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1.
Symptoms of withdrawal after oral Δ9-tetrahydrocannabinol (THC) administration have been reported, yet little is known about the development of dependence on
smoked marijuana in humans. In a 21-day residential study, marijuana smokers (n = 12) worked on five psychomotor tasks during the day (0915–1700 hours), and in the evening engaged in recreational activities
(1700–2330 hours); subjective-effects measures were completed 10 times/day. Food and beverages were available ad libitum from
0830 to 2330 hours. Marijuana cigarettes (0.0, 1.8, 3.1% THC) were smoked at 1000, 1400, 1800, and 2200 hours. Placebo marijuana
was administered on days 1–4 . One of the active marijuana doses was administered on days 5–8, followed by 4 days of placebo
marijuana (days 9–12). The other concentration of active marijuana cigarettes was administered on days 13–16, followed by
4 days of placebo marijuana (days 17–20); the order in which the high and low THC-concentration marijuana cigarettes were
administered was counter-balanced between groups. Both active doses of marijuana increased ratings of “High,” and “Good Drug
Effect,” and increased food intake, while decreasing verbal interaction compared to the placebo baseline (days 1–4). Abstinence
from active marijuana increased ratings such as “Anxious,”“Irritable,” and “Stomach pain,” and significantly decreased food
intake compared to baseline. This empirical demonstration of withdrawal from smoked marijuana may suggest that daily marijuana
use may be maintained, at least in part, by the alleviation of abstinence symptoms.
Received: 2 June 1998 / Final version: 11 September 1998 相似文献
2.
The present study investigated the effect of alprazolam on the pattern of food intake in seven male participants living in
a residential laboratory for 17 days. A wide selection of meals, snacks and beverages was freely available. Capsule administration
occurred at 1300 and 1730 hours. Food intake on days when alprazolam (0.75 mg) was administered (days 2, 11) was compared
to days when no capsule (days 1, 9) or placebo (days 3, 10) was administered. Alprazolam increased total caloric intake by
approximately 975 kcal from a baseline of 2800 kcal. Alprazolam increased the number of eating occasions occurring in the
evening (1700–2330 hour), without altering the size of eating occasions (kcal), or the proportion of total calories derived
from carbohydrate, fat and protein. These data demonstrate alprazolam’s robust effects on food intake in humans.
Received: 18 February 1997 /Final version: 13 April 1997 相似文献
3.
Abstract
Rationale. Symptoms of marijuana withdrawal include increased irritability, depression and anxiety, and decreased sleep quality. Nefazodone,
which is an antidepressant with sedative properties, may attenuate symptoms of marijuana withdrawal.
Objective. The present within-subject, placebo-controlled study investigated the effects of nefazodone during marijuana withdrawal.
Methods. Marijuana smokers [n=7; averaging 6.0 (±1.3) marijuana cigarettes/day, 6.4 (±0.4) days/week], not seeking treatment for marijuana use, were maintained
on two doses of nefazodone (0, 450 mg/day) for 26 days each. Each maintenance condition began with an outpatient phase (9
days) and continued with an inpatient phase (17 days) in a residential laboratory. Marijuana was smoked 5 times per inpatient
day at 1000, 1300, 1600, 1900 and 2200 hours. On days 1–4 (baseline), the first four marijuana cigarettes were placebo (0.00%
THC), while the final marijuana cigarette was active (3.04% THC). On inpatient days 5–8, only active marijuana was smoked,
while on days 9–16, only placebo marijuana was smoked. Mood, psychomotor task performance, food intake and sleep were measured
daily. The order of maintenance dose was counterbalanced between groups.
Results. Nefazodone maintenance did not alter the acute effects of active marijuana as compared to placebo nefazodone maintenance.
During marijuana withdrawal, nefazodone decreased ratings of "Anxious", and "Muscle Pain", while having no effect on the marked
increase in ratings of "Irritable", "Miserable" or decreased sleep quality.
Conclusions. Nefazodone decreased certain marijuana withdrawal symptoms, but participants still reported substantial discomfort. These
data provide further evidence of marijuana withdrawal, and highlight the need for more marijuana treatment options.
Electronic Publication 相似文献
4.
Rationale No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV+ marijuana
smokers.
