I. Bibliographical update on Drug Addiction

Keywords: Hospital detoxification, Outpatient detoxification, Case-management, Primary Care, Drug Court, Urine metabolites, Inhalants

SERVICE ORGANIZATION

Germany: a specialized hospital started operating in the city of Velbert ever since 1978 with a single administration for inpatient services and a single staff for outpatient services which actually enables it to start a therapeutic programme that might guarantee continuity in assistance and therapy (1).

U.S.A.: many hospital centres accommodating drug-addicts for detoxification, shortly after hospitalization, administer cognitive tests with the aim of assessing the patient’s cognitive capacities and facilitating the scheduling of the rehabilitation plan. The subjects were normally under withdrawal which makes it possible to warp cognitive test results. A new short set of questions comprised in the Cognitive Capacity Screening Examination (CCSE) was tested; however, even after applying gender and schooling-linked corrections to the results, they still turned out to be insufficient to provide indications to the therapists (2).

The 21-day inpatient detoxification programme followed by the Veterans Administration is the typical tapering off therapy; the discharge sheets of 38,863 patients from 98 Centres were examined in order to assess the role of the programme’s duration (28, 21 or even fewer days) and the staff-patient ratio on the effectiveness of therapy. The effectiveness was measured on the basis of the frequency of readmissions in the 6 months after discharge. This is like saying that in case of no readmission, the programme was judged to be successful for that single drug-addict. On carrying out further calculations considering the above-stated parameters, it can be stated that the 21-day therapy is more cost-effective than the 28-day therapy and the same holds true for staff down-sizing and for referral of patients to smaller-sized treatment centres. Of course, this type of policy produces longer lag-times for the personnel if compared to those in larger-sized and higher-staffed Centres. The patient characteristics do not affect costs even if, evidently enough, those who already have a hospital record are more likely to be readmitted and therefore represent a failure for the programme at the outset (3).

The public funding arrangements for inpatient treatment Centres are not based on fees but on performance and outcome and this is not limitedly applied to rehabilitation Centres and Nursing Homes in the U.S.A. but also extends, albeit in a piecemeal fashion, to Centres and Institutes treating drug-addicts. A study carried out in the State of Maine illustrated a range of public funding arrangements based on drug-free rates and on improved social severity indeces. Generally speaking however these parameters do not seem suitable to facilitate the programmes aimed at the hard core of drug addiction. It is nonetheless necessary to point to the risk that the system runs of being exploited for its capacity to screen out the most difficult patients (4).

Work environment and personnel attitudes have a considerable effect on outcomes: the analysis of 329 helpers working in 15 treatment centres showed that a supportive environment fostered positive motivation models among the personnel who, in addition to setting albeit gradual objectives involving the patients, also developed the subsequent self-help systems and twelve-step group plans (12).

The primary care physician ranks as one of the prime points of reference in terms of continuity and cost-effectiveness in alcohol and drug addiction treatment and his/her involvement is judged to be essential in British programmes. However, this involvement does not turn out to be all too enthusiastic seen from the General Practitioner’s point of view as comes out of a survey involving 152 G.P.s in the Greater London Area. To begin with, only 52% of the interviewees accepted to respond which is a rather low percentage for a culture based on collaboration as the British is. Respondents stated that the number of alcohol-dependent patients or with some alcohol problem is lower than official recommendations as the average is equal to 3.5.

Not to even mention the percentage rate for drug-addicts which represent 0.75% of the total. It is a well-known fact that physicians have a negative consideration of alcoholics but their judgment of heroin and cocaine addicts is all the more negative and the setting offered by the Primary Health Service is considered as viable for the care of alcoholics but not for opioid addicts. Furthermore, the General Practitioners interviewed do not appear to be at all attracted by financial incentives provided for under government programmes. It might therefore prove advisable to refer to primary care physicians only the least severe cases of alcohol and drug addiction (6).

The British Primary Care facilities have been tested on excessive drinkers. The attribution index was calculated which grossly corresponds to the percentage of drinkers who do not change their behaviour or drop out of the primary care system; these subjects are generally young with high alcohol abuse levels and low schooling levels.This might cast some doubt on whether some of the successes reported in scientific articles might be due to screening in lower risk patients (7).

In Texas, experiments were conducted on two intervention systems for alcoholics, i.e. involvement of the physician and of a psychopedagogical working group. Results were checked not only on the basis of behavioural changes but also of psycho-social problems and the performance of biochemical markers. The patients were randomized into 4 groups (intervention on the part of the physician, of the psycho-social group, physician + psycho-social group and no intervention). The patients were recruited by a primary care centre managed by a public Hospital and had not requested alcohol-related interventions; their alcohol addiction had been detected through a standard test and also through the famous A.S.I. (Addiction Severity Index). After 12 and 18 months the patients, who were mostly Hispano-Americans, improved without large differences between groups. Could this have been due to the detection test? Or the Hathorne effect? Whatever the case may be, we suggest to target control groups not selected with long administration tests (8).

Case-management always attracts endless flows of literature: a series was conducted on 360 IDUs admitted in a take-charge centre and assigned at random either to the case-manager group or to the control group. The information received from the case-manager on the types of treatments was limited but admissions in the therapeutic Services, retention rates and therapeutic successes were unarguably higher in the case-manager than in the control group (9).

The integration of economic models in the assessment of Services to battle drug addiction stems from the revolution staged by the U.S. health care systems in the last decade. Traditional inpatient Services and residential treatment are slowly turning into outpatient facilities and, as we have already seen, traditional hospitalization for detoxification is beoming a memory of the past. But above all, changes are occurring in the treatment planning process which no longer closely depends on the severity of the of the situation but on the insurance cover, i.e. the third party that pays. Admission and authorization procedures are becoming increasingly complex and, above all, take on purely administrative and impersonal characteristics. The criteria used in determining the type of treatment appear to be arbitrary and not clinically based (10).

How can we transplant the US Drug Courts to Great Britain? We should begin by differentiating between 4 different versions of American Drug Courts: they range from the judge who concentrates a large number of drug-related trials and refers offenders under different forms of conditional release to specific Centres, to the all-competent Drug Court of Miami. In this judicial system, the immediate treatment is managed by the magistracy itself and therefore kept under direct control. The more curious readers can also draw information from the review on the ACUTRON system consisting of a series of (auricular) acupunctures which obtained its primary therapeutic legitimation from the Miami Court. Also the other Drug Courts control the treatment centres to which they refer offenders under different forms of conditional release; probation is instead regulated differently. According to the offender’s behaviour, the Court establishes punishments (a 1 week minimum detention for every breach) or rewards (setting treatment sessions further apart). The maximum return to detention is 3 months and treatments range from conventional detoxification to group therapy to individual therapy; urine tests are taken frequently and the results are reported to the Court within an hour.

The Drug Court movement originated from the initiative of a group of magistrates that were frustrated with the failures and paradoxes of the then on-going situation. At the beginning, the Department of Justice was not involved although today the Attorney General guarantees a fund of 12 million Dollars a year allocated for the training programmes alone. It is estimated that for every Dollar that goes into these Courts the Budget saves at least seven. The professionals and help-givers in charge of the treatments are selected on the basis of the therapeutic successes that they can boast and they are generally given financially advantageous contracts. The urine tests are generally sub-contracted and do not fall under the typical contracts of the caregivers working in the Centres. Treatment usually lasts 2 years and, if successful, the offender is written off (although not entirely) the criminal records; oftentimes treatment is followed by a two-year probation period. In case of relapse, persistent criminal activities and drop-out, the offender goes back to jail and may be sbjected to supplementary punishments. However, in order to introduce a similar system in Great Britain, it would be necessary to amend existing laws and set up a different type of Service (11).

Experiences and perspectives for the control of cocaine-addiction treatment: issue N. 175 of the N.I.D.A. Publications, under the Research monographic series (12), contains indications on the pharmacotherapy of cocaine addiction which is currently in the experimental phase as well as the assessment criteria for the effectiveness of treatment. The material is drawn from a Conference held in 1992 and therefore is not extremely updated but problems tend to remain the same. With the aim of experimenting a number of antidepressants and other psychoactive drugs also against psycho-social treatment, urine tests play a significant role. The original tests were designed for on-the-job investigations and are therefore qualitative with ecgonine concentration cut-offs at 300 ng/ml. At a later point in time, quantitative methods were developed (chromatography and fluorescent immunotests) which were also more costly. Apparently, the quantitative methods are more significant in terms of evaluating the effectiveness of treatment although, if they were to be presented as an average, they could be affected by just a few high-dose consumers.

Furthermore, it should be recalled that metabolite bioavailability varies according to the cocaine administration route as it is low when sniffed if compared to when it is injected intravenously. It can therefore be said that quantitative tests are useful to monitor individuals but should be computed in a more sophisticated way if presented as an average. Statistical groupings of averages related to "dirty" urine samples appear to be more reliable although the recent use of fluoxetine provokes an acceleration in metabolic rates. But how could we assess a state of abstinence? In daily consumers, 4 weeks of clean urine samples are sufficient; for those who consume large weekly doses (binges), the observation period should be longer; many consider the fact that a patient manages to abstain for at least half the trial period as a sufficient parameter. Discriminative tests can always apply insofar as an average 10% reduction is significant only if it means that 1 cocaine addict out of 10 has given it up completely whereas it is scarcely significant if it means that they have all reduced consumption by an average 10%. Halfing intravenous administrations from 6 to 3 can prove to be significant as it reduces the risk of HIV, HCV, etc. It is also important to consider the duration of the period of abstinence. Furthermore, it is advisable for the person conducting the test to be "blind" with respect to the name and the clinical characteristics of the subject (13).

