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Biomedical subjects

M Haney

Publications and source records attributed to M Haney.

At least 19 recordsLinked to original sources

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

Beta Particles↗

RBE of quasi-monoenergetic 60 MeV neutron radiation for induction of dicentric chromosomes in human lymphocytes.

The production of dicentric chromosomes in human lymphocytes by high-energy neutron radiation was studied using a quasi-monoenergetic 60 MeV neutron beam. The average yield coefficient [see text] of the linear dose-response relationship for dicentric chromosomes was measured to be (0.146+/-0.016) Gy-1. This confirms our earlier observations that above 400 keV, the yield of dicentric chromosomes decreases with increasing neutron energy. Using the linear-quadratic dose-response relationship for dicentric chromosomes established in blood of the same donor for 60Co gamma-rays as a reference radiation, an average maximum low-dose RBE (RBEM) of 14+/-4 for 60 MeV quasi-monoenergetic neutrons with a dose-weighted average energy [see text] of 41.0 MeV is obtained. A correction procedure was applied, to account for the low-energy continuum of the quasi-monoenergetic spectral neutron distribution, and the yield coefficient alpha for 60 MeV neutrons was determined from the measured average yield coefficient [see text]. For alpha, a value of (0.115+/-0.026) Gy-1 was obtained corresponding to an RBEM of 11+/-4. The present experiments extend earlier investigations with monoenergetic neutrons to higher energies.

Cells, Cultured↗

Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.

The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

Anesthesia↗

Is there reliable experimental evidence for different dicentric yields in human lymphocytes produced by mammography X-rays free-in-air and within a phantom?

We examined the production of dicentrics in human lymphocytes irradiated with 29 kV X-rays to a depth of 13.5 mm in a PMMA phantom. For these irradiation conditions, which are appropriate for the diagnostic application of mammography X-rays, a coefficient alpha of (5.88+/-0.66) x 10(-2) Gy(-1) of the linear quadratic dose-response relationship was determined. This value does not differ significantly from the coefficient alpha of (6.55+/-0.97) x 10(-2) Gy(-1) obtained earlier for a free-in-air set-up using blood of the same donor. The results are interpreted in terms of both the energy distributions of the photon fluence of mammography X-rays free-in-air and those in the PMMA phantom. Based on earlier results of experiments with monochromatic X-rays in the energy range 1.83-40 keV (completed here by an additional measurement at 25 keV), a fit function alpha(E) to the measured alpha coefficients as a function of the energy E of monochromatic X-rays was used to calculate weighted mean values alpha for both the mammography X-ray spectra free-in-air and in the phantom. As a result, weighted mean values of (4.9+/-1.0) x 10(-2) Gy(-1) and (4.5+/-1.0) x 10(-2) Gy(-1) were obtained, respectively. Although the measured alpha coefficients for mammography X-rays appear to be systematically higher than those calculated as weighted mean values alpha, it can be concluded that the modification of the mammography X-ray spectrum to a depth of 13.5 mm in a PMMA phantom compared with the free-in-air spectrum has no significant influence on the dicentric yields in human lymphocytes.

Air↗

Pressure-independent cardiac effects of angiotensin II in pigs.

BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.

Angiotensin II↗

The cardiac effects of intracoronary angiotensin II infusion.

UNLABELLED: Angiotensin II (Ang II) is a potent vasoconstrictor, which recently has been shown to also have significant inotropic effects. Previous results regarding the mechanisms of the acute inotropic effects of Ang II are not conclusive. We designed this study to investigate the local cardiac effects of intracoronary Ang II infusion in doses not affecting systemic circulation. Ang II (2.5-40 microg/h) was infused in the left coronary artery of Yorkshire pigs (n = 9) reaching calculated intracoronary Ang II concentrations of 842 +/- 310, 3342 +/- 1238, and 12448 +/- 4393 pg/mL, respectively. Cardiac systolic and diastolic function was evaluated by analysis of the left ventricular pressure-volume relationship. Coronary flow was measured by using a coronary sinus catheter and the retrograde thermodilution technique. No significant changes were seen in the systolic and diastolic function variables of heart rate, end-systolic elastance, preload recruitable stroke work, the time constant for isovolumetric relaxation, or in coronary vascular resistance and flow. The positive inotropic and chronotropic effects of Ang II seen in previous studies seem thus to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs. IMPLICATIONS: The positive inotropic and chronotropic effects of angiotension II (Ang II) seen in previous studies seem to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs.

Angiotensin II↗

Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated smoked cocaine in humans.

