Diagnostic Criteria for MDMA abuse and dependence

A recent paper on the test / re-test reliability of diagnostic criteria for MDMA abuse and dependence is fascinating. Foremost because the nature of substance abuse is always a fun topic for discussion when you are dealing with a compound which the users argue so strenuously is perfectly benign. Even more so because the advocacy position tends to put a finer point on the argument about just how to draw lines between ordered and disordered behavior within what is very likely a continuous distribution. The paper also shows some of the limitations of trying to fit drugs which have very distinct subjective experience profiles, use patterns and even dependence modes/risks into a single (albeit reasonably flexible) diagnostic strategy.
In their paper Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study, Cottler and colleagues are primarily focused on whether diagnostic criteria for MDMA abuse and dependence (there are distinct diagnoses for some substances of abuse within the Diagnostic and Statistical Manual of Mental Disorders, but not for MDMA which falls under the general abuse criteria) are reliable. As you might imagine, it is a pretty important part of medical diagnosis that a given clinical test gives the same answer when repeated for the same individual in close temporal proximity. It is no great leap of genius to see that reliability is even more important when the diagnostic instrument consists of asking people about their affect and behaviors. Particularly when the behaviors are illegal and socially stigmatized.

One of the more interesting things about 3,4-methylenedioxymethamphetamine (aka “Ecstasy”) is that it has structural, pharmacological, behavioral and human subjective properties that make it similar to both the amphetamine-class psychomotor stimulants and the classic hallucinogens (such as LSD, mescaline, psilocybin, etc). Consequently, one of the additional research goals for the present study was to further characterize the nature of MDMA abuse and dependence; such properties can be quite different between hallucinogen and stimulant drugs. This investigation can also be placed in a broader context of future revisions of the DSM, i.e., to see if MDMA should remain in the generic substance abuse category, if it should be grouped with stimulants vs. hallucinogens or whether a specific category for MDMA needs to be created. At present, MDMA use is considered under the general criteria for substance abuse and substance dependence.
The study took place in St Louis, MS and Miami, FL in the USA and Sydney in Australia, from which the investigators ended up with 593 participants who had used MDMA at least 5 times in their life and at least once in the past year. The sample had a median age of 22 with median MDMA onset at 19 years of age. The median number of lifetime MDMA pills consumed was 50 (mean 212; SD=502), virtually all individuals reported lifetime alcohol and lifetime marijuana use, 64% had used other hallucinogens, 62% other stimulants, 61% cocaine and about half reported use of sedatives, opioids and inhalants. In short, a pharmacologically promiscuous user group that is quite typical of most published reports on Ecstasy using samples.
The overall proportions at test and re-test were 59% / 57 % for dependence and 15%/18% for abuse-without-dependence. Not bad at all. The investigators also used a follow-up interview procedure to identify reasons for discrepancies. The most common were “interpretation of the question changed” (39%) and “did not understand the question” (13%) and “do not know” (12%) which, at least for the former two suggests ways to refine and/or identifies the nature of the beast**. This was the main point of the study since it was based on prior work suggesting MDMA users indeed meet abuse and dependence criteria for that drug. Nevertheless it is interesting to see what this study was able to confirm of the MDMA-dependence profile.
The most-common reported diagnostic criteria for MDMA dependence were ‘withdrawal’ (68%) and ‘continued use despite knowledge of physical or psychological problems from it’ (87%). Signs of ‘tolerance’ came in at about 50% and ‘using more than intended’ at 43%. Interestingly the ‘persistent desire /unsuccessful effort to cut down or control use’ was only reported by 17% of the sample.
To touch briefly on the issue of specificity, there was some evidence from the answers to multiple sub-questions related to withdrawal that MDMA looks very much like a stimulant on this aspect. This has some sort of interesting implications given that many users apparently seek this drug for properties other than the stimulant ones. It is not inconceivable that MDMA might cause a sort-of covert stimulant dependence with the (and I am speaking very generally here) dopamine signal being covered up by the serotonin + ? signal(s) which convey the so-called empathic and pro-social subjective properties. If MDMA dependence tends to look like oral amphetamine(s) dependence then I can see where better understanding of the profile might result in earlier detection. As I always say, the Ecstasy user population tends to be highly engaged in the science of their drug of choice and has the interest and seeming ability to adopt harm-reduction practices. Therefore educating the users has a greater potential to produce harm-reduction results all by itself. Or so I argue anyway…
The recitation of results should give you enough of a flavor of the report to return to the more general topic of what it means to be dependent on a psychoactive substance. Obviously, it can mean quite different things if out of a set of 7 core criteria you only need to endorse three to be dependent. Depending on circumstances and context, some of these criteria may have greater or lesser implications when it comes to having a drug problem. This is where we start to muddy the ability to consistently classify a behavioral disorder with the real-world implications of the behavioral disorder. Conflating substance dependence with a drug problem.
