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Biphasic dose-response relationship for effects of toluene inhalation on locomotor activity.

To investigate the effects of inhalation of toluene on spontaneous locomotor activity, rats were exposed to graded concentrations of toluene and locomotor activity was measured continuously before, during and after exposure. This study used a randomized, cross-over, graded-dose experimental design, with sham-exposure as the control. The locomotor activity pattern during toluene exposure depended upon the toluene concentration in the air. At the lowest effective concentration (5000 ppm) locomotor activity increased monophasically during exposure, and decreased monophasically during recovery. At higher concentrations (10,000-15,000 ppm) locomotor activity initially increased in a concentration-dependent manner. With continued exposure to the higher concentrations, locomotor activity decreased and eventually ceased at the highest concentration. Recovery from exposure to high concentrations of toluene was also biphasic. These results demonstrate that the behavioral responses to extremely high concentrations of toluene are characterized by biphasic actions as demonstrated both by analysis of concentration-response and time-action characteristics. Exposure to concentrations of toluene similar to those used in this study occurs during organic solvent abuse and glue sniffing in humans.

Animals↗

The acute effects of cannabinoids on memory in humans: a review.

RATIONALE: Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects. OBJECTIVE: The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings. RESULTS: Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. CONCLUSIONS: This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.

Animals↗

Fatal accident caused by isoflurane abuse.

A fatal accident after isoflurane abuse is presented in this report. A hospital employee was found dead in the operating area with a plastic bag over his head. In his locker an almost empty bottle of isoflurane was found. Autopsy revealed signs of asphyxiation and toxicological examination revealed nordazepam and isoflurane in non-toxic concentrations in the blood. Quantification of the anaesthetic was also carried out in urine, gastric contents, liver, kidney and brain samples, and in addition, oxazepam, prothipendyl and metabolites of midazolam and prothipendyl were found in the urine. Although the drug problems of the deceased were known before, no efforts had been made to restrict access to these drugs.

Accidents↗

Patterns of opioid and cocaine co-use: a descriptive study in a Canadian sample of untreated opioid-dependent individuals.

This study examined prevalence and patterns of co-use of opioids and cocaine in regular users of illicit opioids (N = 729) recruited from 5 Canadian cities. Fifty-seven percent (n = 417) reported having used both opioids and cocaine in the month and week preceding the interview; of these, 73% (n = 304) were able to identify a typical pattern of daily co-use. In a typical day, injectors of opioids and cocaine (n = 119) and injectors of opioids who inhaled cocaine (n = 111) showed stable opioid use but variable cocaine use, which peaked at 21 hr. Overall, 30% of the individuals used both drugs exclusively in a sequential fashion, 35% reported taking opioids and cocaine within the same hour, and 35% reported taking them together at the same time or mixing them. These findings indicate that different individuals display different patterns of opioids and cocaine co-use.

Adolescent↗

Patterns of drug use among adolescents: the past decade.

In recent years investigators have examined patterns of drug use among various populations. None, however, have examined the changes in drug patterns over time. The present study analyzed changes in patterns of drug use among a population of drug-using adolescent students in Ontario (Canada). Three cross-sectional surveys conducted in 1968, 1977 and 1985, which sampled students in grades 7, 9, 11 and 13 (ranging in age from 12 to 20 years), were employed. Using eight substance types as measures (cannabis, barbiturates, stimulants, tranquillizers, inhalants, LSD, heroin and others), four general patterns were constructed: single-drug psychotherapeutic users; multiple psychotherapeutic users; exclusive cannabis users; and multiple-illicit. The findings indicated the following: a significant decrease in the representation of both exclusive and multiple psychotherapeutic users between 1968 and 1977; a significant increase in exclusive cannabis users between 1968 and 1977, and following this a decline into 1985; and a significant increase in multiple illicit users between 1968 and 1977. In all a major shift from a psychotherapeutic-illicit dichotomy to an overwhelming illicit pattern has occurred during the past decade.

Adolescent↗

Correlates of initiation of injection drug use among young drug users in Baltimore, Maryland: the need for early intervention.

