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cocaine

 Cocaine use is a very difficult problem.  Obtaining help to stop using cocaine can also be difficult.  This is because the withdrawal syndrome from cocaine is not well understood and hard to document.  Increasingly, the insurance companies are ignoring the need for treatment of cocaine withdrawal.


Cocaine works by directly increasing the dopamine levels in the nucleus accumbens or pleasure center of the brain,   Normally, when a nerve releases dopamine into the synapse (which is the space between the nerves), it gathers the dopamine up again after a few milliseconds and then reuses it over and over.  Cocaine interferes with the process of regathering of the dopamine.  The concentration of dopamine in the synapse sharply increases which causes over stimulation of the receptors.  This results in an intense rush of pleasure.  That is why the drug is so highly addictive.

During use, many other  parts of the brain also become over stimulated and overactive.  This causes decreased appetite, inability to sleep, anxiety and tremors and possibly even seizures.    It has long been appreciated that schizophrenia is caused by excessive activity in some areas of the fore brain.  It is no wonder that cocaine use can cause psychosis and hallucination and severely impair judgment.

The body has enzymes in the synapse whose job it is to break down dopamine.  When the dopamine is in the nerve cell, it is protected from theses enzymes.  However, when the dopamine in the synapse, the enzyme is able to break it down.  Since cocaine use causes dopamine to remain in the synapse, dopamine is metabolized more quickly.  After a while, less dopamine is available and the pleasure from using the drug becomes less.  The abuser may try to increase the amount of cocaine they use but, eventually, even that strategy fails. 


Then there is the cocaine crash.  This is caused by a few factors.  One reason is that there is now a lack of dopamine in the brain; this causes an “anti-pleasure” affect or depression.  Also, the lack of stimulation in other parts of the brain causes excessive fatigue.  The lingering effects the drug has on higher thought processes along with depression and fatigue result in an inability to think clearly and exercise good judgment.  This process often takes 3-4 days to recover from.

In addition to the crash, many users experience severe cocaine cravings.  This ranges from excessive thoughts about the drug to severe hunger for the drug.  This severe hunger is often associated with physical symptoms that vary patient by patient.  Many scientists believe that the craving for the cocaine is caused by the relative lack of dopamine in the nucleus accumbens.  It is unclear how long this lack of dopamine lasts but it probably plays a role in the cravings that occur during the first few days.

The cocaine abuser often goes from intoxication to crash and back to drug use.  The depression, fatigue, cravings and inability to think straight often interfere with any ability to break the cycle.  Even after the first few days, cravings occur for the drug.  The mechanism underlying these later cravings is complex and not well understood but may also be partially caused by an alteration of dopamine metabolism in the nucleus accumbens

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Amphetamines and MDMA (ecstasy)

 Amphetamines, traditionally known as SPEED  have been abused for a long times.  These are drugs that lead to an increase in one or more of three neurotransmitters in the brain: dopamine, nor-epinephrine and/or serotonin.

Cocaine is included in this group but has been addressed in a different article.  The other two types of drugs that are commonly abused are Methamphetamine and MDMA, which is more commonly known as Ecstasy.  Methamphetamine dependency has become a significant problem in recent years especially in the West and South East.  In the Northeast, it has not been as significant a problem but will clearly become one.

Other drugs can be included in this group but they are far less addictive.  This is because they have slightly different chemical structures.  This affects the speed at which they begin to work.  These drugs include the medications for ADHD such as Ritalin (methylphenidate), Cylert (pemoline), and Adderall (dextroamphetamine)

Phentiramine, phenmetrazine and other pills used for appetite control are also been included in this category.     However, these last drugs act on norepinephrine to a much greater than they act on dopamine.  For this reason, they do not seem to lead to abuse or addiction even though they have similar side effects as the first group such as irritability, tremors, insomnia and anxiety.


Amphetamine and Methamphetamine work by affecting how dopamine  is transported by the cell.  The drug enters the cell and prevents the dopamine from getting into the storage vesicles.  This increase dopamine in the cell which than will exit the cell into the synapse (the space between cells)    To a lesser extent, it also prevents dopamine from reentering the cell.  The Nucleus Accumbens (pleasure center of brain) is a prime target for this effect and that is why these drugs cause euphoria.  While there are subtle differences between amphetamine and methamphetamine, methamphetamine is stronger and longer lasting.  Both drugs last longer than cocaine.  