Objectives The aim of this study was to compare dronabinol (0, 10, 20, 30 mg p.o.) and marijuana [0.0, 1.8, 2.8, 3.9% Δ9-tetrahydrocannabinol (THC)] in two samples of HIV+ marijuana smokers: those with (n=15) and those without (n=15) a clinically significant loss of muscle mass (<90% body cell mass/height), which is one component of AIDS wasting.
Methods Mood, physical symptoms, self-selected food intake, cardiovascular data, and cognitive task performance were measured before
and repeatedly after dronabinol and marijuana administration in eight 7-h sessions. Marijuana and dronabinol were administered
in randomized order using a within-subject, staggered, double-dummy design.
Results As compared to placebo, (1) marijuana (1.8, 2.8, 3.9% THC) and the lower dronabinol doses (10, 20 mg) were well tolerated
(e.g., few physical symptoms, significant increases in ratings of “good drug effect”) in both groups of participants; the
highest dose of dronabinol (30 mg) was poorly tolerated in a subset of participants; (2) marijuana and dronabinol significantly
increased caloric intake in the low bioelectrical impedance analysis (BIA) group but not in the normal BIA group; and (3)
drug effects on cognitive performance were minor.
Conclusions These data suggest that for experienced marijuana smokers with clinically significant muscle mass loss, both dronabinol (at
acute doses at least four to eight times the current recommendation) and marijuana produce substantial and comparable increases
in food intake without producing adverse effects.
All authors are associated with the Department of Psychiatry at the College of Physicians and Surgeons of Columbia University. 相似文献
5.
A. S. Ward Margaret Haney Marian W. Fischman Richard W. Foltin 《Psychopharmacology》1997,132(4):375-381
Cocaine is frequently used in intermittent cycles of repeated dosing, or “binges.” This pattern of cocaine use has been difficult
to study in humans because currently available laboratory models use only one daily session during which a single dose or
multiple doses are administered. In the present study, seven adult male IV cocaine users completed a protocol investigating
changes in cardiovascular and subjective responses during the repeated self-administration of cocaine. Volunteers participated
in a 2-day and a 3-day access condition. On each day of access, they participated in two 2.5-h sessions, one at 1200 and another
at 1600 hours. In the 2- and 3-day conditions, participants had access to cocaine on 2 or 3 consecutive days, respectively.
During sessions, participants could self-administer up to six doses of IV cocaine (32 mg/70 kg) every 14 min. Participants
chose not to self-administer cocaine on only 10% of the 420 trials. Acute tolerance developed to the cardiovascular and several
subjective effects of cocaine. Heart rate was the only measure that tended to decrease across days of repeated cocaine self-administration.
Ratings of “I want cocaine” decreased at the end of the last self-administration session during both 2- and 3-day conditions.
There was no difference between the 2- and 3-day conditions for any measure. The laboratory model of “binge” cocaine use established
in this study can be used to describe changes in cardiovascular and subjective effects of cocaine within and between bouts
of repeated cocaine use.
Received: 14 November 1996/Final version: 8 March 1997 相似文献
6.
Margaret Haney Carl L Hart Suzanne K Vosburg Jennifer Nasser Andrew Bennett Carlos Zubaran Richard W Foltin 《Neuropsychopharmacology》2004,29(1):158-170
Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence. 相似文献
7.
Introduction Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence.
Objectives The objectives of the study are to determine if THC, a cannabinoid agonist, and lofexidine, an α2-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana withdrawal and relapse, defined
as a return to marijuana use after a period of abstinence.
Materials and methods Nontreatment-seeking, male volunteers (n = 8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo, tetrahydrocannabinol
(THC) (60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase
was separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration
(withdrawal). For the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for
self-administered marijuana using study earnings. Self-administration, mood, task performance, food intake, and sleep were
measured.
Results THC reversed the anorexia and weight loss associated with marijuana withdrawal, and decreased a subset of withdrawal symptoms,
but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine was sedating, worsened abstinence-related
anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination of
lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse
in daily marijuana smokers relative to either medication alone.
Conclusions These data suggest the combination of lofexidine and THC warrant further testing as a potential treatment for marijuana dependence. 相似文献
8.