To study the consequences of repeated smoked cocaine use on central serotonergic and dopaminergic function, the effects of d-fenfluramine (d-FEN) and bromocriptine on plasma hormones were determined at three time-points following repeated cocaine self-administration under carefully controlled conditions. In a 20-day inpatient study, male cocaine abusers (d-FEN: n=10; bromocriptine: n=8) self-administered smoked cocaine (12-50 mg) for 3 days followed by 2 weeks of abstinence. The acute effects of d-FEN (0 or 30 mg po) or bromocriptine (0 or 1.25 mg po) on plasma neuroendocrine levels were determined 1-2, 7-8, and 13-14 days after the last cocaine dose. Blood was drawn before and then every 30-60 min for 4 h after capsule administration. The effects of d-FEN and bromocriptine were also determined in healthy, outpatient controls; d-FEN was removed from medical use in the US midway through the study due to complications associated with chronic administration, so all of the control participants were tested in Italy. Cocaine users had a blunted prolactin and cortisol response to d-FEN that lasted for at least 2 weeks of cocaine abstinence, but had a normal response to bromocriptine, which suppressed prolactin by 50% of baseline. The long-lasting and selective disruptions in serotonin pathways following chronic cocaine use may provide a neurochemical basis for changes in mood commonly reported during cocaine withdrawal.

Adult↗

Bupropion SR worsens mood during marijuana withdrawal in humans.

RATIONALE: Symptoms of withdrawal after daily marijuana smoking include increased ratings of irritability and depression. Similar mood symptoms are reported by cigarette smokers during nicotine abstinence. OBJECTIVE: Given the successful use of sustained-release bupropion in treating nicotine dependence, this study investigated how maintenance on bupropion influenced symptoms of marijuana withdrawal compared to maintenance on placebo. METHODS: Marijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatient on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% delta9-tetrahydrocannabinol (THC)] 5 times/day. For the remaining inpatient days, participants smoked placebo marijuana (0.0% THC) 5 times/day. Participants were then maintained outpatient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administration was double-blind. Mood, psychomotor task performance, food intake, and sleep were measured daily during each inpatient phase. The order of active and placebo bupropion maintenance was counterbalanced between groups. RESULTS: Bupropion had few behavioral effects when participants smoked active marijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal, ratings of irritability, restlessness, depression, and trouble sleeping were increased by bupropion compared to placebo maintenance. CONCLUSIONS: These data suggest that bupropion does not show promise as a potential treatment medication for marijuana dependence.

Adult↗

Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self-administration by humans.

RATIONALE: Data obtained in laboratory animals and humans suggest that dopamine D1 receptor antagonists decrease cocaine self-administration and block cocaine's discriminative stimulus and subjective effects. OBJECTIVES: This study investigates the effects of the selective dopamine D1 antagonist, ecopipam (SCH 39166), on the reinforcing, cardiovascular, and subjective effects of cocaine in humans. METHODS: Ten non-treatment-seeking cocaine smokers (two females, eight males), residing on an inpatient research unit, were maintained on placebo and ecopipam (100 mg p.o.) in random order using a within-subjects, cross-over design. Cocaine self-administration (0, 12, 25, and 50 mg) was tested beginning on the 5th day of each 8-day maintenance condition. A six-trial choice procedure (cocaine vs $5 merchandise vouchers) was utilized, with sessions consisting of one sample trial, when participants smoked the cocaine dose available that day, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one merchandise voucher. RESULTS: In the presence of placebo cocaine, ecopipam significantly decreased cocaine craving while increasing alcohol and tobacco craving. In the presence of active cocaine, ecopipam increased cocaine self-administration (12 mg) and increased ratings of "good drug effect," "high," "stimulated," and dose quality (25 and 50 mg). Ecopipam produced small but significant increases in blood pressure, regardless of cocaine dose. CONCLUSIONS: Maintenance on the long-acting dopamine D1 antagonist, ecopipam, enhanced both cocaine self-administration as well as its subjective effects compared to maintenance on placebo. These data suggest that chronic antagonism of the dopamine D1 receptor may not be a useful approach for the treatment of cocaine abuse.

Administration, Inhalation↗

Effects of repeated oral methamphetamine administration in humans.