FLASHES

Do you know that in India cough syrups containing codeine are a source of dependence formation? According to statistics provided by treatment Centres, dependence involves young city-dwelling males with a good level of schooling; they begin by picking up the suggestion from their friends or out of curiosity and they can even reach remarkably high doses with the onset of withdrawal symptomatology in 85% of the cases. They usually seek a psychostimulant because the combination of an opioid and a sympathomimetic agent provokes a particularly euphoric effect. This is almost totally unrelated to the use that French drug addicts make of codeine tablets (14). Among the Inhu Canadian Indians (those that recently rose up in arms to claim back their lands) this abuse is widespread among young adults while it seems to have reduced among teen-agers. It is often connected to criminal activities, poly drug use and reaction to abrupt changes in the cultural context (15).

A rather different picture is portrayed by the 775 inhalant-provoked deaths that occurred in England in the period 1985-91 and that were concentrated in the 6 regions where the residing population represents 17% of the entire British population. Maximum incidence is recorded among socially deprived subjects (16). The analytical picture of the damage suffered by inhaling solvents is outlined by Rosenberg: acute damage is suffered by heart, lungs, kidneys, liver and brain. Chronic damage is prevalently suffered by the brain and the RMN test shows that it is the white matter that is especially affected. However the damage is not irreversible in terms of the effects on behaviour insofar as aggressive types of therapeutic interventions such as the ones used for patients with head injuries can prove to be effective (17). Inhalant-abusers are often abusers of other drugs and come from a broken family background, have problems in school, a criminal record and friends in criminal circles; they are often subjects suffering from emotional distress and psychopathologies which might offer the opportunity to be investigated in psychopathological research (18).

General remarks on specialized literature: it is difficult to differentiate between all the magazines in circulation while more are forthcoming; most of these come from the U.S.A. and rely on a sociological approach which abunds with research studies that do not much interest Europeans. Outcomes appear to be literally redundant as the very same author or group of authors will publish the same results on different magazines, bringing about slight changes made simple by the universal use of word processing. However, we are recently witnessing an improvement in the presentation of research goals and outcomes and it is wrong to assume that some topics of debate, such as the role of methadone, are unsupported by scientifically sound evidence. Of course, much depends on the criteria used for assessing recovery, remission, relapse and on the very definitions of drug-addiction: in connection to this, you are kindly invited to read the first part of a collection on "Domini della Tossicodipendenza" ("Dominions of Drug Addiction") by Flavio Amico and published on the Bulletin "Persona e Comunita", the monthly issue of FICT, Year 2, issue 1 January 1998, Via Nomentana n. 355, Zip Code: 00162 - ROME, Fax 06-86328229 c/o Istituto Marymount.

II-a. Recent development on cocaine

Keywords: Vaccine, perinatal complications, treatment, Dopamine, craving, PET, RMN, Neuroimaging.

A vaccine? In consideration of the extention of cocaine addiction (it is estimated that there are 2.1 million cocaine addicts in the U.S.) and of the lack of substitution or antagonist therapy as it exists for heroin, the immunological approach follows a rationale of its own: to block cocaine intake with preformed antibodies in order to prevent it from reaching brain centres.

Fox (1) recalls that the most significant action of cocaine is to block the dopamine-carrying system thereby provoking a prolonged stimulation of the dopamine receptors; a collateral effect is that of binding to serotonin and norepinephrine transporters. However, from an immunological standpoint, the theoretical rationale comes across a substantial difficulty: the fact that antibodies present in the bloodstream fail to pass across the blood-brain barrier. Not to even mention the speed at which brain centres are affected when cocaine intake is endonasal. However, research conducted on murine models show that circulating antibodies succeed in slowing down cocaine penetration in the brain. At the same time, this extremely interesting set of animal experimentations has made it possible to exclude some theoretically possible risks such as that of provoking hypersensitivity; indeed, cocaine powder is so fine that the risk of forming immunocomplexes with protein conjugates is highly reduced.

Nevertheless, always from a theoretical point of view, it is difficult to reply to an objection such as: the vaccine certainly slows down the onset of the rush but the inoculated cocaine addict can always increase his dose in order to get a high! This is why other approaches are being taken in addition to traditional vaccination:

1. the use of enzymes that metabolize cocaine in the blood stream; the leading enzyme is butyl-choline-esterase (BChE) that is normally found in the blood-stream and can therefore be injected directly without it causing repercussions;
2. the administration of monoclonal catalytic antibodies that, unlike vaccine-produced antibodies, bind with cocaine molecules and break them down just like BChE. It is difficult however to find the "right" antigens.

Direct BChE injection produces a sizable increase of this enzyme in the blood-stream for several days and this, among other things, might make it possible to plan socio-psychotherapeutic interventions concomitant to periodical administrations (once a fortnight for BChE injections and once a month for catalytic antibodies).

The fact that in none of these cases antibodies or enzymes pass the blood-brain barrier justifies the proposal to compound immunological therapy with a pharmacological one using dopamine antagonists that block receptor activity and reduce craving (2).

Vaccination however gives rise to ethical and medicolegal problems: in case research on cocaine antibodies were used as a pre-hiring screening test, this would be discriminatory against vaccinated subjects (a similar problem to that of recruiting Western volunteers for anti-HIV vaccine testing).

In consideration of these difficulties, some supporters of vaccination procedures suggest that they be universal and mandatory (which, frankly speaking, cannot be considered as a top-ranking priority for Health Care policies) (3). Keeping to the subject of the toxicological tests for cocaine addiction: according to Joseph (4), hair tests produce different results according to hair-colour in the sense that they are more effective on dark hair and less effective on light-coloured hair because cocaine’s melanin-binding capacity is between 5 to 43 times higher in black hair than in light blonde hair.

Cocaine and pregnancy. It is possible to draw the profile of pregnant cocaine addicts on the basis of 229 case studies (5):

1. family record of alcohol addiction;
2. high rate of cigarette smoking;
3. pre-existence of depressive symptoms also in the subject’s partner;
4. insufficient social support.

The most sizable group is that in Florida and Tennessee: 150 cocaine addicts were singled out of 2500 pregnant women and their characteristics were compared to those of an equal number of peer non-drug or cocaine users. The two groups were subjected to quarterly pre-natal visits and a post-delivery follow-up was conducted on neonatal and infant development.

Most of the subjects in the group were Afro-American from low socio-economic backgrounds and multiparous and their cocaine use was often combined with marijuana and cigarette smoking and alcohol. Compared to other surveys, these women had not been recruited through anti-drug services but on the basis of their attendance in pre-natal services (6). Most of them were crack addicts.

The outcome of the survey revealed:

1. no excess of fetal deaths, in contrast with the results of different surveys; this might be partly due to the pre-natal assistence provided to this group;
2. a higher incidence of pre-term births;
3. a correlation between the amount of crack consumed, weight at birth, new-born length and head circumference albeit with scarce statistical significance. The correlation is more relevant in the second and third quarters.

The same group conducted an in-depth study of the neuro-behavioural characteristics of babies born of cocaine- addicted mothers (7). This study, like the previous one, obviously considered the influence of cannabis, tobacco and alcohol but a negative correlation was found between cocaine consumption during the third quarter and shifts from the Neonatal Brazlton Scale (behaviour assessment), especially in respect of:

1. scores on orientation;
2. scores on attention;
3. scores on response speed.

Of course, it will be necessary to monitor these children over time also in consideration of their family and social environment which are far from being the best-suited but the message underlying this research effort is that attention should focus on cocaine consumption during the last phase of gestation. Unfortunately, as Lester (8) points out, very few of these research studies provided a follow-up of these children after the age of three.

Behavioural treatment during pregnancy can prove to be effective: this is revealed by Elk (9) even if the group was numerically small (35 pregnant women); personalized programmes based on self-reinforcement techniques not only achieve abstinence during the gestation period but also during the puerperium and the newborn nursing phase.

The study nonetheless shows a positive correlation between cocaine abuse and abruptio placentae (10): a meta-analysis of 11 different studies reveals a risk of 3.92. It is a well-known fact that the abrupt detachment of the placenta entails morbidity and mortality for both mother and child. This phenomenon can also be partly fostered by simultaneous tobacco abuse while it is also difficult to exclude factors such as malnutrition, insufficient prenatal assistance and multiple drug use. From a biological point of view and taking stock of experiments carried out on sheep, we can state that cocaine use during pregnancy:

1. induces a rise in arterial pressure;
2. provokes vasoconstriction in the uterus.

Other surveys on children born to cocaine addicts show that:

1. length of stay in the hospital nursery is longer than the average and independent of the duration of perinatal intensive assistance;
2. the costs of neonatal hospitalization have increased also due to toxicological tests not only aimed at identifying cocaine metabolites (becgonine), but also those pertaining to different drugs in view of doubts as to the mother’s actual drug consumption (11).

In order to reduce these costs, it seems essential to enhance pre-natal prevention in the case of crack consumers, simplify toxicological controls without however becoming obsessed with the idea of reducing post-partum hospitalization as keeping them a few days longer could prove to be useful to recruiting the women in the Services.

