Details

Category: Research

Published: 11 December 2011

The past 15 years has seen a rapid expansion in the number of studies using neuroimaging techniques to
investigate maturational changes in the human brain. In this paper, I review MRI studies on structural
changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence.
Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the
final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental
neuroimaging in the next twenty years. Future studies might focus on complex questions including
the development of functional connectivity; how gender and puberty influence adolescent brain development;
the effects of genes, environment and culture on the adolescent brain; development of the atypical
adolescent brain; and implications for policy of the study of the adolescent brain.

Details

Category: Research

Published: 05 February 2008

By Fred J. Payne, M.D., M.P.H.
February 2008

Background

Marijuana, or cannabis, is a crude preparation of flowering tops, leaves, seeds, and stems of female plants of the Indian hemp Cannabis sativa; and it is usually smoked as a "recreational" drug. The intoxicating constituents of hemp are found in the resin exuded by the tops of the plants, particularly the females. Male plants produce only a small amount of resin. The resin itself, when prepared for smoking or eating, is known as "hashish." Various cannabis preparations are used as intoxicants throughout the world, with potency varying with the amount of resin present. The tops contain the most resin; stems, seeds, and lower leaves the least. The intoxicants in the resin are called cannabinoids, the most active of which is delta 9-tetrahydrocannabinol (THC).

Although marijuana use in the United States dates back to the 19th century, its early use was confined predominantly to certain groups such as Mexican laborers, inner city Blacks, and some "Bohemian" groups. Restricted by increasingly severe legal penalties imposed during the 1930s, its use in those relatively small groups was not a major cause for public concern. Following the widespread popularity and use of the hallucinogen LSD during the 1960s, an explosion in marijuana use took place, at first on college campuses, followed by downward spread to secondary schools and upward to portions of the middle class.  Public alarm grew over the hazards to the general public posed by the rapidly growing use of marijuana and other mind-altering drugs. Marijuana, plus other drugs like heroin, had a high potential for abuse with limited or no potential for medical use, and they were designated as schedule I drugs – making their use and possession illegal.

The scheduling of dangerous drugs is done by the Drug Enforcement Administration (DEA), but only after the Food and Drug Administration (FDA) decides that a new drug is a suitable medication, albeit one needing to be scheduled because of its abuse potential.  The agencies work closely together, as required by law, and a routine scheduling action cannot be taken by one of the agencies without the concurrence of the other.

Recent developments

During the past two decades in the United States, there has been a steady increase in the number of people entering treatment for marijuana related problems. According to one report, two-thirds of those admitted for treatment were young – between the ages of 12 and 25 years (1). The majority of those admissions were from either the justice or educational systems.

Marijuana use is associated with impaired educational attainment (2), reduced workplace productivity (3), and plays a major role in motor vehicle accidents (4). Marijuana is increasingly recognized as a cause, along with tobacco, of both lung cancer and emphysema (5) (6). In spite of this, an editorial in a major medical journal, the Lancet, stated as recently as 1995 that "the smoking of cannabis, even long term, is not harmful to health."(7).

In the United States, marijuana use remained stable at about 4% during the decade between 1991-1992 and 2001-2002, according to two large national surveys conducted 10 years apart (8). Marijuana use disorders among adults, however, increased significantly during that decade. The potency of THC in confiscated marijuana increased by 66% between 1992 and 2002, and this may have contributed to the problem. The disorders included marijuana abuse, that is, use under hazardous conditions or impairment in social, occupational, or educational functioning related to use.  Another marijuana use disorder is dependence, defined as increased tolerance, compulsive use, impaired control, and continued use despite physical and psychological problems caused by its use.

A major focus for concern has been the extent to which marijuana use leads to the use of and dependence on "hard" drugs. There has been a longstanding debate over whether this association is due to the criminalization of marijuana use, forcing the user to seek suppliers who deal in other illicit drugs, or whether marijuana conditions the user to try other drugs.

