Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses.

Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, Delta(9)tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.

Contribution of substance abuse and HIV infection to psychiatric distress in an inner-city African-American population.

We used Symptom Checklist 90-Revised (SCL90-R) to investigate psychiatric symptom severity in African-American drug-abusing individuals. Three hundred and seventeen African-American volunteers (52 control subjects; 265 drug users) were recruited, 19.2% of whom were HIV-positive. The impact of drug of choice or HIV status on mental distress was assessed. Symptomatic HIV-positive participants were excluded. The intake SCL90-R, Addiction Severity Index, and demographic data were subjected to regression analyses. Drug-abusing African Americans reported increased global distress, a finding that remained robust after we adjusted for HIV status, gender, age, and education. Drug of choice had no influence on the severity of global mental distress in our sample. Asymptomatic HIV-positive African Americans who abused drugs reported more distress than the HIV-negative drug users. Levels of global distress were similar in the HIV-negative and the HIV-positive controls. Subscales of the SCL90-R showed more symptom severity among drug-using, compared with nonusing, African Americans. Except for paranoia, anxiety, and obsessive-compulsive subscales, other symptom dimensions were significantly elevated in HIV-positive, compared with HIV-negative, drug abusers. When taken together, these findings suggest that drug abuse can exacerbate the severity of mental distress in HIV-positive patients. Treatment of these patients may be more successful if both sets of needs are addressed with matched interventions.

Antiviral medications improve cerebrovascular perfusion in HIV+ non-drug users and HIV+ cocaine abusers.

Antiviral medications have been useful in delaying the time course of HIV infection. Antiviral medications have also been reported to delay or reduce symptoms associated with AIDS related dementia and to improve cortical perfusion. The mechanism for this improvement is unclear. Thus, this report studies the effects of antiviral medications on cerebral blood flow velocity in HIV+ cocaine abusers, HIV+ control individuals and appropriate control individuals. Thirty-two unmedicated HIV+ individuals (28 cocaine abusers and 4 control individuals), 22 HIV+ individuals using antiviral medications (16 cocaine abusers and 6 HIV+ control individuals), 47 HIV- cocaine abusers, and 27 control HIV- subjects were studied. Blood flow velocities were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography. HIV+ individuals on antiviral medications had lower pulsatility values, suggesting decreased resistance in the cerebral blood vessels, in comparison to HIV+ individuals not taking antiviral medications. HIV+ cocaine abusers and HIV+ control individuals using antiviral medications had pulsatility values similar to HIV- control subjects. Antiviral medications appear to reduce these cerebrovascular perfusion deficits in HIV+ individuals. The antiviral medications appear to have a direct neuroprotective effect in addition to their antiviral effects. The neuroprotective role of antiviral medications requires further investigation.

Marijuana abusers are at increased risk for stroke. Preliminary evidence from cerebrovascular perfusion data.

We have recorded blood flow velocity in the anterior and middle cerebral arteries by transcranial Doppler sonography in abstinent marijuana abusers (n = 16) and control subjects (n = 19) to assess the effects of prolonged marijuana use of the cerebrovascular system. The pulsatility index, a measure of cerebrovascular resistance, and systolic velocity were significantly (p < 0.005) increased in marijuana abusers compared to the control subjects. These findings suggest that cerebral perfusion observed in 18-30 year old marijuana abusers is comparable to that of normal 60 year-olds. Thus, chronic abuse of marijuana might be a risk factor for stroke.

Neurovascular deficits in cocaine abusers.

The nature of the neurological and cerebrovascular deficits in cocaine abusers and whether they persist in abstinence is unclear. Blood flow velocity of the anterior and middle cerebral arteries was measured by transcranial Doppler sonography in cocaine abusers (n = 50) and control subjects (n = 25). Blood flow velocity was measured within 3 days and again after about 28 days after being admitted to an inpatient research ward to determine whether blood flow velocity improved during monitored abstinence conditions. The mean, systolic, and diastolic velocities as well as the pulsatility index in middle and anterior cerebral arteries significantly differed between controls and cocaine abusers (p < .05). Cerebrovascular resistance is increased in cocaine abusers and the increase persists for over a month of abstinence. Further research is needed to determine whether cerebrovascular resistance can be improved by pharmacological manipulations and whether improved blood flow relates to improved treatment outcome.

The regulation of cerebral blood flow during intravenous cocaine administration in cocaine abusers.

Cocaine abuse is associated with heightened risk of life-threatening neurological complications such as strokes, seizures, and transient ischemic attacks. We used transcranial Doppler (TCD) sonography, a continuous measure of cerebral blood flow velocity, to better understand the changes in cerebral hemodynamics produced by cocaine administration, which may lead to an increased risk for stroke in cocaine abusers. Heart rate and blood pressure were also measured. Blood flow velocity of seven cocaine abusers was studied during placebo, 10-, 25-, and 50-mg intravenous (i.v.) injections of cocaine. A significant increase in mean and systolic velocity which lasted for about two minutes was observed with all doses of cocaine, with no change in the placebo condition. This increase in systolic velocity indicates that cocaine produces an immediate and brief period of vasoconstriction in large arteries of the brain. The present results elucidate the time course of cocaine's acute cerebrovascular effects and provide a better understanding of etiology of cocaine-related stroke and transient ischemic attacks.