Trazodone and triazolam: acute subject-rated and performance-impairing effects in healthy volunteers
C. R. Rush Sudhakar Madakasira Catherine A. Hayes Camella A. Johnson Nancy H. Goldman Peggy J. Pazzaglia 《Psychopharmacology》1997,131(1):9-18
The present study compared the acute subject-rated and performance-impairing effects of trazodone and triazolam in seven
healthy humans. Trazodone (50, 100 and 200 mg), triazolam (0.125, 0.25, 0.50 mg) and placebo were administered orally in a
double-blind, crossover design. Drug effects were measured approximately 30 min before drug administration and repeatedly
afterwards for 6 h. Trazodone and triazolam produced dose-related increases in subject-ratings of drug effect and sedation.
The absolute magnitude of trazodone”s and triazolam”s effects was comparable across these measures, which suggests the doses
tested were equivalent on some behavioral dimension. By contrast, triazolam, but not trazodone, increased subject ratings
of “dizzy”, “excited”, “nervous”, “restless”, “stomach turning” and “itchy skin”. Triazolam, but not trazodone, significantly
impaired learning, recall and performance. The present findings suggest trazodone may be a viable alternative to benzodiazepine
hypnotics like triazolam, especially when needing to minimize drug-induced impairment. Future research could extend the present
findings by replicating them in a clinically relevant population such as individuals with histories of drug abuse.
Received: 9 May 1996 / Final version: 15 September 1996 相似文献
9.
Subjective and cardiovascular effects of intravenous nicotine in smokers and non-smokers 总被引:4,自引:4,他引:0
Rebeca Soria June M. Stapleton Stephen F. Gilson Angela Sampson-Cone Jack E. Henningfield E. D. London 《Psychopharmacology》1996,128(3):221-226
The present study assessed the subjective and cardiovascular effects of intravenous nicotine in smokers and nonsmokers. Nonsmokers
(n = 5) and smokers (n = 5) were administered a single dose of nicotine (0.75 or 1.5 mg) or saline on each of 3 days. The nicotine doses were given
in ascending order in a double-blind fashion. Although smokers and nonsmokers manifested significant increases in systolic
and diastolic blood pressure and heart rate 1 min after administration of all active test doses, the difference between peak
heart rate and that measured at later times was greater in nonsmokers than in smokers. Nonsmokers and smokers also differed
in subjective self-reports. In response to items on visual analogue scales indicative of positive effects (e.g., “good effects,”“like
drug,”“use again,” and “feel energetic”), smokers but not nonsmokers reported high scores (> 40) after nicotine injection.
In addition, responses on the MBG and LSD subscales of the Addiction Research Center Inventory indicated that smokers experienced
positive subjective effects after the test doses, whereas nonsmokers experienced disorientation. The fact that intravenous
nicotine was not associated with positive subjective effects in nonsmokers indicates that repeated exposure is required to
establish positive reinforcing effects of nicotine.
Received: 11 August 1995 /Final version: 30 May 1996 相似文献
10.
Margaret Haney Ziva D Cooper Gillinder Bedi Suzanne K Vosburg Sandra D Comer Richard W Foltin 《Neuropsychopharmacology》2013,38(8):1557-1565
Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ9-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analog of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 men and 3 women), who reported smoking 8.3±3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose (0, 6, 8 mg/day, administered in counter-balanced order on days 2–8). On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule ‘liking'' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment. 相似文献
11.
Mickaël Naassila Elisabeth Legrand Françoise d’Alche-Birée M. Daoust 《Psychopharmacology》1998,140(4):421-428
The effect of cyamemazine a dopamine D2 receptor antagonist on voluntary ethanol consumption in rats and on ethanol withdrawal in mice was examined. Male Sprague-Dawley
rats were tested in a free choice (water and 10% ethanol) experiment and consumed 5 g/kg ethanol daily. Rats were treated
daily IP with cyamemazine ( 0.5, 1, or 2 mg/kg) or acamprosate (100 mg/kg) during 2 weeks. Both acamprosate and 1 mg/kg cyamemazine
significantly decreased ethanol intake by 45% without affecting either fluid or food intake. The lowest dose of cyamemazine
had no effect on alcohol intake but increased food intake. The highest dose had no effect on any variables. During the post-treatment
period, only 1 mg/kg cyamemazine decreased both ethanol and fluid intakes. Mice were made dependent on alcohol using a chocolate
fluid diet containing increasing concentrations of alcohol and withdrawn after 9 days. Mice were treated with cyamemazine
(1 or 0.5 mg/kg, respectively) or with the same doses of lorazepam acutely on the day of withdrawal or chronically (during
alcohol treatment). Both chronic and acute cyamemazine and lorazepam treatments decreased convulsions during ethanol withdrawal.
