CA2037353A1 - Method of self-administering a dopamine 2 receptor agonist - Google Patents
Method of self-administering a dopamine 2 receptor agonistInfo
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- CA2037353A1 CA2037353A1 CA002037353A CA2037353A CA2037353A1 CA 2037353 A1 CA2037353 A1 CA 2037353A1 CA 002037353 A CA002037353 A CA 002037353A CA 2037353 A CA2037353 A CA 2037353A CA 2037353 A1 CA2037353 A1 CA 2037353A1
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- dopamine
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- craving
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Abstract
Abstract of The Disclosure A method of self-administering a dopamine 2 receptor agonist in the treatment of substance abuse. The method comprises the steps of administering predetermined doses of a dopamine 2 receptor agonist over predetermined time intervals until the patient's craving ceases;
then determining the cumulative dosage amount administered in the previous step; administering the cumulative dosage when the patient's craving recurs; and, finally, reducing the cumulative dosage amount as the patient's craving diminishes. Preferably, the dopamine 2 receptor agonist is bromocriptine, which is administered in combination with food after avoiding consumption of nicotine, cocaine, alcohol, amphetamines, and other stimulants for at least ten hours. Ideally, the doses are ingested orally by the patient to facilitate self-administration and control over dosage amount. Stimulating the dopamine 2 receptor with bromocriptine in self-administered doses avoids negative side effects and eliminates the patient's addiction to the treatment method.
then determining the cumulative dosage amount administered in the previous step; administering the cumulative dosage when the patient's craving recurs; and, finally, reducing the cumulative dosage amount as the patient's craving diminishes. Preferably, the dopamine 2 receptor agonist is bromocriptine, which is administered in combination with food after avoiding consumption of nicotine, cocaine, alcohol, amphetamines, and other stimulants for at least ten hours. Ideally, the doses are ingested orally by the patient to facilitate self-administration and control over dosage amount. Stimulating the dopamine 2 receptor with bromocriptine in self-administered doses avoids negative side effects and eliminates the patient's addiction to the treatment method.
Description
2n~73~
METIIOD OF SEL~ DMINISTERING ,~ DOP~NE ~ RECEPIOR AGONIST
Technical Field The present invention penains to methods used in treating withdrawal from nicofine, cocaine, and the like, more particularly, to a me~hod of self-administering a dopamine 2 receptor agonist to stimulate re-uptake of dopamine by the dopamine 2 receptor to thereby alleviate withdrawal symptoms.
Backeround of The Invention Alcohol, cocaine, nicotine, and other drug dependencies have long been recognized as being destructive to an individual's personal life and the individual's efficient and productive contribntion 15 to society. In the past, treatment for substance abuse and addiction was based. in part, on a theory of psvchologic dependance on the substance. However, a more recent theory of addiction that is finding increasing experimental support suggests that withdrawal svmptoms are phvsiologic in origin. More particularly, this new theory suggests that withdrawal symptoms are a result of neural adaptation, which is discussed more fully below.
The main neurotransmitter for the pleasure pathways is dopamine. Once released from the dopaminergic neurone (the dopamine carrying brain cell) into the synapse (the space between the neurones), dopamine activates the dopamine 1 (D1) receptor in the next adjacent neurone.
As a consequence, a pleasure message is transmitted. Part of the released dopamine is destroved while the rest is reabsorbed into the neurone via the dopamine 2 (D2) receptor and is reused. The ~S lost dopamine is replaced by synthesis within the neurone.
Nicotine's main effect, and one of alcohol's effects in the brain, is lo force the dopaminergic neurones to release a larger than normal amount of dopamine. Cocaine and amphetamines prevent the re-uptake of dopamine by the D2 receptors, causing an accumulation 2~3 ~3~3 of dopamine in the svnapsc. The increased levels of dopamine in the svnapse cause an increase in the stimulation of the pleasure pathwavs. D2 receptors are unable to reabsorb the excess ~mount of dopamine, which. as a result, is destroved. The neurone then finds itself in a state of dopamine deficiency.
a To make up the dopamine shonfall, the neuron speeds up dopamine svnthesis and stops releasing dopamine on a regular basis, as it would normally. The neuron begins to release dopamine only when forced to by more nicotine or by olher drugs, or when it has synthesized and accumulated a sufficient amount of dopamine to make up its loss. In the absence of nicotine or other drugs, dopamine is no longer released, and pleasure messages are no longer transrnitted.
Consequently, the affected person suffers from the symptoms of nicotine, alcohol, cocaine, or amphetamine withdrawal. These symptoms tvpically manifest themselves in the form of a craving for the drug.
Medication currently used to alleviate the svmptoms of nicotine withdrawal, for example, aims either to slow the release of dopamine or to reduce the effect of nicotine on the neurone by forcing Ihe neurone to release its dopamine. Clonidine, an anti-hypertensive, slows dovn the neuronal release of dopamine by stimulating its A2 receptors. It has been found to be very effective in alleviating craving in the short term. However, it cannot be used in a large segment of the smoking population, where it is most needed (patients with coronary heart disease, for example), and it also has troubling side effects such as orthostatic hypotension, which is a sudden drop in blood pressure on standing up. When taken intravenously, Clonidine is addictive. Its use is also associated with higher relapse rates than in patients who quit smoking without them.
Among drugs that mimic the action of nicotine, the most widely used is nicotine itself, usually as a chewing gum. The main drawback of nicotine is that it does not address the cause of the withdrawal symptoms brought upon bv the use of nicotine, which is dopamine deficiency.
Indeed, about 15% to 19% of smokers given nicotine chewing gum will become addicted to in As stated above, withdrawal symptoms occur when a deficiency of dopamine inside the neurone prevents its continued release. The ideal drug for nicotine addicfion would be one that helps the neuron replenish its supply of dopamine. This could be accomplished either by directly 2 ~ rj 3 supplying it with dopamine, speeding up the synthesis of dopamine, or bv replenishing the supply of dopamine by re-uptake through the D2 receptors. There are. however. drawbacks associated with each of these methods.