These drugs are abused because of their effect on dopamine; however,  they also have effects on the nor-epinephrine nerves to release norepinephrine.   The nor-epinephrine effect is not addictive and seem more important in regulating appetite and wakefulness.  . As the norepinephrine effects become more  predominate, the drugs become less addictive.  This is why diet drugs, and wake promoting drugs like modafinil are less habit forming



MDMA's (Ecstasy) mechanism of action is different however.  It has an additional nerves that secrete serotonin and causes them to release significant amounts of Serotonin into the synapse.  This still causes activation of the Nucleus Accumbens albeit by a more roundabout  mechanism.   The serotonin effect makes it more potentially hallucinogenic.

Common side effects include irritability, anxiety, increased blood pressure and heart rate (which can lead to heart attack and stroke), chest pain, shortness of breath, lung damage, fevers and seizures.

The stronger amphetamine drugs can cause permanent damage in the brain especially Ecstasy.  Animal studies have shown brain cell death with even a single exposure to the drug.  While we have often heard that drug use kills brain cells, this is usually a cliche.  It is true, however, with Ecstasy.  The user loses Serotonin producing cells.  As a result, there can be long-lasting (or permanent) psychological consequences with depression, anxiety, paranoia, insomnia.

After chronic use, the addict is left with a long-term imbalance in the cells directly responsible for regulating mood, motivation and anxiety.  Treatment needs to focus on these imbalances.

Amphetamine enters the  cell and pushes dopamine into the synapse stimulating the target cells

Amphetamine enters the cell and pushes dopamine into the synapse stimulating the target cells

Nicotine and cigarettes

 It is very easy to dismiss the addiction potential of nicotine .  However, this drug has a mechanism of action that makes it similar to amphetamines and cocaine.

As discussed elsewhere, the stimulant drugs act primarily by increasing dopamine in the Nucleus Accumbens, the pleasure center of the brain.  In order to do this, they cause dysfunction of the dopamine supplying nerve.  They cause either an inability to re-uptake the dopamine back into the cell or an abnormal release of dopamine out of the cell.  Both of these effects are profound but are located at the end terminals of the nerve.  The resultant increase in dopamine leads to euphoria and eventually, tolerance and withdrawal.

Nicotine works in the same cell but outside the synapse (where the nerves communicate with each other).    When the nicotine fills these receptors, the nerve is turned on.  Unlike the illegal drugs, the nerve is working normally but more rapidly.   Dopamine is released and we feel a euphoria.  Unfortunately for most smokers, there is rapid tolerance to the euphoric effect.  


Nicotine  relieves depression, helps our bowels work more strongly and may even be good for memory.   Nicotine has some interesting benefits, however addictive it may be.    Though addictive, it has few other physical consequences.  It is the smoking of cigarettes that causes health issues with the tar, carbon monoxide, oxidants and panoply of cancer causing chemicals that results in lung issues,  vascular issues and cancer.  Nicotine alone has few negative physical effects.


Recently, there has been an explosion in the use of e-cigarettes or nicotine vaping.  These is a harm reduction model where nicotine is inhales on a mist of vapor rather than smoke.  There are still harmful chemicals but far less than what we see in tobacco smoke.  However, it is perceived as harmless.


This is unfortunate since we are getting unintended consequences from e-cigarettes.  They were intended to help smokers switch from more harmful smoking to less harmful vaping.  There is no proof that it helps stop nicotine use,  but it certainly makes it safer.   However, the non smoking teenager has discovered it, and many teens go straight to  cigarettes and become addicted.  Some of them, unfortunately, will subsequently, begin smoking cigarettes.


Additionally, the addictive nature of nicotine actually makes other drugs more addictive.  Research has shown more profound brain and behavior changes when other drugs are used shortly after nicotine.  Compulsive use is more likely to ensue.  That makes it a true gateway drug




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Caffeine

 Caffeine has a different mechanism of action.  It does not directly affect  dopamine levels or even have any effect on the nerves secreting dopamine.   Rather, it works on the nerves  that respond to dopamine and augments that response.  The result is a stimulant effect.

Tolerance develops because the target cells become less sensitive to dopamine.  This in turns leads to withdrawal.  It is a milder syndrome than that seen with the drugs but for certain people, it is significant  Symptoms include irritability, headache, fatigue, sleep issues and some depression.   


The most important thing to realize is that heavy caffeine usage leads to stimulant effects.  During withdrawal from cocaine, nicotine and other stimulants, patients will use  al lot of caffeine.   .  This is counterproductive as it will extend the period of discomfort for most.  


 A  drug is a drug.  Caffeine needs to be watched as well. 

