Tag Archives: Substance dependence

Naltrexone and Alcoholism

September 30, 2014

Naltrexone promising for alcoholism and SUD

NaltrexonePeople addicted to alcohol and other substances may have certain behavioral changes that are not healthy for them and even for the people they live amongst. This therefore means that specific actions should be taken to offer them assistance as they fight addiction to be able to quite these unhealthy cognitive behaviors. Most people addicted to alcoholism and other substances of abuse will experience dysfunctional emotions, maladaptive behaviors and cognitive processes. All these need to be addressed to help the person to overcome. There are several therapies that can be used either singly or in collaboration with other therapies to help in this process. One of these therapies is the cognitive behavioral therapy often shortened as CBT.

Cognitive behavioral therapy (CBT) for substance use disorders has demonstrated efficacy when used as a monotherapy as well as when used with other treatment strategies.  There are articles that have been written that support the use of cognitive behavioral therapy, clinical elements of its application, novel treatment strategies for improving treatment response, and dissemination efforts. Although CBT for substance abuse is characterized by heterogeneous treatment elements such as operant learning strategies, cognitive and motivational elements, and skills building interventions across protocols several core elements emerge that focus on overcoming the powerfully reinforcing effects of psychoactive substances.  Apart from CBT there are also other methods that are used in treating people that are alcohol and other substances dependence. One of these options is the use of Naltrexone.

What is Naltrexone?

Naltrexone is a synthetic drug that is similar to morphine. It is used in treatment of alcohol and heroine addictions. It works by blocking opiate receptors in the nervous system. It helps people to stay away from alcohol as it lowers the cravings for alcohol.

Naltrexone is a medication that is FDA-approved for the treatment of alcohol dependence. Meta-analyses of studies on the impact of Naltrexone medication has demonstrated positive effects on outcomes this treatment was found to work even better in helping the addicts to abstain from taking alcohol. Based on the accumulated evidence of the effectiveness of this medication it received strong recommendations as evidence-based treatments for alcohol dependence in the National Quality Forum’s National Voluntary Consensus Standards for the Treatment of Substance Use Conditions, as well as the VA/Department of Defense Clinical Practice Guidelines for Management of Substance Use Disorders (SUD). Based on these guideline recommendations, the “VA Uniform Mental Health Services Handbook” states that naltrexone and another drug known as acamprosate should be offered and be made available to all Veterans diagnosed with alcohol dependence, if not medically contraindicated. Also noteworthy is that a recent meta-analysis of seven placebo-controlled randomized trials of a newer medication, topiramate, found it had a more positive overall effect size than that from the first seven trials of naltrexone. This therefore makes it is a very promising medication.

However with all the accumulated evidence, clinical practice guideline recommendations, and VA policy, implementation of these medications within the VA healthcare system has been low overall, and highly variable. Among the more than 200,000 VA patients with a documented alcohol dependence diagnosis, less than 6% have received an approved medication. The majority of VA patients with alcohol dependence diagnoses (65%) are never seen in specialty substance use disorder clinics. However, even among those seen in specialty clinics, prescribing rates remain below 10%, with rates varying from 0% to 21% across facilities. Extremely low prescribing rates and significant variation across facilities suggest that significant gaps exist in access to these medications. Owing to their effectiveness they should be made available to every patient.

In most cases the medications for alcohol and substance abuse dependence are approached as cocktail where various strategies are used in treatment of the patient. It is however recommended that naltrexone should be part of the treatment offered and made available to patients with alcohol dependence. This is because of their effectiveness in fighting alcohol as well as other substances dependence

The role of naloxone rescue in Heroin users

Naloxone is a drug that has found favor with most health experts owing to its effectiveness in fighting heroin overdose. For WHO it is an essential drug. The use of naloxone in health institutions is legal since it is approved by food and drug act (FDA).  Not long ago, the Food and Drug Administration approved a new hand-held auto-injector of naloxone. This device may be of great help to family members of heroin addicts as well as caregivers.

How does it work?