A study was reported from Australia of a volunteer sample of 311 young, adult, monozygotic and dizygotic, same sex twins discordant for early cannabis use i.e. less than 17 years (1). The outcome measures included subsequent non-medical use of prescription sedatives, hallucinogens, cocaine or other stimulants, and opioids leading to abuse or dependence on these drugs. Abuse and/or dependence on cannabis or alcohol were also outcome measures. Twins who used cannabis by age 17 had odds of other drug use or alcohol dependence plus drug abuse from two to five times higher than those of their discordant twin. These associations did not differ between monozygotic and dizygotic twins.  The findings indicate that early use of cannabis is associated with increased risks of progression to other illicit drug use. Since the subjects were twins neither genetic nor environmental factors were likely to have produced the results. However, since marijuana use is illegal in Australia the study was unable to establish whether having to obtain the drug from dealers involved with other illegal drugs exposes the marijuana user to other illicit drugs.

A similar study was conducted in the Netherlands, where out of a group of 6000 twins, 219 same sex pairs were chosen, one of whom had begun using marijuana before age 18 while the other twin had not (9). The study showed that the twin who used marijuana before the age of 18 had a significantly greater risk of using hard drugs and of drug dependence. Since marijuana is legal and widely available in the Netherlands, the findings from both studies clearly indicate that marijuana serves as a gateway for use and abuse of other addictive drugs in adolescents whose central nervous system is still not fully developed.

Marijuana and psychoses

The relationship of marijuana to the development of psychoses has been a cause for concern in recent years. Large intakes of cannabis are able to trigger acute psychotic episodes and may worsen the effects of established psychoses. Chronic daily users often report increased levels of anxiety, depression, fatigue, and low motivation (10).

A number of prospective studies have been conducted in the past decade to determine whether marijuana use is associated with psychoses. In summary the studies produced suggestive evidence of a causal link between marijuana and psychoses or psychotic behavior, but were unable to adjust for the effects of the many confounding variables in these studies.

In an effort to overcome these problems, a systematic review of a number the studies was published recently (11). The review used meta-analysis to analyze the data from cohort studies of psychosis reported in the literature. The studies were located in the United States, Germany, the Netherlands, the United Kingdom, Sweden, and New Zealand.  The psychoses included schizophrenia and other types of abnormal behavior regularly classified as psychotic disorders. The presence of delusions, hallucinations, or thought disorder was a requirement for all psychosis outcomes. The analysis found that there was a 40% increase in the development of psychosis in individuals who had ever used marijuana compared to those who had never used it. Individuals who had used marijuana daily or weekly had more than an 80%, or twofold, increase in the risk of psychosis. The increased risks of psychosis persisted independent of other drug use or existing mental health problems. The evidence for affective disorders, i.e., depression or anxiety, however, was less strong. The authors state that although the individual lifetime risk of chronic psychotic disorders such as schizophrenia among marijuana users is likely to be less than 3%, even among those who use the it regularly, it can be expected to have a substantial effect on the incidence of psychotic disorders in the general population, because use of the drug is so common. No evidence was found in this review to link the development of psychosis with early use of marijuana.

The evidence from this study is compelling and can be interpreted to indicate that marijuana use has been, and will continue to be, an important factor in the large numbers of homeless, mentally ill adults in American cities. The Lancet has altered its stand on marijuana and now states that governments should invest in sustained and effective education campaigns on the risks to health posed by using cannabis (7).

Recent findings from comparative research

Work on the pharmacology of the cannabinoids has found that there are cellular receptors for these substances located on cells throughout the body. These receptors are most widely expressed in the brain, but they are also found on cells in other parts of the body—such as the cardiovascular system, the lungs, liver, kidneys, and cells of the immune system. The receptors are part of a normal system within the body and are activated by intercellular signaling molecules known as endocannabinoids. Although these molecules are unrelated to the cannabinoids produced by marijuana, they carry the name cannabinoids by virtue of their discovery through cannabis research.

The normal functions of these receptors is still incompletely understood, but experiments in animal models are beginning to show the importance of some receptors in neuronal growth and the maturation of nerve connections in the brain. Activation of these receptors by marijuana cannabinoids can interfere with their normal function (12).

A recent report indicates that THC can affect brain development and induce cognitive and behavioral deficits in prenatally exposed infants which are sustained into adolescence. These data show that maternal marijuana use may affect early neurodevelopment by interfering with immature nerve cells. (13). There is obviously much more to be learned from this type of animal research involving cannabinoid receptors and the effects of their activation by cannabinoids found in marijuana.

