You are on page 1of 9

Pathways to heroin dependence: time to re-appraise

self-medication
Shane Darke
National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia
ABSTRACT
The self-medication hypothesis emphasizes the role of distressing affect as the primary motivator for the compulsive use
that leads to substance dependence. The model also postulates that there will be psychopharmacological specificity
between symptom presentation and the primary drug of dependence. In this review, the self-medication hypothesis is
examined in relation to the development and chronicity of heroin dependence. It is argued that if self-medication has
a role in engendering and extending substance dependence, it should be apparent in the use of a drug that carries such
overwhelming personal risk. The psychopathology seen among adult users is certainly consistent with the model. More
importantly, however, are the extraordinarily high levels of childhood trauma and psychopathology that occur typi-
cally well before the initiation of heroin use. In contrast, the postulate of drug specificity appears less supported by the
polydrug use patterns typical of heroin users, and does not appear to be a necessary corollary of the model.
Keywords Heroin, psychopathology, self-medication, theory.
Correspondence to: Shane Darke, National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052, Australia.
E-mail: s.darke@unsw.edu.au
Submitted 11 December 2011; initial review completed 6 March 2012; final version accepted 22 June 2012
INTRODUCTION
A perusal of any major drug and alcohol journal gives
the impression that our field is curiously atheoretical.
Theories of addiction, however, remain crucial to our
understanding of the origins of dependence and to
appropriate clinical responses [1]. One such model is the
self-medication hypothesis (SMH) [2–9]. First proposed in
the 1980s, the SMH may be argued to have a far longer
provenance in popular folklore (‘I drink to forget’). This
model has aroused much opposition [1,10–12], and has
been labelled ‘dangerously false and misleading’ [10].
In this piece, I aim to encourage theoretical debate by
examining the SMH in relation to the development and
chronicity of heroin dependence.
Why focus on heroin? It is certainly true that the gross
societal burden of disease due to alcohol and tobacco
exceeds that of the opioids. The SMH, however, is a theory
of the individual. In contrast to societal harm, the cost of
opioid dependence to the individual far exceeds that
of any other drug class. They have the highest stigma,
highest mortality risk, highest dependence liability of any
drug apart from nicotine, the greatest treatment demand
and lowest rates of remission [13]. It is also associated
with a clinical picture of extremely poor physical and
mental health, chronic unemployment, criminality and
imprisonment. Importantly, this clinical picture is con-
sistent across widely differing countries and societies.
It is a dangerous life-style, pursued by a small minority
(between 0.3 and 0.5%) [14]. The compulsive use of a
substance that carries such harm certainly warrants
explanation. If the SMHdoes not accord with the depend-
ent use of such a substance its utility in relation to other,
less dangerous substances, would be questionable.
THE SMH
The SMH is a psychodynamic model of substance
dependence that emphasizes the role of distressing affect
as the primary motivator for the compulsive use that
leads to dependence [2–9]. The model was first proposed
by Edward Khantzian in the 1980s, and has two formal
components, which I shall refer to as the ‘psychopathol-
ogy’ and ‘drug specificity’ postulates.
1 The psychopathology postulate. The genesis of dependent
substance use lies in the relief fromdistressing psycho-
logical symptoms that substances give. The motivation
for substance use is thus the relief of negative affect,
FOR DEBATE
bs_bs_banner
doi:10.1111/j.1360-0443.2012.04001.x
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
rather than the pursuit of euphoria or the result
of peer pressure. It should be noted that it is not a
psychiatric condition per se that is medicated by the
individual, but symptoms and distressing affect.
2 The drug-specificity postulate. There will be psycho-
pharmacological specificity in the primary drug of
dependence. The drug of choice will reflect its ability to
ameliorate particular distressing symptoms. Opioids
are argued to attenuate intense, rageful and violent
affect. In contrast, psychostimulants are seen as aug-
menters for hypomanic individuals, energizers for
the depressed and medicators of attention deficit-
hyperactivity disorder.
In some respects, we may consider the SMH to be a
form of disease model, with psychiatric morbidity engen-
dering problematic use, rather than use per se being
the disease. Dependent use is a symptom of underlying
pathology. Indeed, the user is not engaging in deliberate
self-destruction (although this may well ensue), but in an
attempt to ‘self-repair’ [4]. While the hypothesis has its
genesis in psychoanalytical theory of ego defence mecha-
nisms, the basic tenets may be also be re-conceptualized
within a cognitive–behavioural framework, with sub-
stance use being sustained by negative reinforcement
[15].
Opponents of the model challenge the primacy of psy-
chopathology as a causative agent, in the development
and maintenance of dependence. As noted above, some
regard the model as dangerous, as it places the clinical
focus on psychopathology at the expense of the drug
problem itself [10]. The fact that dependent substance
use may actually increase distress is also considered anti-
thetical to the model, as it is symptom relief that is sup-
posedly being sought [1,10–12].
THE PSYCHOPATHOLOGY POSTULATE
Parents, childhood and pathology
It is first necessary to examine the clinical picture of users
before their heroin use began. This is crucial to the model,
as it postulates that distress preceding the onset of heroin
use is the motivator for use.
Two major socio-demographic factors stand out from
the backgrounds of heroin users. First, they are highly
likely to come froma disadvantaged background. It is well
documented that social disadvantage is associated with
poorer physical and mental health [16,17]. Indeed, each
increment in socio-economic status reduces the odds of
the child becoming substance-dependent. Moreover, chil-
dren from lower socio-economic families are more likely
to experience abuse and neglect, as well as depression and
hopelessness [16,18,19]. The second factor of relevance
concerns their parents. Rates of substance abuse among
such parents are many magnitudes those of the general
population, a third or more of heroin users having had at
least one substance-dependent parent [20–23].