Both acute treatments decreased locomotor activity in control and alcohol dependent mice. Chronic treatment had no effect
on locomotor activity. We suggest that cyamemazine could reduce alcohol consumption by antagonizing the activation of the
dopaminergic pathways during the induction of alcohol dependence. The action of cyamemazine on 5-HT3 receptors could also explain its effect on alcohol convulsions during withdrawal convulsions.
Received: 19 October 1997/Final version: 6 April 1998 相似文献
12.
Comparison of smoked marijuana and oral Δ<Superscript>9</Superscript>-tetrahydrocannabinol in humans
Abstract
Rationale. Although smoked marijuana contains at least 60 cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) is presumed to be the cannabinoid primarily responsible for many marijuana-related effects, including increased food
intake and subjective effects. Yet, there has been no systematic comparison of repeated doses of oral Δ9-THC with repeated doses of smoked marijuana in the same individuals.
Objective. To compare the effects of oral Δ9-THC and smoked marijuana in humans under controlled laboratory conditions.
Methods. Eleven healthy research volunteers, who reported smoking an average of six marijuana cigarettes per day, completed an 18-day
residential study. Marijuana cigarettes (3.1% Δ9-THC, q.i.d.) were smoked or Δ9-THC (20 mg, q.i.d.) was taken orally using a staggered, double-blind, double-dummy procedure for three consecutive days.
Four days of placebo administration separated each active drug condition. Psychomotor task performance, subjective effects,
and food intake were measured throughout the day.
Results. Relative to placebo baseline, oral Δ9-THC and smoked marijuana produced similar subjective-effect ratings (e.g., "high" and "mellow"), although some effects of
smoked marijuana were more pronounced and less prone to the development of tolerance. Additionally, participants reported
"negative" subjective effects (e.g., "irritable" and "miserable") during the days after smoking marijuana but not after oral
Δ9-THC. Both drugs increased food intake for 3 days of drug administration, but had little effect on psychomotor performance.
Conclusion. These results indicate that the behavioral profile of effects of smoked marijuana (3.1% Δ9-THC) is similar to the effects of oral Δ9-THC (20 mg), with some subtle differences.
Electronic Publication 相似文献
13.
R. Koytchev R.-G. Alken O. Mayer I. Smith M. Greenwood 《European journal of clinical pharmacology》1996,50(4):315-319
Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone.
Methods:
The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered
to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg
were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite
were determined up to 24 hours after administration by a sensitive, specific HPLC method.
Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years,
respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only
data from the rapid hydroxylators were used in the statistical analysis.
Results:
Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow
hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal
relationship to food.
Received: 24 July 1995/Accepted in revised form: 4 January 1996 相似文献
14.
Using radio-biotelemetry, the timecourse of recovery and sensitivity to ambient temperature (Ta) of the thermogenic response
of methylenedioxymethamphetamine (MDMA or “Ecstasy”) was examined. Ambient temperatures of 17 and 22°C produced very different
response profiles, with the lower temperature producing a hypothermic response to 10 and 15 mg/kg doses of MDMA, and the higher
temperature producing a profound hyperthermia to the same doses. Although the peak responses to the drug had subsided within
5 h of administration, residual effects, in the form of an elevation of body temperature during the “low” phase of the diurnal
cycle, were present for a further 48 h. Long-lasting disruption of the thermoregulatory system following a short series of
MDMA administrations (10 mg/kg once per day for 4 days) was shown by exposing the rats in the undrugged state to a thermoregulatory
challenge, consisting of 60-min exposure to a Ta of 30°C, at 1 week before, and at 4 weeks and 14 weeks after the drug administration.
MDMA-treated rats showed a prolonged hyperthermic response to the challenge at both post-drug intervals compared with fenfluramine-treated
rats and saline-treated controls. Thus, the results indicate both that MDMA’s thermogenic effects are more sensitive to Ta
than previously demonstrated, and that the serotonergic neurotoxicity of the drug may produce long-lasting changes in thermoregulatory
mechanisms.
Received: 7 December 1997/Final version: 23 January 1998 相似文献
15.