Marijuana as medicine

There have been a number of successful efforts, both through referenda and through legislation, to legalize the use of marijuana for medical purposes. The proponents argue that either smoked or ingested marijuana is safe and effective for the treatment of cancer chemotherapy induced nausea and vomiting and for pain associated with spinal cord injury or peripheral neuropathies. Advocates also suggested that using marijuana is effective in treatment of a variety of other conditions including malnutrition, movement disorders, epilepsy, and glaucoma. The Office of National Drug Control Policy funded a study by the Institute of Medicine to evaluate the scientific evidence for benefits and risks of using marijuana as a medicine. The report was issued in 1999, and a summary of the report was published the following year (14). The report focused principally on marijuana's use for nausea and vomiting, wasting syndrome, neurological disorders, and glaucoma. The review found a modest therapeutic potential for various cannabinoids found in marijuana, particularly for pain relief, control of nausea and vomiting, and appetite stimulation. The review stated, however, that most of the medical conditions studied already have good to excellent medications currently available. The authors went on to state that the future of cannabinoid medication would lie in the preparation of pure drugs, delivered using non-smoked means, under standard federal and state regulatory systems.

References:

1) Lynsky MT, Heath AC, Bucholz KK, et al. Escalation of drug use in early-onset cannabis users vs. co-twin controls. JAMA 2003; 289: 427-433

2) Lynsky MT, Hall W. The effects of adolescent cannabis use on educational attainment: a review. Addiction. 2000; 95: 1621-1630

3) Lehman WI, Simpson DD. Employee substance abuse and on-the-job behaviors. J Appl Psychol 1992; 77: 309-321

4) National Highway Traffic Safety Administration. Traffic Safety Facts 2001 Washington: D.C.

5) Aidington S, Harwood M, Cox B, et al. Cannabis use and the risk of lung cancer: a case-control study. European Respiratory Journal 2008; 31:280-286

6)  Beshay M, Kaiser H, Niedhart D, et al. Emphysema and secondary pneumothorax in young adults smoking cannabis. European J. Cardio-Thoracic Surgery 2007; 32: 834-838

7) Editorial: Rehashing the evidence on psychosis and cannabis. The Lancet 2007; 370: 292

8) Compton WH, Grant BE, Colliver JD et al. Prevalence of marijuana use disorders in the United States 1991-1992 and 2001-2002 JAMA 2004; 291: 2114-2121

9) Lynsky MT, Vink JM, Boomsa DI Early onset cannabis use and progression to. other drug use in a sample of Dutch twins. Behav Genet 2006; 36: 195-200

10) Patton GC, Coffey CC, Carlin JB, et al. Cannabis use and mental health in young people: a cohort study BMJ  2002; 325: 1195-1198

11) Moore HM, Zammit S, Hughes AL et al. Cannabis use and risk of psychotic or affective mental health outcomes; a systematic review.The Lancet  2007; 370: 319-328

12) Stern PR NEUROSCIENCE:.Cannabis use impairs brain development. Science 2005; 309:222

13) Berghuis P, Rajnick AM, Morozov YM et al. Hardwiring the brain: endocannabinoids shape neuronal conductivity. Science 2007; 316: 1212-1216

14) Watson SJ, Benson JA, Joy JE. Marijuana and medicine: assessing the science base
Arch Gen Psychiatry 2000; 57:  547-552

Details

Category: Research

Published: 29 October 2011

Cannabis is one of the most widely used drugs of abuse. Approximately 6% of the general US population aged 12 years and older admitted to recent cannabis use [1]. The widespread use of cannabis has also increased the prevalence of cannabis in the general driving population. Overall, 6.8% of drivers tested positive for D9-tetrahydrocannabinol (THC), the active ingredient of cannabis, in blood. The prevalence in young drivers aged 16–20 years was even higher, at 15.2% [2]. Moreover, 13% of drivers involved in fatal accidents were positive for THC [3]. High prevalence rates of THC among drivers may pose a serious problem, as experimental and epidemiological studies have demonstrated that THC increased driving impairment and crash risk in a dose-related manner [4–6].

Details

Category: Research

Published: 21 February 2006

An Evidence Based Review of Needle Exchange
Does It Reduce Harm?