NaltrexoneIn case of and heroin overdose, the respiratory and central nervous systems are depressed to life-threatening levels and the addict may stop breathing. When this happens is no action is taken the patient may die. So when the person is treated with naloxone the drug will block the heroine receptors hence making it impossible for it to bind on the receptors that are located in the brain and spinal cord.

Finally, dependence to any substance is dangerous and so should be fought seriously. Here at AWAREmed we are dedicated to finding the best solutions to all addicts and that is why Dr. Dalal Akoury (MD) is always in the forefront advocating for integrative medicine since it is only through integrative medicine that a person can be healed wholly. Do not hesitate to call on her for help in managing any sort of drug addiction as well as other diseases.

Naltrexone promising for alcoholism and SUD

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Ketamine Intoxication Abuse Could Lead To Dependence

September 26, 2014

Ketamine Intoxication Abuse and Dependence

Ketamine Intoxication Any drug when taken for non-medical purposes then it is termed abused. Today there are very many drugs that are being used for sheer feeling of euphoria the users derive from them. These drugs are common in streets needless to mention some of the drugs that are used in hospitals for medicinal purposes have also been abused greatly. When a particular drug is used for quite a long time for non-medical purpose it becomes very toxic to the body. Substance abuse is a vice that needs to be fought at all costs and from all fronts as it has opened avenues through which lives have been lost. The problems that a person can suffer from long-term drug abuse spring from all the dimensions of a person’s health be it psychological health, mental health, physical health as well as his social relations. A person who is a victim to drug abuse may fail to cater for family needs, school obligations and even fail to have peace within him as he will be having lots of personal and interpersonal conflicts. Drug and substance dependence is commonly known as addiction. Drug or substance dependence is characterized by change in behaviors of a person. Most common behavior being the need to use more quantities of the substance. When a person is dependent on a given substance his life begins to revolve around it and it seems rather hard for him to live without using the substance. The person often suffers such symptoms as withdrawal among other symptoms associated with drug abuse and dependence.

Drug abuse and dependence are dangerous for an individual; however when a person has just began using a particular substance he may be easily helped to quit the habit than when he has used it for so long that he has become dependent on the drug and has begun showing those side effects that are associated with drug dependence. It is also good to note that a person may become dependent on a drug without abusing it. It is also good to note that person may abuse substance for quite a long time without ‘graduating’ to drug dependence.

One of the drugs that are being abused today is the Ketamine. Ketamine is one of the drugs that are very useful in hospitals. It is a perfect example that even some drugs that help us in gaining good health can also be abused. Ketamine is a medication that has been used to treat many illnesses. It is used in medical procedures with humans and other animals and that means it is an accepted medication in hospitals hence can be easily accessed by medical practitioners such as nurses and doctors. In hospitals it is mainly for starting and maintaining general anesthesia especially in scenarios where the patient is to go through intense pain. It also has other uses and these include sedation in intensive care, as a pain killer. It is however commonly used as a painkiller in emergency cases when the patient is allergic to other known drugs used in suppressing pain such as opiate drugs. This drug can be used as treatment of bronchospasm, and as a treatment for complex regional pain syndrome.

Ketamine has been found to work better since its administration does not affect the Respiratory function. For this reason it has become a very valuable anesthetic. However one of the known side effects often associated with administration of ketamine is agitation.

Ketamine is a NMDA noncompetitive Receptor antagonist

Ketamine is an arylcyclohexylamine derivative of phencyclidine. It is also a non-competitive NMDA antagonist. Scientist, Lodge and his colleagues the first showed that ketamine, phencyclidine, related arylcyclohexylamines and congeners were antagonists of excitatory amino acids like aspartate and glutamate in 1983. The early history of the development of ketamine as an anesthetic agent was documented by McCarthy in 1981. Other scientists Corssen and Dundee reviewed the historical introduction of ketamine into human anesthesia and the term dissociative anesthesia in 1990.  These scientists found that for ketamine to be used safely in clinical therapies, it had to be tamed.

Low doses of ketamine in humans do not necessarily alter perception in a negative way. Foster gave an IV infusion of three different sub anesthetic doses of ketamine (0.05, 0.1 and 0.2 mg/kg/h) to six patients with Alzheimer’s disease. The patients showed no drowsiness and their reaction times and digit span were unaffected by any of the doses of ketamine used. This study however is rather controversial. This is because NMDA receptors are involved in brain function, including arousal and memory, this study requires further research and explanation because one would have predicted exactly the opposite effects even with the small doses of ketamine used.

