Substance Abuse: Substance Abuse Craving – Reduction Therapies

One example of an attempt to treat substance abuse behavior is U.S. Pat. No. 5,013,752, issued May 7, 1991, entitled “Prevention and Treatment of Alcoholism by the use of Dietary Chromium.” While the claim that chromium deficiency is by itself a cause of alcoholism is debatable, the use of chromium has become well established since that time as an ingredient in anti-craving compounds.

Amino-acids have been known for some time as potential agents for dealing with various conditions. U.S. Pat. No. 4,357,343 issued to Madsen, et al on Nov. 2, 1982, entitled “Nutritional Composition for Management of Renal Failure” is a typical example. A recent development in addiction therapy is the use of craving-reduction medications based upon amino-acid precursors of neurotransmitters such as serotonin and dopamine. In this approach, the patient is administered with an oral medication containing substances selected for their ability to promote healthy neurotransmitter function. Certain amino-acids are known to be precursors of the neurotransmitters. For example, the amino-acid 5-hydroxytryptophan is believed to be a precursor of serotonin while the neurotransmitter L-phenylalanine is believed to be a precursor of dopamine. Other amino-acids also function as metabolic precursors of the desired neurotransmitters.

Unfortunately the complexity of the human brain can substantially reduce the efficacy of merely providing a patient with a precursor amino-acid. The reward/pleasure system is not dependent upon any one single biochemical reaction, nor even upon a small number or class of biochemicals, nor does it occur in any one region of the brain. The interactions between the different chemicals in the human anatomy mean that even a subtly different medicinal formulation may have surprising or unexpected results.

In greater detail: the reward/pleasure response in the brain is a complex process in which stimulus in one part of the brain controls stimulus in others, which may in turn lead to stimulation of yet another part of the brain. Each of the steps of release, reception or uptake of neurotransmitters takes place at simultaneously at different locations, and for different substances, and different steps in the neurotransmission cycle may be under the influence of different neurotransmitters or other biochemicals: the release, reception or uptake of neurotransmitters is frequently under the control of other substances: amino-acids, vitamins and minerals. A short example is provided: a low level of a neurotransmitter in the brain can be partially or wholly offset by application of precursor amino-acids which help to build up the level. However, the level of the precursor amino-acids in the brain may be determined by their ability to cross the blood/brain barrier, which in turn may be governed by the amount of a given mineral in the blood stream.

The rate of breakdown and maintenance of the same neurotransmitter in the brain may also be effected or even controlled at that point by the availability of some vitamin or mineral in the system acting upon the enzyme controlling the neurotransmitter. And a mineral which promotes the crossing of the blood/brain barrier by one amino-acid might act to reduce the crossing of the same barrier by other amino-acids. To provide details of this short example: L-tryptophan is a precursor which promotes neurotransmitter activities, while D-phenylalanine promotes neurotransmitter activity by inhibiting enzymatic cleavage. Administration of niacinamide, a form of the vitamin niacin, reduces the premature breakdown of L-tyrptophan in the blood stream because tryptophan is typically used in a 60 to 1 ratio to produce niacinamide. Niacinamide later appears to reduce the rate of serotonin breakdown in the brain by inhibiting the action of tyrptophan pyrrolase.

The mineral calcium assists L-tryptophan to enter the brain, and then further assists conversion of tryptophan to serotonin, but drives other amino-acids into muscle tissue instead. L-tryptophan is desired for its ability to elevate serotonin levels, act as asleep agent, and reduce depression. When a patient is sleeping well and not depressed, the L-tryptophan may actually be removed from alternative embodiments of the present invention. Obviously while L-tryptophan is desirable, it is not desirable to encourage L-tryptophan’s action at the expense of the other amino-acids used in the present invention. There are literally hundreds of such interactions taking place, creating a system too complex for present day modeling techniques to interpret.

Thus formulation of amino-acid based anti-craving medications is an unpredictable task, and anti-craving medications tend to involve a spectrum of ingredients designed to assist the combined efficacy or efficiency of the anti-craving effect. Examples of anti-craving compounds show the wide variation in formulations. For example, as referenced previously, U.S. Pat. No. 6,132,724, issued on Oct. 17, 2000 to Blum and entitled “ALLELIC Polygene Diagnosis of Reward Deficiency Syndrome and Treatment” provides a great deal of background material on RDS and the probable genetic causes thereof, and furthermore discloses and claims an oral anti-craving composition comprising a substance which inhibits the enzymatic destruction of a neuropeptidyl opiate, a neurotransmitter-precursor amino-acid, chromium, and either an herbal extract from Rhodiola rosea or huperzine. U.S. Pat. No. 4,761,429 (“Enkephalinase and Endorphinase Inhibitors as Anti-Craving Compositions”, issued Aug. 2, 1988) and U.S. Pat. No. 5,189,064 (“Treatment of Cocaine Disorders”, issued Feb. 23, 1993) both to the same inventor as the ‘724 patent, disclose craving reduction by means of administering amino-acids which “inhibit the destruction of neuropeptidyl opiates . . . in an amount sufficient to reduce the craving”.