Forward

Needle/syringe exchange programs (NEP) were developed nearly 20 years ago in the Netherlands, the United States and elsewhere in the face of the soaring incidence of AIDS, i.e. the Human Immunodeficiency Virus (HIV) infection among addicts who injected their drugs (IDU). The rationale for needle exchange is simple; if the injection drug users had access to clean needles and syringes and would use them consistently without sharing them, the chain of HIV transmission from person to person through needle sharing would be broken. Although this is a seemingly plausible idea, the effectiveness of these programs has been difficult to evaluate. The European Union is currently planning massive increases in needle exchange and methadone services along with expanded condom distribution in an attempt to better control the growing HIV epidemic among member states. These programs, some operating illegally, continue to be controversial

A review of the reports published in the literature from 1994 through mid-2003 was conducted to determine whether the widely proclaimed success of NEPs in preventing or reducing HIV transmission among IDUs was supportable with “hard” data. A search of Medline on the National Library of Medicine’s web-site for journal articles published after Jan.1, 1994 on needle/syringe exchange programs yielded hundreds of citations.  The exclusion of editorials, letters, news items and review articles as well as other articles that lacked abstracts revealed few cohort studies of NEPs whose design and results might allow evaluation of their efficacy in reducing HIV transmission. Data on the hepatitis viruses, Hepatitis B (HBV), and Hepatitis C (HCV), were considered surrogates for HIV when incorporated into an NEP study. Those selected should have been able to show differences in viral seroprevalence between users of needle/syringe exchange and non-users, reduction in viral incidence, or show differences in an endpoint such as mortality.

At the time most of these studies were inaugurated it was thought that risky injection behavior such as needle sharing was the principle route of HIV transmission among IDUs. Now, however, high-risk sexual behavior is recognized to be equally important. It is reasonable to assume, nevertheless, that NEPs should confer some measurable protective effect at least if the participants use them regularly and avoid risky injection practices.

Seven reports out of the total were identified which by design might provide a credible measure of the effectiveness of NEPs in preventing or reducing HIV, HBV, or HCV transmission among IDUs.

Epidemiological Studies

Researchers in Montreal studied a cohort of nearly 1600 needle-exchange participants for an average of 21.7 months (Bruneau J, et al.  Am J Epidemiol. 1997; 146: 904-1002).  The study revealed 89 incident cases of HIV infection with a seroconversion probability of 33 percent among needle exchange users and 13 percent among non-users. The case-control study suggested that consistent needle exchange use continued to be associated with HIV seroconversions during follow-up. Despite adjustments for confounders, the researchers noted that HIV risk elevations related to needle exchange remained both substantial and consistent in their cohort of intravenous drug users.

Results from a cohort study in Vancouver failed to show a measurable beneficial effect of the needle exchange program on an on-going HIV epidemic among IDUs  (Strathdee SA, et al. AIDS. 1997; 8: F56-65). Instead, participation in the NEP was a predictor, along with other variables, for HIV seropositivity.  This happened in spite of the fact that the program was the largest NEP in North America. This study was re-examined later to determine whether the NEP itself was responsible for the increased spread of HIV among participants (Schechter M T, et al. AIDS. 1999; 13(6): F45-51).  The re-examination of the data showed that this was unlikely and due, in part, to the age (young), drug injected (cocaine), and sex trade among frequent attendees who seroconvert during the study period. The data, of course, did not indicate any effect of the NEP on HIV transmission during the outbreak.

Looking back now, it appears likely that many, if not most, of the infections during the on-going epidemic were the result of sexual transmission rather than needle sharing.

A study was reported that measured the impact of HIV and other risk factors on mortality in a cohort of IDUs and non-injecting drug users in Amsterdam (van Haastrecht HJ, et al. Am J. Epidemiol 1996; 143: 380-91).  The participants were recruited between 1985 and 1992 and followed up through 1993. A total of 77 deaths occurred among the 632 participants during the study period. The death rate among HIV positive IDU was 3.5 times higher than among HIV negative IDU and 8 times higher than among HIV negative non-injecting drug users. When data were analyzed only for IDUs neither the daily use of methadone or participation in needle and syringe exchange programs were associated with lower mortality.

Another report from Amsterdam involved prospective studies of a cohort of 582 HIV-negative drug users in a harm reduction program that included high dose methadone maintenance, needle exchange, counseling, and HIV testing. (Langendam MW, et al. AIDS 1999; 13 (13): 1711-1716). The authors stated that, in this setting, methadone use and needle exchange did not reduce the spread of HIV. During 1,906 person-years, 58 of the 582 drug injectors became infected with HIV.