This article examines individual and social factors associated with initiation of illicit drug injection, with a focus on racial differences. Data were derived from across-sectional survey of young injection and noninjection drug users in Baltimore, Maryland. Participants were aged 15 to 30 and had initiated use of heroin, cocaine, and/or crack within the prior five years. Bivariate and multivariate logistic regression models were used to identify correlates of injection initiation. Of 579 drug users, 73% were injectors, 56% were male, and 41% were African American. In a multivariate model controlling for age, correlates of injection initiation were: being an African American male [Adjusted Odds Ratio (AOR): 0.08; 95% Confidence Interval (CI): 0.04, 0.17] or female (AOR = 0.12; 95%CI: 0.06, 0.27) compared to being a White male; younger age of first use of alcohol, marijuana, or inhalants (AOR=0.73; 95%CI: 0.65, 0.82); shorter time between first use of alcohol, marijuana, or inhalants and first use of heroin, crack, or cocaine (per year decrease, AOR=0.63, 95%CI: 0.40, 0.87); parental drug use (AOR=0.54, 95%CI: 0.32, 0.92); seeing someone inject prior to injection, AOR=1.96, 95%CI: 1.01, 3.50); and crack smoking (AOR=1.77, 95%CI: 1.07, 2.99). Early drug use patterns and drug exposure factors are associated with initiation injection. Interventions are needed that target noninjection drug users to prevent transition to injection drug use.

Adolescent↗

An investigation of 140 deaths associated with volatile substance abuse in the United Kingdom (1971-1981).

1 In the UK, from 1971 to 81, 140 deaths associated with volatile substance abuse (VSA) were identified from press reports and a variety of other sources. Data about each death were obtained from inquest proceedings, post-mortem and toxicological reports, and death certificates. 2 Based on the year 1981, in which 39 deaths occurred, VSA deaths accounted for over 1% of deaths from all causes, and nearly 2% of deaths from injury and poisoning in males aged 10-19 years. 3 The median age was 16.8 years (range 11-63), and 79% were under age 20. The male to female ratio was 13:1. 4 Death rates were highest in conurbations, and in Scotland, Northern Ireland and Northern England. Deaths tended to be more frequent among manual social classes but this association was not marked. 5 The chief substances were butane (28%), solvents in adhesives (23%), other solvents (26%), aerosols (15%) and fire extinguishing agent (5%). Solvents in adhesives were more important with increasing age. 6 Most deaths occurred alone, at home. In about 41% of cases, death appeared to be only indirectly associated with VSA (trauma 8%, plastic bag over head 19%, and inhalation of stomach contents 14%). In 49% death was attributed to the direct toxic effects of the substance; this proportion was highest with aerosols and lowest with solvents in adhesives. 7 The implications of these findings for prevention, monitoring and research are discussed.

Age Factors↗

Transient cognitive deficits and high-frequency hearing loss in weanling rats exposed to toluene.

In a previous experiment we found that weanling rats subchronically exposed to toluene by inhalation were deficient in learning a multisensory conditioned avoidance response (CAR) task and a tone-intensity discrimination task when trained several hours after each daily 14-hour exposure ended. The present experiment was done to determine whether this deficit represented a residual pharmacologic effect or more persisting nervous system damage. Independent groups of rats were trained on the CAR task either during the last week of a 5-week exposure to 1400 or to 1200 pm toluene (14 hr/day, 7 days/week) or during the first or third weeks after the exposures ended. None of the three groups of toluene-exposed rats were able to acquire the auditory CAR, whereas it had been 4 kHz in the previous experiment. Subsequent tests, in which the frequency and intensity of the tone were varied, revealed that hearing in these rats was unimpaired at 4 kHz, slightly impaired at 8 kHz, and markedly impaired at 12 kHz and above. Thus, although toluene has been shown to be relatively innocuous as a toxicant, this new finding suggests that this solvent should be examined further in terms of its potential hazard, especially with regard to its frequent abuse.

Animals↗

Background demographics and risk behaviors of injecting drug users in Karachi, Pakistan.