Even if we have no sign of the U.S. crack epidemic spreading, we are still faced with several points to clarify regarding the reasons underlying its diffusion: a detailed analysis casts doubts as to its low cost (12). A comparison between street value in 14 different American cities between 1986-1991 showed a difference in prices, mainly due to contingent reasons. Furthermore, on considering the average doses of other street drugs, we can see that:

• if a gram of LSD costs $100,000, i.e. 1000 times more than 1 g of cocaine, the average dose of LSD is 20-80 mg which means that the cost of 1 dose of LSD is $5;
• $5 also amounts to the average cost of a rock of crack;
• $20 is the cost of 0.25 g of cocaine powder which represent 5 snorts but of course a lot depends on individual doses and the number of snorts.

Generally speaking however it is not true that crack costs less than cocaine: the reason for its popularity is estimated to lie in the higher speed and intensity of the effects of cocaine when smoked, in addition to cultural and social proselytism and mimetism.

David Lewis, editor of DATA, a Brown University magazine (13), recently wrote that in a conference held in New York, data were reported on the neuro-behavioural development of 11,811 children whose mothers had consumed crack during pregnancy: the data do not appear to confirm the pessimistic forecasts of the past (when people talked in terms of a crack-produced epidemic of sub-normal children). It should be noted however that, when one month old, these newborn babies are more irritable and difficult to pacify than peers; their lower body-weight and length does not appear to be significant. What instead emerges as increasingly important is the influence of the socio-cultural and pedagogical habitat. In this respect it should be pointed out that crack-abusing women generally score a lower social competence, that is to say the capacity to utilize community resources, compared to crack-abusing men even if there are no gender differences in the psychiatric aspects of addiction (14).

There is a proliferation of investigations on the relationship between the Post-Traumatic Stress Disorder (PTDS) and Drug-Abuse with frequency of use ranging from 12 to 34% in both sexes but with higher rates among women, especially if single. Harvard University’s Psychiatry Department reported that out of 122 adult cocaine addicts who, on entering psycho-social treatment had, among other things, filled out a questionnaire on traumatic experiences that could possibly fall within the PTSD framework, 30.2% of the women and 15.2% of the men revealed to have a clear PTSD record in compliance to the DSM-III-R criteria. The men typically reported traumatic experiences and physical violence whereas women routinely reported sexual abuse. Keeping these characteristics in mind can optimize intervention planning (15).

Dopamine and Cocaine: as already mentioned at the beginning of this overview, Wang’s investigation (16) on 20 cocaine addicts shows that these subjects did not incur losses of dopamine transporters with the progressing of age that are instead physiological in normal subjects. This quite probably

constitutes final proof of the blocking effect that cocaine has on DATs which is essential in order to interpret the specific reinforcement phenomena of this drug (these phenomena can be detected through a PET scan). This characteristic action is not, or only limitedly, modified by alcohol abuse (17) which has given rise to a number of assumptions on the effect of genetic factors such as the polymorphism of VNTR which is the gene whose function is to produce DATs.

However, if it is a straight-forward fact that cocaine determines an increase of dopamine at the nucleus accumbens level, what is still unclear is the role of dopamine in the loss of control and in the self-administration compulsion. The expression of dopamine-mediated behaviours requires the activation of GABA (gamma-amino-butyric acid). This explains why a PET scan can show a reduction of D2 dopamine receptors of the corpus striatum of cocaine users even after thy stop taking the drug. Volkow of the Psychiatry Department of New York(18) proved that cocaine addicts are hypersensitive to the action of several benzodiazepines such as lorazepam which reveals an alteration of the GABA transmission paths. This phenomenon partly explains the drowsiness that is not correlated with benzodiazepine blood levels; it is a warning against exceeding minimum doses of BDZ in treating cocaine addicts, especially in the phase of abstinence.

Craving remains a mystery in terms of its neurobiological mechanisms; the use of neuroimaging such as the RMN which is based on blood oxygenation has made it possible to use the blood oxygenation level (BOLD) as a function of the activation of the craving mechanisms triggered by the cocaine addict’s exposure to suggestive pictures of the purchase, consumption and effects of cocaine (19). It was in fact shown that there is a significant activation at the level of the anterior cingulate region and of the left dorsolateral cortex. The results show the usefulness of these neuroimaging systems in studying agents capable of modifying craving mechanisms. However, on the basis of non-human primate (ie. apes) models, it is possible to study the effect of the D1 agonists both in low and high dosage as well as partial agonists vs. antagonists (20).

Keeping to the subject of craving: the close correlation between alcohol and cocaine abuse (85% of cocaine-addicts are also alcoholics) led to the testing of the effect of naltrexone (50mg/dl) on craving symptoms aroused in 26 cocaine and alcohol addicts by watching provocative films; the initial experimentation phase was aimed at singling out the triggering mechanism and the experiment was repeated a week later during which an antagonist agent(or placebo) was administered but no preventive effect was revealed either on the alcohol or on cocaine addiction syndrome. These results may imply that the effectivess of naltrexone which is so underscored at least in the United States in the treatment of alcohol addiction cannot be relied on in the treatment of both alcohol and cocaine addiction. It should also be pointed out that so-called "neutral" films were also used in the experiment (21).

HIV+ Cocaine and heroin addicts are almost always submitted to methadone maintenance treatment as it is a well-known fact that subjects under methadone are more prone to increasing their dose of cocaine, perhaps in the attempt to reduce the sedative effects of methadone. Now, faced with the cognitive deficit typical of drug-addiction, we can also single out those due to HIV infection (22) which is made possible by comparing a more or less numerically equivalent group of HIV-positive and HIV-negative subjects. The HIV-positive group scored greater cognitive deficits requiring more intensive psychotherapeutic approaches and techniques.

There is surely nothing new in the assumption that behind cocaine abuse is a tendency to treat oneself against depression: in fact, a recent clinical series scoring depression in cocaine addicts before and after therapeutic interventions lasting at least three months showed that the most severe forms of depression did not benefit from treatment whereas alcohol abuse had a considerable effect on the severity and duration of depressive symptoms (23).

Of course counselling can be effective more so than for the treatment of cocaine abuse for the reduction of risky behaviours especially connected to HIV status (for example, unprotected sexual contacts). These were the outcomes of an experiment conducted on 232 cocaine addicts subjected to a 23-week counselling focused on hazardous behaviour (24).

Coffee and cocaine generally reinforce each other as they are both psychostimulants and reinforcement and substitution mechanisms can also be drawn from animal testing outcomes. Experiments on ex-cocaine addicts (11 for the record) who have abstained for at least four years but that still feel a craving if stimulated visually, the intake of extremely high doses of coffee did not, if compared to the control group which was drinking caffeine-free drinks, arouse renewed cravings or behaviours different from those produced by the same high dosage of the drink administered to non ex-cocaine addicts (25).

Finally, saliva can represent a good control test for cocaine administered through different ways (whether intake is endonasal, by smoking or intravenous). It is advisable to avoid taking on-the-spot samples as there might be an intraoral contamination (26).

II-b. Recent development on amphetamines, buprenorphine, therapeutic communities

Keywords: Amphetamines administered intravenously, amphetamines mixes, amphetamine induced psychosis, amphetamines dependence, efficacy of buprenorphine, buprenorphine dependency, therapeutic communities, residential centres, CREST Programme.

Amphetamines

Apart from epidemic-size diffusion in the Far East, little attention is focused on Western endemic foci: perhaps, as Peters indicates (27), because street prices are much lower. The same author points out that, at least in Edinburgh, IV use of amphetamines involves at least 44% of consumers. These can be subdivided into two separate groups:

1) Poly drug users with a long record of drug injecting and needle sharing;

2) A smaller group comprising periodical amphetamine users (their number is nonetheless now growing).

The former group naturally presents numerous risk factors in terms of HIV contamination and shares many of the administration modes for psychostimulants typical in Australia. Furthermore, there is a generalised fear that the latter group might gradually tend to inject different drugs and that amphetamines might consequently constitute a sort of "gateway" towards poly drug use. In this respect, consideration should also be given to the operation of needle exchange programmes which are generally located in different places as compared to those traditionally provided for heroin addicts and special attention should also be focused on outreach activities.

On examining 21 poly-psychostimulant drug users, Parrott (28) compared the effects of MDMA (ecstasy) with those of LSD and of pure amphetamines; this is in fact the triad most commonly used by poly drug users and it is also important to specify that we should more appropriately speak in terms of self-administration of drugs at different points of time rather than of a drug mix. Highest scores for mood changes are generally obtained with MDMA intake, at least if we apply a Mood State Profile test.

Psychoses induced by methamphetamines emerge with an undulating pattern: Yui (29) studied a group of 50 women whose blood plasma contained metabolites of monoamine neurotransmitters (norepinephrine, dopamine and 5-HT). Typical flashback cases are accompanied by an enhancement of noradrenergic activity.

Dependence on amphetamines is connected to psychological-type deficits (feeling empty, difficulty in concentration) and mention has already been made of the typical injecting behaviour in Australia. In fact it is this country that originated a research study on a group of subjects who had 3-4 amphetamine injections a day (30). The most frequent results of the battery of tests showed loss of memory and of concentration; results also seemed to exclude that these deficits existed prior to amphetamine dependence although it is important not to overestimate the effects of memory and concentration deficiencies in everyday activities. However, these phenomena are dose-dependent insofar as they become manifest in sub-clinical forms among occasional and "soft" drug users . Consideration should also be given to the possible influence of concomitant cannabis use and it appears essential to check whether these alterations persist after amphetamine dependence stops and therefore, whether they can be the product of neurological alterations.

From the medicolegal point of view, it is not very simple to detect chronic amphetamine use as is also proved by a survey carried out on 20 volunteers (31): this especially refers to hair testing and differential diagnostics between different types of amphetamines.