A study of needle exchange programs in Seattle found no protective effect of needle/syringe exchange on the transmission of HBV or HCV among participants (Hagan H, et al. Am J Epidemiol.  1999; 149: 203-218). The highest incidence of infection with both viruses occurred among current users of the exchange. The authors stated that the goal of elimination or substantial reduction in risk behavior that may transmit HIV among IDUs had not been achieved.  Risk behavior for HBV and HCV transmission were still practiced by a substantial proportion of Seattle area drug injectors.

The virological efficacy of a needle exchange program in Sweden was evaluated in a cohort study (Mansson AS, et al. Scand J Infect Dis 2000; 32 (3): 253-256). Transmission of HBV, HCV and HIV was measured among 698 IDU’s.  Despite free syringes and needles, both HBV and HCV continued to spread at high rates during the study. During a median time of 31 months, however, no spread of HIV was observed. The authors observed that the low HIV prevalence at baseline, 2.5 %, might have been partly responsible for this. While these results could be interpreted as showing the effectiveness of needle exchange programs in preventing or reducing the spread of HIV in IDU populations with low HIV prevalence, the rapid spread of both HBV and HCV during this study casts doubt on the role of needle exchange in limiting the spread of HIV.

The results of a 10-year study of initially HIV negative male and female IDUs in Baltimore were published recently (Strathdee SA, et al. Arch Intern Med. 2001; 161(10): 1281-128).  Study participants included 1,447 males and 427 females. The participants were primarily African American (91%) with a median age at entry of 35 years. The median duration of injecting drug use at enrollment was 14 years. Younger age (less than 30) was an independent predictor of seroconversion among both men and women. Significantly higher HIV incidence was seen among participants of both sexes who injected cocaine alone or in combination with other drugs. Among male participants less than a high school education, needle sharing with multiple partners, daily injection and shooting gallery attendance were all independent predictors of HIV seroconversion. The incidence of HIV was double for men who recently engaged in homosexual activity and cocaine injection.  Among women, behavior consistent with high-risk heterosexual activity was a more important predictor of HIV seroconversion than drug related activity. Incidence of HIV was double among women who reported a sexually transmitted disease during the previous 6 months compared to that of women who had not. Condom use also was associated with a significantly increased risk among women. The effect of methadone maintenance on HIV serostatus among both males and females was negligible. There also was no significant difference in HIV seroconversion rates among either males or females between those who attended needle exchange programs and those who did not. This study highlights the overriding importance of sexual behavior as a risk factor for HIV infection in IDUs, especially among women and men who have sex with men.  Some of the major data from this study has been illustrated graphically in “Notes” published by the National Institute on Drug Abuse (Mathias R. NIDA Notes 2002/2003; 17: no.2).

Three of the above studies also measured the effect of methadone maintenance on HIV transmission but all failed to show a beneficial effect.

Other Studies

In May 2001, the Canadian Bureau of HIV/AIDS, STD and TB’s Update Series published an article in Health Canada titled “Risk Behaviors Among Injecting Drug Users in Canada”( Bureau of HIV/AIDS, STD and TBUpdate Series-Index May 2001). The article is well written and takes into account risk behaviors other than needle sharing as factors in HIV transmission among IDUs such as prostitution both male and female and other risky sexual practices. Findings of studies of NEPs in Montreal, Ottawa, the Province of Quebec including Quebec City, Winnipeg, and Prince Albert in Saskatchewan were cited in the report. The following points are made at the outset:

1. The sharing of drug injection equipment remains unacceptably high among IDUs.
2. The level of reported, unprotected sexual intercourse is also high among IDUs.
3. Needle exchange programs alone are not sufficient to prevent HIV transmission among IDUs and should be complemented with a range of appropriate additional services.

Studies conducted at Vancouver, B.C., formed part of the information base for the findings in the above article by Health Canada. The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users that was formed in May, 1996. In addition to the epidemiological articles from Vancouver cited earlier in this article, reports from the study are published periodically and yield up to date information on the study findings. According to a report published in July 2003, the prevalence of HIV in the cohort had reached 35% (http://www.ccsa.ca/ccendu/pdf/report/vancouver 2003).