OBJECTIVE: To find the prevalence of HIV infection and risk behaviors among injecting drug users (IDUs) in Karachi, Pakistan. DESIGN: A cross-sectional study of IDUs conducted in Karachi, Pakistan from February through June 1996. RESULTS: Of the 242 IDUs, 11 (4%) refused HIV testing. One (0.4%; 95% confidence interval (CI) = 0.37-0.48%) was HIV positive. All subjects were male. Over the past 6 months 47% had engaged in receptive needle sharing, 38% had perceived a change in their social network, 22% had had sexual intercourse, of whom only 7% always used condoms, and none had washed their needles with bleach. Younger age (28 vs. 31 years; p = 0.01), younger age at first injection (25 vs. 28 years; p = 0.001), fewer years of schooling (3 vs. 5 years; p = 0.001), lower monthly income (70 dollars vs. 80 dollars; p = 0.03), inhaling fumes of heroin from a foil in the year before injecting (OR = 4.8; CI = 2.2-10.3), injecting first time with heroin (OR = 3.6; CI = 1.2-12.6), having a temporary job (OR = 2.5; CI = 1.2-5.2), and a perceived change in one's social network (OR = 4.4; CI = 2.4-7.9) were all associated with receptive needle sharing. IDUs who knew about HIV spread through contaminated needles were less likely to share (OR = 0.4; CI 0.2-0.8). In the final logistic regression model receptive needle sharing was associated with inhaling of fumes of heroin on a foil in the year prior to injecting (adjusted OR = 5.6; CI = 2.6-12.0), a perceived change in one's social network (adjusted OR = 4.0; CI = 2.2-7.4), and inversely associated with age at first time of injection (beta = -0.07; p = 0.002). CONCLUSION: Background HIV prevalence was low among IDUs in Karachi despite high-risk behavior in 1996. In order to control HIV transmission among IDUs in Pakistan, continual HIV surveillance with well-coordinated and effective HIV risk reduction, and drug demand reduction programs need to be implemented among drug users.

Adult↗

[Knowledge of the damages of wrong nutrition and of the effect of stimulants. (Results of questioning 100 employees of a large industry].

In an unselected collective of 100 employees of a big concern the knowledge with regard to body weight, nutrition and nicotine abuse was studied and the eating habits as well as the principles of education connected with them were ascertained. Nearly all questioned persons knew their body weight. Half of them were able to indicate their ideal weight with a precision of +/- 10%. The rate of the considerably overweight persons in the collective showed a dependence on higher age and female sex. Among the questionees with secondary education more normalweight persons were found. The test persons were well informed about the disadvantages of overweight and controlled their body weight in two thirds of the cases at least once a week. They stated to have met the term "diet" above all in the mass media. About half of them were able to define the term "calorie" approximately precisely. The questionees, however, often underestimated the required caloric quantity, apparently without drawing conclusions. The caloric content of alcoholic drinks was underestimated. Beer ranked first among the consumed alcoholic drinks. Only one fifth of the test persons "reward" their children with sweets and wish that they eat up their dinner. About half of the questionees were smokers. One fourth had never smoked, while another fourth had given up smoking. Mostly cigarettes were consumed, although nearly all test persons regarded inhaling smoking as harmful. The sole knowledge of factors that have a detrimental effect on the state of health (e.g. overweight, smoking) seems to be not sufficient to lead a healthy life. Since the test persons are, however, willing to do something for their health it would be useful to concentrate adipose persons and smokers into groups that should be treated by behaviour therapy and be positively motivated.

Adult↗

Risk factors for hepatitis C virus infection in United States blood donors. NHLBI Retrovirus Epidemiology Donor Study (REDS)

Injection drug use (IDU) is a known risk factor for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear. In 1997, we performed a case-control study of 2,316 HCV-seropositive blood donors and 2,316 seronegative donors matched on age, sex, race/ethnicity, blood center, and first-time versus repeat-donor status. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Questionnaires were returned by 758 (33%) HCV(+) and 1,039 (45%) control subjects (P =.001). The final multivariate model included only the following independent HCV risk factors: IDU (OR = 49.6; 95% CI: 20.3-121.1), blood transfusion in non-IDU (OR = 10.9; 95% CI: 6.5-18.2), sex with an IDU (OR = 6.3; 95% CI: 3.3-12.0), having been in jail more than 3 days (OR = 2.9; 95% CI: 1.3-6.6), religious scarification (OR = 2.8; 95% CI: 1.2-7. 0), having been stuck or cut with a bloody object (OR = 2.1; 95% CI: 1.1-4.1), pierced ears or body parts (OR = 2.0; 95% CI: 1.1-3.7), and immunoglobulin injection (OR = 1.6; 95% CI: 1.0-2.6). Although drug inhalation and a high number of lifetime sex partners were significantly more common among HCV seropositives, they were not associated with HCV after controlling for IDU and other risk factors. IDU, blood transfusion among non-IDU, and sex with an IDU are strong risk factors for HCV among United States blood donors. Weaker associations with incarceration, religious scarification, being stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection must be interpreted with caution.

Adult↗

Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans.