Buprenorphine

Buprenorphine is a partial agonist of m receptors and antagonist of k receptors: Pani (32) offers the first indications on research efforts conducted in Italy on behalf of the Ministry of Health on the basis of a double-dummy randomized multicentric study over a period of two years. After a careful preparatory phase, a comparison was drawn between 60 mg/dl of methadone and 8 mg/dl of sublingual buprenorphine administered over a period of 6 months. In addition to the Substance Abuse Detection Form and ASI, the other control tests comprised a Check List of Symptoms, DSM-IV GAF, a form to check Side-Effects as well as urine tests for opiates and psychostimulants. The data analysis is still under way although it could generally be stated that buprenorphine ranks somewhere between methadone and naltrexone and it might facilitate the recruitment of drug addicts who still resist resorting to methadone and who are incapable of using antagonists as they lack sufficient motivation.

O’Connor of Yale University reports on a comparitive study of clonidine, clonidine + naltrexone and buprenorphine in the detoxification of 162 heroin addicts (33). The investigation was carried out in double blind and randomized and the success of detoxification was assessed after at least 8 days of participation in the programme, with the administration of 50 mg of naltrexone and in the presence of withdrawal symptomatology. The success rate (81%) of buprenorphine administered alone outscored the other two systems (60-65%) and withdrawal symptoms were also reduced.

The fear that buprenorphine might induce dependence now appears to limitedly apply to parenteral posology: for example if we compare intravenous posology to that of heroin, according to the findings of an experiment conducted on volunteers, the former unarguably produces greater effects than the latter but also a number of alterations in cognitive capacities and side-effects in the psychomotor system which doesn’t exactly make it a likely option (34).

Therapeutic communities

This therapeutic model is also starting to spread in China (35) based on a rather hard disciplinary approach (their motto is: "no pain, no gain", which implies that improvements can be achieved only by enduring pain, or better still, suffering). It should be pointed out that a highly pure mix of heroin is being marketed in China which very quickly leads to dependence.

There are different types of Therapeutic Communities that host drug addicts suffering from psychiatric disorders (36): a few experiments conducted on about 100 poly drug-users with mental disorders seem to show the possibility of obtaining a drug-free state. The programme leader is Greenhouse Bellevue.

A general outline of these so-called "Therapeutic Communities adjusted for mentally ill patients" is given by Sacks (37) while De Leon (38) analyzes the most effective ways of accommodating cocaine addicts and poly-drug-users in the Therapeutic Communities. The winning formula lies on motivation and on retargeting therapy from drugs to the individual patient as this is who needs to be the focus of therapy. It is the dynamic variables that determine attendance.

Half-Way Houses seem to be especially effective for drug and alcohol addicts and their therapeutic success rate is measured against ASI and another test called SOCRATES (39); the latter is based on the different conventional phases of predisposition to change models referred to frequently in these reviews.

In this respect, the experience gathered in four Residential Centres having special arrangements with the Municipal Authorities of Milan seem to be especially important: two of these are for emergency treatment, one is a Half-Way House providing more definite treatment and one accommodates more or less severe cases of drug addicts with mental disorders (40). The report on the activities carried out in 1996 outlines different reasons for dropping out which does not necessarily imply failure while successful outcomes not only refer to physical detoxification but above all to motivation favouring continuation of treatment and acquisition of relational and employment skills; the success rate referred to 41.4% of the patients (40).

Now, let us go back to Country where Therapeutic Communities originated, that is to say the U.S.A.: the CREST programme refers to a network of Therapeutic Communities accommodating subjects convicted for different offences but especially for drug trafficking and who are under different forms of probation (41). The programme is based on counselling activities, group interaction, confrontation and educational interventions. Stays can range from 6 to 18 months and the percentage of relapses after discharge is rather low. The success of this type of TC is due to the combination of a general accommodation facility and the availability of treatment especially based on dynamic methods (42). A group of Brazilian psychologists followed life in one of these CREST Therapeutic Communities for a month and outlined the importance of the different phases of the process, ie. the following:

• Phase I: change in behaviour through model imitation and confrontation;
• Phase II: intellectual and affective understanding of the changes that have occurred in Phase I through the so-called "feeling groups", gender-specific groups and counselling sessions;
• Phase III: actual changes and monitoring beyond CREST.

According to this group, the key to the issue lies in foreseeing problems that might arise outside the TC and training patients to face them.

Deiths (44) outlines a brief historical overview of the first TC in the U.S., of the errors made but also of the enthusiasm pervading these communities. He also realizes that changes in the framework of drug-addiction require diversified models and not only the traditional model drawn from community experience with heroin-addicts. This further leads to the need to outline different generation-linked conditions among the very social workers of the Therapeutic Communities.

III. Drugs, Violence and Crime

Keywords: Violence, Crime, SPECT, PET, Genetics, Neurobiology, Rape, Domestic Violence, Antisocial Personality Disorder (APD), Substance Use Disorder (SUD), Behaviour Disorder, HIV risk, Early Diagnosis, Prevention, Treatment

The entire issue of the Journal of Psychoactive Drugs 29:4, October-December 1997 is devoted to this topic and comprises a presentation by Dr. Robert L. Du Pont, president of the Behaviour and Health Institute of Rockville, Maryland, then (in the‘70s) director of N.I.D.A. and relentless defender of methadone who later radically changed opinion as readers might recall (Bulletin n.2/96, p.113). The prohibitionist stand assumes that alcohol and drugs provoke violence and crime due to a common neuropsychological condition so that, if drugs were to be liberalized, acts of violence would increase. The solution of course is to re-establish a society based on values and to reinforce self-help systems and especially twelve-step groups for alcohol and drug addicts. It is interesting to note how Dr. Du Pont, besides quoting himself, reminds the reader of his 30 years of clinical experience.

However, his assumption is partly endorsed by the results of a SPECT test (Single Photon Emission Computerized Cerebral Tomography) carried out on over 350 subjects with aggressive behaviour in a California-based outpatient clinic that was named by the author (AMEN). As is widely known, the SPECT studies cerebral perfusion and, after its recent technological upgrading, obtains better results than the PET (Positron Emission Tomography) scan with the advantage of exposing the patient to a minimum dosage of ionizing radiation.

Numerous research studies highlight the fact that some areas of the brain, especially the temporal lobes, contain vulnerable zones and that changes in the dominant, i.e. left, hemisphere can trigger aggressive and violent reactions. Often enough a head injury jeopardizes a fictitious equilibrium; nonetheless, alcohol has been experimentally proved to determine the suppression of the control function of the prefrontal cortex as well as the regulation of the temporal lobe function. This gives rise to an alteration of the cognitive capacity and of drive control with a consequent loss of the subject’s capacity to use past experience. Subjects whose temporal lobe epilepsy is difficult to control suffer from problems of aggressiveness. In a recent series of tests carried out by the Amen outpatient clinic, psychiatric patients with violent behaviour were observed to have a net bilateral reduction of the prefrontal cortex activity with and an enhancement in the activity of the anterior cingulate gyrus associated with cognitive rigidity. Instead the alterations of the temporal lobe are associated with mood changes, memory problems, difficulties in speaking and reading and a heightened suspiciousness. An increased activity of the dominant basal ganglia and of the limbic area is associated with heightened anxiety and depression.

Having said this, drug and especially cocaine and amphetamine addicts are described to have frontal, periventricular and temporo-parietal hypoperfusion. Alcohol addicts, especially those with a positive family record, are instead found to have frontal and temporal hypoperfusion. The data relative to marijuana consumers are more ambiguous: chronic consumers are found to have a decrease in cerebral flow comparable to tobacco smokers.

Correlation between drugs and violence:

1. Alcohol and other drugs can trigger violent behaviour, especially in the presence of some vulnerability and a medical record of head injury. Alterations mainly occur in the frontotemporal region and the major cause is consumption of cocaine, methamphetamines, phencyclidine and anabolic steroids.
2. Alcohol and drugs may alter the execution functions and increase the chances of aggressiveness, especially in subjects that have a record of childhood hyperactivity.
3. Alcohol and drugs can constitute forms of self-medication of aggression-inducing brain pathologies. This is the case of drug addicts with dual diagnosis, i.e. with psychiatric problems (depression, panic, post-traumatic anxiety).
4. Alterations in the anterior cingulate gyrus, concomitant with prefrontal and temporal lesions may exacerbate drug dependence and potentially violent situations; the subject suffers from shifts of attention and falls prey to negative thinking and violent behaviour. Typical of this case is lack of attention and feedback.
5. Alcohol and drugs can in turn reduce perception of risk and thus provoke reactions on the part of other equally intoxicated individuals.

Faced with these neurobiological alterations, psychopharmacology provides the answer in consideration of the fact that greatest alterations are detected in the levels of serotonin, norepinephrine and gamma-amino-butyric acid (GABA) and also of the EEG alterations. It is also necessary to consider the co-existence of psychiatric disorders and clinical treatment relies on the use of serotonin reuptake inhibitors (SSRIs), Lithium carbonate, adrenergic beta-blockers, anti-epyleptics, anti-anxiety drugs alongside new additions to the compendium of prescriptions such as anti-androgens used as chemical castrating agents in the case of sex crimes and the so-called quieting 5-HTIA and 5-HTIB drugs such as L-toperazine which reduces aggressiveness but which has not yet been sufficiently experimented. It is to be pointed out that in pedophiles anti-androgenic treatment does not remove sexual attraction towards minors but only dampens sexual drives.