Consistent with the association between psychopa-
thology and dependence, we also see high rates of psy-
chopathology among the parents of users [24,25]. Given
high levels of parental psychopathology and substance
dependence, it is likely that there will be an environment
of family disruption and conflict, including a higher like-
lihood of childhood abuse and neglect. Not surprisingly,
high rates of conflict are reported among the parents of
heroin users [21]. Parental separation or absence during
childhood is also common, with a third or more reporting
such circumstances [20,21,24]. This is important, in and
of itself, as parental separation or absence is associated
with increased risk for mood, conduct and substance use
disorders [26,27].
Are the socio-economic stressors, parental psychopa-
thology and drug use seen in the backgrounds of many
heroin users associated with high levels of childhood
abuse? The answer is an unequivocal ‘yes’. Rates of abuse
and neglect are many magnitudes higher than those of
the general population or matched controls [21,27–31].
The proportion who experienced childhood sexual abuse
is extraordinarily high, with a third to more than half
having experienced such abuse [21,27–31]. There is a
marked gender difference, with female heroin users sub-
stantially more likely to have experienced suchabuse, and
to have experienced it more frequently. Indeed, female
rates are typically double or more those of males [21,27–
31]. The average age at which such abuse commences is
in the order of 8–12 years, and multiple incidents occur
in half of those abused [21,29,32,33].
Abuse also includes non-sexual physical abuse. As
noted above, rates of substance dependence are high
among the parents of opioid users, and such dependence
is associated with a higher risk of familial violence
[34,35]. Rates of childhood physical abuse are compara-
ble to those of sexual abuse. Unlike sexual abuse, males
and females appear equally likely to be victims. Finally,
there is emotional abuse and physical neglect. Where
reported, rates of childhood emotional abuse and phy-
sical neglect are typically 50% or higher [21,36–39].
The picture of extensive abuse that we have built has
been termed ‘shattered childhood’ [24]. We must bear in
mind that the different forms of abuse are not mutually
exclusive, and large proportions of users suffer multiple
types of abuse [24,28,33,39]. Given the ‘shattered child-
hoods’ of so many users, the high rates of adult psycho-
pathology seen among this population are not surprising,
and we would expect many of these disorders to manifest
first during childhood. This is exactly what we find
[24,29,40–45]. Rossow & Lauritzen [24], for instance,
reported that half their sample had experienced
660 Shane Darke
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
psychiatric problems prior to the age of 16. Similarly,
Pugatch et al. [44] reported that one in four adolescent
heroin users had psychiatric histories. Conduct disorder
(the antecedent of antisocial personality disorder) is diag-
nosed retrospectively in approximately half these users
[46–48].
The adult heroin user
We must now examine the mature user. They will typi-
cally be using daily, be unemployed and deeply involved
in criminal activities or sex work to fund use. They are
also likely to experience repeated overdoses, and be in
chronically poor health [12,13,49–63].
The domain of greatest interest here is psychopathol-
ogy. It is fundamental to the SMH that psychopathology
be highly prevalent among established, dependent users,
as it is the motivational force behind continued use. Such
is the case. Studies show consistently that approximately
three-quarters of dependent heroin users qualify for at
least one comorbid diagnosis and, most commonly, mul-
tiple diagnoses [61,64–67]. The life-time prevalence
of major depression and dysthymia are in the order of a
third to half, and current rates range between a quarter
to a third [64,67,68]. A third to half will qualify for life-
time diagnoses of anxiety disorders [62,65,66,69–72].
Of particular relevance, life-time diagnoses of post-
traumatic stress disorder (PTSD) are in the order of half
or more, with current diagnoses seen in a fifth to half
[62,69–72]. Importantly, all these disorders occur at
rates many orders of magnitude greater than those seen
in the general population [73]. These high levels of dis-
tress are reflected in the rates of suicide and self-harm.
Approximately 10% of heroin users will die by suicide,
and rates of life-time and recent suicide attempts are
in the order of 20–40% and 6–10%, respectively
[20,24,67–78]. Indeed, the annual rate of attempted
suicide is higher than the life-time rate of the general
population [79,80].
The other class of disorders we see in abundance are
the personality disorders, long-term maladaptive traits
that commence in childhood [81]. The most commonly
diagnosed personality disorders are antisocial personality
disorder (ASPD) and borderline personality disorder
(BPD). ASPD is seen in at least a third of heroin users,
compared to only 4% among the general population
[81–84]. Importantly, conduct disorder is a necessary
diagnostic antecedent to the adult diagnosis. Similarly,
while the prevalence of BPD in the general population
is approximately 2%, rates among heroin users range to
65% [81,83,85].
The high levels of distress seen among users are ame-
nable to amelioration, with enrolment in long-term drug
treatment resulting in marked reductions in both drug
use and psychopathology [49,57,74,76,83,84]. While
levels of distressing psychopathology and suicide do
decline significantly, they do not return to general popu-
lation rates. Of course, personality disorders are, by their
nature, considered strongly resistant to treatment.
Clearly, the extensive distress seen among adult
heroinusers is consistent withself-medication. Of course,
it could well be argued that, given their life-style, it is not
surprising that rates of psychiatric distress are high
[10–12]. This cuts to the core question of aetiology. Cer-
tainly, such a life-style is pathogenic. The fact that levels
of pathology and suicide attempts do not decline to
population levels during and after treatment is sugges-
tive, however, of a different aetiology, although it cannot
be denied that symptoms are exacerbated by life events.
The age of onset for these disorders is clearly crucial.
For the SMHto be credible, onset should precede the onset
of heroinuse, whichcommences typically around the age
of 19–20 years [13]. In the case of BPD and ASPD, this
is axiomatic. For Axis I disorders, the clinical evidence
from childhood indicates that for large proportions of
users, trauma and psychopathology emerge well before
the use of any psychoactive substance, and of heroin in
particular.
