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Understanding the dynamics of polysubstance dependence.

By definition, polysubstance dependence means a person is using three or more groups of addictive substances over a 12-month period with no one substance predominating. In practice, if one holds to rigorous use of this definition, this condition would certainly be less prominent than that of individuals who have a predominant drug of choice and also use other substances.

There are also combination drug users who have "patterned" use not specified by the DSM-IV. These include alcoholics who use cocaine only after having enough alcohol to inhibit them to use; addicts who "speed-ball" (mixing cocaine and heroin for intravenous use); and many other combinations that would not meet the strict criteria for polysubstance dependence, but would clearly show dependence on more than one substance in some routine pattern of use.

This article will address problems associated with both polysubstance dependence and what I would like to term "multisubstance" dependence.

Chemical dependence, by definition, means that three of the following seven criteria are present in the same 12-month period:

1. Tolerance--using more of a substance over time to get the desired effect, or decreased effect of the substance using the same amount.

2. Withdrawal.

3. The substance is used in larger amounts or over a longer period of time than intended.

4. Inability to cut down despite efforts to do so.

5. Large amounts of time attempting to acquire, use or recover from the substance.

6. Important social, occupational or recreational activities are given up or reduced because of substance use.

7. Continued use despite recognized harm.

As has been shown by neurobiological research, the central problem in addiction from a neurophysiologic standpoint is a dysregulation of the dopaminergic pathways in the limbic system. This dysregulation appears to begin with recurrent stimulation of the limbic system with substances of abuse. Over time, individuals with a genetic predisposition for addiction experience the loss of dopamine regulation that normally allows one to remain in control of the compulsive use of addictive substances.


Once this dysregulation occurs, the individual experiences loss of control over the substance, changes in tolerance and the inability to stop using despite harm.

Also of importance is an understanding of the physiology of individual neurons with respect to multiple substances. Neurons have receptors for individual substances. There are specific dopamine receptors for cocaine, morphine receptors, THC receptors, etc. This is important because there are genetic variations of these receptors accounting, at least in part, for variations in why certain individuals respond differently to certain substances.

Most importantly, substances of abuse have a "final common pathway" connection to the limbic system, which contributes to the dysregulation of the dopaminergic pathways mentioned above.

Interestingly, individuals use substances of abuse in many cases to control physiologic dysphoria prior to the onset of addictive behavior. We call this phenomenon "self-medication." Arousal levels in baseline EEG data show wide individual variations.

Individuals who unconsciously find themselves under-aroused tend to use amphetamines and "uppers" to make themselves feel "normal." Over-aroused individuals with lots of beta and high-beta brainwave activity have difficulty calming themselves and tend to use alcohol and opiates to "slow down." Obviously, this would not be the way a psychiatrist would recommend that someone relax, but $1 billion a year of alcohol advertisements make alcohol attractive to the average person.

Defining the population

In practice, I believe that polysubstance dependence occurs in roughly two subpopulations. Before going further, I would like to say that there is a lot of overlap with the populations I am about to describe. I do think, however, that there is some distinction to be made here.

Population one represents the adolescent addict who has been using multiple substances because of the desire for general mood alterations. I do not think there is a selective use of substances with this population as there is with the second population, which is the adult who is clearly attempting to do some sort of self-medication for anxiety, chronic depression, or other psychiatric problems, or who has been using certain substances for years as a drug of choice for whatever reason.

The latter patients frequently are addicted to substances such as alcohol or cocaine and also have been prescribed benzodiazepines or opiates by their physicians, or have obtained prescription medications from friends, relatives or the Internet. These patients also may be on psychotropic medications for psychiatric diagnoses. The literature supports this, in that polysubstance dependence has a high correlation with psychiatric comorbidity.

So what do we do with these populations? Obviously, every case is an individual one. However, I believe there is a general approach to the two populations.