Intranasal cocaine (COC) and oral ethanol (ETOH) were administered to one group of seven research volunteers during daily experimental sessions. Following the determination of baseline subjective and performance measures, an ETOH cocktail (0, 19.4, 38.7 or 58.1 g of ETOH in lemonade) was consumed over a 10-min period. COC hydrochloride (4, 48, 96 mg) was inhaled 35-min after the start of ETOH drinking. In a separate experiment, seven research volunteers received intravenous cocaine and smoked marijuana (MJ), alone and in combination during daily experimental sessions. Following the determination of baseline measures, a 1-g MJ cigarette (0-2.7% delta 9-THC, w/w) was smoked and 13 min after the start of MJ smoking COC hydrochloride (0, 16, 32 mg) was given intravenously. ETOH increased simple-reaction time and decreased DSST trials. COC decreased DSST trials, increased incorrect responses on a list-learning task and attenuated the effect of ETOH on DSST performance. Only combinations of the high COC dose and the high MJ dose increased errors on a repeated acquisition task. Intranasal COC increased ratings of 'Stimulated,' and 'High' and LSD scores on the ARCI which were unaffected by ETOH. Increased ratings of 'Sedated' following ETOH alone were attenuated by intranasal (i.n.) COC. Intravenous COC and smoked MJ alone both increased ratings of 'Stimulated' and 'High.' There was a trend for combinations of i.v. COC and MJ to prolong these elevations. The results suggest that the interactive effects of COC in combination with ETOH or MJ, after acute administration, are subtle and in need of further analyses to better understand polydrug abuse.

Administration, Intranasal↗

Reinforcing, subjective, and psychomotor effects of sevoflurane and nitrous oxide in moderate-drinking healthy volunteers.

AIMS: To characterize the reinforcing, subjective and psychomotor effects of sevoflurane, a volatile anesthetic, across a range of subanesthetic concentrations in non-drug-abusing humans. In addition, a concentration of nitrous oxide was included in the design in order to compare and contrast behavioral effects of a gaseous to a volatile anesthesic. DESIGN: Repeated measures, double-blind, placebo control experiment. SETTING: Human psychopharmacology laboratory. PARTICIPANTS: Fourteen moderate-drinking healthy volunteers. INTERVENTION: In each of four sessions, subjects first sampled placebo-oxygen and an active drug (end-tidal concentrations of 0.2, 0.4, 0.6% sevoflurane and 30% nitrous oxide in oxygen) and then chose between the two MEASUREMENTS: Mood and psychomotor performance during the sampling trials, and choice of drug or placebo-oxygen during choice trial. FINDINGS: Nitrous oxide was chosen by 71% of the subjects, and 0.2, 0.4 and 0.6% sevoflurane were chosen by 50%, 57% and 50% of the subjects, respectively. Neither drug was chosen at levels that exceeded that of chance. Sevoflurane and nitrous oxide both impaired psychomotor performance and produced changes in mood. There were several differences in subjective effects between sevoflurane and nitrous oxide at concentrations which were considered to be equivalent in anesthetic effect. Finally, although sevoflurane did not function as a reinforcer in the majority of individuals tested, there was evidence that sevoflurane functioned as a reinforcer in some volunteers: subjects who chose to inhale sevoflurane over placebo-oxygen tended to report a positive spectrum of subjective effects during the sevoflurane sampling trial, relative to those subjects who chose placebo-oxygen over sevoflurane. CONCLUSIONS: Although sevoflurane did not function as a reinforcer in the majority of subjects tested, the correspondence between positive subjective effects of sevoflurane and subsequent sevoflurane choice suggests that the volatile anesthetic drug can function as a reinforcer in some moderate drinkers.

Adult↗

The second National Epidemiological Survey on illicit drug use at six high-prevalence areas in China: prevalence rates and use patterns.

AIMS: This is the first part of the Second National Epidemiological Survey on Illicit Drug Use in six high-prevalence areas in China in 1996. The scale of illicit drug abuse and patterns of use in the survey areas were assessed. DESIGN, SETTING AND PARTICIPANTS: 67 319 registered permanent residents in the community and those who were at institutions at the point of the survey (15 years old and over, males 34 755, 51.6%; females 32 564, 48.4%) in selected areas in China were screened and interviewed by trained psychiatrists. MEASUREMENTS: Demographics and drug-related data were assessed using the Epidemiological Inventory for Illicit Drug Use developed by the authors. Illicit drugs in this study were defined as a group of psychoactive substances controlled by international and national laws, used for non-medical purposes, including opiate, cocaine, amphetamine-type stimulants (ATS), cannabis, hallucinogens, etc. FINDINGS: The lifetime prevalence of illicit drug use was 1.60% (male, 2.58%, female 0.57%), and 1-year prevalence was 1.17% (male 1.80%, female 0.48%). There were 67 cases who used a drug initially before 1952; no new cases of illicit drug use could then be found during the period of 1952-86. However, the number of new drug users in each year has been rising steadily since 1986. The majority of drugs used were opiates in which heroin dominated, although there was some variability among the six sites. The main routes of administration were inhalation and intravenous injection. More than half the users (59.1%) took drugs on seven occasions or less per week, and 15.8% users used drugs on 21 occasions or more per week. CONCLUSION: Compared with the data from the 1993 survey, illicit drug use has continued to escalate across the areas, calling for priority concern in various sections of the country.