Ketamine Intoxication

Ketamine as nicotinic inhibitor

Initially the effect of ketamine blockade on niconitic receptors was unknown. But today after many researches and experiments scientists have shown that racemic ketamine and the isomers inhibits nAChRs and K channels in a concentration-dependent and reversible manner. In an experiment racemic ketamine inhibited nAChRs and K channels, with the anesthetic concentration inducing the half-maximal effect being 1.4 and 300 micrometer, respectively. Only inhibition of the nAChRs was stereo selective. The half-maximal concentrations were 0.8 and 3.6 micrometer for S (+) – and R (-)-ketamine. The K channels were 350 and 70 times less sensitive to the effects of S (+) – and R (-)-ketamine.

Ketamine at concentrations found during clinical anesthesia exerts stereospecific effects on human ganglionic nAChRs but not on voltage-dependent K channels. The results found from this experiment supports the view that ketamine impairs sympathetic ganglionic transmission. Nonspecific effects on voltage-dependent K channels may underlie psychomimetic side effects.

Finally, Dr. Dalal Akoury (MD) is an experienced doctor who has been in the frontline fighting drug addiction. He runs a website that equips readers of better ways to overcome not only drug addiction but also serious health problems that have caused nightmares to the world population. Get in touch with her today and learn more.

Ketamine Intoxication Abuse and Dependence

 

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Phenethylamine Analogues and Addiction

September 24, 2014

Phenethylamine Analogues Are Potentially Addictive

PhenethylamineAmphetamine was used to treat children with attention deficit disorder until its addictive potential was recognized. The fact that it could be abused led the physicians to do lots of research in order to come up with its substitute in medical field that did not have much adverse effects. However to the youths amphetamine has become a substance of abuse that many are familiar with. Here are details of the experiments, the substitutes or other the amphetamine analogues and how they work.

In an experiment Methylphenidate was found to inhibit competitively the striatal dopamine transporter (DAT) and bind at sites on the DAT in common with both cocaine (a non-substrate site ligand) and amphetamine (a substrate site ligand). Some methylphenidate analogues modified on the aromatic ring or at the nitrogen were tested to determine whether the profile of inhibition could be altered. None was found to stimulate the release of dopamine in the time frame of 60 seconds of the experiments conducted, and each of the analogues tested was found to noncompetitively inhibit the transport of dopamine. It was found that halogenating the aromatic ring with chlorine (threo-3, 4-dichloromethylphenidate hydrochloride; compound;

1) Increased the affinity of Methylphenidate to inhibit the transport of dopamine. A derivative of Methylphenidate with simultaneous, single methyl group substitutions on the phenyl ring and at the nitrogen (threo-N-methyl-4-methylphenidate hydrochloride; compound

2) Bound at a site in common with Methylphenidate. A benzyl group positioned at the nitrogen (three-N-benzylmethylphenidate hydrochloride; compound

3) Imparted properties to the inhibitor in which binding at substrate and non-substrate sites could be distinguished. This analogue bound at a mutually interacting site with that of methylphenidate and had a Kint value of 4.29 mM. Furthermore, the N-substituted analogues (compounds 2 and 3), although clearly inhibitors of dopamine transport, were found to attenuate dramatically the inhibition of dopamine transport by amphetamine, suggesting that the development of an antagonist for substrate analogue drugs of abuse may be possible.

PhenethylamineMethylphenidate is currently the most commonly prescribed drug to treat children with attention deficit disorder and is also used to treat narcolepsy. Originally, amphetamine was used to treat children with attention deficit disorder until its addictive potential was recognized. It was estimated in 1992 that 3% of school age children were being treated with Methylphenidate for some extended interval. These numbers have continued to increase. Methylphenidate is not thought to stimulate dopamine synthesis or induce release of dopamine from nerve terminals. The action of Methylphenidate is to block the inward transport of dopamine into the presynaptic terminal, resulting in a prolonged dopamine stimulus.