Rape is closely correlated to violence. Literature is full of references to rape cases among teen-age and young drug addicts and rape falls under the post-traumatic stress pathologies. The Department of Nursing of the University of Miami (Teets) distinguishes between five forms of rape that frequently occur in the medical record of drug addicts:

1. rape by a shooting mate;
2. rape while under the effect of alcohol or drugs and therefore when the victim was incapable of resisting;
3. rape in the process of prostitution;
4. rape by a friend;
5. rape by a member of the family.

Compared to the mention of rape in the case history of 24% of the adult female population, among drug-addicted women, the proportion hikes to 60-70%. Of course mimetism can also come into play and neither should we neglect the role of megalomania or underestimate the fact that only 20% of these women reported the rape to the Police which seems to be characteristic of the female population at large. The women’s medical histories often contain different forms of violence suffered which is a datum that should be given consideration in the treatment programme.

Domestic violence shares an analogous pattern with drug addiction to the extent of describing it as "the hidden side of dependence" in addition to the visible side of sexual abuse. The shared aspects mainly lie in loss of control, persevering in behaviour despite even disastrous consequences, the worsening of the obsession, developing tolerance and involving the rest of the family. It is exactly this involvement that determines a vertical transmission of violence to the children and the subsequent reproduction of violent domestic behaviour in future generations. This gives rise to a great many shared characteristics such as negative repercussions on the victim’s sex life, periods of repentance and wishful thinking, gradual extention of the problems from the domestic sphere to the outside world, feelings of guilt and reduced self-esteem. Of course it is incorrect to state that drug addiction alone provokes domestic violence because these are two parallel disorders that need to be treated separately especially considering the common response of denial, minimization and rationalization. However, these disorders can also be treated in organizations such as Alcoholics Anonymous. The major problem however remains the fact that it is a multi-generation condition mainly requiring prevention.

Shame of criminal behaviour is the feeling that pervades the community and therefore produces a continuous stress that in turn provokes fury, and in this respect, groups of violent prisoners have often been treated with a view to reducing their feelings of frustration and aggressiveness. Greater attention should in fact be placed on the treatment of drug-addicted patients suffering from fits of rage: experiments have been conducted on the use of individual inoculating techniques for cognitive behavioural systems aimed at reducing stress. Among other things, the typical acting out of drug addicts under treatment vis-a-vis the personnel and the setting is a "legendary" fact.

All the contributions to this issue (which is part of the publications of the famous Haight-Ashbury of San Francisco) present different clinical cases and acknowledge the fact that in addition to neurobiological factors, importance should also be given to socio-cultural elements and they tend to highlight the role of imaging techniques to be used as a diagnostic support following the example, by the way, of the N.I.D.A. itself.

Drug and Alcohol Dependence is presented as an international magazine with a biomedical and psycho-social approach which devotes its entire third issue, volume 49, February 1998, to the problem of the antisocial behaviour of drug addicts.

A.P.D. is the acronym of Antisocial Personality Disorder, a behaviour that is estimated to be spread among 2-3% of the general population while it reaches 14-18% among drug addicts. In actual fact, focus is placed more on Substance Use Disorder (SUD) than on drug dependence and it is suggested that subjects suffering from a combined form of APD and SUD present a more severe condition, suffer relapses and run a greater risk of acquiring an HIV-infection.The APD is characterized by a set of behaviours that take no consideration whatsoever of the rights of others and of complying to accepted norms of social living, there is a tendency to cheat on others, be impulsive, aggressive, irresponsible, irritable; there is no feeling of remorse after harmful behaviour. The characteristics common to APD and SUD subjects seem to suggest the same etiology also because they mainly affect men, share several clinical aspects and occur with greater frequency within the same family. However, investigations on twins with and children adopted by alcohol-abusing families seem to endorse the theory whereby prevailing factors of influence are environmental even if there are gender-linked differences. It should also be pointed out that the high APD-SUD comorbidity rates can be explained with the fact that only subjects with more severe conditions seek help from the Centres. Nonetheless, the study of the genetic origin of both conditions can rely on structural equation analytic methods which should not only make this approach accademically interesting but also conducive to interventions aimed at prevention and treatment.

But how do we go about establishing the diagnosis of ADP? Patients are given a diagnosis-oriented interview drawn from the DSM-III-R model that differentiates between childhood behaviour and adult attitudes and the interview is repeated after a week. Controls on the truthfulness of answers and the techniques identifying the "liars" underscore the greater significance of results obtained with items related to adult behaviour. There still remains the problem of identifying the liars even if many of their answers are reliable and can therefore be equalized. It generally appears to be important to detect the onset of childhood-adolescence antisocial behaviour even if there is a separate syndrome which only sets in during "adulthood": in any case, behavioural disorders, arrogance, megalomania, taking flight and the tendency to start trouble are all common elements in the combined forms.

The incidence of APD among heroin addicts on methadone might entail the early suspension of the programme especially in the presence of psychopathological symptoms which are more closely correlated with positive urine tests if compared to typical test results in APD subjects. The debate often becomes complex because of the overlap in definitions (sociopathology, antisocial personality disorder, etc.). It also becomes difficult to correlate the different elements of APD with indeces such as A.S.I. (a well-known acronym to Bulletin readers). In the case of juvenile delinquents with SUD, this condition is compounded with the ADHD syndrome which implies an attention deficit and a state of hyperactivity associated with depression. Not all of these symptoms persist in adult life while data is now being produced on the improvements obtained with residential treatment both in terms of drug use and of violent behaviour. Of course, the severity of symptoms in adolescence can predict a worsening in adulthood but at the same time is indicative of the need for intensive treatment.

Also from the point of view of prevention interventions vis-a-vis hazardous behaviour in terms of HIV contagion, the subjects suffering from SUD associated with APD can improve as much as those affected by APD although a difference remains. The fact of being affected by APD in itself worsens the risk of contagion exactly for the behavioural characteristics involved so that even if these hazardous behaviours are reduced, they still remain higher than for non-APD subjects.

The situation referred to is in the USA and therefore APD treatment is essentially based on a highly structured management of the contingency which yields encouraging outcomes although it does not result in the equation: the more intense the intervention = the better the results.

It is the behaviouralist "focus" that might be the reason of success: almost a century ago Emil Kraepelin underscored the futility of psychiatric treatment on those whom he classified as "morally healthy", a definition that comes close to that of APD. This pessimistic approach now seems to have been outdated by the application of positive and negative contingency techniques even if they are still admittedly at experimental level if compared to the bulk of research studies focused on the risk of comorbidity and the ongoing debate on diagnostic definitions is particularly lively.

Another magazine in the medley of publications on drug addiction is the European Addiction Research which, in its issue 1-2, 1998, focuses its attention on the situation of drug addiction in Germany and on the surveys under way in that country for the Early Detection of Substance abuse (EDSP). These surveys relie on shared techniques and parameters:

1. In the northern part of the country (Lubeck) 4000 subjects between the ages of 18 to 64 were investigated in order to establish the beginning and the progress of abuse with particular concern for natural remissions; this is actually like tracing the natural history of abuse;
2. In Munich, cohorts of drug addicts are being monitored in order to identify the pattern of abuse and verify the effect of different prevention strategies;
3. still in Munich, the Max Planck Institute is carrying out a 5-year longitudinal study on adolescents and young adults in order to identify the initial risk factors (the EDSP study);
4. Under this same EDSP study, a sub-sample is subjected to "genetic and neurobiological surveys" so as to establish the family component of the syndrome.

The study comprises 3021 subjects between the ages of 14 to 24 and applies a CIDI version of the WHO modified for the DSM-IV, which seeks to find the incidence and the prevalence of several mental disorders in correlation to substance consumption as well as vulnerability and risk factors. Further indications can be provided upon the readers’ request.

IV. Recent Trends in HIV Infection among Injecting Drug Users

Keywords: Heroin vs. cocaine, Reduction of Precaution, Hepatitis A , Decentralization of Treatment Centers, North-East of Italy.

In an area of low HIV endemicity such as that of Vancouver, the percentage of HIV-positive subjects among IDUs rose from 3 to 7% between January 1993 and December 1997 (1); a detailed psycho-sociological investigation was conducted on 16 serumconverters. An increase in drug addiction was reported in the central-eastern part of town which seemed to be connected to the spread of generalised violence and risk-taking larceny which normally precedes drug injection whereas social context appears to determine behaviour leading to lack of precaution (needle sharing). Furthermore, participation in local needle exchange programs, at least in the case of Vancouver, does not give rise to less risky behavior: actually, according to Strathdee(2), those with the highest attendance scores appear to be the most frequent injecting drug addicts.

The primary cause of the epidemic in Canada is the passing from the use of heroin to that of cocaine. Virological studies show that in the primary phase of HIV infection, the viral charge is very high indeed and, in the course of this epidemic uptrend, it was shown how essential it is to take blood tests while distributing hypodermic needles so as to single out serumconverters and subject them to immediate treatment. It could thus be possible to avoid the spread of contagion that, in the case of Vancouver, originated from the first serumconverters in 80% of the cases.

Archibald (3) also recorded some of the characteristics of this episode and thereby confirmed the significant role of cocaine abuse combined, to a lesser or greater extent, to the use of heroin: it is important to point out that educational efforts as well as needle exchange programs had been launched locally and that the onset of contagion dated back to 1994.

