Implications of plasma Delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers.

Delta(9)-Tetrahydrocannabinol (THC) is commonly found in toxicological specimens from driving under the influence and accident investigations. Plasma cannabinoid concentrations were determined in 18 long-term heavy cannabis smokers residing on an in-patient research unit for seven days of monitored abstinence. THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) were quantified by two-dimensional gas chromatography-mass spectrometry with cryofocusing.

Do Delta9-tetrahydrocannabinol concentrations indicate recent use in chronic cannabis users?

Aims: To quantify blood Delta(9)-tetrahydrocannabinol (THC) concentrations in chronic cannabis users over 7 days of continuous monitored abstinence.

Participants: Twenty-five frequent, long-term cannabis users resided on a secure clinical research unit at the US National Institute on Drug Abuse under continuous medical surveillance to prevent cannabis self-administration.

Measurements: Whole blood cannabinoid concentrations were determined by two-dimensional gas chromatography-mass spectrometry.

Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure.

Background: Generally, urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (THCCOOH) after alkaline hydrolysis is monitored to detect cannabis exposure, although last use may have been weeks prior in chronic cannabis users. Delta9-Tetrahydrocannabinol (THC) and 11-hydroxy-THC (11-OH-THC) concentrations in urine following Escherichia coli beta-glucuronidase hydrolysis were proposed as biomarkers of recent (within 8h) cannabis use.

Objective: To test the validity of THC and 11-OH-THC in urine as indicators of recent cannabis use.

EEG and cerebral blood flow velocity abnormalities in chronic cocaine users.

EEG and cerebral blood flow abnormalities have been documented in chronic cocaine abusers. To identify possible relationships between EEG and blood flow changes and their relationship to the intensity of cocaine use, we recorded the resting eyes-closed EEG and anterior (ACA) and middle (MCA) cerebral artery blood flow velocity during systole (V(S)) and diastole (V(D)) by transcranial Doppler (TCD) sonography of 99 (76 male, 23 female; mean [SD] age 34.3 [5.

Intra- and intersubject whole blood/plasma cannabinoid ratios determined by 2-dimensional, electron impact GC-MS with cryofocusing.

Background: Whole-blood concentrations of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) are approximately half of those in plasma due to high plasma protein binding and poor cannabinoid distribution into erythrocytes. Whole blood is frequently the only specimen available in forensic investigations; controlled cannabinoid administration studies provide scientific data for interpretation of cannabinoid tests but usually report plasma concentrations. Whole-blood/plasma cannabinoid ratios from simultaneously collected authentic specimens are rarely reported.

Caffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: cerebral blood flow velocity, quantitative EEG, and subjective effects.

Rationale: Although the subjective effects of caffeine abstinence, acute and chronic administration, and tolerance are well described, the corresponding neurophysiological effects are not.

Objectives: Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic caffeine administration were investigated using cerebral blood flow velocity, quantitative electroencephalography (EEG), and subjective effects.

Materials And Methods: Sixteen regular caffeine users participated in this double-blind, within-subject study during which they received acute caffeine and placebo challenges (1) while maintained on 400 mg caffeine daily for > or =14 days and (2) while maintained on placebo for > or =14 days.

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.

EEG of chronic marijuana users during abstinence: relationship to years of marijuana use, cerebral blood flow and thyroid function.

Objective: Marijuana abuse is associated with neurological changes including increases in frontal EEG alpha during abstinence. Research is needed to assess to what extent these EEG patterns are indicative of cerebral perfusion deficits.

Methods: We recorded the resting eyes closed EEG of 75 abstinent marijuana users and 33 control subjects.

EEG absolute power during extended cocaine abstinence.

We examined the effects of cocaine withdrawal on EEG during 3 months of abstinence. Twenty physically healthy cocaine users (80% men, 80% African American, mean (SD) age, 34.8 (4.

Neurological assessments of marijuana users.