Svnthesis of dopamine is alreadv accelerated in smokers. Giving patients dopamine directlv 5 through medication such as L-DOPA would allow them to palliate their dopamine deficiencv The risks, however, might be the creation of a state of dependency on exogenous dopamine. It has been found, for example, that patients on long-term opiates decrease their synthesis of endorphins and endorphine receptors, thus becoming dependant on exogenous opiates. Long-term dopamine recipients might also be subject to this dependency.
Thus, the safest and most effective vay to replenish neuronal dopamine appears to be to stimulate the D2 receptors. This speeds up the reabsorption by the neurone of previously released dopamine. This has the advantage of allowing a greater proportion of the released dopamine to be reused by the neurone rather than to be broken down in the synapse. Presently, there are several drugs available to stimulate D2 receptors. These drugs include bromocriptine, lergotrile, 15 and apomorphine. The latter two have the disadvantage of producing negative side effects, such as vomiting and hypotension. Consequently, bromocriptine would be the drug of choice. Other drugs now reaching the market may also prove useful for drug withdrawal. These drugs include pergolide and lisuride.
While bromocriptine has achieved some success in the rehabilitation of alcoholics and 20 cocaine addicts, the manufacturer of bromocriptine has found it to be ineffective as an agent for smoking cessation. The reasons for this is that the dose and method of administration of bromocriptine has been rigidly established. That is, the current dosage of bromocriptlne has been formulated for patients suffering from Parkinson's disease when indigenous production of dopamine is extremely low. Smokers, and other stimulant addicts, on the other hand, have accelerated 25 dopamine synthesis. Administering to these addicts the dosage of bromocriptine administered to patients having Parkinson's disease can result in an overload of dopamine in the neurone, with the resultant release of large amounts of excess dopamine. Smokers who smoke too fast also have an over release of dopamine. The symptoms of dopamine over-release are well known: headache, ~7~s~
dizziness, feeling faim, nausea. vomiting, abdominal pain, em. These identical svmptoms occur in pafients who ingest an excess of bromocriptine or who smoke while taking this drug. This is because the extra dopamine ~hat has accumulated in lhe cell will be released, resulting in an overload of dopamine in the neurone. It has been found that ,0% of pafients treated with bromocriptine for cocaine withdrawal dropped out because of negative side effects. The dose used with those patients, 1.25 mg to 2.50 mg taken 2 to 3 times a day, was the starting dose for the treatment of Parkinson's disease.
Consequently, there is a need for a method of administering bromocriptine that enables a patient to overcome substance addiction while experiencing little or no side effects.
Summar~ of The Invention The present invention is directed to a method for self-administering a dopamine 2 receptor agonist in Ireating withdrawal from nicotine, cocaine, alcohol, amphetamines, and other stimulants.
Broadly stated, the method comprises the steps of:
(a) administering a predetermined dose of a dopamine 2 receptor agonist;
~b) administering subsequent doses of the dopamine 2 receptor agonist after waiting a predeterrnined time interval and only in response to the patient's craving until craving ceases;
(c) determining the cumulative dosage amounts administered in the previous step;(d) administering the cumulative dose when the patient's craving reoccurs; and (e) reducing the cumulative dose amount as the patient's craving diminishes.
Preferably, the patient will first avoid consumption of stimulants and amphetamines for at least ten hours prior to taking the first dose.
In accordance with another aspect of the pre~sent invention, the step of administering the predetermined doses further comprises the steps of:
(a) administering a first dose in ~he range of 0.5 mg to ().10 mg;
(b) adminislering a second dose in the range of 0.5 mg to 0.10 mg only in response to the patient's craving;
20373~3 (c) administering a third dose in the range of 0.10 mg to 0.150 mg only in response to the patient's craving;
(d) administering a fourth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving;
(e) administering a fifth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving;
(f) administering a sixth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving; and (g) administering a final seventh dose in the range of 1~0 mg to 1.50 mg only in response to the patient's craving.
In accordance with another aspect of the present invention, the preferred dosages are 0.625 mg for the first dose, 0.625 mg for the second dose, 1.25 mg for the third dose, 1~25 mg for the fourth dose, 1.25 mg for the fifth dose, 1.25 mg for the sixth dose, and 1.25 mg for the seventh dose.
In accordance with yet another aspect of the present invention, the preferred predetermined time intervals are in the range of 30 minutes between doses. Ihe dosages and time intervals for skher D2 agonists will vary according to their pharmacoriinetics.
In accordance with a further aspect of the present invention, the preferred dopamine 2 receptor agonist is brcmocriptine.
In accordance with still yet another aspect of the present invention, each of the doses are preferably ingested orally.
In accordance with a further aspect of the present invention, each of the doses are taken in conjunction with food and, preferably, ~3~3~
after avoiding consumption of nicotine, alcohol, cocaine, am~hetamines, and other stimulants for at least 10 hours.
Also according to the i~vention, there is provided a method of self~administering a dopamine 2 receptor agonist, comprising the steps of:
~a) ingesting a predetermined dose of a dopamine 2 receptor agonist in an amount no greater than 2.0 mg;
(b) waiting a predetermined time interval not greater than 60 minutes to determLne if craving persists;
(c) in response to craving, ingestLng subsequent predetermined doses of said agonist after each predetermined time interval until craving ceases, and, in any event, no more than seven total doses;
(d) determlnlng the cumulative dosage amount ingested in the previous step;
(e) ingestLng said cumLlative amount in one dose when craving recurs; and (f) reducing said cumwlative dosage as craving diminishes.