This reveals the increasing advisability of relying on Anthropological Medical approaches aimed at singling out the hang-outs and shooting galeries as well as the cultural characteristics to be targeted: this is the effort being made in Miami (4) where an average of 1000 inoculations a year are reported among IDUs participating in needle exchange programs (NEP).

A prospective study conducted in Amsterdam on 879 subjects between 1986 and 1997 showed that the reduction in the percentage of serumconversions in the first phase (1986-91) was closely associated with a reduction in high-risk injections which endorsed the success of a number of prevention initiatives and promoted the implementation of education and needle exchange programs. However, no further reduction was recorded in the following phase (5) and the conversion rate levelled off at around 3-4% per year. It also appears evident that it is the youngest IDUs who are most at risk also in view of the fact that today they do not seem to be as fearful of the AIDS syndrome as in the past in the light of dissemination of information on AIDS therapy. Furthermore, hepatovirus contagion rates remain high; an effort was made to favour needle exchanges among HIV-negative IDUs but this was only achieved in a third of the cases.

It appears self-evident that the aim is to prevent injecting drug use and that, in this respect, the action of the personnel of the Centers and Units that have contacts with IDUs acquire special relevance. Edinburgh is to be taken as a model in the HIV-drug-addiction sector and, in this connection, attention should be focused on the survey conducted on 61 social-workers and 42 IDUs concerning the concept of health and and the priority ranking to be attributed to the social worker-patient relationship (6). While the social workers insisted on reinforcing independence in the patients’ decision-making, the patients set their priority on obtaining more information rather than on being given the freedom to decide on their therapy. This clearly goes to say that patients are overwhelmed by a sense of fear whereas social workers are wary of being considered paternalistic and are also perhaps haunted by the rhetoric of empowering the patient.

The impact of education and prevention efforts carried out by the management of the U.S. Anti-Drug Service was analysed in a National Survey conducted in 1990 (7): it is not simple to trace clear-cut differences in the presence of a considerable number of selective factors. Nonetheless a greater effectiveness seems to issue from the type of relationship existing with other social and health care Services.

But let us now go back to the epidemic upswings: the hepatitis A virus is known to be an oro-faecal transmission agent: however, it has recently been associated to parenteral transmission among hemophiliacs and drug addicts. In Norway, out of 621 cases of HAV-induced hepatitis notified in the 1995-97 period, 79% occurred among IDUs in the south-eastern region, in connection with having moved the Treatment Center from Oslo to the County of Ragaland. On the other hand, no case was reported in the northern and western regions of the Country which means that the drug addicts treated in the Centers of Bergen, Tromso and other cities are not closely connected with their counterparts in Oslo. The focus has become extinguished and anti-HAV vaccination has now been extended. A sequential analysis of isolated viral strains was conducted (8) using the 348bp region of the VP1/2PA junction of the virus genoma so as to be able to document the resemblance between the viral strains and the PCR-isolated RNA while other cases of imported hepatitis were sustained by different strains.

In the Netherlands, molecular epidemiology studies have succeeded in showing that the gp120 and V3 sequences of strains isolated from IDUs are equal to those of an HIV-positive group that had certainly been infected through heterosexual contact which confirms that a considerable proportion of heterosexual contagions in the Netherlands originates from the community of drug addicts (9). It is a well known fact that heterosexual transmission represents the prime cause of HIV infection throughout most of the world. At the outstart, Porto Rico was a primary focus of the virus (88.4 cases of AIDS per 100,000 inhabitants) and sexual contact represents the most frequent form of contagion among heroin and cocaine as well as crack addicts. A little over 1000 drug addicts participating in educational efforts were monitored and showed an increase in the percentage of both risk-free relationships and reliance on condoms (10). With respect to condoms, their use is extended mainly among HIV-positive subjects, patients in out-treatment for sexually transmitted diseases and subjects who do not have a stable partner. In the light of these results, it becomes important to focus greater attention on drug addicts who have a stable partner and who are still HIV-negative.

The San Francisco General Hospital has acquired a considerable experience in the anti-HIV treatment of drug addicts and the recent introduction of protease inhibitors has acted as a prevention factor in the transmission of contagion insofar as they reduce the viral charge. However, IDUs under methadone maintenance treatment in particular, give rise to a problem of compliance with the other medicines administered. A system was tested of administering medicines on the spot which issued positive results but whose effects were limited to the period of treatment. An effort was therefore made to "personalize" treatment by providing counselling centered on problems arising from non-compliance with prescriptions (11) and especially highlighting the role of depression and of relapses in drug use. It has been proved profitable to rely on contingency-based behaviour techniques because of their effectiveness in making drug addicts comply to anti-tuberculosis treatment.

Coming back to Vancouver and British Columbia where treatments combining protease inhibitors and antiviral agents are free of charge for IDUs with CD4 lymphocytes < 500 and RNA > 5000 copies/ml, only 40% of those entitled undergo treatment and percentages are even lower among those treated by physicians who are under-informed on the Guidelines on Antiviral Treatment (11bis).

Risk-taking behavior among IDUs is the subject of the usual avalanche of surveys and observations: in the Los Angeles District, the survey focused on the answers to routine questionnaires passed out to all Police arrests. Between 1987 and 1995, there was a reduction in the percentage of people who stated that they shared needles (12). This was mainly true on the long term because, on the short term, this trend was significant up to 1994-95 after which it dropped steeply; the use of bleach shot up till 1991 but then it flattened off on the levels reached. No reduction in the number of sexual partners was recorded although there was a slight increase in the use of condoms. Particular consideration should be given to the reduction in two high-risk behaviors: sharing needles with other unknown drug addicts and heroin-shooting in the famous "shooting galeries".

In Scotland there is a difference in the proportion of HIV-infected subjects among IDUs living in urban centers and those living in rural areas: among the latter, the HIV-positive subjects do not exceed 3.7% of IDUs whereas the proportion in cities reaches 26.8% (13). It is a well-known fact that the historical nucleus of city-dwelling HIV-positive subjects were infected in the period between 1980-84 and they generally had no contacts with country-dwelling IDUs. The latter however do not disdain sharing needles and syringes but they confine this exchange to their own little group and refuse to accept intruders, especially if they come from the city. Therefore, from an organizational viewpoint, it is advisable to avoid centralizing the anti-drug Services in urban centers insofar as if rural IDUs went into town for treatment, they would come in contact with peers who are more extendedly infected.

In New England the introduction of counselling services and HIV-testing in methadone maintenance centers seems to have stimulated a reduction in both injecting and risk-taking sexual behaviors (14). Naturally, the best results that issued from quarterly interviews in the course of one year were scored by the drug addicts who had stuck with the program. The "ad hoc" counselling provided to HIV-positive IDUs proved to be particularly useful: it is in fact among this group that the most significant reductions in risk-taking behaviour was detected thus endorsing the importance of persisting with prevention efforts.

This does not go to say that drug addicts without a fixed abode or with mental disorders should be systematically excluded from residential treatment: in New York, out of almost 700 of these subjects, there was a high drop-out rate from the therapeutic community although 33% of those who began treatment also concluded it and the ones who resisted treatment most were those with psychotic obsessions, depressive symptoms and hostile behavior which goes to prove how important it is to take unbiased stands (15).

Of course Amsterdam remains a test-bench for drug addiction and HIV infection: a cohort of HIV-infected male and female subjects was monitored with the aim of tracing the origin of the infection; the group comprised 100 women and 139 men (16). In the primary phase, the women complained of a relevant number of symptoms, which also proved to be true in the cohort of 163 women and 232 men comprising the HIV-negative IDU group. This goes to show that the larger number of symptoms reported by women does not derive from a higher incidence of HIV infection in women but rather from their greater predisposition to disease and its onset which also holds true for the population at large.

Death rate among IDUs in the pre-AIDS period: data were collected on 664 European IDUs (Dutch, Spanish, Scottish, Swiss, French and Austrian) in order to ascertain pre-AIDS death rates: the major causes of pre-AIDS mortality were overdose and suicide (49%), followed by bacterial infections and cirrhosis in addition to involuntary traumatisms without these giving rise to substantial differences between groups belonging to the different Countries considered in the study. Pre-AIDS mortality did not increase in proportion to serumconversion but in connection to the lymphocyte CD4+ count. There was no correlation between the serum status and the increase in overdoses or suicides.

Data relative to the North-East of Italy were presented by Mezzelani (18) over the 1984-94 period covering 26 Centers with 1022 cases of death. As of 1991, AIDS emerges as the prime cause of death and on a continuous uptrend also in the low HIV endemicity areas. The fact that AIDS deaths concern a higher average age group essentially depends on the long period of incubation. The data relative to the North-East of Italy confirms the lack of correlation between the status of HIV+ and the increase in deaths due to overdose and suicide.

Similar results were obtained in Edinburgh (19) over the 1981-97 period concerning 535 IDUs (123 deaths). In 52.8% of the cases, the decisive factor was the HIV infection; of course, a strong reduction was recorded in 1997 thanks to innovative therapies. Cases of overdose occurred in 11.4% of HIV-positive and in 18% of the HIV-negative subjects which does not lead us to think that awareness of being HIV-positive enhances risk-taking behavior.

Specific areas:

Vietnam: a third of the 100,000 IDUs live in Ho Chi Minh City (Saigon) and 87% of them are HIV+ (20), have a long history of contact with opiates (including opium), have rather high schooling levels and abuse of "Western" type of tranquillisers and sedatives; the potential spread of infection is enormous.