Before moving on, we must briefly address the concept
of the high functioning user. The picture drawn here is
derived primarily from clinical populations. It is often
argued that there is a hidden group of employed, ‘recrea-
tional’ heroin users that may, indeed, be larger in size
than the poorly functioning group seen as ‘typical’. I
remain sceptical about the existence of this group. They
do not appear at police stations, prison, treatment or,
importantly, as overdose fatalities [13]. Moreover, the
levels of psychopathology seen among non-treatment
populations from venues such as needle exchanges are
similar to those of treatment populations [64–66,68].
THE DRUG SPECIFICITY POSTULATE
The developing heroin user
Heroin users progress typically through a sequence
of drug use before they use heroin [13,85]. Tobacco is
generally the first substance used, at approximately
12–14 years [13,85]. Alcohol use commences typi-
cally at approximately 13–14 years. Typically, cannabis
follows next, with an average onset of 14–16 years. Psy-
chostimulant use frequently precedes heroin use, with
the average onset age for methamphetamine typically
between 17–19 years and cocaine initiation also around
this time, or slightly later. Finally, we come to heroin. The
average age of onset is just under 20 years, with remark-
able consistency across the world [13,85]. The time-lag
between initial use and the development of regular,
Self-medication and heroin 661
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
dependent use is approximately 18 months. More
broadly, over approximately 8 years, the average user
moves from cigarettes, through many other drugs, to
using heroin.
The mature heroin user
Given the progression preceding heroin use, it is not sur-
prising that it is a rare heroin user who uses opioids only.
As we have seen, heroin use occurs typically well into the
sequence. Importantly, however, drugs used in earlier
stages are not discarded. Rather, there is an accretion
of substances with vastly different pharmacodynamics
[13,49–60]. On average, we would expect a typical user
to have used approximately 10 different drug classes in
their lives, and half a dozen in any one year [13]. Studies
of adult heroin users consistently show tobacco smok-
ing to be almost universal. A quarter or more will meet
criteria for alcohol dependence. Life-time cannabis use
is typically in excess of 90%, and more than half of
mature users will be using the drug. As with cannabis,
life-time exposure to psychostimulants is close to univer-
sal, and a fifth to half will be using cocaine and/or
methamphetamine. Finally, a third to half will be using
benzodiazepines.
While the phenomenally high levels of psychopathol-
ogy and suicidal behaviours discussed above are consist-
ent with self-medication, the extensive polydrug use seen
in adolescence and adulthood use is more problematic. It
will be recalled that the hypothesis postulates an isomor-
phism between symptoms and relieving agents. As we
have seen, however, heroin users regularly use a wide
range of pharmacologically distinct drugs that extends
from central nervous system (CNS) depressants to psy-
chostimulants. It is difficult to conceptualize how the
regular use of five or so different classes of drugs can be
seen as isomorphic. It begins to appear more like intoxi-
cation, in and of itself, that is the aim. Indeed, it has been
demonstrated repeatedly among heroin users (and the
general population) that the extent of polydrug use
per se is strongly predictive of a poorer clinical profile,
regardless of the drugs used [65,74,79,86]. Rather than
selecting drugs that appear to ameliorate particular psy-
chopathological symptoms, users may be using as many
drugs as possible to ‘dull the pain’. We will return to this
issue below.
SELF-MEDICATION: AN EXPLANATION
OF HEROIN DEPENDENCE?
How, then, do the two major aspects of the SMH accord
with what we know of heroin users? The clinical picture
is certainly consistent with the first postulate. Levels of
psychopathology are high, and very large proportions of
users experience childhood trauma and psychopathology
well before their use of heroin. The clinical picture is
one of distressing affect and symptoms. Indeed, this is
consistent with longitudinal research indicating that pre-
existing psychopathology and distress increases the risk
of heroin use [42,86–88]. It is difficult to see how, if self-
medication is not a driving force into opiate dependence,
the pathogenic childhoods of users could be accounted
for adequately. Furthermore, recent clinical interventions
suggest that reductions in PSTD symptomatology result
in reductions in drug use, but that the reverse does
not apply [70,89–91] [Correction added after online
publication. 5 February 2013. Reference citations 91
and 92 have been removed and subsequent citations
renumbered].
The model is clearly a consistent, and parsimonious,
explanation of the prevalence of pathology and child-
hood abuse. Does this mean that we must argue that all
heroin dependence is due to self-medication? I think
not. Indeed, given the complexity of the phenomenon, no
single theory is likely to explain all cases. Not all users will
have been abused as children, and their heroin use may
well be due to subgroup culture. These would appear,
however, to be a minority. Trauma and psychopathology
appear a major path to heroin dependence, and of par-
ticular relevance to the genesis of female heroin use [92].
Similarly, must we view each and every individual use
episode as an instance of medication? Again, I think not,
at least not in a proximal relationship. Self-medication
may be viewed as a driving force through the drug stage
progressions that ends in the rare phenomenon that is
heroin dependence. Once dependent, other factors such
as neuroadaptation and withdrawal relief clearly come
into play. It would be naive to argue that the dynamics
of dependence itself are irrelevant. Neuroadaptation is
not, however, an argument against self-medication. What
we see in the mature user is an interaction between
long-standing, underlying pathology and the everyday
exigencies of heroin dependence. It might be argued
that defence mechanisms are involved in any affective
experience, and that staving off distressing withdrawal
symptoms might be seen as self-medication [93],
although this involves stretching the medication beyond
the psychodynamics of the individual to the physical
sequelae of dependence.