Further according to the invention, there is provided a method for a patient to self-administer a dopamine 2 receptor agonist in treating withdrawal from nicotine, the method comprising the steps of:
2~373~3 (a) abstaining from smoking, drinking alcohol, taking cocaine and amphetamines for a period of at least 10 hours;
(b) ingesting a predetermmed dose of a dopamine 2 receptor agonist in the range of 0.50 mg to 0.10 mg;
(c) waiting a predeterm med time interval in the range of 15 m mutes to 60 minutes for the manifestation of side effects;
(d) ingesting a second predbeer:ined dose in the range of 0.50 mg to 0.10 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(e) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(f) administering a third predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(g) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(h) administering a fourth dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(i) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(j) ingesting a fifth predetermined dose in the range of 2~373~3 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to ~Lavings;
(k) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifes~ation of side effects;
(1) administering a sixth predetermlned dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(m) waiting a predetelmunsd time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(n) admunistering a final seventh predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in respo~se to craving;
(o) determ mlnq the cumulative dosage amount ingested in steps (b) through (n);
(p) ingesting said cumLlative dosage amount in response to cravings; and (q) reducing said cumulative dosage amount as craving diminishes.
As will be readily appreciated from the foregoing description, it will be apparent that at least two conditions are necessary for the successful use of bromocriptine in the treatment of substance abuse. The first condition is that the proper dosage must be administered to the patient. The second condition is that total abstention from nicotine, alcohol, cocaine, amphetamines, or 2 ~
other stimulants must be maintained by the patient. Furthermore. because the doses arc administered in amounts that are dictated bv the patient's craving, the correct and effective dose will be administered. In addition, because bromocriptine does not decrease Ihe svnthesis of dopamine nor increase the supply of dopamine, the patient will not suffer the risk of becoming 5 dependent on the treatment. Finally, because the amount of each dose is controlled by the patient in response to craving, the chances of suffering negative side effects are reduced or eliminated in most cases. Finally, most patients utilizing bromocriptine have been found to spontaneously reduce their caffeine and alcohol intake when being treated for smoking cessation.
Detailed Description of The Invention The present invention is directed to a method of substance abuse treatment that relies on a theory of addiction that was described above. Briefly, this theory is based on the reabsorption or re-uptake of dopamine 2 into a neurone via the dopamine 2 (D2) receptor, where it is reused.
Initially, the dopamine used for activating a dopamine 1 (D1) receptor in adjacent neurone is 15 normally replaced through synthesis. However, during Ihe synthesis process the neurone stops releasing dopamine on a regular basis. In addition, neuronal re-uptake of dopamine through the D2 receptors can absorb only a limited amount of dopamine before the excess is destroyed. As a result, a palient no longer receives pleasure messages and consequen~ly suffers from the symptoms of withdrawal. The present invention provides a method of self-administering a drug 20 that stimulates the D2 receptors to speed up the reabsorption of dopamine by the neurone. This permits a greater portion of the released dopamine to be used by the neurone rather than to be broken down in the synapse.
At the present time, several drugs on the market are available that stimulate D2 receptors.
These drugs are bromocriptine, lergotrile, and apomorphine. Clinical uses have found that 25 lergotrile and apomorphine are likely to produce negative side effects, such as vomiting and hypotension. Consequently, the preferred drug in the present invention is bromocriptine. This drug is available under the trademark Parlodel (bromocriptine mesylate) through Sandoz C~nada, Inc., located in Quebec, Canada. The drug is currently marketed in 2.5 mg tablets and 5.0 mg 2~3 ~3e~3 capsules. Other drugs now reaching the market may also prove useful for drug withdrawal. These include pergolide and lisuride.
In order to administer a correct and effective dose of bromocriptine, the dose amount must be adjusted according to the patient's need for dopamine and the effectiveness with which the 5 patient absorbs and uses bromocriptine. The patient's need for dopamine is subjective, and the absorption and metabolism of bromocriptine can vary considerably between individuals. It is known that the effect of an ingested dose of bromocriptine begins in about 20 minutes. The duration of the effect depends on many factors, but typically lasts approximately 8 hours.
Taking an excess of bromocriptine will generally result in the patient feeling ill, making 10 an overdose very unlikely. In addition, it has been found in at least 50% of cases that bromocriptine blocks the Dl (or pleasure) receptors. As a result, these patients cannot get a ~high" from bromocriptine or from other drugs while taking bromocriptine. The temptation to abuse bromocriptine or other drugs while on bromocriptine is therefore much reduced.
For these reasons, it has been found that patients themselves can safely adjust the dose 15 of bromocriptine that they take without the risk of becoming addicted to it. This is particularly relevant in lhe case of nicotine users, such as smokers, who, as a rule, adjust their intake of nicotine to a steady state regardless of the nicotine concentration in the product they use. For instance, smokers given cigarettes with a lower nicotine concentration will tend to smoke more cigarettes. The same holds true for alcoholics and, most likely, for cocaine and amphetamine users.
20 Hence, these palients are used to adjusting the dosage of a drug to meet their needs.
While in the past bromocriptine has been administered using a predetermined schedule with predetermined dosage amounts, the present invention utilizes the first dose to determine subsequent doses, and the dosing is carried out entirely by the patient.
In the preferred method of administering the drug, the patient abstains from smoking, 25 drinking alcohol, taking cocaine or amphelamines, or other stimulants, overnight. Ihis avoids the concurrent effect of these drugs and bromocriptine.
In the next step, ~he patient takes small predetermined doses of the drug at predetermined time intervals. The drug must always be taken with food to slow its absorption and effecl. After 2~373~ c~
each initial small dose, the patient waits Ihe predetermined time interval for the manifestafion of negative side effects. If negative side effects are not present and the patient continues to experience craving after 15 to 60 minutes, and, more preferably, 30 minutes. another dose is taken.
This cominues every half hour unfil a maxtmum number of seven doses have been taken.
S The pafient then delermines the cumulative amount of all previous doses taken and this cumulative amount becomes the subsequent dose amount when the patient experiences craving.
In response to craving, the palient takes Ihe cumulative dosage amount, usuallv every four to eight hours inidally, then less often as the neurones accumulate dopamine. ~s this occurs, the cumulatjve dose of bromocriptine is reduced by the patient in response to reduced craving and reduced effects of an overload of dopamine in the neurones are felt.
The duration of the treatment is entirely dictated by the patient's symptoms and can last from one day to several months, or even longer in the case of alcoholics and multiple-drug addicts.
T~te patient is instructed to always keep a supply of bromocriptine with him/her in case craving recurs.