At the time of enrollment, the prevalence of HCV among participants was already 82% and had reached 92% by 2001 – near saturation.  According to an earlier report published in 2001, 124 of the participants had died since the study’s inception in 1996;

• 28 deaths were attributed to HIV/AIDS
• 41 died of drug overdose
• 55 died of other causes

(Wood E, et al. CMAJ 2001; 165(4); 405-410). Although needle sharing is an important means of HIV transmission among IDUs, the study found that the proportion of IDUs who reported needle sharing (27.6%) did not decrease during the next 5 six-month follow-up visits. This was seen in spite of the availability of the large needle-exchange program serving the participants. The authors concluded that needle sharing remained an alarmingly common practice in the cohort. An article published in 2005 again expressed alarm and called for action on the rising incidence of HIV and HCV infections in Vancouver's youth (Miller CC, et al. Can J. Public Health. 2005; 96(2):107-108).

British Columbia finally added HIV to the list of reportable diseases in 2003. Without such reporting and the programs of partner notification that rely on it, the most important means of intervention in the HIV epidemic had been through the needle exchange program along with counseling about the risks of contaminated needles and needle sharing.

Heroin Injectors and Sniffers

A recent study compared the HIV prevalence rates among heroin sniffers, new heroin injectors and long term heroin injectors (Chitwood E, et al. J Psychoactive Drugs 2003; 35 (4): 445-453). The study population consisted of 900 heroin users equally divided into 3 groups; heroin sniffers, new heroin injectors and long-term heroin injectors. New heroin injectors were defined as those who had initiated injection during the previous four years, and long-term injectors were defined as those who had initiated injection prior to January 1, 1984, when it was assumed that the risks of infection with HIV were still unknown. The HIV prevalence rate among sniffers and new injectors was nearly the same, about 13%. The rate among long-term heroin injectors was almost double that, nearly 25%.  The higher rate among long-term injectors was attributed to a maintained level of risky sexual activity over time as well as to the sharing of needles and drug paraphernalia.  The authors attributed slightly more than half of the increased HIV prevalence among long-term IDU to high-risk injection behaviors, attributing the remainder to high-risk sexual activity. Race and ethnic group were important variables as determinants of the risk of infection. Hispanics were almost three times as likely to be HIV positive as non-Hispanic whites and African-Americans were over five times as likely to be infected as non-Hispanic whites. Men who had sex with men were at increased risk for infection with HIV compared to men who had sex with women only. A history of crack cocaine use among sniffers of heroin was also associated with higher rates of HIV infection. The authors stress that any interventions such as needle exchange must stress sexual risk as a component equal to that of injection.

Another report by some of the same authors studied HIV prevalence rates among heroin sniffers with no history of drug injection (Sanchez J, et al. AIDS Care. 2002; 14(3): 391-398). Here the HIV prevalence rate among men was 8.7% while among women the rate was more than double, 18.1%.

Both articles stressed the importance of sexual behavior in the high rates of HIV transmission among heroin addicts. As in the Baltimore study the higher HIV risk among women was probably attributable to selling or trading sex for drugs.  It should be noted here that the latter two reports concern heroin use only. The Baltimore study included cocaine as well.

Relevant Studies of Cocaine

A number of studies have been reported on the effects of cocaine, both crack and injected, on sexual behavior. One of these found that HIV antibody seroconversion among women was higher among crack users than non-crack or injection users  (Webber MP et al. Arch AIDS Res. 1991; 5(1-2): 45-47).

The strongest predictor of seroconversion was prostitution. The study reported that cocaine use in any form was associated with very high-risk heterosexual activity.

A second report cited the effects of drug counseling in four different treatment groups on sexual behavior of 487 cocaine dependant patients (Woody GE, et al. J Acquir Immune Defic Syndr. 2003; 33(1): 82-87). Most of the patients, 79%, were crack users. The most common HIV risks were having sex with multiple partners and unprotected sex. After six months of therapy cocaine use fell dramatically to an average 1 day per month and was associated with an average 40% reduction in HIV risk behavior across all treatment, gender and ethnic groups. Most of the reduction was a result of having fewer sexual partners and less unprotected sex.