RATIONALE: Although methamphetamine use has increased over the past several years, few studies have evaluated the effects of repeated methamphetamine administration in humans. OBJECTIVES: Because methamphetamine is often taken in a pattern of repeated use followed by a period of abstinence, the present study sought to evaluate the effects of repeated methamphetamine administration in humans. The hypothesis was that tolerance would develop to methamphetamine's effects. METHODS: Seven normal, healthy volunteers participated in a 15-day residential study. Participants completed subjective-effects questionnaires and psychomotor performance tasks repeatedly throughout the experimental day. Oral methamphetamine (5, 10 mg BID) was administered on days 4-6 and 10-12; placebo was administered on all other study days. RESULTS: Relative to placebo baseline, only two "positive" subjective ratings ("I feel a good drug effect" and "I feel high") were significantly elevated, and only on the 1st day of methamphetamine administration. In contrast, numerous "negative" ratings, including "I feel..." "a bad drug effect," "dizzy," and "flu-like symptoms" were elevated on the 3rd day of methamphetamine administration. Total caloric intake decreased and sleep was disrupted after methamphetamine administration, relative to baseline. CONCLUSIONS: The pattern of methamphetamine's positive subjective effects were altered with chronic administration such that tolerance, or a decreased effect, occurred after repeated administration. In contrast, methamphetamine's negative subjective effects increased over days. These results suggest that in this population of normal volunteers, the abuse liability of oral methamphetamine is relatively low.

Adult↗

Methamphetamine self-administration by humans.

RATIONALE: Methamphetamine abuse has become increasingly problematic. Yet, the reinforcing effects of methamphetamine in humans have not been systematically evaluated. OBJECTIVE: To characterize methamphetamine's reinforcing effects in human research participants under controlled laboratory conditions. METHODS: Eight healthy research volunteers (one female, seven males) completed this 20-day residential study. On days 1, 5, 9, 13 and 17, at 1000 hours, participants received the "sample" oral dose of methamphetamine (0, 5, 10 mg) that was available for the next 3 days and they also received an alternative reinforcer, a $1 voucher (redeemable for cash at study's end). Over a 3-day period, volunteers participated in an eight-trial choice procedure, during which they had the opportunity to self-administer the dose of methamphetamine they most recently sampled or to receive the $1 voucher. RESULTS: Participants' choice to self-administer methamphetamine significantly increased when active methamphetamine (5 mg and 10 mg) was available compared to placebo. No difference of choice was noted between low-dose and high-dose methamphetamine. However, the sampled 10 mg methamphetamine dose significantly increased several "positive" subjective ratings including "High," "Good Drug Effect," and "Stimulated," whereas the sampled 5 mg methamphetamine dose did not. Both active methamphetamine doses caused significant reductions in daily total caloric intake, relative to the respective placebo conditions. CONCLUSION: These data demonstrate that oral methamphetamine is a positive reinforcer in humans.

Adult↗

Effects of acute smoked marijuana on complex cognitive performance.

Although the ability to perform complex cognitive operations is assumed to be impaired following acute marijuana smoking, complex cognitive performance after acute marijuana use has not been adequately assessed under experimental conditions. In the present study, we used a within-participant double-blind design to evaluate the effects acute marijuana smoking on complex cognitive performance in experienced marijuana smokers. Eighteen healthy research volunteers (8 females, 10 males), averaging 24 marijuana cigarettes per week, completed this three-session outpatient study; sessions were separated by at least 72-hrs. During sessions, participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% Delta(9)-THC w/w), and completed additional cognitive tasks. Blood pressure, heart rate, and subjective effects were also assessed throughout sessions. Marijuana cigarettes were administered in a double-blind fashion and the sequence of Delta(9)-THC concentration order was balanced across participants. Although marijuana significantly increased the number of premature responses and the time participants required to complete several tasks, it had no effect on accuracy on measures of cognitive flexibility, mental calculation, and reasoning. Additionally, heart rate and several subjective-effect ratings (e.g., "Good Drug Effect," "High," "Mellow") were significantly increased in a Delta(9)-THC concentration-dependent manner. These data demonstrate that acute marijuana smoking produced minimal effects on complex cognitive task performance in experienced marijuana users.

Adult↗

Acute effects of angiotensin II on myocardial performance.

BACKGROUND: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are well described. This study was designed to assess left ventricular function during administration of Ang II using relatively load-independent methods in a whole-animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h(-1)) in anaesthetised instrumented pigs (n=10). Cardiac systolic and diastolic function were evaluated by analysis of the left ventricular pressure-volume relationship. RESULTS: Heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased dose-dependently with Ang II, while cardiac output (CO) remained unchanged. Systolic function indices, end-systolic elastance (Ees) and preload recruitable stroke work (PRSW), demonstrated dose-dependent increases. The diastolic function parameter tau (tau) did not change with increasing Ang II dose. CONCLUSION: Ang II infusion caused increases in contractility indices in anaesthetised pigs in the doses used in this study. The mechanisms for these systolic function effects may be a direct myocardial effect or modulated through changes in autonomic nervous system activity.