A typical treatment schedule would be as follows:
First, the patient avoids nicotine, alcohol, cocaine, amphetamines, or other stimulants overnight. The patiem then takes a first dose of 0.625 mg of bromocriptine with food. If craving persists after 30 minutes and no side effects have occurred, another dose of 0.625 mg with food is repeated. One hour after the first dose, if there is still craving and no manifestation of negative 20 side effects, a dose of 1.25 mg of bromocriptine is taken with food. This same dosage, 1.2S mg with food, is taken every half hour until a max~mum seventh dose is taken. Each dose is taken only if craving persist and no side effects are experienced.
The cumulative amount of the previous dosages comes to an absolute maximum of 7.50 mg. The cumulative dosage amount ~vill be the dosage amount taken by the patient when he/she 25 next begins to feel craving. The cumulative dosage amount is then repeated whenever the syrnptoms of craving begin to recur, usually every four to eight hours initially, then less oiten as the neurons accumulate dopamine.
2~37~5C~
It is tO be noled lhat the smallesl unit dose was chosen as 0.625 mg because it is one-fourth of the smallest amount of bromocripfine commercjally available (a 2.5 mg tablet). The best initial unit lo use could va~y between 0.5 mg and 1.0 mg.
One patient treated with this method was an ex-alcoholic, ex-multiple-drug addict, and 5 currently drinking 30 cups of coffee per day and smoking 3 packs of cigarettes per day. The patient smoked his last cigarette the night before treatment began. On the first day of treatment, he took 7.5 mg of bromocriptine five times. On the second day, the patient took 5.0 mg of bromocriptine five times. On the third day, the patient took 5.0 mg of bromocriptine four times.
On the fourth day, the patient took 3.75 mg of bromocriptine four times. The pafient continued 10 at the level of 3.75 mg four limes per day for three veeks. Following that, the patient then went to æs mg of bromocriptine three times per day, then æs mg of bromocriptine twice a day, and finally skipping bromocriptine every other day. By six weeks, the patient was no longer taking bromocriptine and was still a non-smoker. In addition, the patient reduced his coffee consumption to five cups per day. The patient keeps bromocriptine with him in case craving recurs. This 15 example represents an extreme case. Most patients typically need between 0.625 mg and l.æS mg every six to eight hours initially.
While a preferred embodiment of the invention has been illustrated and described, it is to be understood that various changes may be made therein without departing from the spirit of the invention. Consequently, the invention is to be limited only by the scope of the claims that follow.
METIIOD OF SEL~ DMINISTERING ,~ DOP~NE ~ RECEPIOR AGONIST
Technical Field The present invention penains to methods used in treating withdrawal from nicofine, cocaine, and the like, more particularly, to a me~hod of self-administering a dopamine 2 receptor agonist to stimulate re-uptake of dopamine by the dopamine 2 receptor to thereby alleviate withdrawal symptoms.
Backeround of The Invention Alcohol, cocaine, nicotine, and other drug dependencies have long been recognized as being destructive to an individual's personal life and the individual's efficient and productive contribntion 15 to society. In the past, treatment for substance abuse and addiction was based. in part, on a theory of psvchologic dependance on the substance. However, a more recent theory of addiction that is finding increasing experimental support suggests that withdrawal svmptoms are phvsiologic in origin. More particularly, this new theory suggests that withdrawal symptoms are a result of neural adaptation, which is discussed more fully below.
The main neurotransmitter for the pleasure pathways is dopamine. Once released from the dopaminergic neurone (the dopamine carrying brain cell) into the synapse (the space between the neurones), dopamine activates the dopamine 1 (D1) receptor in the next adjacent neurone.
As a consequence, a pleasure message is transmitted. Part of the released dopamine is destroved while the rest is reabsorbed into the neurone via the dopamine 2 (D2) receptor and is reused. The ~S lost dopamine is replaced by synthesis within the neurone.
Nicotine's main effect, and one of alcohol's effects in the brain, is lo force the dopaminergic neurones to release a larger than normal amount of dopamine. Cocaine and amphetamines prevent the re-uptake of dopamine by the D2 receptors, causing an accumulation 2~3 ~3~3 of dopamine in the svnapsc. The increased levels of dopamine in the svnapse cause an increase in the stimulation of the pleasure pathwavs. D2 receptors are unable to reabsorb the excess ~mount of dopamine, which. as a result, is destroved. The neurone then finds itself in a state of dopamine deficiency.
a To make up the dopamine shonfall, the neuron speeds up dopamine svnthesis and stops releasing dopamine on a regular basis, as it would normally. The neuron begins to release dopamine only when forced to by more nicotine or by olher drugs, or when it has synthesized and accumulated a sufficient amount of dopamine to make up its loss. In the absence of nicotine or other drugs, dopamine is no longer released, and pleasure messages are no longer transrnitted.
Consequently, the affected person suffers from the symptoms of nicotine, alcohol, cocaine, or amphetamine withdrawal. These symptoms tvpically manifest themselves in the form of a craving for the drug.
Medication currently used to alleviate the svmptoms of nicotine withdrawal, for example, aims either to slow the release of dopamine or to reduce the effect of nicotine on the neurone by forcing Ihe neurone to release its dopamine. Clonidine, an anti-hypertensive, slows dovn the neuronal release of dopamine by stimulating its A2 receptors. It has been found to be very effective in alleviating craving in the short term. However, it cannot be used in a large segment of the smoking population, where it is most needed (patients with coronary heart disease, for example), and it also has troubling side effects such as orthostatic hypotension, which is a sudden drop in blood pressure on standing up. When taken intravenously, Clonidine is addictive. Its use is also associated with higher relapse rates than in patients who quit smoking without them.
Among drugs that mimic the action of nicotine, the most widely used is nicotine itself, usually as a chewing gum. The main drawback of nicotine is that it does not address the cause of the withdrawal symptoms brought upon bv the use of nicotine, which is dopamine deficiency.