Researchers at Harvard Medical School have reported that cocaine may impair the function of an important component of the immune system’s response to infection (Halpern JH, et al. J Clin Endocrinol Metab. 2003; 88(3): 1188-1193). In a controlled experiment 30 volunteers, including both sexes, with a history of cocaine use were given an injection of either saline or cocaine after 30 minutes exposure to an immune stimulant. A blood sample taken 4 hours later showed a marked (3-fold) diminution in the level of interleukin-6 (IL-6) in the blood of those injected with cocaine compared to those who received saline.  IL-6 is a cytokine, an intercellular messenger, that acts primarily as an activator of inflammation and as a mediator of the acute-phase response to infection. Although, at present, this finding must be regarded as preliminary it points the way to further investigations into the effects of cocaine on the body’s ability to ward off infections. It could help to explain the higher HIV incidence that has been noted among users of cocaine.

Discussion

Although part of the problem in the seven needle/syringe exchange studies cited here may in some instances have been a less than adequate number of needles and syringes supplied to the IDUs (the CDC has estimated that on average an IDU uses over 1000 sets a year) the main problem appears to have been the high level of risky sexual and injection behaviors practiced by both male and female IDUs. The Baltimore study demonstrated that sexual activity was responsible for an important part of the HIV transmission occurring among participants of both sexes. Similar findings were cited in the report published on-line by Health Canada. Both of the studies of heroin sniffers and injectors highlighted the strong role of sexual behavior in the transmission of HIV in both groups of addicts.

While it is possible that needle/syringe exchanges might have some effect in reducing the rate of HIV transmission among their participants, it is fair to say that NEP were not measurably effective in limiting the spread of HIV, HBV or HCV in any of the studies reviewed here. Some of them like those in Vancouver, Seattle, and Baltimore had been operating in areas that lacked basic public health programs such as HIV name reporting and partner notification, programs usually used for control of serious sexually transmitted infections. The needle exchange and counseling apparently were the primary means of "harm reduction."

Other Needle/Syringe Exchange Studies

A number of other articles were found during this literature search that were designed to show an effect of NEP in reducing HIV transmission by changing injection risk behavior, but they failed to provide hard evidence to substantiate such a reduction. Only a few presented seroprevalence or incidence data in support of their behavioral findings.

One of the studies presenting seroprevalence data used an inappropriate statistical method in data analyses to achieve a significant result (Des Jarlais DC, et al. Lancet 1996; 348: 987-91).  The authors used meta-analysis of three very disparate groups to show a statistically “significant” difference between NEP participants and non-participants.

Another study used HIV recovery rates in discarded syringes as surrogates for IDU to estimate the annual incidence of new HIV infections in NEP participants in New Haven CT ( Kaplan EH, et al. Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10 (2):175-176).

A national study was conducted in Australia to compare HIV seroprevalence rates among NEP participants by sex, sexual behavior and injecting behavior (MacDonald M, et al. Med J Aust. 1997; 166(5): 237-240).

One study compared changes over time in HIV seroprevalence in injecting drug users worldwide. The authors compared seroprevalence rates from published and unpublished sources in 81 cities with and without NEPs. The average annual change in seroprevlence was 11% lower in cities with NEPs (Hurley SF, et al. Lancet 1997; 349: 1997-1800).

Some of the studies show an impact of the NEPs on reducing risk behavior such as needle sharing among participants. The data, however, is based primarily on self-reporting by individual IDU either on questionnaires or by face-to-face interviews. The reliability of self reported behavior by addicts is always open to question under the best of circumstances. While informative this data lacks the probative effect of confirming the risk reduction by, for instance, comparing HIV seroconversion rates among the study participants.

In another study, primary health care services were provided for 551 street sex workers, 89% of whom injected drugs, during 1992-94 in Glasgow (Carr S, et al. AIDS Care, 1996; 8: 489-97). The prevalence of HIV remained under 5% during the study. Most of those infected were known to be infected prior to entry into the study.

Comment:

Without intervention and treatment both heroin and cocaine addiction can last for years, for many, particularly heroin, a lifetime ( Hser Y, et al. Arch Gen Psychiarty. 2001; 58: 503-508). Although some studies have indicated that among heroin addicts a process of “maturing out” to abstinence takes place among a major proportion of the addict population, a recent report from the Amsterdam study cohort raises questions about the frequency of this process (Termorshuizen F, et al. Am J Epidemiol. 2005; 161(3): 271-279). The authors state that although they found a favorable trend towards abstinence in the cohort, the high mortality rates and the low prevalence of abstinence among those who survived over the long term indicate that the concept of natural recovery, “maturing out”, to a drug free state doesn’t apply to a substantial portion of the addict population. This suggests that for many addicts a need for needles, whether clean or not, will persist for years, even decades.  Early in the course of this pandemic, it seemed that needle/syringe exchange programs might provide an effective intervention in the growing epidemic of HIV disease among drug injectors; however, hard evidence to show this is lacking. Without credible evidence of efficacy, the provision of clean needles and syringes appears primarily to support the individual’s addiction and, with it, drug related high-risk behavior.