This chapter summarizes the neurological approaches used to assess the potential long-term effects of drugs on the nervous system of drug abusers. These include the use of neuropsychological assessments, transcranial Doppler (TCD) sonography, and electroencephalographic (EEG) recordings. Neuropsychological procedures are used in an effort to provide an unbiased estimate of the individual's cognitive capacity, and included tests of language skills, attention, memory, and motor skills.

Neuropsychiatric alterations in MDMA users: preliminary findings.

The use of marijuana is rampant among 3,4-methylenedioxymethamphetamine (MDMA) users. The co-occurrence of abuse of these two drugs has made it difficult to assess the specific residual effects of MDMA alone. As a first step toward identifying the effects of long-term MDMA use, we studied 8 MDMA abusers, 8 marijuana/MDMA abusers, 15 marijuana abusers (matched in marijuana use without MDMA use), and 17 control subjects.

Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans.

The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three doses (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design.

Cerebrovascular perfusion in marijuana users during a month of monitored abstinence.

Objective: To determine possible effects of prolonged marijuana use on the cerebrovascular system during a month of monitored abstinence and to assess how the intensity of current use might have influenced cerebrovascular perfusion in these marijuana users.

Method: The authors recorded blood flow velocity in the anterior and middle cerebral arteries using transcranial Doppler sonography in three groups of marijuana users who differed in the intensity of recent use (light: n = 11; moderate: n = 23; and heavy: n = 20) and in control subjects (n = 18) to assess the nature and duration of any potential abnormalities. Blood flow velocity was recorded within 3 days of admission and 28 to 30 days of monitored abstinence on an inpatient research unit in order to evaluate subacute effects of the drug and any abstinence-generated changes.

Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease.

Background: Preclinical data indicate a crucial role of stress in the acute effects of drugs of abuse, maintenance of self-administration, and susceptibility to relapse. Stress system activation may serve as a marker for a neurochemical dysfunction with prognostic significance in patients with addiction.

Methods: We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects without depressive symptoms, and seven subjects with substance abuse and depressive symptoms.

Treatment-seeking inpatient cocaine abusers show hypothalamic dysregulation of both basal prolactin and cortisol secretion.

Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks.

EEG deficits in chronic marijuana abusers during monitored abstinence: preliminary findings.

Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence.

Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin.

Opiate replacement therapy has been useful in reducing heroin use and in keeping patients in treatment programs. However, neuropsychological and neurophysiological effects of this treatment regimen have not been evaluated systematically. To determine whether methadone treatment reduces the magnitude of cerebral blood flow alternations in polysubstance (heroin and cocaine) abusers, we compared blood flow parameters in control subjects (n=26), polysubstance abusers (n=28) maintained on methadone for 24 weeks, and polysubstance abusers (n=22) who were not seeking treatment.

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.

Cerebral blood flow pulsatility deficits in HIV+ poly substance abusers: differences associated with antiviral medications.

This study examines the influence of HIV-seropositivity and antiviral medications on cerebral blood flow in cocaine abusers. Forty-five HIV negative (HIV-) cocaine abusers, 36 HIV positive (HIV+) cocaine abusers (CD4; mean 378, +/-229) and 27 control HIV- subjects were studied. Blood flow velocity and pulsatility were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography (TCD).

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.

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.

Gender differences in the EEG of abstinent cocaine abusers.

Gender differences in the EEG were explored in cocaine-abusing individuals not seeking treatment. Twenty currently abstinent cocaine-abusing females aged 21-41 were studied. Their cocaine use history was matched to 20 currently abstinent cocaine-abusing males.

Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity.

Rationale: Cessation of daily caffeine consumption produces a withdrawal syndrome comprised of subjective symptoms and functional impairment. Few controlled studies have examined the physiological effects of caffeine withdrawal.

Objective: The present study examined the effect of caffeine withdrawal on cerebral blood flow velocity and quantitative EEG.

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.