Indeed, about 15% to 19% of smokers given nicotine chewing gum will become addicted to in As stated above, withdrawal symptoms occur when a deficiency of dopamine inside the neurone prevents its continued release. The ideal drug for nicotine addicfion would be one that helps the neuron replenish its supply of dopamine. This could be accomplished either by directly 2 ~ rj 3 supplying it with dopamine, speeding up the synthesis of dopamine, or bv replenishing the supply of dopamine by re-uptake through the D2 receptors. There are. however. drawbacks associated with each of these methods.
Svnthesis of dopamine is alreadv accelerated in smokers. Giving patients dopamine directlv 5 through medication such as L-DOPA would allow them to palliate their dopamine deficiencv The risks, however, might be the creation of a state of dependency on exogenous dopamine. It has been found, for example, that patients on long-term opiates decrease their synthesis of endorphins and endorphine receptors, thus becoming dependant on exogenous opiates. Long-term dopamine recipients might also be subject to this dependency.
Thus, the safest and most effective vay to replenish neuronal dopamine appears to be to stimulate the D2 receptors. This speeds up the reabsorption by the neurone of previously released dopamine. This has the advantage of allowing a greater proportion of the released dopamine to be reused by the neurone rather than to be broken down in the synapse. Presently, there are several drugs available to stimulate D2 receptors. These drugs include bromocriptine, lergotrile, 15 and apomorphine. The latter two have the disadvantage of producing negative side effects, such as vomiting and hypotension. Consequently, bromocriptine would be the drug of choice. Other drugs now reaching the market may also prove useful for drug withdrawal. These drugs include pergolide and lisuride.
While bromocriptine has achieved some success in the rehabilitation of alcoholics and 20 cocaine addicts, the manufacturer of bromocriptine has found it to be ineffective as an agent for smoking cessation. The reasons for this is that the dose and method of administration of bromocriptine has been rigidly established. That is, the current dosage of bromocriptlne has been formulated for patients suffering from Parkinson's disease when indigenous production of dopamine is extremely low. Smokers, and other stimulant addicts, on the other hand, have accelerated 25 dopamine synthesis. Administering to these addicts the dosage of bromocriptine administered to patients having Parkinson's disease can result in an overload of dopamine in the neurone, with the resultant release of large amounts of excess dopamine. Smokers who smoke too fast also have an over release of dopamine. The symptoms of dopamine over-release are well known: headache, ~7~s~
dizziness, feeling faim, nausea. vomiting, abdominal pain, em. These identical svmptoms occur in pafients who ingest an excess of bromocriptine or who smoke while taking this drug. This is because the extra dopamine ~hat has accumulated in lhe cell will be released, resulting in an overload of dopamine in the neurone. It has been found that ,0% of pafients treated with bromocriptine for cocaine withdrawal dropped out because of negative side effects. The dose used with those patients, 1.25 mg to 2.50 mg taken 2 to 3 times a day, was the starting dose for the treatment of Parkinson's disease.
Consequently, there is a need for a method of administering bromocriptine that enables a patient to overcome substance addiction while experiencing little or no side effects.
Summar~ of The Invention The present invention is directed to a method for self-administering a dopamine 2 receptor agonist in Ireating withdrawal from nicotine, cocaine, alcohol, amphetamines, and other stimulants.
Broadly stated, the method comprises the steps of:
(a) administering a predetermined dose of a dopamine 2 receptor agonist;
~b) administering subsequent doses of the dopamine 2 receptor agonist after waiting a predeterrnined time interval and only in response to the patient's craving until craving ceases;
(c) determining the cumulative dosage amounts administered in the previous step;(d) administering the cumulative dose when the patient's craving reoccurs; and (e) reducing the cumulative dose amount as the patient's craving diminishes.
Preferably, the patient will first avoid consumption of stimulants and amphetamines for at least ten hours prior to taking the first dose.
In accordance with another aspect of the pre~sent invention, the step of administering the predetermined doses further comprises the steps of:
(a) administering a first dose in ~he range of 0.5 mg to ().10 mg;
(b) adminislering a second dose in the range of 0.5 mg to 0.10 mg only in response to the patient's craving;
20373~3 (c) administering a third dose in the range of 0.10 mg to 0.150 mg only in response to the patient's craving;
(d) administering a fourth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving;
(e) administering a fifth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving;
(f) administering a sixth dose in the range of 1.0 mg to 1.50 mg only in response to the patient's craving; and (g) administering a final seventh dose in the range of 1~0 mg to 1.50 mg only in response to the patient's craving.
In accordance with another aspect of the present invention, the preferred dosages are 0.625 mg for the first dose, 0.625 mg for the second dose, 1.25 mg for the third dose, 1~25 mg for the fourth dose, 1.25 mg for the fifth dose, 1.25 mg for the sixth dose, and 1.25 mg for the seventh dose.
In accordance with yet another aspect of the present invention, the preferred predetermined time intervals are in the range of 30 minutes between doses. Ihe dosages and time intervals for skher D2 agonists will vary according to their pharmacoriinetics.
In accordance with a further aspect of the present invention, the preferred dopamine 2 receptor agonist is brcmocriptine.
In accordance with still yet another aspect of the present invention, each of the doses are preferably ingested orally.
In accordance with a further aspect of the present invention, each of the doses are taken in conjunction with food and, preferably, ~3~3~
after avoiding consumption of nicotine, alcohol, cocaine, am~hetamines, and other stimulants for at least 10 hours.
Also according to the i~vention, there is provided a method of self~administering a dopamine 2 receptor agonist, comprising the steps of:
~a) ingesting a predetermined dose of a dopamine 2 receptor agonist in an amount no greater than 2.0 mg;
(b) waiting a predetermined time interval not greater than 60 minutes to determLne if craving persists;
(c) in response to craving, ingestLng subsequent predetermined doses of said agonist after each predetermined time interval until craving ceases, and, in any event, no more than seven total doses;
(d) determlnlng the cumulative dosage amount ingested in the previous step;
(e) ingestLng said cumLlative amount in one dose when craving recurs; and (f) reducing said cumwlative dosage as craving diminishes.