It is also undeniable that the life-style itself may be
pathogenic and contribute to yet more distress. Tempo-
rary relief comes at a great cost. In particular, however,
the pathogenic role of childhood trauma and the sheer
chronicity of PTSD symptoms [94,95] should always be
borne in mind. Finally, it is clear that all those who expe-
rience childhood abuse and adversity do not develop
heroin dependence. What is clear, however, is that such
abuse greatly increases the risk of substance dependence,
662 Shane Darke
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
and heroin dependence in particular. These associations
are not mere coincidence, and it is entirely reasonable to
postulate a causal relationship.
In contrast, the postulate of drug/symptom specificity
appears less sustainable, at least in terms of a specific
relationship of heroin with controlling anger and rage.
Heroin users progress through stages of drug use initia-
tion from first intoxication at the age of approximately
12–13 years, and exhibit an accretion of polydrug use
from this time onwards [13]. While there is a rapid tran-
sition from heroin initiation to dependence, earlier drugs
are rarely discarded. We must also bear inmind that users
will present with a number of disparate psychiatric diag-
noses, rendering symptom specificity even more tenuous
[65–67]. While users present with high rates of external-
izing disorders such as ASPD, which contain elements
of anger and rage, they also present with high levels of
major depression, dysthymia, hopelessness and anxiety.
The clinical picture is one of far broader distress than
rageful anger. Indeed, not only is this postulate not well
supported, it appears unnecessary. Rather than focus on
specific drugs and symptoms, a more fruitful means of
understanding these behaviours is in terms of intoxica-
tion per se. Heroin users use a wide variety of drugs to
achieve intoxication and, thus, the temporary ameliora-
tion of distress, be that anxiety, depression or anger.
While heroin is a drug that may offer symptomatic relief
and is a psychic, as well as a physical, painkiller, it does
not appear to be ‘enough’. It would appear that it is
psychic numbing from all distressing affect that is being
sought. Higher levels of polydrug use consistently predict
a higher likelihood of overdose, suicide, psychopathology
and poor treatment outcome [65,74,79,85], and might
fruitfully be considered as a measure of the extent of
self-medication.
It is beyond the scope of this piece to review alternate
theories of substance use, which are numerous and
reviewed excellently elsewhere [1]. Two of the most
prominent, however, deserve mention: genetic theory and
gateway theory. Much attention has been paid in recent
years to possible genetic explanations of heroin depend-
ence [96–101]. Most researchhas focusedongenetic vari-
ations inthe muopioidneuroreceptors. Todate, there is no
conclusive evidence that links any particular gene reliably
to opioid dependence. Does such biological research
render models such as the SMH irrelevant? Clearly not.
Again, we must revert to the clinical profile developed
across decades, continents and cultures. Even if there are
variants in alleles that relate to the metabolismof opioids,
the clinical picture of pathology and abuse remains to be
explained. In my opinion, such approaches offer a net loss
of information, as the importance of environmental and
psychological factors areundervalued. Of course, wemust
not ignore recent developments in epigenetics of possible
interactions between environment and gene expres-
sion, and it is certainly true that not all who are abused
will develop psychopathology or substance use disorders
[102]. Even if we accept that there are genetic differences
inresilience totrauma, this does not alter the causal role of
trauma in engendering pathology and substance depend-
ence as conceptualized in the SMH. Indeed, the idea that
genetic predisposition is a more potent explanatory force
than psychopathology, and that the adult pathology dis-
played is engendered primarily by drug use itself [10–12],
relegates the ‘shattered childhoods’ of users to the level of
coincidence or artefact.
Gateway theory postulates a progressive sequence, in
which the use of drugs that are earlier in the sequence
predicts progression to drugs later in the sequence [85].
There are four developmental stages: (i) licit drug use, (ii)
cannabis use, (iii) the use of other illicit ‘hard’ drugs, such
as heroin, and (iv) the use of prescribed psychoactive
pharmaceuticals. While there is considerable evidence for
this sequence, the mechanisms that could underlie such
sequences are unclear, given the differing neuromecha-
nisms of action of the various substances comprising the
sequence. Also, these sequences are not inviolate, with
the primary sequence depending upon both the country
and time in which it was observed [103]. Importantly,
gateway theory provides no rationale as to why people
progress throughthe postulated stages, or mechanisms to
underpin it. Rather than posit gateway drugs, it has been
proposed that sequencing can be more explained parsi-
moniously by a common-factor model, in which common
causal factors underlie all substance use [86]. In such a
model, the entire concept of a ‘gateway’ is discounted.
Rather, some individuals are willing to try psychoactive
substances, and ‘gateway’ drugs are merely the ones that
are more readily available. There are thus common
factors that underlie drug use per se, with psychopathol-
ogy in particular being noted [103]. The high levels of
abuse, neglect and psychopathology seen among heroin
users may thus be seen within the SMH as engendering
the progression to the use of opioids, and thence to
dependence.
CONCLUSIONS
It appears that self-medication plays a prominent, and
plausible, role in generating and maintaining heroin
dependence. Moreover, the role of childhood abuse
appears central. The clinical picture is clear: heroin use is
associated with high levels of psychopathology, and the
onset of traumatic events and/or symptoms typically
occurs well before the use of heroin. Of course, such clini-
cal evidence is consistent with the SMH, but certainly not
proof of it. It would be passing strange if these events
were not related causally. Again, this does not mean that
Self-medication and heroin 663
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
each and every use episode will be self-medication. What
it does mean, however, is that this is a prominent, indeed
dominant, pathway to heroin use.
The observed patterns of polydrug use appear to
render the drug specificity component tenuous. At the
risk of over-statement, all dependent heroin users are
polydrug users. Specificity is not essential in any way to
the core concept, and a more fruitful avenue is to explore
the role of polydrug use as self-medication.
In my opinion, self-medication has a major clinical
role in the development of heroin dependence, and may
well play similar roles in other low-prevalence, high-risk
drug use. The childhoods of heroin users are not inci-
dental. They are core.