Although Methylphenidate, a psychomotor stimulant agent, has been shown to have abuse potential, it is still the drug of choice for the treatment of children with attention deficit disorder. Methylphenidate has been shown to bind at the dopamine transporter (DAT) and its binding is saturable and specific for the DAT but it is not clear where Methylphenidate binds on the transporter relative to dopamine and other inhibitors of transport.

Methylphenidate is thought to have behavioral, pharmacological, and binding properties similar to those of amphetamine. Therefore, Methylphenidate has been classified as a non-transported inhibitor of DAT as well as a substrate analogue for DAT when present at high concentrations these discrepancies have led to the current study, which focuses on comparing the inhibition properties and binding sites of Methylphenidate with those of some Methylphenidate structural analogues, amphetamine, and cocaine. The results of previous work by this laboratory in a kinetic model of the actively transporting DAT have shown that amphetamine and m-tyramine bind to the same site on the DAT and at a site competitive with dopamine .Thus, it was shown that amphetamine and m-tyramine are substrate analogues for the DAT. It was shown that amphetamine binds at a site that is separate but interacting with the inhibitory site of cocaine on the DAT.

Different Methylphenidate derivatives have been synthesized in an attempt to develop compounds that will block cocaine binding to the DAT but do not interfere with substrate binding or transport. The test used for their assessment has been to compare the IC50 for inhibition of the transport of dopamine with the IC50 of the test analogue for the displacement of [3H] WIN 35,428 binding.

In this current study, amphetamine, cocaine, and selected structural analogues of Methylphenidate were used to decipher whether Methylphenidate resembles amphetamine or cocaine in its effects on the function of DAT. The Methylphenidate derivatives studied in this work were chosen for their particular characteristics. Compound 1, a dichloro-substituted derivative, is one of the more potent Methylphenidate derivatives with respect to inhibition of [3H] WIN 35,428 binding. It differs from most other Methylphenidate derivatives that have been synthesized in that  it is equipotent as an inhibitor of [3H]WIN 35,428 binding and [3H]DA uptake and  it also has an equilibrium Hill coefficient (nH) determined against [3H]WIN 35,428 binding of dopamine. Most of the other Methylphenidate analogues are at least threefold less potent as inhibitors of [3H] DA uptake and have nH values of unity. Compounds 2 and 3 were included because they are some of the most effective analogues in discriminating between [3H] WIN 35,428 binding and [3H] DA uptake, with a five- to sevenfold separation in potency to inhibit binding versus transport.

Finally, Dr. Dalal Akoury (MD) is an experienced doctor who has been in the frontline fighting drug addiction. He runs a website that equips readers of better ways to overcome not only drug addiction but also serious health problems that have caused nightmares to the world population. Get in touch with her today and learn more.

Phenethylamine Analogues Are Potentially Addictive

 

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The Prefrontal Cortex and It’s Executive Control In Addiction

September 20, 2014

Role of the prefrontal cortex and executive control in addiction

prefrontal cortexThe prefrontal cortex is the part of the brain that is the cerebral cortex, which covers the front part frontal lobe. PFC’s most typical psychological term for its functions is executive function. The prefrontal cortex has been associated with a person’s personality by more than one scientist. It is associated with decision making, planning complex cognitive behavior, expressing ones personality as well as controlling and moderating social behaviors. Decision making is a process that is carried out in the brain through the interaction of the prefrontal cortex and the subcortical regions involved in reward and motivation. As a result, it is common that failure in self-regulatory behavior, common in addicted subjects, could be dependent upon the alteration of the interactions between the prefrontal cortex and the subcortical regions.

The PFC has plays a great role in regulating and governing behavior. This function is achieved through a complex interaction of different areas within the prefrontal cortex together with the subcortical areas integrating cognitive and executive functions to produce the “optimal choice”. The result of this interaction can also result in dangerous decisions some of which are observed in drug addicts. The PFC functional abnormalities are very much attributed to the continued use of drugs or traumatic experiences. PFC plays a role in the onset and in the progression of psychiatric disorders associated with very poor decision making such as schizophrenia, attention deficit or the hyperactivity disorder, and depression all of which are very likely to be suffered by drug addicts after a prolonged period of drug and substance abuse.