Further according to the invention, there is provided a method for a patient to self-administer a dopamine 2 receptor agonist in treating withdrawal from nicotine, the method comprising the steps of:
2~373~3 (a) abstaining from smoking, drinking alcohol, taking cocaine and amphetamines for a period of at least 10 hours;
(b) ingesting a predetermmed dose of a dopamine 2 receptor agonist in the range of 0.50 mg to 0.10 mg;
(c) waiting a predeterm med time interval in the range of 15 m mutes to 60 minutes for the manifestation of side effects;
(d) ingesting a second predbeer:ined dose in the range of 0.50 mg to 0.10 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(e) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(f) administering a third predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(g) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(h) administering a fourth dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(i) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(j) ingesting a fifth predetermined dose in the range of 2~373~3 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to ~Lavings;
(k) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifes~ation of side effects;
(1) administering a sixth predetermlned dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(m) waiting a predetelmunsd time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(n) admunistering a final seventh predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in respo~se to craving;
(o) determ mlnq the cumulative dosage amount ingested in steps (b) through (n);
(p) ingesting said cumLlative dosage amount in response to cravings; and (q) reducing said cumulative dosage amount as craving diminishes.
As will be readily appreciated from the foregoing description, it will be apparent that at least two conditions are necessary for the successful use of bromocriptine in the treatment of substance abuse. The first condition is that the proper dosage must be administered to the patient. The second condition is that total abstention from nicotine, alcohol, cocaine, amphetamines, or 2 ~
other stimulants must be maintained by the patient. Furthermore. because the doses arc administered in amounts that are dictated bv the patient's craving, the correct and effective dose will be administered. In addition, because bromocriptine does not decrease Ihe svnthesis of dopamine nor increase the supply of dopamine, the patient will not suffer the risk of becoming 5 dependent on the treatment. Finally, because the amount of each dose is controlled by the patient in response to craving, the chances of suffering negative side effects are reduced or eliminated in most cases. Finally, most patients utilizing bromocriptine have been found to spontaneously reduce their caffeine and alcohol intake when being treated for smoking cessation.
Detailed Description of The Invention The present invention is directed to a method of substance abuse treatment that relies on a theory of addiction that was described above. Briefly, this theory is based on the reabsorption or re-uptake of dopamine 2 into a neurone via the dopamine 2 (D2) receptor, where it is reused.
Initially, the dopamine used for activating a dopamine 1 (D1) receptor in adjacent neurone is 15 normally replaced through synthesis. However, during Ihe synthesis process the neurone stops releasing dopamine on a regular basis. In addition, neuronal re-uptake of dopamine through the D2 receptors can absorb only a limited amount of dopamine before the excess is destroyed. As a result, a palient no longer receives pleasure messages and consequen~ly suffers from the symptoms of withdrawal. The present invention provides a method of self-administering a drug 20 that stimulates the D2 receptors to speed up the reabsorption of dopamine by the neurone. This permits a greater portion of the released dopamine to be used by the neurone rather than to be broken down in the synapse.
At the present time, several drugs on the market are available that stimulate D2 receptors.
These drugs are bromocriptine, lergotrile, and apomorphine. Clinical uses have found that 25 lergotrile and apomorphine are likely to produce negative side effects, such as vomiting and hypotension. Consequently, the preferred drug in the present invention is bromocriptine. This drug is available under the trademark Parlodel (bromocriptine mesylate) through Sandoz C~nada, Inc., located in Quebec, Canada. The drug is currently marketed in 2.5 mg tablets and 5.0 mg 2~3 ~3e~3 capsules. Other drugs now reaching the market may also prove useful for drug withdrawal. These include pergolide and lisuride.
In order to administer a correct and effective dose of bromocriptine, the dose amount must be adjusted according to the patient's need for dopamine and the effectiveness with which the 5 patient absorbs and uses bromocriptine. The patient's need for dopamine is subjective, and the absorption and metabolism of bromocriptine can vary considerably between individuals. It is known that the effect of an ingested dose of bromocriptine begins in about 20 minutes. The duration of the effect depends on many factors, but typically lasts approximately 8 hours.
Taking an excess of bromocriptine will generally result in the patient feeling ill, making 10 an overdose very unlikely. In addition, it has been found in at least 50% of cases that bromocriptine blocks the Dl (or pleasure) receptors. As a result, these patients cannot get a ~high" from bromocriptine or from other drugs while taking bromocriptine. The temptation to abuse bromocriptine or other drugs while on bromocriptine is therefore much reduced.
For these reasons, it has been found that patients themselves can safely adjust the dose 15 of bromocriptine that they take without the risk of becoming addicted to it. This is particularly relevant in lhe case of nicotine users, such as smokers, who, as a rule, adjust their intake of nicotine to a steady state regardless of the nicotine concentration in the product they use. For instance, smokers given cigarettes with a lower nicotine concentration will tend to smoke more cigarettes. The same holds true for alcoholics and, most likely, for cocaine and amphetamine users.
20 Hence, these palients are used to adjusting the dosage of a drug to meet their needs.
While in the past bromocriptine has been administered using a predetermined schedule with predetermined dosage amounts, the present invention utilizes the first dose to determine subsequent doses, and the dosing is carried out entirely by the patient.
In the preferred method of administering the drug, the patient abstains from smoking, 25 drinking alcohol, taking cocaine or amphelamines, or other stimulants, overnight. Ihis avoids the concurrent effect of these drugs and bromocriptine.
In the next step, ~he patient takes small predetermined doses of the drug at predetermined time intervals. The drug must always be taken with food to slow its absorption and effecl. After 2~373~ c~
each initial small dose, the patient waits Ihe predetermined time interval for the manifestafion of negative side effects. If negative side effects are not present and the patient continues to experience craving after 15 to 60 minutes, and, more preferably, 30 minutes. another dose is taken.
This cominues every half hour unfil a maxtmum number of seven doses have been taken.
S The pafient then delermines the cumulative amount of all previous doses taken and this cumulative amount becomes the subsequent dose amount when the patient experiences craving.