Declaration of interests
None.
Acknowledgements
This research was funded by the Australian Government
Department of Health and Ageing. The author would like
to thank Kath Mills and Joanne Ross for their insights.
References
[Correction added after online publication. 5 February 2013.
Reference 91 (Reed P., Anthony J., Breslau N. Incidence of drug
problems in young adults exposed to trauma and posttraumatic
stress disorder. Do early life experiences and predispositions
matter? Arch Gen Psychiatry 2007; 64: 1435–42) and reference
92 (Brown P. J., Stout R. L., Gannon-Rowley J. Substance use
disorder-PTSD comorbidity. Patient’s perceptions of symptom
interplay and treatment issues. J Subst Abuse Treat 1997; 15:
445–8) have been removed from this paper].
1. West R., Hardy A. Theory of Addiction. London: Blackwell
Publishing; 2006.
2. Khantzian E. J. Psychological (structural) vulnerabilities
and the specific appeal of narcotic. Ann NY Acad Sci 1982;
398: 24–32.
3. Khantzian E. J. The self-medication hypothesis of addictive
disorders: focus on heroin and cocaine dependence. Am J
Psychiatry 1985; 142: 1259–64.
4. Khantzian E. J. Addiction: self-destruction or self-repair?
J Subst Abuse Treat 1989; 6: 75.
5. Khantzian E. J. The self-medication hypothesis of sub-
stance use disorders: a reconsideration and recent applica-
tions. Harvard Rev Psychiatry 1997; 4: 231–44.
6. Khantzian E. J. Treating Addiction as a Human Process.
Northvale: Jason Aronson; 1999.
7. Khantzian E. J., Albernese M. J. Understanding Addiction as
Self-Medication. Finding Hope Behind the Pain. Lanham:
Rowman and Littlefield; 2008.
8. Khantzian E. J., Mack J. E., Schatzberg A. F. Heroin use as
an attempt to cope: clinical observations. Am J Psychiatry
1974; 131: 160–4.
9. Khantzian E. J., Schneider R. J. Treatment implications
of a psychodynamic understanding of opioid addicts. In:
Meyer R. E., editor. Psychopathology and Addictive Disorders.
NewYork: Guilford Press; 1986, p. 323–33.
10. DuPont R. L., Gold M. S. Comorbidity and ‘self-
medication’. J Addict Dis 2007; 26: 13–23.
11. Goldsmith R. J. An integrated psychology for the addic-
tions: beyond the self-medication hypothesis. J Addict Dis
1993; 12: 139–54.
12. Vaillant G. R. E., Milofsky E. S. The etiology of alcoholism:
a prospective viewpoint. Am Psychol 1982; 37: 494–
503.
13. Darke S. The Life of the Heroin User: Typical Beginnings,
Trajectories and Outcomes. Cambridge: Cambridge Univer-
sity Press; 2011.
14. United Nations Office of Drug Control. World Illicit Drug
Report 2011. New York: United Nations Publications;
2011.
15. Blume A., Schmaling K., Marlatt G. Revisiting the self-
medication hypothesis froma behavioral perspective. Cogn
Behav Pract 2000; 7: 379–84.
16. Graham H., Power C. Childhood disadvantage and
health inequalities: a framework for policy based on
lifecourse research. Child Care Health Dev 2004; 30:
671–8.
17. Wilkinson R., Marmot M., editors. The Solid Facts: Social
Determinants of Health, 2nd edn. Copenhagen: Centre for
Urban Health World Health Organization; 2003.
18. Galea S., Nandi V. V., Vlahov D. The social epidemiology of
substance use. Epidemiol Rev 2004; 26: 36–52.
19. Poulton R., Caspi A., Milne B. J., Thomson W. M., Taylor
A., Sears M. R. et al. Association between children’s expe-
rience of socioeconomic disadvantage and adult health: a
life-course study. Lancet 2002; 360: 1640–5.
20. Darke S., Ross J. The relationship betweensuicide and over-
dose among methadone maintenance patients in Sydney,
Australia. Addiction 2001; 96: 1443–53.
21. Conroy E., Degenhardt L., Mattick R., Nelson E. C. Child
maltreatment as a risk factor for opioid dependence: com-
parison of family characteristics and type and severity of
child maltreatment with a matched control group. Child
Abuse Negl 2009; 33: 343–52.
22. Coviello D. M., Alterman A. I., Cacciola J. S., Rutherford M.
J., Zanis D. A. The role of family history in addiction sever-
ity and treatment response. J Subst Abuse Treat 2004; 26:
1–11.
23. Hser Y. Predicting long-term stable recovery from heroin
addiction: findings from a 33-year follow-up. J Addict Dis
2007; 26: 51–60.
24. Rossow I., Lauritzen G. Shattered childhood: a key issue in
suicidal behavior among drug addicts. Addiction 2001; 96:
227–40.
25. Ravndal E., Lauritzen G., Jansson S. O., Larsson J. Child-
hood maltreatment among Norwegian drug abusers in
treatment. Int J Soc Welfare 2001; 10: 142–7.
26. Fergusson D. M., Horwood L. J., Lynskey M. T. Parental
separation. Adolescent psychopathology, and problem
behaviors. J Am Acad Child Adolesc Psychiatry 1994; 338:
1122–31.
27. Lipman E. L., Boyle M. H., Dooley M. D., Offord D. R. Child
well-being in single mother families. J Am Acad Child
Adolesc Psychiatry 2002; 41: 75–82.
28. Heffernan K., Cloitre M., Tardiff K., Marzuk P., Portera L.,
Leon A. Childhood trauma as a correlate of lifetime opiate
use in psychiatric patients. Addict Behav 2000; 25: 797–
803.
