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PubMedDate not supplied

Behavioral sensitization after repeated formaldehyde exposure in rats.

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary studies indicated that repeated daily Form inhalation (20 days, as above) produced a greater avoidance to subsequent Form presentation, suggesting that daily Form inhalation may serve as a stressor. The results support the hypothesis that repeated chemical exposure in rats may produce CNS plasticity manifest as greater sensitivity to dopaminergic drugs, enhanced fear conditioning to odor paired with an aversive event, and greater avoidance of odors. Some of these behavioral changes observed in rats may provide a link with symptoms in a subset of individuals with MCS.

Administration, Inhalation↗
PubMed2006

Adolescent drug & alcohol use in the 21st century.

Screening for drug abuse should be a part of adolescent health maintenance visits. Good interviewing skills using open-ended, nonjudgmental questions in a private setting may elicit a history of drug abuse. A detailed and comprehensive history is important to recognize family dynamics, early behavioral changes (Table 5, see page 198), comorbid psychiatric conditions, and the adolescent's attitude toward substances of abuse. A good physical exam may reveal clinical sequelae of drug abuse. Testing for drug abuse should be done with the patient's consent except in cases where judgment is impaired. Periodic screening for drugs is a part of drug treatment and rehabilitation. The typical pediatrician is not equipped to provide drug counseling and treatment to the abusing adolescent. Specialized referral centers would be ideal, and clinicians need to be aware of local resources in their communities. Anticipatory guidance explaining the ill effects of drugs is mandatory. Prevention should be aimed at increasing public awareness of the consequences of drug abuse, improving parenting techniques, and introducing school-based drug prevention programs. The fight against substance abuse needs to be a community effort in which the individual, the family and the primary care physician play important roles.

Adolescent↗
PubMed2000

Distinction of inhaled and oral salbutamol by urine analysis using conventional screening procedures for doping control.

Salbutamol administration in athletes is permitted only by inhalation, for the management of asthma. The authors discuss different criteria for suspecting oral use of salbutamol, taking into account the data obtained by application of two conventional screening procedures for doping control: gas chromatography/mass spectrometry (GC/MS) and enzyme-linked immunosorbent assay (ELISA). Urine samples obtained after administration of oral and inhaled salbutamol to asthmatic and nonasthmatic swimmers were analyzed using both analytical approaches. As expected, concentrations obtained by the ELISA test (detection of total salbutamol) were higher than those obtained using the GC/MS procedure (detection of nonsulfated salbutamol). After oral administration, the ELISA test detected significantly higher salbutamol concentrations than those detected after inhalation, reflecting the greater doses administered orally. Urine samples with total salbutamol greater than 1400 ng/mL were obtained after oral doses, but no sample reached this value after inhaled doses. Higher concentrations of nonsulfated salbutamol have also been detected after oral intake, although there is an overlap between the distributions of concentrations after oral and inhaled doses. A cut-off concentration of 500 ng/mL can be used for nonsulfated salbutamol to select suspicious samples, giving 11.8% false negative results and 4.3% false positive results. An additional criterion evaluated was the androsterone-salbutamol peak height ratio, which was lower after oral doses because of the higher concentrations of salbutamol in urine. This ratio was lower than 2 for all the samples collected after oral administration, although 6.8% false positive samples resulted because of low concentrations of androsterone in female urine. Several possibilities for detecting suspicious samples from athletes who have taken prohibited oral salbutamol are available with conventional screening procedures in doping control.

Administration, Inhalation↗
PubMed1990

Fatal abuse of nitrous oxide in the workplace.

Abuse of nitrous oxide (N2O) while on the job caused at least 11 deaths in 1984 to 1987, as found in investigations by the Occupational Safety and Health Administration and in reports to the Consumer Product Safety Commission. Although nitrous oxide has had a reputation as a "clean and safe" analgesic and anesthetic, the possibility of asphyxiation by inhalation is not widely recognized, and there are no requirements for warning labels on nonmedical sources of N2O. The 11 deaths involved recreational inhalation of N2O by young male employees from tanks or cylinders normally used for legitimate business purposes. In six cases, the victims worked in food serving establishments and inhaled N2O that was used to power whipped cream dispensers. Commercial users of N2O, particularly in the restaurant industry, should be aware of this hazard. Warning labels for N2O sources and tighter control over supplies are warranted.

Humans↗
PubMedDate not supplied

Drug use among adolescents in Asturias (Spain).