The same inventor (Dr. Kenneth Blum, a leader in the field) has also stated that he has a pending patent application which was filed on Mar. 21, 2000, (application and number are unavailable to the present applicant) regarding short-term bolus administration of amino-acids and Rhodiola extract. Useful as these methods are, they nonetheless represent theoretical research towards the formulation of a compound of high efficacy. One result is that these compounds often do not take into account the special medical situations of typical substance abuse patients. For example, oral compounds are in practice administered with calcium, with consequent losses of efficiency due to the fact that calcium tends to drive several of the desired amino-acids from the blood stream into the muscles, rather than the across the blood/brain barrier. For another example, these three granted patents rely upon an oral administration of the medication. However, the typical substance abuse patient has severe damage to the stomach lining and intestinal tract caused by the ingestion of substances such as alcohol. Even individuals suffering the effects of intravenous substance abuse have stomach lining and intestinal damage.

Thus, such oral formulations tend to pass through the digestive tract with relative alacrity and a low rate of absorption. As a result, the “amount sufficient to reduce the craving” is unnecessarily higher than it need be. But the stomach/intestinal lining damage is merely one practical barrier to efficient use of the medication by the body of the patient. In fact, the bodies of substance abuse patients present several barriers to the absorption, metabolization and usage of such compounds; these “substance-abuse derived” barriers will be discussed in the detailed description to follow. Another barrier to efficient usage of administered amino-acids, albeit a barrier present in all human beings rather than just those suffering from substance abuse disorder, is the blood/brain barrier.

U.S. Pat. No. 4,650,789 and U.S. Pat. No. 4,897,380, respectively issued to Pollack and to Pollack, et al, on Mar. 17, 1987 and Jan. 20, 1990, for “Method and Composition for Increasing Production of Serotonin” and “Method and Composition for Relieving Dietary-Related Disorders” also propose amino-acid medications for neurotransmitter re-balancing. These two patents both teach the use of L-tryptophan as the amino-acid, along with ingredients designed to assist it across the blood/brain barrier. However, in order to assist L-tryptophan in crossing the blood/brain barrier, both patents suggest the use of fructose to drive other amino-acids in the patient’s blood stream into the muscles, thus increasing the relative concentration of L-tryptophan and speeding its passage to the brain. Obviously, this is counterproductive if the objective is to administer a group of amino-acids.

Another example of this problem is the administration of cyanocobalamin (vitamin B12). While cyanocobalamin is the form of vitamin B 12 which is metabolized in oral administration, and thus the form known in the art in anti-craving compositions, it is also a form which must first pass through the metabolic machinery of the liver to become hydroxycobolamin, then be metabolized by the liver a second time in order to become the metabolically active form of the agent vitamin B12. This known process is disadvantageous for use by substance abuse patients, as will be explained below in the detailed description of the present invention.

All of these compositions contain weaknesses in terms of their practical efficiency of use by the body of a substance abuser. In some cases, important components are administered in a form which decreases their ability to be absorbed into the blood stream at all. Some of the same references offer important active agents in forms which are slow or difficult to metabolize in the body of an individual who has abused substances. Other references teach the use of agents such as fructose which assist the use of one amino-acid at the expense of all others. Finally, compounding of numerous amino-acids, vitamins and minerals into a formula suitable for IV administration, with the consequent advantages thereof, is quite difficult. Amino-acid medications via intravenous drip may require the administration of a dozen or more vials of medication. Combinations of numerous ingredients, however, are likely to precipitate or react in storage. This both teaches away from the creation of multiple agent medications and also makes it difficult to find suitable formulas for such agents.

A second issue which arises is that of form of administration. The efficacy of a given medication will be a function of the concentration in the body of the individual achieved by a given method of administration and the time for which that concentration is maintained. Known oral medications are inefficient in terms of the concentration achieved. Direct injection via short-term bolus therapy on the other hand will merely “spike” the desired active agents in the body of the patient without providing a substantial amount of time for the agents to take effect. The knowledge that the active anti-craving agents would quickly depart the metabolic system appears to have caused previous researchers in the field to tend to avoid water soluble forms of the active anti-craving agents.

Thus, a need remains for an anti-craving medication which is formulated and administered for high efficacy due to the combination of active agents, but which is also formulated for efficient usage by the body of an individual suffering from the typical conditions of a substance abuser.

 

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