Adolescent↗

Rapid spread of hepatitis C virus among injecting-drug users in the Philippines: Implications for HIV epidemics.

From the trends of human immunodeficiency virus (HIV) epidemics in South and Southeast Asia, it was postulated that an HIV epidemic would start as a blood-borne infection among injecting-drug users in the Philippines. In 2002, 560 individuals were recruited in Metro Cebu, Philippines and tested for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections. The seroprevalence of anti-HCV among injecting-drug users (70.1%, 61/87) was significantly higher than those among inhalation drug users (16.3%, 7/43; P = 0.00; OR = 12), sex workers (0%, 0/130; P = 0.00; OR = infinity), antenatal clinic attendees (0%, 0/100; P = 0.00; OR = infinity), and students/health care workers (2%, 4/200; P = 0.00; OR = 115). The seroprevalence of HBsAg among injecting-drug users (10.3%, 9/87) was significantly higher than those among sex workers (2.3%, 3/130; P = 0.01; OR = 4.9), and antenatal clinic attendees (3%, 3/100; P = 0.04; OR = 3.7), but was not statistically different from those among inhalation drug users (9.3%, 4/43; P = 0.9) and students/health care workers (4.5%, 9/200; P = 0.06). None of the study population was reactive to anti-HIV antibody. The HCV strains obtained from the injecting-drug users belonged to either genotype 1a or 2b and the strains in each genotype clustered closely to each other. There was no dual infection with genotype 1a and 2b. These results suggest that the HCV infection in injecting-drug users may be emanating rapidly from limited number individuals in Metro Cebu, Philippines.

Adolescent↗

Systemic absorption and abuse liability of snorted flunitrazepam.

Benzodiazepine hypnotics are widely abused as part of a polydrug misuse culture. This study set out to investigate some pharmacokinetic and pharmacodynamic characteristics of a novel method of abuse, snorting, of flunitrazepam. Twenty healthy volunteers took part: three took 0.5 mg, three took 1 mg, three took 1.5 mg, six took 2 mg and five took placebo. Blood was sampled and ratings of mood, bodily symptoms, strength and liking of drug effect were completed pre- and at 5, 15, 30, 60, 90, 120 and 240 minutes and at 24 hours post-drug. It was found that flunitrazepam could be detected in venous blood 5 minutes after intake. As the dose increased, the peak plasma concentration was higher but also occurred progressively later, the levels reached being comparable to oral or intramuscular administration at 110 minutes. Subjects reported sedation but complained of few side-effects. They liked the drug effects and subjective ratings of strength were correlated with liking and with plasma drug levels.

Administration, Inhalation↗

Acute reinforcing effects of low-dose nicotine nasal spray in humans.

Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.

Administration, Inhalation↗

Fentanyl-related deaths in Ontario, Canada: toxicological findings and circumstances of death in 112 cases (2002-2004).

In order to characterize fentanyl-related deaths in the province of Ontario, Canada, a retrospective study of all cases in which fentanyl was quantitated in blood was conducted for the time period between 2002 and 2004. A total of 112 fentanyl-related deaths were identified. Decedents ranged in age from 4 to 93 years and comprised 63 men and 49 women. A variety of routes of administration of the drug were identified: transdermal application of Duragesic patches, intravenous injection of patch contents or fentanyl citrate solution, oral/transmucosal administration, and volatilization and inhalation of Duragesic systems. Blood fentanyl concentrations were determined for all modes of drug administration and are provided. There were 54 cases in which death was attributed solely to fentanyl intoxication; the mean blood concentration was 25 microg/L (range: 3.0-383 microg/L). This concentration range overlapped with blood fentanyl concentrations measured among cases where the presence of the drug was considered incidental. For example, a mean blood concentration of 12 microg/L was observed among 12 cases of natural death (range: 2.7-33 microg/L). Detailed case reports of six individuals are also included and provide additional insight into the use of this drug for both therapeutic and illicit means.

Adolescent↗