Cocaine dependence. A clinical syndrome requiring neuroprotection.

Cocaine use has increased the frequency of medical complications among younger individuals. Neurological and neurovascular complications include strokes, seizures, transient ischemic attacks, and headaches. Subclinical deficits in cerebral perfusion and EEG have been noted in this population. Although these subclinical deficits may be an indication of increased risk of medical complications, the prophalactic treatment of cocaine abusers with neuroprotective agents has not yet been advocated. Blood flow of the anterior and medial cerebral arteries was measured by transcranial Doppler sonography in cocaine abusers (n = 70) and control subjects (n = 20) to determine whether cocaine abusers might have reduced cerebral blood flow in large cerebral arteries. Blood flow was measured within three days of and again about 28 days after admission of subjects to an inpatient research ward to determine whether blood flow improved with monitored abstinence. The mean, systolic, and diastolic velocities as well as the Pulsatility Index (PI) in both arteries differed between the control and cocaine abusers (p < 0.05). After about a month of abstinence, blood flow for the cocaine-dependent subjects increased. These preliminary findings suggest that blood flow is reduced in cocaine abusers and that there is a slight improvement with abstinence. Further research is needed to determine whether blood flow in abstinent cocaine abusers can be increased by pharmacological manipulations.

Neurophysiological signs of cocaine dependence: increased electroencephalogram beta during withdrawal.

To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n = 10) and drug group who abused drugs, but were not cocaine dependent (n = 20)]. The EEG was recorded from eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p < .05) as well as a normative database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days. High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men.

Cognitive brain potential alterations in boys exposed to opiates: in utero and lifestyle comparisons.

Several studies have observed that intrauterine exposure to opiates results in emotional and cognitive complications for the child, but genetic and postnatal social-environmental factors may also affect the CNS development of these children. To assess the relative contribution of the in utero and social-environmental (lifestyle) effects of opiate exposure, event-related potentials (ERPs) and performance were studied in three groups of 7- to 12-year-old boys: (1) the in utero/lifestyle group (IU/LS) contained 16 boys who were exposed to opiates (in utero and lived with opiate-abusing mothers, (2) the lifestyle group (LS) included 14 boys who lived with opiate-abusing mothers, and (3) the control group (CON) composed of 13 boys. The cognitive ERP components and task performance were recorded in the Auditory Rare Event Monitoring (AREM) task and the Sternberg Memory task (Sternberg, 1975). On the AREM and Sternberg Memory tasks, P200 component was significantly decreased for the IU/LS and LS groups. On the Sternberg Memory task, percent correct was also significantly impaired in IU/LS and LS groups. The ERP alterations in the boys living with opiate-abusing mothers with and without intrauterine opiate exposure were similar. A dysfunctional social environment may contribute to the cognitive deficits seen in the sons of opiate-abusing mothers.

Hyperthermia of mouse lungs: technique and control of critical parameters.

A microwave heating technique which combines essential life support, monitoring and heating systems has been developed, and is in use for the investigation of pathophysiological responses of the murine lung to hyperthermia alone and in combination with other therapeutic modalities. The technique enables heating of most of the lung volume to within 1 to 1.5 degrees C of the target temperature. To ensure reproducibility and develop a programmed heating regimen, we have controlled microwave power, coupling of microwave power into the animal and surface temperature as well as respiration frequency, volume and temperature of inspired air and central core temperature. Cardiac function is also monitored via EKG and heart rate. With these controls, and a thermal probe in contact with the lung, we can achieve a given target temperature at a specified microwave power level and maintain that temperature within +/- 0.5 degree C for the desired heating time without surface burns and little or no procedure-related acute lethality.

The use of swine in brain interstitial radiation studies.

Swine offer an excellent, but previously unused, model for brain interstitial ionizing and non-ionizing radiation research. Significant advantages include size, cost, maneuverability, availability and conditioning. The methodology and some experimental results from studies of the effects of interstitial microwave hyperthermia and iridium-192 irradiation are presented.

Progressive hypertension in dogs by avoidance conditioning and saline infusion.

A group of dogs was trained on a free-operant avoidance-conditioning task that evoked acute increases in arterial pressure and heart rate during each of three daily 30-minute sessions. After 15 days of exposure to this procedure under conditions of normal sodium intake, 24-hour mean levels of arterial pressure remained unchanged. Another group of dogs received continuous intrarterial infusion of isotonic saline at a constant rate of 185 mEq/24 hrs for 15 days, but no avoidance sessions. Again, 24-hour mean levels of arterial pressure did not change significantly. However, 24-hour mean levels of systolic (19.5 +/- 6.2 mm Hg) and diastolic (13.7 +/- 2.9 mm Hg) pressure rose progressively over a 15-day period in a third group of dogs exposed concurrently to the avoidance schedule and saline infusion procedure. The progressive hypertension was accompanied by no consistent changes in heart rate. These experiments indicate that behavioral stress can potentiate sodium hypertension and provide a new method for the study of physiological and behavioral factors in long-term blood pressure control.