Thailand: in the Northern part of the country, a high incidence is recorded among the Thais, an ethnic group living on the plains, in fact 4 times higher than among the inhabitants of the hilly regions; Thais are accustomed to IV drug use whereas no injecting behaviors are recorded in the hills.

Indian Reserves (now referred to as natives): the monitoring of risk-taking sexual behaviour reveals insufficient use of condoms especially among women and the highest risk rates are recorded between native women and white men. Conversely, native men make a more regular use of condoms which goes to show that the problem should be tackled from different standpoints.

Conclusions: the very same experts that disclosed the epidemic upswings in Vancouver and the trends in Amsterdam set forth a number of considerations on the causes of the epidemic peaks due to the delay in introducing prevention measures or in partially applying them. Furthermore, it is necessary to apply traditional Health Care methods in order to prevent contagion from spreading between IDUs from high to low HIV endemicity areas. Of course, it goes without saying, the most effective approach is preventing IV drug use.

The previous overview on this topic was published in n.2/1996.

V. Is HIV-infection prevention making progress among Injecting Drug Users?

Key words: Needle exchange, Epidemiology, Risk Factors, Clinical Indicators

In most of the U.S.A. there is still a limit on the production, sale and possession of syringes and injecting equipment without medical prescription despite numerous reports by scientific Committees highlighting the fact that the percentage of IDUs among AIDS cases have increased from 12% in the first period of the epidemic to the current 36% (1). The incidence of AIDS among Afro-American IDUs reaches 50.9 per 100,000 inhabitants while among Hispano-Americans it amounts to 21.9 and among whites it is only 3.5.

It appears to be extremely urgent therefore to "deregulate" thus at least allowing the sale of syringes and providing an adequate information and training to pharmacists on preventing infections transmitted through the blood chain. It is also important to leave the local authorities the necessary flexibility to handle the needle exchange programmes. The federal funds supporting the NEPs (Needle Exchange Programmes) have been suspended and in any case were rather limited before as well. Now, in consideration of the effectiveness of these programmes in Australia, Lurie (2) calculates how many cases of HIV infections among IDUs could have been avoided if there had been a continuous effort to develop NEPs: from a minimum of 4394 to a maximum of 9666 cases of serumconversion with a saving in medical expenses of between 244 and 538 million Dollars. If these constraints were to persist, by the year 2000 there will be between 5150 and 11,320 cases in the U.S.A.

One of the reasons why the U.S. federal funds were suspended is the circulation of preliminary reports of "observational" prospective studies that are said to show that there is a higher rate of serumconversion in IDUs enrolled in NEPs. One of these reports has now been published by the American Journal of Epidemiology (3). It deals with the experience drawn from the CACTUS programme which has been in operation in Montreal since 1988 comprising a cohort of 1599 subjects that at the time of enrollment had an average serumpositivity of 10.7%. The survey is observational and the comparison with non-participants in the programme was carried out on the basis of three different statistical models. After an observation period of 21.7 months, it was noted that there was a 33% serumconversion among NEP participants against 13% in non-participants. The authors exclude that this difference might be due to selection factors and think that the NEP favours needle exchanges thus conveying teems of IDUs towards distribution centres. The health authorities, after having been informed of the fact, eliminated the limit to the individual concession of syringes but, as was already mentioned, the negative aspect was exploited by the opposers of harm reduction who are more active now than ever before in the American Administration. So the State of Michigan, instead of sending reinforcements, only echoed the sour remark by Peter Lurie (4) who, after having listed the positive reports on serumconversion prevention among IDUs participating in NEPs, makes the following observations:

• the CACTUS programme was located in an area teeming with prostitutes and 9p.m. to 4A.M. opening hours attracted into the programme only the highest-risk IDUs;
• the research study fails to indicate the average number of syringes picked up by serumconverters and does not report on gender-specific hazardous behaviour;
• paradoxically, the fact that the programme attracted the highest-risk IDUs can be considered to be a success.

For the record, Lurie’s comment is entitled "Le Mystere de Montreal"!

At least in New York, despite the positive changes in the hazardous behaviour of IDUs participating in NEPs, there remains a group that, notwithstanding easy access to sterilized syringes, continues to use dirty syringes (5). Out of 2465 participants in 4 NEPs which were requested to list both hazardous injecting and sexual behaviour during the 30 days prior to enrollment and again after one month, no hazardous behaviour was reported in 77.4% of the cases.

Instead, in the non-participating group, there was quite a large amount of needle sharing: the latter occurred within a social group comprising subjects that injected cocaine at least once a day. A predictive factor that had already been reported in previous surveys is constituted by psychological distress (anxiety, depression or post-traumatic stress syndrome). It also appears to be important to act upon the social network of IDUs.

The experience drawn from the Baltimore series (6) also appears to be a positive one: it comprised 221 participants who, in the course of several interviews, indicated a reduction both in needle sharing and borrowing as well as in the exchange of other injecting paraphernalia. The exchange of paraphernalia (spoons, water pipes, etc.) is the topic of an interesting research study carried out in London (7) on 303 IDUs with who were contacted on the streets; the sharing of these implements is actually much more frequent than needle and syringe sharing. Of course implement sharing occurred among close friends. It would therefore appear to be reasonable to aim not only at preventing needle sharing but also the sharing of all those instruments that might be hazardous in terms of virus transmission (HIV, HBV, HCV).

Going back to Canada, at some distance from Montreal lies Vancouver (8), where an investigation on the characteristics of the participants in NEPs found that the programmes mainly attract male cocaine addicts with high-risk behaviour and a discontinuous style of life. NEPs seem to play an important role as catchment areas for the highest-risk groups.

The disinfection of syringes plays a role as important as that of needle exchanges: The Rand Corporation based in Santa Monica (California) conducted a study on the psycho-social background of 136 IDUs (9). Those with a high degree of self-control and perception of risk reduction as well as of the transmission routes of HIV and who live within a group with a positive attitude vis-a-vis harm reduction, more frequently carry out appropriate disinfections although there wasn’t always a correlation between intentions and actions.

But to what extent, at least with respect to heroin, is injecting the sole administration route? In Spain (10) it was shown that out of 54,132 admissions to a treatment programme, the incidence of intravenous injections dropped from 50% in 1991 to 38% in 1993 and that "chasing the dragon", ie. heroin smoking, was the favourite route especially among new drug addicts.

More generally however, prevention is aimed at risk reduction: in connection to programmes for female IDUs conducted in Hospitals it was found that,for example, a brief intervention targeted on acquiring control capabilities succeeds in having these women make greater use of condoms and reduce their intravenous drug injecting after discharge (11).

In Rio de Janeiro, a study conducted on slighly more than 800 IDUs followed by three different programmes (12) with an average age of 19 and of which 25% were HIV+, reported that there was a lower incidence of needle sharing but not of hazardous sexual behaviour among the youngest of the group and also among new recruits. This however does not match the experience of Amsterdam (13) where a study on cohorts of IDUs from 1989 to 1995 showed that serumconversion is higher among the youngest and among those who only recently began injecting drugs. This highlights the opportunity of intensifying prevention and education on younger IDUs. Another pilot study in Holland relied on the snowball system whereby other IDUs were identified through the collaboration of IDUs under methadone maintenance treatment (14): high-risk behaviours were reported among the IDUs contacted in this way as well as paraphernalia sharing.

Counselling seems to play a positive role also in the case of IDUs that are not under treatment as well as in that of hazardous injecting and sexual behaviours (15). Out of the 648 IDUs contacted through outreach programmes who received some counselling and of which half also received a second reinforcement intervention after six months, a good percentage complied with the suggestions made to use more prevention measures; this programme was conducted in Philadelphia.

To what extent can a close relationship with their children affect hazardous behaviour among female IDUs? Sharp (16), a sociologist of the University of Oklahoma, relied on a modified version of the theory of social control in order to assess the influence of affective relationships on devious behaviour such as the one reported among female IDUs: comprehensive investigations and detailed individual stories reveal that a reduction in the affective relationship with their children precedes an increase in hazardous behaviour. However, this correlation is not simple especially when an IDU’s child lives elsewhere as is often the case. There seems to be nonetheless a continuum in devious behaviour and one of the characteristics indicative of the transition to high-risk behaviour is represented by the weakening of social relations.

It is interesting to note that in Nordic Sweden, HTLV infection appears in some cases of IDUs even prior to the HIV infection (which, by way of reminder to readers, was initially called HTLV-III): out of 905 participants in a screening, 3.2% proved positive in the HTLV-II test (and not one in the HTLV-I). More specifically, 12% of HIV+ IDUs were also affected by HTLV-II whereas only 1.8% of HIV- IDUs suffered from this concomitant infection (17). In Sweden the traditional injection drug has always been and partly still is amphetamine although heroin prevails in the HTVL-II group and especially among the drug addicts that began injecting prior to 1975 and that were often "hosted" in the national jails. No shared risk factor was found for HIV and HTLV-II infections.

Some epidemiological data.

The European AIDS Epidemiological Monitoring Center of Saint Maurice (France) analysed the AIDS cases among IDUs, both homo and bi-sexual, their heterosexual partners and children with HIV+ IDU mothers, that is to say not only those that "shoot" but the entire network of consequent contagions. This group represents 43% of the over-all 73,119 cases notified in Europe (18), 90% of which are concentrated in South-Western European Countries (the absolute record is held by Italy with 68 cases per million, followed by 42 in Portugal, and 38 in France). During the 1990-95 period there was an 11% increase in the annual incidence that was almost entirely due to an increase of more than 23% in Eastern and Central European Countries and more generally speaking among older IDUs while a reduction was reported in the 13-24 age group (-6%). While Western Europe is witnessing a constant downtrend, in the former-USSR countries, the introduction of serological screenings revealed an epidemic explosion of contagions.