A survey of drug use, based on a sample of 2,537 school students in the 15-17 year age group selected from 11 schools in central Asturias (Spain), showed that 697 respondents, or 29.1 per cent, were drug users. Cannabis was the most widely abused drug: 500 respondents, or 20.8 per cent of the total sample, became involved with this drug at some time in their lives. The percentages of the total sample show that the use of cannabis at any time ("ever" use) was followed by use of: tranquillizers (10.3 per cent), amphetamines and amphetamine-like substances (7.9 per cent), inhalants (2.3 per cent), hallucinogens (2.0 per cent), sedatives (1.7 per cent), opiates (1.4 per cent) and cocaine (1.2 per cent). Males were generally more involved with drugs than females were. The average age at first drug use was 15.4 for males and 15.5 for females.

Adolescent↗
PubMed1981

[On the evaluation of health factors in high-rise buildings. 2. Bioclimatological consequences resulting from comparative measurements of the air ionisation in a high-rise building located in a heavily contaminated suburban area and at certain altitudes (author's transl)].

According to accepted scientific theories inhaled small ions deliver their charges in the pulmonary alveoli and this leads to local recharges. This process stimulates structures of the central nervous system and the activity of the endocrine is excited, resulting in an enhancement of the general well-being. These possibilities of interpretation regarding a biological ionic effect are supported, with reservations (e.g. effects produced by a change in climate), by positive medical effects during and after a stay in a well-ventilated mountain climate or also in a sea-climate. Owing to their lower mobility the large ions are inhaled as small ions to an increasing extent. The chemical and physical noxa are delivered and deposited in the respiratory tract. They "stick" the epithelia in the trachea and in the bronchi as well as the endothelia in the lung vesicles. The number of the ciliary movements is reduced. Similar effects are known to be caused also by nicotine abuse. This results in a decreased ability of expectoration and a lower intake of oxygen by the alveoli. These facts could furnish an explanation for the increased vulnerability of city dwellers to infections diseases and to catarrh. The changed ionisation of air in urbanised areas (mainly large ions in high concentrations) definitely represents only one of the many risk factors. In addition to the attempt to characterize bioclimatically local weather conditions by means of the non-conventional parameter "air ionisation" our study has also been intended to establish biologically oriented criteria for the living in a high-rise building in a particularly unfavourable location. Under specific microclimatic conditions the uppermost storeys were at times bioclimatically favoured over the lowermost, especially when shallow air inversion is present. In such cases, small ions exclusively were registered in the upper storeys and large ions in the lower floors.

Air Ionization↗
PubMed2006

Evidence of acute tolerance to remifentanil in intensive care but not in anesthesia.

We report the case of a 19-year-old man with a drug abuse history, admitted to the intensive care unit for head and chest trauma, who experienced an acute tolerance to sedative and respiratory depression effects of remifentanil, which was given as the sole agent for sedation. He did not exhibit any signs of drug tolerance or intraoperative awareness during prolonged remifentanil-based anesthesia using propofol or sevoflurane as adjuvants. Several recent studies support the hypothesis of a possible involvement of N-methyl-d-aspartate glutamate receptors. The clinical relevance of this report is that if a patient with a previously acute tolerance to remifentanil during sedation undergoes long-term surgery, and propofol or sevoflurane is coadministered in a remifentanil-based anesthesia, the patient will not necessarily develop opioid tolerance. It is of interest for anesthesiologists, given the high frequency of patients with drug abuse history who are admitted to intensive care units, often sedated with remifentanil, who undergo anesthesia for emergency surgery.

Adjuvants, Anesthesia↗
PubMed1999

Transitions in the route of cocaine administration--characteristics, direction and associated variables.

AIMS: To examine transitions in the route of administration of cocaine and the variables associated with them. DESIGN: A cross-sectional study undertaken between January 1996 and October 1997. SETTING: Fifteen different services that offer treatment, counselling or assistance to drug users or HIV-positive patients in the State of São Paulo, Brazil. PARTICIPANTS: Two hundred and ninety-four current or ex-cocaine and crack cocaine users. MEASUREMENTS: A structured interview schedule was developed consisting of 246 questions covering socio-demographic details, drug history, cocaine transitions and HIV-risk behaviours. FINDINGS: Eighty-seven per cent of patients began using cocaine by snorting and 74% subsequently underwent a transition of route--68% towards smoking and 20% to injecting. Half of all transitions occurred in the first 3 years following initiation into cocaine use. Factors associated with transitions were: younger age at cocaine initiation, more frequent use at peak usage, initial use of cocaine by snorting or injecting, a lower level of scholastic attainment and experience with a wider range of drug classes. A cohort effect was apparent with younger cocaine users and those who had begun using after 1990 being more likely to undergo a transition to smoking crack and less likely to start injecting. CONCLUSIONS: Cocaine transitions are very common and are usually towards routes associated with a higher dependency potential and increased HIV-risk behaviour. Further research is needed to see if transitions can be prevented by early identification of potential cases.

