

Answer 62

false. there are minimal effects seen in accomprosate.
- other studies have shown a + effect of naltrexone but no + effect of acamprosate. there has been no beneficial effect seen in combining acamprosate and naltrexone.

Acamprosate was shown only to support abstinence; it did not influence alcohol consumption after the first drink.

CBT and AA helps with alcohlism too, but there is no increase in abstinence if CBT is paired with naltrexone.

Question 63

According to the hedonistic homeostatic dysregulation theory, there are implications of reward deficinecy hypothesis in terms of treatment for underarousal in DA systems. Using Da agonists to stimulate the DA system may actualy result in further down regulation and may result in compulsive use of DA agonists. Instead, what is a potential treatment for DA dysregulation that doesn’t involve DA agonists?

How does it work?

Answer 63

Pro-DA regulator KB220. Still in clinical trials.

KB220 is meant to reduce/have less effect on D2 downregulation than traditional Da agonists, while still massages the DA levels back into homeostatic functioning. It is a “gentle” DA regulator; maintains balance/straightens out the DA system and thus all the other NT systems involved in alcohlism/addiction (ie/rockman wheel)

• KB220 is a glutaminergic dopaminergic optimization complex, composed of a variety of precursor Amino acids.
• studies have indicated that DA pathways were activated one hour POST treatment of pro-Da regulator KB220 fmRI Data suggest “DA- Homeostasis” achieved.

Question 64

KB220 is a _____-_____ ____ complex, composed of a variety of precursor ___ ___.

Answer 64

KB220 is a glutaminergic dopaminergic optimization complex, composed of a variety of precursor Amino acids.