L. J. M. J. Vanderschuren Guno H. K. Tjon Patrizia Nestby Arie H. Mulder Anton N. M. Schoffelmeer Taco J. De Vries 《Psychopharmacology》1997,131(2):115-122
The development of behavioural sensitization is thought to depend on the dose and temporal pattern of drug treatment. Previous
studies have shown that two distinct morphine pretreatment regimens cause different long-term neuroadaptations in rat striatum.
Therefore, in the present study the ability of these pretreatment regimens to induce long-term behavioural sensitization was
investigated. One pretreatment regimen, termed “chronic”, consisted of three daily injections, for 5 days, with escalating
doses (10–50 mg/kg) of morphine, and the other, termed “intermittent”, of 14 daily injections with morphine (10 mg/kg). Both
intermittent and chronic morphine pretreatment caused sensitization to the locomotor effects of morphine, 3 weeks post-treatment,
although the former induced a far greater level of sensitization. Moreover, 3 weeks post-treatment, intermittent, but not
chronic, morphine pretreatment induced cross-sensitization to the locomotor stimulant effects of amphetamine. Behavioural
sensitization following intermittent morphine pretreatment was clear-cut both 1 day and 3 weeks post-treatment, while after
9 weeks, the locomotor effects of morphine were still slightly augmented. It is concluded that intermittent morphine pretreatment
is far more effective in inducing long-term behavioural sensitization than chronic morphine pretreatment.
Received: 1 July 1996/Final version: 12 December 1996 相似文献
16.
We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study
with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice
between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate
drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg
per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day).
Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions
remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the
rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external
conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls:
0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during
withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day).
Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol
and opiates.
Received: 3 April 1998/Final version: 26 August 1998 相似文献
17.
Varvel SA Wiley JL Yang R Bridgen DT Long K Lichtman AH Martin BR 《Psychopharmacology》2006,186(2):226-234
Rationale Interest persists in characterizing potential interactions between Δ9-tetrahydocannabinol (THC) and other marijuana constituents such as cannabidiol (CBD). Such interactions may have important implications for understanding the long-term health consequences of chronic marijuana use as well as for attempts to develop therapeutic uses for THC and other CB1 agonists.Objectives We investigated whether CBD may modulate the pharmacological effects of intravenously administered THC or inhaled marijuana smoke on hypoactivity, antinociception, catalepsy, and hypothermia, the well characterized models of cannabinoid activity.Results Intravenously administered CBD possessed very little activity on its own and, at a dose equal to a maximally effective dose of THC (3 mg/kg), failed to alter THC’s effects on any measure. However, higher doses of CBD (ED50=7.4 mg/kg) dose-dependently potentiated the antinociceptive effects of a low dose of THC (0.3 mg/kg). Pretreatment with 30 mg/kg CBD, but not 3 mg/kg, significantly elevated THC blood and brain levels. No interactions between THC and CBD were observed in several variations of a marijuana smoke exposure model. Either quantities of CBD were applied directly to marijuana, CBD and THC were both applied to placebo plant material, or mice were pretreated intravenously with 30 mg/kg CBD before being exposed to marijuana smoke.Conclusions As the amount of CBD found in most marijuana strains in the US is considerably less than that of THC, these results suggest that CBD concentrations relevant to what is normally found in marijuana exert very little, if any, modulatory effects on CB1-receptor-mediated pharmacological effects of marijuana smoke. 相似文献
18.
Amphetamine-induced locomotion and stereotypy depend on dopamine (DA), yet, while extracellular DA concentrations peak early,
and then begin to decline, intense stereotyped behaviors continue for relatively prolonged periods. These observations suggest
that DA may act as a “trigger” for the entire multi-phasic behavioral response. To test this hypothesis in rats, haloperidol
(HAL) was injected at different times with respect to (AMPH), and automated and videotaped measures of the behavior were recorded.
HAL (0.1 mg/kg, IP) or saline was administered either 15 min prior to AMPH (4.0 mg/kg, SC); 60 min following AMPH (during
the phase of intense oral stereotypy); or 140 min after AMPH (during post-stereotypy locomotion). When administered prior
to AMPH, HAL prevented the development of stereotypy, and an increase in locomotion was displayed in place of stereotypy.