Statistics about addiction in young people show that the population from ages 12 to 25 represents about half of the nation's illicit drug users. More than half of adolescents have used an illicit drug by the end of 12th grade. It is estimated that 2 million young people need treatment for their drug and alcohol problems, but only 8 percent of them actually receive treatment.

At the Caron Foundation, our data show that marijuana, alcohol and heroin are the primary drugs of abuse for both male and female adolescents. Psychostimulants are abused by 33 percent of adolescent patients, with a higher prevalence of abuse by individuals diagnosed with attention-deficit/hyperactivity disorder (ADHD). Twenty percent of ADHD-diagnosed individuals at Caron report diverting their psychostimulant medication to others.

Polysubstance abuse is the rule rather than the exception in the adolescent population. Marijuana, alcohol, dextromethorphan, MDMA (Ecstasy), opiates in multiple forms, cocaine, hallucinogens and inhalants all contribute to adolescent polysubstance dependence. A recent survey at Caron revealed polysubstance use by 33 percent of the patients currently in adolescent treatment.

From an epidemiological perspective, adult polysubstance dependence seems to have a more complex configuration. Looking at the literature, adult polysubstance dependence is associated with additional mental health considerations, as the population gets older. Polysubstance dependence in adults is associated with personality disorders, homelessness and major psychiatric disorders such as major depression, psychosis and bipolar illness.

This overlap of psychiatric problems and polysubstance dependence backs up the assertion that polysubstance dependence in the adult population has something to do with the idea of self-medication.

Then there are the "multiple substance users" who do not meet the strict DSM-IV definition of polysubstance dependence, but who are clearly not able to identify one particular drug of choice. Typically, these are individuals who used alcohol or marijuana at an early age, then "added" substances and switched their drug of choice without necessarily stopping the older substances.

There is also a subgroup, usually adults, who had an ongoing addiction to alcohol and then developed a pain syndrome either by injury or surgery and were placed on opiates. These individuals then begin mixing substances, or switch to opiates as their drug of choice.

Treatment implications

What does all this mean for treatment? There are a number of problems with polysubstance addiction that present to clinicians.

To begin with, detoxification can become much more problematic. It is important at the outset to obtain an accurate history of substance use and to determine with urine, blood or breath screens the actual substances being used.

In my experience, I have admitted patients for detoxification in which they stated that opiates were their drug of choice--then after several hours, the patient began having classic alcohol withdrawal symptoms. This is one of the reasons we routinely treat detoxification patients with thiamine until we have determined that there is no history of alcohol use.

Occult benzodiazepine use is also problematic. If a patient is unable or unaware of benzodiazepine use and is several days out from his or her last use, there can be a lag time for the onset of withdrawal symptoms, and urine drug screens may not detect the presence of the drug.

Once the drug use pattern and specific substances are identified, the case of someone using multiple substances also demands specific treatment. Since polysubstance use is identified with psychological and psychiatric comorbidity, a thorough psychological evaluation is important.

And, since it is difficult to discern a true psychological picture in someone with recent drug use, enough time must be taken for detoxification, a history evaluation and observation in order to gain an understanding of the true face of any psychiatric comorbidity that exists. Frequently patients are placed on psychotropic medications while active in their addiction, which further complicates the true psychiatric picture and diagnosis.

Last, it is important to educate the patient on the nature of cross-addiction and the need for sobriety, avoidance of self-medication and sober-living techniques to ensure that there is no misunderstanding about why all addictive substances must be avoided to maintain stability.

By Joseph A. Troncale, M.D.

Caron Foundation

Joseph A. Troncale, M.D., is medical director at the Wernersville, Pa.-based Caron Foundation. His articles on medication decisions in the treatment of patients with addiction and attention-deficit hyperactivity disorder (ADHD) appeared in the January 2003 and September 2003 issues of Addiction Professional.
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Author:Troncale, Joseph A.
Publication:Addiction Professional
Geographic Code:1USA
Date:May 1, 2004
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