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Pathways to heroin dependence: time to re-appraise

Shane Darke
National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia
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.
Submitted 11 December 2011; initial review completed 6 March 2012; final version accepted 22 June 2012
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 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,
© 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
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].
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
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
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 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,
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© 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
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.
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
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,
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© 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
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
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
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.
[Correction added after online publication. 5 February 2013.
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