Administration, Inhalation↗
PubMed2006

Is inhalant use a risk factor for heroin and injection drug use among adolescents in the United States?

PURPOSE: We examined whether inhalant use was associated with heroin and injection drug use (IDU) among adolescents aged 12 to 17 in the United States. METHODS: Data were drawn from the 2002/2003 administrations of the National Survey on Drug Use and Health (NSDUH). We conducted logistic regression analyses to estimate associations of inhalant use with heroin use, heroin injection, and IDU, respectively, among adolescent drug users (N=8161). RESULTS: Approximately 30.9% of adolescents had ever used at least one illicit drug. More than one-fifth (22.2%) of adolescents were past-year or recent drug users. Among past-year adolescent drug users, 1.4% had progressed to heroin use and 1.2% reported IDU. Adolescents who had used inhalants and marijuana were 2.8 and 2.9 times as likely as adolescents who had used marijuana but not inhalants to report heroin use and any IDU, respectively. Adolescents who had used inhalants or other drugs but not marijuana were unlikely to use heroin. However, inhalant users, irrespective of their marijuana use histories, had greater odds of IDU than drug users who had not used inhalants. Adolescent drug users who were females, school dropouts, whites, or delinquents had significantly increased odds of heroin use and IDU. Cigarette smoking before the age of 15 was strongly associated with heroin use, and a history of foster care placement was associated with IDU. CONCLUSIONS: This national study of American adolescents identifies several subgroups of recent drug users, such as females, school dropouts, and youth who have used inhalants and marijuana, which have substantially increased odds of heroin use and IDU. Screening, prevention, and treatment interventions targeted to these groups might reduce medical and social complications of heroin use and IDU.

Administration, Inhalation↗
PubMed1990

Opioids and designer drugs.

Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

Ambulatory Care↗
PubMed2004

Acute arterial thrombosis associated with cocaine abuse.

PURPOSE: Cocaine-induced arterial thrombosis is uncommon, and most reported cases involved small-diameter vessels such as the cerebral and coronary arteries. This study was undertaken to review our experience with peripheral arterial thrombosis presumed caused by cocaine abuse. METHODS: Hospital records were reviewed for all patients admitted over 10 years with acute arterial occlusion involving the peripheral arterial system. Patients with confirmation of cocaine use or of its derivative, crack cocaine, within 24 hours of hospital admission formed the basis of this study. Symptoms at presentation, management, and outcome in these patients were reviewed. RESULTS: Three hundred eighty-two patients with acute peripheral arterial occlusion were identified during the study period. The presumptive diagnosis of cocaine-induced arterial occlusion was made in 5 patients (4 men, mean age 38 years). Cocaine use was achieved via intranasal inhalation in 2 patients (40%), whereas the 3 remaining patients smoked crack cocaine (60%). The mean time between cocaine use and onset of arterial thrombosis was 9.2 hours (range, 2-20 hours). Symptoms at presentation included acute limb ischemia without pedal Doppler signals (3 patients, 60%) and abdominal pain without femoral pulses (2 patients, 40%). Arterial occlusion was confirmed on angiograms in all patients, which revealed aortic thrombosis in 1 patient (20%), iliac thrombosis in 2 patients (40%), superficial femoral artery thrombosis in 1 patient (20%), and popliteal artery occlusion in 1 patient (20%). Surgical thrombectomy was successfully performed in 4 patients (80%), and 1 patient (20%) underwent successful thrombolytic therapy for femoropopliteal artery occlusion. There was no perioperative mortality. All 5 patients who were discharged were available for follow-up (mean, 36 months; range, 6-75 months). There was 1 late death from myocardial infarction. In 1 patient recurrent lower extremity arterial thrombosis developed after 28 months, which was successfully treated with thrombolytic therapy. CONCLUSIONS: Our study underscores cocaine abuse as a potential cause of acute arterial thrombosis. Cocaine-induced arterial thrombosis should be suspected in patients with recent history of cocaine abuse with acute limb ischemia without an identifiable source or overt cardiovascular risk factors. Prompt angiography with operative or endovascular intervention should be performed to avert arterial ischemic sequelae.

Adult↗
PubMed2003

Early substance use by juvenile offenders.

