The 1995 Marijuana Rescheduling Petition

Contemporary Evaluation of Dependence Liability


Any evaluation of marijuana's real or potential for abuse for scheduling purposes under the Controlled Substances Act (CSA) must rely on the legally and scientifically significant professional standards currently employed by the CPDD.

The CPDD's policy is that evaluation of dependence liability should be based on markers that reflect biological actions of the substance in question. The CPDD relies on animal models to test for dependence liability. A 1984 review of CPDD's animal testing procedures notes that:

"It is important, however, in testing drugs for physical dependence liability, to ensure that the same test paradigm is employed throughout, so that the behavioral influences are kept constant for all drugs under comparison."(10)

Cicero described the College's work in a background paper for the Office of Technology Assessment (OTA) of the U.S. Congress. Cicero lists harmful, "compulsive drug self-administration" as the first of five characteristics of a drug with significant abuse potential. The second characteristic Cicero notes is a "preoccupation with drug seeking behavior to the exclusion of all other activities." Craving, tolerance, and withdrawal symptoms are the other three markers of drug dependence."(11)

These criteria are "semi-quantitative" and are used to evaluate "the degree to which a drug possesses dependence liability."(12) Tolerance and withdrawal symptoms develop for many compounds, but that does not qualify them as drugs with a significant dependence liability. Cocaine use, for example, lacks evidence of significant tolerance but satisfies the first three criteria.

"Thus, it is essential that one look at the full spectrum of the drug's effects and the degree to which it satisfies the foregoing criteria before any conclusions regarding its dependence potential are drawn. However, it should be clear that the first three criteria mentioned above [harmful self-administration, compulsive drug seeking behavior, and craving] must be satisfied in all cases to classify a drug as having significant dependence liability."(13)

Cicero explains that people self-administer many substances because of perceived beneficial effects. It is when this behavior results in adverse consequences that self-administration becomes an indication of drug dependence.

"To summarize, self-administration of a drug to the point where the behavior becomes obsessive and detrimental to the individual is the primary criterion which must be met to classify a drug as one with significant potential for dependence."(14)

The CPDD's conceptual framework for screening drugs for abuse potential is the same for opiates, stimulants, depressants, hallucinogens and inhalants. (15) Animal models are used to evaluate self-administration, drug-discrimination, and tolerance or other neuroadaptation.

Animal models are a powerful tool, and their use by CPDD creates legal standards by which the dependence liability of drugs is determined in comparison to other drugs. Cicero concedes that animal models are not perfect.

"It must be clearly recognized that the ultimate answer to the issue of whether a drug has significant abuse potential is long-term experience once the drug has become available. Specifically, when a drug is introduced into the general population, either legally or illegally, the true incidence of its relative abuse can be assessed with far greater precision than can be achieved using animal models or limited clinical screening. Nevertheless, animal models serve as the only practical means of initially screening drugs for dependence liability and have proven to be the most effective means of detecting whether there is likely to be a problem in humans."(16)

On the basis of Cicero's and other reports, the Office of Technology Assessment concluded that:

"The capacity to produce reinforcing effects is essential to any drug with significant abuse potential, whereas tolerance and physical dependence most commonly occur but are not absolutely required to make such a determination . . . The predominant feature of all drugs with significant abuse potential properties is that they are self-administered . . . Animal models of self-administration provide a powerful tool that can give a good indication of the abuse liability of new or unknown drugs."(17)

Brady succinctly summarizes the significance of reinforcement:

"If the abuse liability of a substance as defined by the likelihood of it supporting drug-seeking and drug-taking, is to be evaluated, an assessment of its reinforcing functions by self-administration is clearly the method of choice."(18)

At CPDD's 1989 annual meeting, a presentation on reinforcing characteristics of drugs also explains that this is the preeminent criterion:

"If the abuse liability of a substance as defined by the likelihood of it supporting drug-seeking and drug-taking, is to be evaluated, an assessment of its reinforcing functions by self-administration is clearly the method of choice."(19)

Cicero's defense of CPDD's testing paradigms rests on a considerable foundation of published material, including the work of noted researchers such as Brady, Griffiths, Schuster, and Woods. Criticism of reliance on self-administration studies will be addressed below.

 

 
 
 
  
 
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