A Swiss epidemiological study (19) made a comparative analysis of the trend of the cases of AIDS notified among IDUs in Europe up to 1994 and in the USA up to 1993. Despite the different groupings of IDUs and homosexuals, both Europe and the U.S. are witnessing an aging of AIDS-affected subjects among IDUs whereas the rate of infection is either stable or on the downtrend among the younger age groups. This, among other things, coincides with the constant increase in the average age of Service-users which readers know only too well!

In Spain, a study on cohorts of IDUs who later became infected by AIDS, reveals a continuous increase of cases among the generations born in the last 50 years with a peak for males born in 1962 and one for females born in 1964 (20). This period was followed by a slight drop in number of cases which stabilized after the cohort born in 1972; however, the study of the incidence of infection and disease subdivided per cohort of year of birth seems to be a very enlightening approach.

In the Netherlands, a review of the causes of death among IDUs led to the acknowledgement that official reports were underestimated; the review actually led to a 30% upward adjustment (21).

Des Jarlais compared epidemiological trends in New York and Bangkok and thereby showed the levelling off of HIV-infections in the "Big Apple" and a steep uptrend in the Thai capital where 4 IDUs per 100 persons/year are infected (22).

Further North of Bangkok, in Northern Thailand which is a region characterized by different cultural and ethnic patterns, there is a prevalence of seropositivity among IDU males living in the plains which is four times higher than in hill-side inhabitants (23). The most likely cause: opium is smoked in the hills whereas heroin is injected in the plains.

It is interesting to note that the Indian sub-continent shows an inverted trend compared to what is occurring in some parts of the West: quite a few heroin smokers change over to injecting it because of the scarceness of smoking heroin on the markets. 66% of IDUs in Calcutta share needles within their group and are very little informed on the risk of HIV (24). The scarce availability of smoking heroin depends on the Police’s seizing activities but a sizable abuse of injected buprenorphine is currently emerging.

In Australia, younger IDUs tend to inject amphetamines, hallucinogens and "designer" drugs while the olders ones use heroin and "poly drug use" is the rule in both groups. More recently however, there has been a gradual tendency to change from amphetamine to heroin (25). The prevalence of females is constant among the younger IDUs and generally speaking the rate of needle sharing is minimum.

Clinical aspects and death predictive parameters.

In Switzerland a study was carried out on the range of pathologies found in hospitalized IDUs who were differentiated between HIV+ and HIV- (26). The study comprised a 9-year retrospective survey. Total admissions in Hospital were 35 per 1000 persons/year among the HIV- and 120 among the HIV+ group. The latter group was hospitalized more frequently for non-opportunistic forms like pneumonia, TBC and infections of the soft tissues as well as for non-infective complications. However, infective pathologies prevailed and the length of hospital stays for HIV-negative subjects was shorter. In practice, HIV-infection is responsible for the difference of 2,700 more hospital days attributed to 500 HIV+ IDUs.

But let’s go back to Swedish HTLV-II-infected IDUs: not many research studies have been carried out on the most common pathologies of this group. Modahl (27) pointed to the increase in hospital admissions caused by bacterial pneumonia, abscesses and lymphadenopathy. Not that these conditions were absent in HTLV-negative IDUs although they were considerably fewer: a debate is currently ongoing on the possible pathogenetic role of the retrovirus on pulmonary and abscess-provoking pathologies.

Glasgow always represents a pilot location for many aspects of HIV contagion among IDUs: an interesting parameter is based on the comparison between mortality among IDUs and in the general population after being adjusted for gender and age. It might also be interesting to compare this parameter with the data referred to other cities with comparable problems of drug addiction and HIV infection. Now, the average annual death rate among IDUs living in the Scottish city, i.e. 1.8% a year between 1982 and 1994, comes very close to that of London-dwelling IDUs followed up from 1969 to 1991. However, the fact that in Glasgow the average age of dead IDUs is lower than that in London (26.3 years of age against 38.2) actually doubles the age-adjusted mortality ratio vis-a-vis the general population (22.0 against 11.9). The principle cause for hyper-mortality among the young Glasgow-dwellers was overdose.

Parameters predictive of an acceleration of the death progression pattern among IDUs can be the following:

1) In a series of 522 HIV+ subjects, almost entirely Afro-American and who were recruited between 1988-89 and followed up for a 7.9 year average, the viral charge, both independently of and in association with the CD4 decline, represents a prognostic factor for the insurgence of infective pathologies (29);

2) In the series comprising 605 HIV+ IDUs followed in Baltimore (30) the initial average was of 513 CD4s with a CD4 decline of -3.2 cells per month and a higher decline speed in those who had higher counts to start off with and among older IDUs. However, in contrast with what emerges in murine models, administration modes (continuous administration, frequency between troughs, type of injected drug) do not seem to affect CD4 decline (30);

3) In a partly HIV-negative cohort of IDUs recruited in a New York-based programme, low titres of thiol constitute an unfavourable prognostic element even in absence of an HIV infection. The cohort comprised a total of 133 HIV+, 13 HIV- and another 116 IDUs with different forms of AIDS (31). Those with low titres of thiol from the time of recruitment run a 2.83% higher risk of dying. Thiol is inversely proportional to the oxydation stress and the low titre effect was higher among IDUs who had been diagnosed as having AIDS.

Now, the higher average age of HIV+ IDUs is concomitant with a higher incidence of depression and psychological stress among subjects over 35 years of age; In the Pittsburgh series, the most frequent pathologies among the older IDUs in addition to a state of depression were: excess of tension and anxiety, hostility characterized by fits of rage, hyper-confusion and periodical distress (32). Furthermore, intravenous drug injecting already represents a psychologically stressing factor in and of itself.

Now, to take a glance at the Italian situation: between January 1995 and February 1997, an epidemic of cryptococcosis occurred in a Therapeutic Community. 19.6% of the subjects were HIV+ and they had all previously been IDUs (33). The incidence of clinical forms was equal to 30.7% among HIV+ and to 13.6% among HIV-negative subjects despite exposition conditions being equal. The HIV+ subjects were found to have the HIV infection associated with a low CD4 count; a chronic symptomatology was observed only among those with a CD4 count < 150. 14.1% of the subjects were found to have antibodies against cryptosporidium even before the epidemic arose and 51.2% had an immune response after its occurrence. It proved difficult to perform an intestinal drainage on HIV+ immunosuppressed subjects and the infection is therefore likely to become chronic in these cases.

Still too many cases of Pneumocystis Carinii Pneumonia (PCP) are being reported among the IDUs living in the rich state of California (34): a study on 326 patients showed that only 35% did some preventive treatment against PCP and this only partially depended on financial difficulties (lack of health insurance coverage) because the main reason was due to the fact that IDUs ignored their serumstate and were not regularly subjected to medical examinations. This unfortunately highlights the shortcomings of the health care service provided in the Californian anti-drug services.

Viral Hepatitis: In Australia, the HCV has been present in the blood circulation of IDUs since at least 1971, with incidences reaching up to 60-70%. The risk of infection begins with the very first injection and is greater for heroin than for amphetamines even if there has been a minimum drop after the ‘80s but not of the same order of magnitude as that typical for HBV. At present, the incidence is of 15 per 100 persons/year (35). In practice therefore, the whole HCV epidemic in Australia is linked to the spread of the virus among IDUs which makes it all the more urgent to single out the specific characteristics of contagion.

Last but not least, China: numbers are still small compared to demographic density: 176 IDUs, 23 of which affected by AIDS and almost all of which belong to non-Han minority groups. The HCV is serologically present in 35.8% of the cases while the HBV is present in over 50% of the cases; dual infections are present in 22.7% of the cases (36) and the prevalence of B Hepatitis markers was greater among needle-sharing IDUs. However, on oberving this "minor" epidemiology, we can state that there is a reciprocal promotion between the three HIV, HCV and HBV viruses.

Sexual Habits and HIV Infection Risk: the frequency of HIV-related hazardous behaviours among female IDUs and crack consumers who have homosexual relationships was calculated in a series of 3,856 women recruited "on the street" (or rather in lesbian bars) of 19 American cities (37). The results also showed both the frequency of sharing needles and that of crack-smoking and injecting paraphernalia. Oral sex was almost always practised without any protection and bisexuals used a condom only 30% of the times they had sex with a male partner. More comprehensive investigations are needed on this group of subjects which would normally be expected to reveal fewer hazardous behaviours.

Again in the world of women: this time in Germany where a study was conducted on the incidence of syphilis among 386 heterosexual IDUs who were HIV+ in 68% of the cases; the Service for the diagnosis and treatment of sexually-transmitted diseases (38) reported syphilis in 12% of the female subjects against 3% of the male subjects; furthermore, syphilis in women seemed to be associated with the number of partners whereas no such correlation was noted among men and nor was there an association between syphilis and HIV infection.

Many of the surveys on the spread of HIV infection among IDUs were conducted in epicentres of HIV epidemics: but what are the two ways of acquiring HIV in the low HIV endemicity areas? Williams (37) recruited 9,492 IDUs residing in low HIV endemicity areas (11 towns). Results showed that it was homosexual relationships in high HIV endemicity areas more than needle sharing that represented higher risk factors. Of course, there was also some correlation between the frequency of injections and other ethnical (Afro-American) characteristics.