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Medications to treat cocaine, amphetamine, and ecstasy dependence


Psycho-stimulant use (cocaine and amphetamines) produces a high by releasing dopamine in the Nucleus Acumbens or pleasure center of brain.  Although this causes initial euphoria, there will be a profound disruption in the balance of dopamine and other downstream brain chemicals..  Specifically, dopamine levels are significantly reduced for at least 3-4 days after cocaine use and perhaps much longer with amphetamine use.  In addition nor-epinephrine and serotonin may also be affected.  What results is a profound depression immediately after cessation of these drugs as well as significant drug cravings.  


The process is referred to as a CRASH .  Even though there are no measurable physical withdrawal symptoms, the psychological suffering rivals that experienced with any other drug.   During this time, cognitive ability is decreased, resulting in a relative inability to resist the impulse to continue using the drug.  For this reason, many users who are trying to quit often find themselves using again within 1-3 days.

 

During intoxication there are effects on the heart and muscles as well as agitation.  There is the possibility of seizures, heart disturbances and hallucinations or even death.  Initial treatment is focused on reducing these effects.  Later on, we may use drugs that restore dopamine balance or try to restore the balance of the other affected brain chemicals.  While some patients may not respond significantly others have a big improvement in depression and the level of craving.

 

Treatment of Acute Intoxication

 

1-Sedatives-This category includes tranquilizers like Valium and Ativan.  When a person is quite agitated calming them down is the first order of business


2-Lopressor- this is a heart medication that protects against high blood pressure, heart attacks and abnormal heart rhythms.  Side effects include fatigue, lightheadedness, and slow heartbeat. Its use may complicate the care of pre-existing asthma and/or diabetes.


3-Zyprexa, Risperdal, Haldol- these are anti-psychotics useful in controlling hallucinations and/or anxiety.  Common side effects include fatigue.  


Treatment to Reduce Cravings

 

1-Baclofen-This is a medication that has traditionally been used as a muscle relaxer.  However, it has a unique pharmacological properties and it might interfere with cue-associated cravings.   


2-Antabuse- Although better known for its effects in alcohol, it actually slows down break down of dopamine and it reduces cravings


3-Wellbutrin- This is an antidepressant that has a clinical effect on dopamine physiology.  It may serve to chronically increase dopamine in the synapse thereby relieving cravings.  It will take some time for it to kick in. The tendency of Ecstasy to permanently damage seratonin-producing neurons suggests serotonin agents might be especially helpful in Ecstasy abusers.  I would opt for Zoloft as this agent is also has more effects on dopamine than other drugs in the class.


4- BROMOCRIPTINE   A lot of work has been done with a drug called bromocriptine.  This drug is otherwise known as Parlodel.  This drug mimics dopamine and is able to stimulate dopamine receptors; it becomes an artificial dopamine.  Perhaps this effect can help to reduce cravings for cocaine as well.

It is approved for treating Parkinson’s disease.  Woman use it for treating excessive secretion of milk.  In both cases, the drug works by imitating dopamine.

Initial studies with animals were encouraging.  Animals who were addicted to cocaine were less drug seeking after they were given bromocriptine.  However, the studies in people were mixed.  Some showed a mild decrease in craving while others did not.  Relapse was not significantly reduced.  The FDA would not give the drug an indication to be used for this purpose.

However, I began to use Bromocriptine in 1989 before the studies found it ineffective.  My own experience runs contrary to the published studies.  Over 75% of my patients describe significant reductions in drug cravings and I have continued to use it.  This reduction of craving is especially apparent in the first weeks of treatment.  Perhaps, it is a placebo effect.  Nevertheless, I will take whatever benefit I can get.

Side effects include fatigue, headache and nausea but the drug is well tolerated by most people.  Psychosis is caused by too much dopamine in the brain.   Bromocriptine can cause psychosis in susceptible people and I will not use it in any one with a history of hallucinations or schizophrenia.

5 Amantidine is a drug for treating the flu.  It has effects on dopamine and may cause an increase in dopamine levels.  Despite some reports showing a benefit, I have not seen it work yet. 


6-N-Acetyl Cysteine  an amino acid that stabilizes certain neurological circuits in the brain, triggered cravings are reduced


7-Chantix-In smokers, nicotine and cocaine interact at the same cellular connections.   They both cause dopamine surges with intoxication and dopamine reduction as the source of cravings.  Chantix will restore dopamine activity and reduces  cravings for both nicotine and cocaine


8-Naltrexone- although the effect is mild, this has a generalized anti-craving effect


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