The extreme example I use is of the independently wealthy adult, with no dependents or family to speak of, who just sits around and consumes his or her readily available supply of heroin, cocaine, methamphetamine, cannabis or what have you. As much or as little as s/he wants at any given time with minimal implications for being intoxicated, in withdrawal or whatever. This person may very well meet criteria for substance dependence and likely does. Does this individual have a drug problem?
The other extreme example is of the person who uses a drug very sparingly but has children and a dependent spouse. Is perhaps living economically on the edge, in a job with minimal sick days and zero tolerance for absenteeism. This individual may have very little to report in terms of the physiological criteria that most people think of as being genuine dependence. Yet his or her single criterion of interference with ‘recreational, occupation or social activities’ may represent a huge drug problem.
I believe this is exactly the place where I get into the more fervent discussions when I assert that cannabis or MDMA cause dependence. Because many people have a hard time dissociating the concept of a drug problem from specific diagnostic criteria that they find highly salient (such as directly observable and highly dramatic somatic signs of withdrawal from opiate dependence). Difficulty considering anything that does not involve essentially daily use as a true addiction. Add to this the fact that recreational, occupational and social problems can be disguised and are highly variable in importance to different people. If recreational drug use attenuates educational and vocational attainment…is this a problem? Opinions vary.
Others insist from an individual liberties position that if someone chooses to keep using despite knowing it is degrading their health (or social or vocational pursuits for that matter), they can choose to do so and this is no sign of a problem. (Skydiving and rock climbing has a tendency to come up at this point.) I think this one misses a pretty important point about our erroneous attribution of our motivations for drug consumption. I am not certain why but people hate to consider that they are subject to behavioral conditioning. Especially when there is a psychoactive compound involved which triggers reward pathways and, ultimately, co-opts or disrupts those pathways. When someone is well along the addiction path, it is not at all clear to me that libertarian concepts of free-choice really apply. And I think it is unduly and inhumanely punitive to adopt the notion that an individual has to suffer the consequences of the presumptively “free” choices made in the initial uses of a given drug.
This paper creates the impression in this reader that MDMA dependence is characterized more by pharmacological issues of tolerance and withdrawal and less by life-interference issues. Although knowledge of MDMA-induced harm was a common criterion endorsed, the issues of interference with recreational, social or vocational pursuits were comparatively less frequent. Having difficulty cutting down use or quitting was likewise uncommon which may very well be related to the prior issue of real-life implications of MDMA dependence. Personally, I tend to think of this as less of a drug-problem when it comes to compulsive use (acute harm is a different kettle of fish) issues. For me, one of the biggest backstops on what represents a problem is a treatment seeking population who has tried (frequently repeatedly) to quit and can’t quite manage to avoid relapsing. The data in this paper do not seem to argue strongly for such a population, despite a rather impressive percentage of users that endorse the more directly pharmacologically related dependence criteria.
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*DSM-IV-TR defines substance abuse as
A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions or expulsions from school; neglect of children or household)
2. Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
3. Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct)
4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)
B. The symptoms have never met the criteria for Substance Dependence for this class of substance.
and substance dependence (ibid) as:
…substance dependence by the American Psychiatric Association) is defined as a maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three (or more) of
the following, occurring any time in the same 12-month period:
1. Tolerance, as defined by either of the following:
(a) A need for markedly increased amounts of the substance to achieve intoxication or the desired effect
or
(b) Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
(a) The characteristic withdrawal syndrome for the substance
or
(b) The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms.
3. The substance is often taken in larger amounts or over a longer period than intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover
from its effects.
6. Important social, occupational, or recreational activities are given up or reduced because of substance use.
7. The substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused or exacerbated by the substance (for example, current cocaine use despite recognition of cocaine-induced depression or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).
**It is not shocking that being asked if you attribute certain behaviors or feelings to MDMA use or discontinuation might start a rumination process that leads you to a different answer the next time you are asked.
Citation:
Cottler, L., Leung, K., & Abdallah, A. (2009). Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study Addiction, 104 (10), 1679-1690 DOI: 10.1111/j.1360-0443.2009.02649.x