There is no easy way to intervene in an epidemic that feeds on the injection of mind-altering drugs and their associated high-risk injecting and sexual behaviors. Although injecting illicit drugs is harmful to both the user and to society, the HIV epidemic that was spawned by this practice has become a public health disaster. Since the beginning of the epidemic, there have been nearly 210,000 reported cases of AIDS in injection drug users and 77,000 cases reported among their sexual contacts (Center for Disease Control and Prevention HIV/AIDS Surveillance Report 2002). Incomplete data for 2002 indicated there were nearly 11,000 new HIV/AIDS cases reported in the United States citing injection drug use as the source. A lesser number of cases among their contacts was also reported. Using very incomplete data, the Center for Disease Contol and Prevention (CDC) estimates that more than 54,000 cases of HIV infection, including AIDS, classified as IDU related, were alive at the end of 2002. A substantial proportion of all HIV infections in the United States were spun out of this continuing epidemic among IDU during the past 20 years.

Ideally, every individual who is HIV infected should receive evaluation and be considered for appropriate antiretroviral (ARV) therapy. Therapy and/or monitoring will be necessary for the rest of the individual’s life. A large percentage of HIV infected IDU; however, fail to undergo appropriate treatment after their infection has been diagnosed ( Celentano DD, et al. AIDS. 2001; 15(13): 1707-1715, Sherer R. JAMA. 1998; 280: 567-568, Strathdee SA, et al. JAMA. 1998; 280: 547-549).

In the large Vancouver injection drug use study only 35% of those infected with HIV are on ARV therapy. Active injection drug use is usually incompatible with current ARV therapies. Compliance with medication schedules is essential for adequate suppression of the virus and to minimize the risk of treatment failure due to drug resistance. Adherence to treatment schedules in future years is equally important for the same reason. Newly diagnosed HIV infected IDU will often need to undergo treatment for drug dependence before starting ARV therapy.(Celentano DD, et al. JAMA. 1998; 280: 544-546, Bouhnik AD, et al. J Acquir Immune Defic Syndr. 2002; 31 Suppl 3:S149-53).  A recent report from a longitudinal study of 1851 HIV infected individuals attending a university clinic for ARV therapy presented outcome data on three groups of participants:  those who were not injecting drugs, those who injected intermittently, and those who persisted with drug injection while on therapy. (Lucas GM et al. Am J Epidemiol .2006; 163: 412-420). Compared to non-drug users the mortality was approximately twofold higher among intermittent users and threefold higher among those who persisted in their drug use while on ARV therapy.

Heroin injectors who accept treatment with methadone or buprenorphine are more likely to adhere to ARV therapy than are cocaine injectors for whom there is as yet no medical treatment. Because of this a high percentage of cocaine dependent injectors and crack users who are HIV infected remain untreated. Access to health care is important and IDU who have health insurance coverage, for example, are more likely to undergo treatment both for their drug dependency and for their HIV infection. Untreated or improperly treated infections will continue to serve as a rich reservoir of HIV for transmission within communities of injection drug users.

The cumulative costs in money and lives of the IDU HIV epidemic are already large and will continue to grow absent effective intervention. The energy and resources used for free-standing needle/syringe exchange programs should be redirected to support the creation of badly needed additional drug treatment and rehabilitation services. The outreach performed by the NEPs should be replaced by outreach from substance abuse programs acting as liaison for drug treatment programs and linked to public health HIV prevention and treatment services. Existing public health, disease prevention, and control programs should be strengthened with active HIV surveillance in areas where injection drug use is known to be prevalent. IDU who become infected with HIV should be referred for appropriate treatment for their drug dependence as well as for ARV therapy. Far from reducing harm, simply bringing needle/syringe exchange into this maelstrom only adds more fuel to the fire.

Fred J. Payne, MD, MPH
 2/21/2006
Source: Children's AIDS Fund