Dopamine is a neurotransmitter that helps control the brains reward and pleasure areas as well as regulating movement and emotional responses. Dopamine enables us to not only see the reward but to also take actions to move towards them. Addictive drugs such as cocaine, marijuana and nicotine cause an excess of dopamine in the brain. According to scientific theories, dopamine is released in the brain when something very important happens, whether that is an expected reward or an accident. Since it is involved in learning, memory and motivation, the chemical dopamine helps us to store the important information we need to survive as well as to remember it in the future. Drugs however hijack that process sending five to ten times more dopamine surging through the nucleus accumbens and forcing the brains motivational and attention mechanisms to focus purely on the drug. The drug therefore becomes the most important thing in the world which leads to addiction.

Improved performance  in cognitive tasks requiring working memory and inhibition have been observed in people that carry variations in the catechol-O-methyltransferase (COMT) gene which degrade the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. As a result, when the role of COMT is altered, there could be increased likelihood of making the drug addiction even stronger. Addiction is therefore as a result of a number of factors and the PFC circuitry contributes to the expression of several behaviors that are associated with it. A large number of addicted people do not seek treatment, mostly because they do not even recognize their condition as a disease that requires a medical attention. This condition is probably brought about by viewing the abused substance as an essential ingredient of their life regardless of the consequences of its use.

Imbalance between two separate but interacting neural systems can lead to addiction. These neural systems could be an immediate one that generates decision making, based on the impulsivity-related amygdala system for transmitting pain or pleasure of the immediate prospects and a reflective one, whose basis are for the signaling pain or pleasure of future prospects. The level of controlling behavior is challenged by the ability of cues associated with strengthening activities such as drug abuse, food or sex. Self-control efforts however involve increased activity in the regions of the PFC regulating emotions and cognition and reduced activity in the regions that are associated with reward processing and craving. PFC could be associated with long term outcomes whereas sub-cortical activity is associated with more immediate outcomes.

The PFC is also responsible for the decision to quit taking a certain drug after a period of addiction. Abstinence is a multiple component condition in which the lack of drug effects is highly associated with the inner struggle between the desire of the reward brought about by intake of the drug and the assessment of the consequences of that behavior in terms of money, social life and environmental involvement for example smoking marijuana. This will very fast lead to appearance of withdrawal syndrome that is characterized by depressed mood, irritability, mild cognitive deficits accompanied by other peripheral psychological symptoms as the PFC tries to adjust. Some addicts who struggle to go through the abstinence of a certain drug at times relapse to their old habits. This relapse can be categorized into three major types which are; drug induced relapse, reinstatement of self-administration behavior upon exposition to drug related cues and stress induced relapse. This is a major setback in the recovery of the addicts.

prefrontal cortex/

Research has shown that addicts of strong drugs such as marijuana or cocaine have more problems in their daily lives both physically as well as emotionally. Their health is also very much at risk as this drugs alter the working mechanism of the brain and especially the prefrontal cortex. They report lower life satisfaction, poorer mental and physical health, more relationship problems, and they also have less academic and career success compared to those who do not abuse drugs. Decision making becomes a problem for them and they tend to choose the easy way out which to them is the choice to keep using the drugs. Eventually, they could lose their mind all together as the brain function mechanism gets more and more accustomed to the drug effects.

Role of the prefrontal cortex and executive control in addiction

 

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Neural circuits of preoccupation/ anticipation “craving” stage

September 19, 2014

Addiction and It Stages

Drug addiction is a slow developing disorder that is long lasting characterized mainly by the urge to seek and take the drug, loss of control in limiting intake and development of a negative emotional state of anxiety and irritability. When the drug is prevented, the user exhibits withdrawal symptoms. Drug addiction has been viewed as a condition that involves element of both impulsive and compulsive behavior that is brought about by the addiction circle. The circle is made up of three stages: the intoxication stage the negative or the withdrawal effect, and the anticipation stage/ preoccupation which is the craving stage.