Haloperidol administration during stereotypy interrupted the response, and resulted in an increase in locomotion for the remainder
of the stereotypy phase. In neither of these cases did HAL affect post-stereotypy locomotion. However, when injected during
the post-stereotypy phase, HAL caused a decrease in the magnitude of the locomotor response, suggesting that both the stereotypy
and locomotor components of the response remain sensitive to HAL at times when DA levels have significantly declined. These
results do not support the hypothesis that the early increase in extracellular DA produced by AMPH, acts as a “trigger” for
a non-dopaminergic receptor-mediated expression of the later phases of the AMPH response. Instead, it appears that both stereotypy
and post-stereotypy locomotion remain sensitive to DA receptor blockade when extracellular DA levels are below the levels
produced by non-stereotypy-inducing doses of AMPH.
Received: 15 August 1996/Final version: 24 October 1996 相似文献
19.
We have shown previously that pupil diameter increases and the amplitude of the pupillary light reflex is reduced when subjects
are under threat of an aversive event (electric shock), and that light reflex amplitude correlates negatively with subjective
anxiety. We have suggested that the “fear-inhibited light reflex” paradigm could be used as a laboratory model of human anxiety.
In the present study, we examined whether two doses (5 mg and 10 mg) of the anxiolytic drug diazepam would antagonize the
effects of threat on the pupillary light reflex. Twelve healthy male volunteers participated in three weekly sessions, each
associated with one of three treatments (diazepam 5 mg or 10 mg or placebo) in a double-blind, balanced, cross-over design.
The light reflex was recorded during either the anticipation of a shock (“threat” blocks) or periods in which no shocks were
anticipated (“safe” blocks). At the end of each “threat” or “safe” block, subjects rated their anxiety using visual analogue
scales. Two-factor ANOVA (treatment × condition) showed that diazepam treatment antagonized the effect of threat on light
reflex amplitude in a dose-dependent manner but it did not affect the threat-induced increase in pupil diameter. Diazepam
had no effect on the pupillary light reflex in the “safe” condition. Diazepam also reduced subjective anxiety and alertness
in the threat condition. These results show the sensitivity of the threat-induced reduction of light reflex amplitude to anxiolytic
drugs, and provide further evidence for the utility of the fear-inhibited light reflex paradigm as a laboratory model of human
anxiety.
Received: 20 March 1997/Final version: 7 July 1997 相似文献
20.
Roberto Ciccocioppo Izabela Panocka Carlo Polidori Colin T. Dourish M. Massi 《Psychopharmacology》1997,134(1):55-63
Selective serotonin reuptake inhibitors (SSRIs) or serotonin precursors inhibit ethanol and food intake by increasing the
synaptic availability of 5-HT in the central nervous system. However, these agents can also increase 5-HT levels at somatodendritic
5-HT1A autoreceptors, with negative effects on serotonergic transmission. (+)WAY100135 [N-ter-butyl 3-4-(2-methoxy-phenyl) piperazin-1-yl-2-phenylpropa-namide
dihydrochloride] is a selective antagonist both at pre-and post-synaptic 5-HT1A receptors. The present study investigated the effect on ethanol and food intake of (+)WAY100135, given alone or coadministered
with the SSRI fluoxetine or the 5-HT precursor 5-hydroxytryptophan (5-HTP) in genetically selected alcohol-preferring rats.
Blockade of presynaptic 5-HT1A receptors after injection of (+)WAY100135, 0.1 or 1 μg/rat, into the dorsal raphe did not significantly modify ethanol, food
or total fluid intake. The same doses of (+)WAY100135 did not modify the inhibition of ethanol and food intake induced by
intraperitoneal (IP) injection of fluoxetine, 5 mg/kg. Subcutaneous (SC) administration of (+)WAY100135 (1 or 10 mg/kg) did
not affect the 3-h, or the overnight intake of ethanol, food or total fluids. Given together with IP fluoxetine (5 mg/kg)
or SC 5-HTP (100 mg/kg plus carbidopa, 12.5 mg/kg), the same SC doses of (+)WAY100135 did not modify their inhibitory effect
on ethanol and food consumption. Present findings suggest that blockade either of pre-or of pre-and postsynaptic 5-HT1A receptors does not potentiate the inhibitory effect of fluoxetine or 5-HTP on ethanol and food intake.
Received: 2 November 1996/Final version: 23 April 1997 相似文献