664 Shane Darke
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
29. Ompad D. C., Ikeda R. M., Shah N., Fuller C. M., Bailey S.,
Morse E. et al. Childhood sexual abuse and age at initiation
of injection drug use. AmJ Public Health 2005; 95: 703–9.
30. Westermeyer J., Wahmanholm K., Thuras P. Effects of
childhood physical abuse on course and severity of sub-
stance abuse. Am J Addict 2001; 10: 101–10.
31. Wu N. S., Schairer L. C., Dellor E., Grell C. Childhood
trauma and health outcomes in adults with comorbid
substance abuse and mental health disorders. Addict Behav
2010; 35: 68–71.
32. Braitstein P., Lia K., Tyndall M., Spittal P., O’Shaughnessy
M. V., Schilder A. et al. Sexual violence among a cohort of
injection drug users. Soc Sci Med 2003; 57: 561–9.
33. Gilbert L., El-Bassel N., Schilling R. F., Friedman E. Child-
hood abuse as a risk for partner abuse among women in
methadone maintenance. Am J Drug Alcohol Abuse 1997;
23: 581–95.
34. Fergusson D. M., Lynskey M. T. Physical punishment/
maltreatment during childhood and adjustment in young
adulthood. Child Abuse Negl 1997; 21: 617–30.
35. Knutson J., DeGarmo D., Reid J. Social disadvantage and
neglectful parenting as precursors to the development
of antisocial and aggressive child behavior: testing a
theoretical model. Aggress Behav 2004; 30: 187–205.
36. Bartholomew N. G., Courtney K., Rowan-Szal G. A.,
Simpson D. D. Sexual abuse history and treatment out-
comes among women undergoing methadone treatment.
J Subst Abuse Treat 2005; 29: 231–5.
37. Branstetter S. A., Bower E. H., Kamien J., Amass L. A
history of sexual, emotional, or physical abuse predicts
adjustment during opioid maintenance treatment. J Subst
Abuse Treat 2008; 34: 208–14.
38. Oviedo-Joekes E., Marchand K., Guh D., Marsh D. C.,
Brissettte S., Krausz M. et al. History of reported sexual or
physical abuse among long-term heroin users and their
response to substitution treatment. Addict Behav 2011; 36:
55–60.
39. Sansone R. A., Whitecar P., Wiederman M. W. The
prevalence of childhood trauma among those seeking
buprenorphine treatment. J Addict Dis 2009; 28: 64–7.
40. Ahmadi J., Arabi H., Mansouri Y. Prevalence of substance
use among offspring of opioid addicts. Addict Behav 2003;
28: 591–5.
41. Darke S., Ross J., Lynskey M. The relationship of conduct
disorder to attempted suicide and drug use history among
methadone maintenance patients. Drug Alcohol Rev 2003;
22: 21–5.
42. Hahesy A. L., Wilens T. E., Biederman J., Van Patten S. L.,
Spencer T. Temporal association between childhood psy-
chopathology and substance use disorders: findings from
a sample of adults with opioid or alcohol dependency.
Psychiatry Res 2002; 109: 245–53.
43. Lynskey M. T., Fergusson D. Childhood conduct pro-
blems, attention deficit behaviors, and adolescent alcohol,
tobacco, and illicit drug use. J Abnorm Child Psychol 1995;
23: 281–301.
44. Pugatch D., Strong L. L., Has P., Patterson D., Combs C.,
Reinert R. et al. Heroin use in adolescents and young
adults admitted for drug detoxification. J Subst Abuse
2001; 13: 337–46.
45. Wilens T. E., Biedeman J., Bredin E., Hahesy A. L.,
Abratntes A., Neft D. et al. A family study of the high-risk
children of opioid- and alcohol-dependent parents. Am J
Addict 2002; 11: 41- 51.
46. Brooner R. K., Greenfield L., Schmidt C. W., Bigelow G. E.
Antisocial personality disorder and HIV infection in drug
abusers. Am J Psychiatry 1993; 150: 53–8.
47. Darke S., Williamson A., Ross J., Teesson M., Lynskey M.
Borderline personality disorder, antisocial personality dis-
order and risk-taking among heroin users: findings from
the Australian Treatment Outcome Study (ATOS). Drug
Alcohol Depend 2004; 74: 77–83.
48. Rouser E., Brooner R. K., Regier M. W., Bigelow G. E.
Psychiatric distress in antisocial drug abusers: relation to
other personality disorders. Drug Alcohol Depend 1994; 34:
149–54.
49. Gossop M., Marsden J., Stewart D., Treacy S. Change and
stability of change after treatment of drug misuse. 2 year
outcomes fromthe National Treatment Outcome Research
Study. Addict Behav 2002; 27: 155–66.
50. Ross J., Teesson M., Darke S., Lynskey M., Ali R., Ritter A.
et al. The characteristics of heroin users entering treat-
ment: findings from the Australian Treatment Outcome
Study (ATOS). Drug Alcohol Rev 2005; 24: 411–8.
51. Bargagli A. M., Faggiano F., Amato L., Salamina G., Davoli
M., Mathis F. et al. VEdeTTE, a longitudinal study on effec-
tiveness of treatments for heroin addiction in Italy: study
protocol and characteristics of study population. Subst Use
Misuse 2006; 41: 1861–79.
52. Brugal M. T., Barrio G., Fuente L., Regidor E., Royuela L.,
Suelves J. M. Factors associated with non-fatal heroin
overdose: assessing the effect of frequency and route
of heroin administration. Addiction 2002; 97: 319–
27.
53. Darke S., Williamson A., Ross J., Teesson M. Reductions
in heroin use are not associated with increases in other
drug use: two year findings from the Australian Treat-
ment Outcome Study. Drug Alcohol Depend 2006; 84:
201–5.