In response to craving, the palient takes Ihe cumulative dosage amount, usuallv every four to eight hours inidally, then less often as the neurones accumulate dopamine. ~s this occurs, the cumulatjve dose of bromocriptine is reduced by the patient in response to reduced craving and reduced effects of an overload of dopamine in the neurones are felt.
The duration of the treatment is entirely dictated by the patient's symptoms and can last from one day to several months, or even longer in the case of alcoholics and multiple-drug addicts.
T~te patient is instructed to always keep a supply of bromocriptine with him/her in case craving recurs.
A typical treatment schedule would be as follows:
First, the patient avoids nicotine, alcohol, cocaine, amphetamines, or other stimulants overnight. The patiem then takes a first dose of 0.625 mg of bromocriptine with food. If craving persists after 30 minutes and no side effects have occurred, another dose of 0.625 mg with food is repeated. One hour after the first dose, if there is still craving and no manifestation of negative 20 side effects, a dose of 1.25 mg of bromocriptine is taken with food. This same dosage, 1.2S mg with food, is taken every half hour until a max~mum seventh dose is taken. Each dose is taken only if craving persist and no side effects are experienced.
The cumulative amount of the previous dosages comes to an absolute maximum of 7.50 mg. The cumulative dosage amount ~vill be the dosage amount taken by the patient when he/she 25 next begins to feel craving. The cumulative dosage amount is then repeated whenever the syrnptoms of craving begin to recur, usually every four to eight hours initially, then less oiten as the neurons accumulate dopamine.
2~37~5C~
It is tO be noled lhat the smallesl unit dose was chosen as 0.625 mg because it is one-fourth of the smallest amount of bromocripfine commercjally available (a 2.5 mg tablet). The best initial unit lo use could va~y between 0.5 mg and 1.0 mg.
One patient treated with this method was an ex-alcoholic, ex-multiple-drug addict, and 5 currently drinking 30 cups of coffee per day and smoking 3 packs of cigarettes per day. The patient smoked his last cigarette the night before treatment began. On the first day of treatment, he took 7.5 mg of bromocriptine five times. On the second day, the patient took 5.0 mg of bromocriptine five times. On the third day, the patient took 5.0 mg of bromocriptine four times.
On the fourth day, the patient took 3.75 mg of bromocriptine four times. The pafient continued 10 at the level of 3.75 mg four limes per day for three veeks. Following that, the patient then went to æs mg of bromocriptine three times per day, then æs mg of bromocriptine twice a day, and finally skipping bromocriptine every other day. By six weeks, the patient was no longer taking bromocriptine and was still a non-smoker. In addition, the patient reduced his coffee consumption to five cups per day. The patient keeps bromocriptine with him in case craving recurs. This 15 example represents an extreme case. Most patients typically need between 0.625 mg and l.æS mg every six to eight hours initially.
While a preferred embodiment of the invention has been illustrated and described, it is to be understood that various changes may be made therein without departing from the spirit of the invention. Consequently, the invention is to be limited only by the scope of the claims that follow.
Claims (19)
1. A method of administering a dopamine receptor agonist, comprising the steps of:
(a) administering a predetermined dose of a dopamine 2 receptor agonist;
(b) administering subsequent doses of said dopamine 2 receptor agonist at the conclusion of predetermined time intervals only in the event a patient's craving persists;
(c) determining the cumulative dosage amount administered in the previous steps:
(d) administering said cumulative dosage amount of said dopamine 2 receptor agonist when the patient's craving recurs; and (e) reducing said cumulative dosage amount as the patient's craving diminishes.
(a) administering a predetermined dose of a dopamine 2 receptor agonist;
(b) administering subsequent doses of said dopamine 2 receptor agonist at the conclusion of predetermined time intervals only in the event a patient's craving persists;
(c) determining the cumulative dosage amount administered in the previous steps:
(d) administering said cumulative dosage amount of said dopamine 2 receptor agonist when the patient's craving recurs; and (e) reducing said cumulative dosage amount as the patient's craving diminishes.
2. The method of Claim 1, wherein said step of administering said predetermined doses further comprises the steps of:
(a) administering a first dose in the range of 0.5 mg to 0.10 mg, (b) administering a second dose in the range of 0.5 mg to 0.10 mg in response to the patient's craving;
(c) administering a third dose in the range of 0.10 mg to 0.150 mg in response to the patient's craving;
(d) administering a fourth dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving;
(e) administering a fifth dose in the range of 1.0 mg to 1.50 mg in response to he patient's craving;
(f) administering a sixth dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving; and (g) administering a final seventh dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving.
(a) administering a first dose in the range of 0.5 mg to 0.10 mg, (b) administering a second dose in the range of 0.5 mg to 0.10 mg in response to the patient's craving;
(c) administering a third dose in the range of 0.10 mg to 0.150 mg in response to the patient's craving;
(d) administering a fourth dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving;
(e) administering a fifth dose in the range of 1.0 mg to 1.50 mg in response to he patient's craving;
(f) administering a sixth dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving; and (g) administering a final seventh dose in the range of 1.0 mg to 1.50 mg in response to the patient's craving.
3. The method of Claim 2, wherein the preferred dosages are 0.625 mg for said first dose, 0.625 mg for said second dose, 1.25 mg for said third dose, 1.25 mg for said fourth dose, 1.25 mg for said fifth dose, 1.25 mg for said sixth dose, and 1.25 mg for said seventh dose.
4. The method of Claim 2, wherein the preferred time intervals are in the range of 15 to 60 minutes after each dose.
5. The method of Claim 1, wherein said dopamine 2 receptor agonist comprises bromocriptine.
6. The method of Claim 1, wherein said doses are administered orally.
7. A method of self-administering a dopamine 2 receptor agonist, comprising the steps of:
(a) ingesting a predetermined dose of a dopamine 2 receptor agonist in an amount no greater than 2.0 mg;
(b) waiting a predetermined lime interval not greater than 60 minutes lo determine if craving persists;
(c) in response to craving, ingesting subsequent predetermined doses of said agonist after each predetermined time interval until craving ceases, and, in any event, no more than seven total doses.