Although the interconnection between delinquency and substance use in adolescence is well documented, considerably less is known about substance-use initiation in childhood for juvenile delinquent populations. This descriptive study examined early substance initiation in childhood as reported by adolescents who were incarcerated for juvenile offenses (93 males, 96 females; 58% African American, 42% European American). Youth were individually interviewed using an adapted version of substance-related questions from the National Household Survey. Juvenile justice system records were reviewed to characterize offense histories. A majority of males and females reported using at least one substance (other than cigarettes) such as alcohol, marijuana, or inhalants by age 13. Alcohol use reportedly occurred by age 10 for 17% of the youth. For a substantial portion, early initiation turned into frequent early use. For example, 32% of the males and 39% of the females reported drinking alcoholic beverages at a frequency of several times per month or greater by age 13. Limited evidence related early substance initiation with subsequent substance abuse. Offense status was related to early substance initiation for females but not males. The study provided clear evidence that very early substance use is a significant problem among youth who end up in the juvenile justice system and that we need to find out more about the environmental and social variables affecting very early substance initiation.

Adolescent↗
PubMed2002

The Anthrax Vaccine Program: an analysis of the CDC's recommendations for vaccine use.

The anthrax vaccine was never proved to be safe and effective. It is one cause of Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War illnesses. The vaccine's production has been substandard. Without adequate evaluation, the Food and Drug Administration recently approved (retrospectively) significant changes made to the vaccine's composition since 1990. The vaccine's mandatory use for inhalation anthrax is "off-label." A skewed review of the vaccine literature by the Centers for Disease Control and Prevention (CDC) led to remunerative collaborative research with the army, involving civilian volunteers. Despite acknowledging possible fetal harm, the CDC offered the vaccine to children and pregnant women. New trends could weaken prelicensure efficacy and safety review of medical products intended for biodefense and avoid manufacturer liability for their use.

Anthrax↗
PubMed2004

Cannabis-induced propriospinal myoclonus.

We report on a case of a 25-year-old woman with clusters of myoclonus induced by a single exposure to inhaled cannabis. Investigations excluded a structural abnormality of the spine. Multi-channel surface EMG with parallel frontal EEG recording confirmed the diagnosis of propriospinal myoclonus.

Adult↗
PubMed2004

Injecting and non-injecting cocaine use in Sydney, Australia: physical and psychological morbidity.

This study aimed to examine the physical and psychological harms of cocaine use and investigate the role of injecting versus non-injecting routes of administration in the severity of such harms. Two hundred and twelve cocaine users from inner-city and south-western Sydney were administered a structured interview containing sections on demographics, drug treatment history, drug use history, cocaine use patterns, cocaine dependence and physical and psychological problems associated with cocaine use. Serious physical and psychological symptoms were prevalent among both injecting and non-injecting cocaine users. The prevalence and extent of symptoms was greater among injecting cocaine users, however route of administration did not prove to be a significant independent predictor of harm when other factors, such as frequency of use and level of dependence, were taken into account. While the level of physical and psychological harm was greater among cocaine injectors, it would appear that factors engendered by injecting, such as more frequent use and higher levels of dependence, result in higher levels of harm, rather than the route of administration per se. Physical and psychological problems were also reported among infrequent users, suggesting that cocaine can cause harm irrespective of frequency or method of use. Harm reduction initiatives should be targeted towards all cocaine users, not just those who seek treatment for dependence or present with acute medical complications.

Administration, Inhalation↗
PubMed1981

Exposure to nitrous oxide and neurologic disease among dental professionals.

Questionnaires, mailed to approximately 30,000 dentists and an equal number of dental assistants requesting information regarding professional exposure to anesthetics and health problems, showed an increased incidence of neurologic complaints in dental professionals who worked with nitrous oxide. The most striking differences were noted in individuals reporting symptoms of numbness, tingling, and/or muscle weakness. For dentists heavily exposed to nitrous oxide, the rate of these complaints was 4-fold greater than for nonanesthetic-exposed dentists. For dental assistants heavily exposed to nitrous oxide, a 3-fold increase in these same complaints was noted. In view of recent evidence that nitrous oxide abuse may lead to polyneuropathy, the results suggest that occupational exposure to nitrous oxide by both dentists and dental assistants may be associated with similar neuropathy.

Adult↗
PubMed1983

Does consumption of alcohol in the presence of disulfiram cause brain damage?

After blocking aldehyde dehydrogenase activity with disulfiram in rats, a single injection of ethanol or a single day of inhaling ethanol vapor resulted in neuronal degeneration in the cerebral cortex and elsewhere that was detected by a specific silver stain and by electron microscopy. Treatment of rats with alcohol alone and with disulfiram alone did not cause neuronal degeneration. The minimum blood alcohol levels and disulfiram doses administered to the rats which caused neural degeneration are not distant from those values described in a clinical case of abuse of disulfiram.

Acetaldehyde↗
PubMed2003

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.

Administration, Sublingual↗