54. Darke S., Ross J., Mills K., Teesson M., Williamson A.,
Havard A. Benzodiazepine use amongst heroin users:
baseline use, current use and clinical outcome. Drug
Alcohol Rev 2010; 29: 250–5.
55. Flynn P. M., Joe G. W., Broome K. M., Simpson D. D., Brown
B. S. Recovery from opioid addiction in DATOS. J Subst
Abuse Treat 2003; 25: 177–86.
56. Haasen C., Verthein U., Degkwitz P., Berger J., Krausz M.,
Naber D. Heroin-assisted treatment for opioid dependence
randomised controlled trial. Br J Psychiatry 2007; 191:
55–62.
57. Hubbard R. L., Craddock S. G., Flynn P. M., Anderson J.,
Etheridge R. M. Overview of one year follow-up outcomes
in the Drug Abuse Treatment Outcome Study (DATOS).
Psychol Addict Behav 1997; 11: 261–78.
58. Miller C. L., Kerr T., Strathdee S. A., Li K., Wood E. Factors
associated with premature mortality among young
injection drug users in Vancouver. Harm Reduct J 2007; 4:
1–7.
59. Quan V., Vongchak T., Jittiwutikan J., Kawichai S., Srirak
N., Wiboonnatakul K. et al. Predictors of mortality among
injecting and non-injecting HIV-negative drug users in
northern Thailand. Addiction 2007; 102: 441–6.
60. Williamson A., Darke S., Ross J., Teesson M. Effect of
baseline cocaine use on treatment outcomes for heroin
dependence over 24 months. J Subst Abuse Treat 2007; 33:
287–93.
61. Cacciola J. S., Alterman A. I., Rutherford M. J., McKay J. R.,
Mulvaney F. D. The relationship of psychiatric comorbidity
Self-medication and heroin 665
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
to treatment outcomes in methadone maintained patients.
Drug Alcohol Depend 2001; 61: 271–80.
62. Lofwall M. R., Brooner R. K., Bigelow G. E., Kindbom K.,
Strain E. C. Characteristics of older opioid maintenance
patients. J Subst Abuse Treat 2005; 28: 265–72.
63. Darke S., Ross J., Williamson A., Mills K. L., Havard A.,
Teesson M. Patterns of non-fatal heroin overdose over a
three year period: findings from the Australian Treatment
Outcome Study. J Urban Health 2007; 84: 283–91.
64. Brienza R. S., Stein M. D., Chen M. H., Cogineni A., Sobota
M., Maksad J. et al. Depression among needle exchange
and methadone maintenance clients. J Subst Abuse Treat
2000; 18: 331–7.
65. Darke S., Ross J. Polydrug dependence and psychiatric
comorbidity among heroin injectors. Drug Alcohol Depend
1997; 48: 135–41.
66. Kidorf M., Disney E. R., King V. L., Neufeld K., Beilenson
P. L., Brooner R. K. Prevalence of psychiatric and sub-
stance use disorders in opioid abusers in a community
syringe exchange program. Drug Alcohol Depend 2004; 74:
115–22.
67. Maloney E., Degenhardt L., Darke S., Nelson E. C. Investi-
gating the co-occurrence of self-mutilation and suicide
attempts among opioid dependent individuals. Suicide Life
Threat Behav 2010; 40: 50–62.
68. Teesson M., Havard A., Fairbairn S., Ross J., Lynskey M.,
Darke S. Depression among entrants to treatment
for heroin dependence in the Australian Treatment
Outcome Study (ATOS): prevalence, correlates and
treatment seeking. Drug Alcohol Depend 2005; 78: 309–
15.
69. Dore G., Mills K., Murray R., Teesson M., Farrugia P.
Post-traumatic stress disorder, depression and suicidality
in inpatients with substance use disorders. Drug Alcohol
Rev 2012; 33: 294–302.
70. Hien D. A., Jiang H., Campbell A. N. S., Hu M., Miele G. M.,
Cohen L. R. et al. Do treatment improvements in PTSD
severity affect substance use outcomes? A secondary
analysis from a randomized clinical trial in NIDA’s
Clinical Trials Network. Am J Psychiatry 2010; 167:
95–101.
71. Hien D. A., Nunes E., Levin F. R., Fraser D. Posttraumatic
stress disorder and short-term outcome in early metha-
done treatment. J Subst Abuse Treat 2000; 19: 31–7.
72. Mills K., Lynskey M., Teesson M., Ross J., Darke S. Post-
traumatic stress disorder among people with heroin
dependence in the Australian Treatment Outcome Study
(ATOS): prevalence and correlates. Drug Alcohol Depend
2005; 77: 243–9.
73. Kessler R. C., Berglund P., Demler O., Jin R., Merikangas
K. R., Walters E. E. Lifetime prevalence and age-of-onset
distributions of DSM-IV disorders in the National Comor-
bidity Survey replication. Arch Gen Psychiatry 2005; 62:
593–602.
74. Darke S., Ross J., Williamson A., Mills K. L., Havard A.,
Teesson M. Patterns and correlates of attempted suicide by
heroin users over a three year period: findings from the
AustralianTreatment Outcome Study. Drug Alcohol Depend
2007; 87: 146–52.
75. Rossow I., Lauritzen G. Balancing on the edge of death:
suicide attempts and life-threatening overdoses among
drug addicts. Addiction 1999; 94: 209–19.
76. Roy A. Characteristics of opiate dependent patients who
attempt suicide. J Clin Psychiatry 2002; 63: 403–7.
77. Roy A. Risk factors for attempting suicide in heroin
addicts. Suicide Life Threat Behav 2010; 40: 416–20.
78. Trémeau F., Darrey A., Staner L., Corrêa H., Weibel H.,
Khidichian F. et al. Suicidality in opioid-dependent sub-
jects. Am J Addict 2008; 17: 187–94.