Angiotensin II↗

Use of telehealth technology to extend child protection team services.

OBJECTIVE: In response to increased referrals to Florida's Child Protection Teams and concern regarding statewide availability of medical expertise in the area of child abuse and neglect, Children's Medical Services of the Florida Department of Health established a telemedicine project to facilitate immediate expert medical evaluations of alleged child abuse or neglect. This article describes a baseline examination of the project, including the technique of concept mapping, to examine how larger systematic factors influence the adaptation of telemedicine technology in child abuse examination settings. METHODS: This study included interviews of key staff plus the incorporation of concept mapping, which takes qualitative data (individual statements and opinions) and quantifies them (sorts and ranks them by order of group importance). RESULTS: Findings from interviews revealed that the frequency of use of telehealth services varies across the state as a result of several factors, including space limitations and staff training. Patients, however, seem to be comfortable with the use of the new technology. The concept mapping exercise displayed a progression of issues that are perceived to have an impact on the use of this technology. CONCLUSIONS: Technology use is affected by unforeseen variables, such as physical space limitations and examination room availability. Family concerns about patient privacy issues were rare and were resolved quickly by the health care practitioner. Although using this equipment is not difficult, the search for user-friendliness should be continued. Staff engagement early in the process likely will result in a greater likelihood of use of the technology.telehealth, telemedicine, child protection, child abuse and neglect, concept mapping.

Child↗

Conditioned effects of environmental stimuli paired with smoked cocaine in humans.

RATIONALE: Clinical data suggest that stimuli paired with cocaine use acquire emergent stimulus effects, such as the ability to elicit cocaine craving. OBJECTIVES: The purpose of this study was to determine the conditioned effects of neutral stimuli paired with cocaine smoking. METHODS: Eight experienced adult cocaine smokers participated in 22 experimental sessions while residing on a Clinical Research Center. One set of cues (CS-) was paired with placebo smoked cocaine and one set of cues (CS+) was paired with 25 mg smoked cocaine. RESULTS: After 18 training trials, the effects of cocaine on heart rate and ratings of "anxious" were greater, and skin temperature and ratings of "tired" were smaller when compared to the effects of cocaine after the first training trial. When instructed to select a cue to experience after training, seven of eight participants selected the CS+, while only three of the participants selected the CS+ prior to training, i.e., the CS+ functioned as a conditioned reinforcer. Presentation of the CS+ alone without cocaine during extinction trials increased HR, SP, and ratings of "anxious" "tired", and "I want cocaine" and decreased skin temperature. These changes elicited by presentation of the CS+ decreased over the course of the extinction sessions. CONCLUSIONS: The present results indicate that classical conditioning is one mechanism by which stimuli paired with cocaine acquire emergent stimulus effects.

Adult↗

Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside.

BACKGROUND: The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. METHODS: Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. RESULTS: Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. CONCLUSIONS: Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.

Angiotensin II↗

Alternative reinforcers differentially modify cocaine self-administration by humans.

Six experienced cocaine smokers (two men, four women) participated in an inpatient study to compare self-administration of smoked cocaine when either a $5 money or merchandise voucher was available as an alternative reinforcer. A six-trial choice procedure was used, with sessions consisting of (1) one sample trial, where participants received the cocaine dose and the alternative reinforcer available that day, and (2) five choice trials, where participants chose between the available cocaine dose and the alternative reinforcer. There were eight sessions: in separate sessions, each dose of cocaine (0, 12, 25, 50 mg) was paired with a money voucher and with a merchandise voucher. The choice to self-administer cocaine significantly increased with escalating cocaine doses, and significantly less cocaine was self-administered when money vouchers were available as compared to merchandise vouchers. These data demonstrate that money vouchers are a more effective alternative reinforcer than merchandise vouchers in cocaine abusers.

Adult↗

Abstinence symptoms following oral THC administration to humans.

Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral delta9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in private or social recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1-3, 8-11, and 16-19. Active THC was administered on days 4-7 (20 mg qid) and on days 12-15 (30 mg qid). Both active doses of THC increased ratings of "High," "Good Drug Effect," and "Willingness to Take Dose Again" compared to baseline (days 1-3). THC also increased food intake by 35-45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of "Anxious," "Depressed," and "Irritable," decreased the reported quantity and quality of sleep, and decreased food intake by 20-30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.

Administration, Oral↗