The neural circuits of the brain affected

Study on human behavior has revealed discrete circuits that play a major role in binding a major stage of the addiction circle. The ventral tegmental area and ventral striatum is the main focal point for the intoxication stage. The extended amygdala plays the role in the withdrawal while the  orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula are involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control which is the preoccupation/anticipation stage. Drug addiction therefore alters the normal functioning of the neural circuits which may begin with changes in the mesolimbic doper mine system and the process of neural adaptations from the ventral striatum to dorsal striatum of the frontal cortex and eventually deregulates the prefrontal cortex and extended amygdala.

neural circuits

Of late there have been studies aimed at understanding the genetic cellular and molecular mechanisms that mediate the transitions from once-in-a-while drug use to the loss of a person’s control of a drug abuse and to the final stage of a relapse even after trying to abstain. Drug addiction has aspects of both impulsivity and compulsivity disorders. Impulse control disorder is precisely an increased sense of tension before engaging in an impulsive act and a feeling relieved at the time of committing the act. They are categorized as the positive and strengthening mechanisms. On the other hand compulsive disorders are characterized by anxiety and stress before taking part in a compulsive redundant behavior and relieve from the stress by carrying out the compulsive behavior. The compulsive disorders are greatly associated with negative reinforcement’s mechanisms.

Impulsivity and compulsivity.

As the stage of addiction moves from one cycle to the other, the user moves from a stage of impulsivity to a stage of impulsivity and compulsivity. As a result, they are no longer positively reinforced by the drug but negatively influenced. These three stages of addiction are attributed to interacting with each other getting more intense and finally leading to the pathological stage called addiction.  The brain neural circuitry system is engaged at each stage of the addiction cycle and changes with increased intake of the drugs of abuse hence producing the disorder known as addiction. Since the brain responds to stimulus the entire system becomes oriented specifically toward drug related stimuli leading to an increased drive for seeking and taking drugs.

Executive dysfunction

Executive dysfunction is a range of cognitive, emotional and behavioral difficulties which occur after the frontal lobe of the brain is injured. The executive function include abilities such as: planning and organization, social behavior, controlling emotions, safe awareness among others. Drug abuse alters the normal functioning of the frontal lobe of the brain and leads to executive dysfunction. This leads to deficits in cognitive skills which involves thinking, personality and social behavior. Executive dysfunction also makes it difficult to solve problems and as a result drug addicts do not make accurate judgments or find solutions if things are going wrong. They are also irritable find it hard to concentrate lose their r memory and do not get enough sleep. It is very hard for people with this this problem to get along with others as they appear antisocial and can be misunderstood as depression lack of motivation, selfishness and aggression.

Future treatment targets.

neural circuitsGABA receptor substance that does not act as agonist or antagonist but affects the gamma-amino butyric acid receptor-ionophore complex. The GABA receptors play a role in almost every single activity of the brain. Ultimately glutamate and GABA do the information processing; they’re the ones that encode sensory inputs and thoughts (GABA directly modulates the effect of glutamate). There is the cognitive enhancement which requires the knowledge of cognition and what it involves. This cognitive enhancement could be aimed at improving short-term memory, improving information processing improving recall, or enhancing long-term potentiation. Each of this involves different circuits that involve multiple neurotransmitter systems.

Homeostatic resetters refers to the process of removal of toxic substances from the body of an individual through a process called detoxification in that at the end of the process the body returns to homeostasis after a long term use of an addictive substance.

CRF is brain stress systems that is engaged during the withdrawal/negative affect stage. This will reduce the dopamine activity and also help in restoring the frontal lobe of the brain. Therefore, the CRF increases in the effects that occur with sudden withdrawal from drugs and have motivational significance not only for the anxiety effects of acute withdrawal but also for the increased drug intake associated with dependence.

Glutamate modulators are used to reduce the habits of addiction by greatly improving the mood of the user and treating major depressive disorder. Glutamate is the most abundant excitatory neurotransmitter in the brain. There has been studies carried out which have shown altered glutamate levels in serum and cerebrospinal fluid from patients with mood disorders. Administering glutamate to this patients will therefore greatly improve their mood.

Neural Circuits Of Preoccupation/ Anticipation “Craving” Stage

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