79. Borges G., Walters E. E., Kessler R. C. Associations of
substance use, abuse, and dependence with subsequent
suicidal behaviour. Am J Epidemiol 2000; 151: 781–9.
80. Johnston A., Pirkis J., Burgess P. M. Suicidal thoughts and
behaviours among Australian adults: findings from the
2007 National Survey of Mental Health and Wellbeing.
Aust NZ J Psychiatry 2009; 43: 635–43.
81. American Psychiatric Association. Diagnostic and Statis-
tical Manual of Mental Disorders, 4th edn. Text revision.
Washington, DC: American Psychiatric Association;
2000.
82. Trull T. J., Sher K. J., Minks-Brown C., Durbin J., Burr R.
Borderline personality disorder and substance use disor-
ders: a review and integration. Clin Psychol Rev 2000; 20:
235–53.
83. Teesson M., Mills K. L., Ross J., Darke S., Williamson A.,
Havard A. The impact of treatment on 3 year outcomes for
heroin dependence: findings from the Australian Treat-
ment Outcome Study (ATOS). Addiction 2008; 103: 80–8.
84. Havard A., Teesson M., Darke S., Ross J. Depression among
heroin users: 12 month outcomes from the Australian
Treatment Outcome Study (ATOS). J Subst Abuse Treat
2006; 30: 355–62.
85. Kandel D. B., editor. Stages and Pathways of Drug Involve-
ment: Examining the Gateway Hypothesis. Cambridge:
Cambridge University Press; 2002.
86. DeMaria P. A., Sterling R., Weinstein S. P. The effect of
stimulant and sedative use on treatment outcome of
patients admitted to methadone maintenance treatment.
Am J Addict 2000; 9: 145–53.
87. Chilcoat H. D., Breslau N. Investigations of causal path-
ways between PTSD and drug use disorders. Addict Behav
1998; 23: 827–40.
88. Martins S. S., Keyes K. M., Storr C. L., ZhuH., Chilcoat H. D.
Pathways between nonmedical opioid use/dependence
and psychiatric disorders: results from the National Epide-
miologic Survey on Alcohol and Related Conditions. Drug
Alcohol Depend 2009; 103: 16–24.
89. Back S. E., Brady K. T., Jaanimagi U., Jackson J. L. Cocaine
dependence and PSTD: a pilot study of symptoms interplay
and treatment preferences. Addict Behav 2006; 31: 351–4.
90. Back S. E., Brady K. T., Sonne S. C., Verduin M. L. Symptom
improvement and co-occurring PTSD and alcohol depend-
ence. J Nerv Ment Dis 2006; 194: 690–6.
91. Read J. P., Brown P. J., Kahler C. W. Substance use and
posttraumatic stress disorders: symptoms interplay and
effects on outcome. Addict Behav 2004; 29: 1665–72.
92. Plotzker R. E., Metzger D. S., Holmes W. C. Childhood sexual
and physical abuse histories, PTSD, depression, and HIV
risk outcomes in women injection drug users: a potential
mediating pathway. Am J Addict 2007; 16: 431–8.
93. Gottdiener W. H., Murawski P., Kucharski L. T. Using the
delay discounting test for failures in ego control in sub-
stance users: a meta-analysis. Psychoanal Q 2008; 25:
533–49.
94. Chapman C., Mills K. L., Slade T., McFarlane A., Brysant
R., Creamer M. et al. Remission from post-traumatic stress
disorder in the general population. Psychol Med 2012; 42:
1695–1703.
666 Shane Darke
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667
95. Pietrzaka R. H., Goldstein R. B., Southwick S. M., Grant
B. F. Prevalence and Axis I comorbidity of full and partial
posttraumatic stress disorder in the United States: results
from Wave 2 of the National Epidemiologic Survey on
Alcohol and Related Conditions. J Anx Dis 2011; 25:
456–65.
96. Agrawal A., Lynskey M. Are there genetic influences
on addiction: evidence from family, adoption and twin
studies. Addiction 2008; 103: 1069–81.
97. Clarke T. K., Krause K., Li T., Schumann G. An association
of prodynorphin polymorphisms and opioid dependence
in females in a Chinese population. Addict Biol 2009; 14:
366–70.
98. De los Cobos J. P. Association of CYP2D6 ultrarapid
metabolizer genotype with deficient patient satisfaction
regarding methadone maintenance treatment. Drug
Alcohol Depend 2007; 89: 190–4.
99. Haile C. N., Kosten T. A., Kosten T. R. Pharmacogenetic
treatments for drug addiction: alcohol and opiates. Am J
Drug Alcohol Abuse 2008; 34: 355–81.
100. Mayer P., Hollt V. Pharmacogenetics of opioid receptors
and addiction. Pharmacogenet Genomics 2006; 16: 1–7.
101. Tyrfingsson T., Thorgeirsson T. E., Geller F., Runarsdóttir
V., Hansdóttir I., Bjornsdottir G. et al. Addictions and their
familiality in Iceland. Ann NY Acad Sci 2010; 1187: 208–
17.
102. Rutter M., Bishop D. V., Pine D. S., Scott S., Stevenson J.,
Taylor E. et al., editors. Rutter’s Child and Adolescent Psy-
chiatry, 5th edn. Boston: Blackwell Publishing; 2008.
103. Degenhardt L., Chiu W. T., Conway K., Dierker L., Glantz
M., Kalaydjian A. et al. Does the ‘gateway’ matter? Asso-
ciations between the order of drug use initiation and the
development of drug dependence in the National Comor-
bidity Study Replication. Psychol Med 2009; 39: 157–67.
Self-medication and heroin 667
© 2012 The Author, Addiction © 2012 Society for the Study of Addiction Addiction, 108, 659–667