(d) determining the cumulative dosage amount ingested in the previous step;
(e) ingesting said cumulative amount in one dose when craving recurs; and (f) reducing said cumulative dosage as craving diminishes.
(a) ingesting a predetermined dose of a dopamine 2 receptor agonist in an amount no greater than 2.0 mg;
(b) waiting a predetermined lime interval not greater than 60 minutes lo determine if craving persists;
(c) in response to craving, ingesting subsequent predetermined doses of said agonist after each predetermined time interval until craving ceases, and, in any event, no more than seven total doses.
(d) determining the cumulative dosage amount ingested in the previous step;
(e) ingesting said cumulative amount in one dose when craving recurs; and (f) reducing said cumulative dosage as craving diminishes.
8. The method of Claim 7, wherein said step of ingesting said predetermined doses comprises the further steps of:
(a) ingesting a first dose in the range of 0.5 mg to 0.10 mg;
(b) ingesting a second dose in the range of 0.5 mg to 0.10 mg;
(c) ingesting a third dose in the range of 1.0 to 1.50 mg;
(d) ingesting a fourth dose in the range of 1.0 to 1.50 mg;
(e) ingesting a fifth dose in the range of 1.0 mg to 1.50 mg;
(f) ingesting a sixth dose in the range of 1.0 to 1.50 mg, and (g) ingesting a final seventh dose in the range of 1.0 to 1.50 mg.
(a) ingesting a first dose in the range of 0.5 mg to 0.10 mg;
(b) ingesting a second dose in the range of 0.5 mg to 0.10 mg;
(c) ingesting a third dose in the range of 1.0 to 1.50 mg;
(d) ingesting a fourth dose in the range of 1.0 to 1.50 mg;
(e) ingesting a fifth dose in the range of 1.0 mg to 1.50 mg;
(f) ingesting a sixth dose in the range of 1.0 to 1.50 mg, and (g) ingesting a final seventh dose in the range of 1.0 to 1.50 mg.
9. The method of Claim 8, wherein said predetermined time interval is in the range of 15 minutes to 60 minutes.
10. The method of Claim 8, wherein the preferred dosages are 0.625 mg for said first dose, 0.625 mg for said second dose, 1.25 mg for said third dose, 1.25 mg for said fourth dose, 1.25 mg for said fifth dose, 1.25 mg for said sixth dose, and 1.25 mg for said seventh dose.
11. The method of Claim 8, wherein the preferred predetermined time intervals are 30 minutes.
12. The method of Claim 7, wherein said dopamine 2 receptor agonist comprises bromocriptine.
13. The method of Claim 7, wherein said doses are ingested orally.
14. A method for a patient to self-administer a dopamine 2 receptor agonist in treating withdrawal from nicotine, the method comprising the steps of:
(a) abstaining from smoking, drinking alcohol, taking cocaine and amphetamines for a period of at least 10 hours;
(b) ingesting a predetermined dose of a dopamine 2 receptor agonist in the range of 0.50 mg to 0.10 mg;
(c) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(d) ingesting a second predetermined dose in the range of 0.50 mg to 0.10 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(e) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(f) administering a third predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(g) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(h) administering a fourth dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(i) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(j) ingesting a fifth predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(k) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(l) administering a sixth predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(m) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(n) administering a final seventh predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(o) determining the cumulative dosage amount ingested in steps (b) through (n);
(p) ingesting said cumulative dosage amount in response to cravings; and (q) reducing said cumulative dosage amount as craving diminishes.
(a) abstaining from smoking, drinking alcohol, taking cocaine and amphetamines for a period of at least 10 hours;
(b) ingesting a predetermined dose of a dopamine 2 receptor agonist in the range of 0.50 mg to 0.10 mg;
(c) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(d) ingesting a second predetermined dose in the range of 0.50 mg to 0.10 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(e) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(f) administering a third predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(g) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(h) administering a fourth dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(i) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(j) ingesting a fifth predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(k) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(l) administering a sixth predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to cravings;
(m) waiting a predetermined time interval in the range of 15 minutes to 60 minutes for the manifestation of side effects;
(n) administering a final seventh predetermined dose in the range of 1.0 mg to 1.50 mg of said dopamine 2 receptor agonist in the absence of side effects and only in response to craving;
(o) determining the cumulative dosage amount ingested in steps (b) through (n);
(p) ingesting said cumulative dosage amount in response to cravings; and (q) reducing said cumulative dosage amount as craving diminishes.
15. The method of Claim 14, wherein the preferred dosages are 0.625 mg for said first dose, 0.625 mg for said second dose, 1.25 mg for said third dose, 1.25 mg for said fourth dose, 1.25 dose for said fifth dose, 1.25 mg for said sixth dose, and 1.25 mg for said seventh dose.
16. The method of Claim 14, wherein said predetermined time interval is 15-60 minutes.
17. The method of Claim 14, wherein said dopamine 2 receptor agonist comprises bromocriptine.
18. The method of Claim 14, wherein said doses are ingested orally.
19. The method of Claim 14, wherein said dosages are ingested in combination with food.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63348590A | 1990-12-27 | 1990-12-27 | |
| US07/633,485 | 1990-12-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2037353A1 true CA2037353A1 (en) | 1992-06-28 |
Family
ID=24539823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002037353A Abandoned CA2037353A1 (en) | 1990-12-27 | 1991-02-28 | Method of self-administering a dopamine 2 receptor agonist |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2037353A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001848A (en) * | 1996-03-25 | 1999-12-14 | The Regents Of The University Of California | Bromocriptine for the treatment of alcoholics diagnosed with the D2 dopamine receptor DRD2 A1 allele |
-
1991
- 1991-02-28 CA CA002037353A patent/CA2037353A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001848A (en) * | 1996-03-25 | 1999-12-14 | The Regents Of The University Of California | Bromocriptine for the treatment of alcoholics diagnosed with the D2 dopamine receptor DRD2 A1 allele |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19940831 |