Abstract:
RATIONALE:Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG). OBJECTIVES AND METHODS:We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice. RESULTS:All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile. CONCLUSIONS:These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Deiana S,Watanabe A,Yamasaki Y,Amada N,Arthur M,Fleming S,Woodcock H,Dorward P,Pigliacampo B,Close S,Platt B,Riedel Gdoi
10.1007/s00213-011-2415-0subject
Has Abstractpub_date
2012-02-01 00:00:00pages
859-73issue
3eissn
0033-3158issn
1432-2072journal_volume
219pub_type
杂志文章abstract::The central effects of acetylsalicylic acid (ASA) are discussed controversially. In animal models, it has been shown that ASA can interact with the central serotonergic and catecholaminergic neuronal system. However, the relevance of this interaction for humans is still unknown. We performed a study on the influence o...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002130050683
更新日期:1998-08-01 00:00:00
abstract::When tested in adulthood, male rats that had been treated daily with 50 mg/kg hydroxyzine HCl SC at 10--29 or 23--29 days of age were significantly facilitated in performance of delayed spontaneous alternation relative to saline-injected rats. Treatment at 10--16 days of age did not produce significant facilitation in...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427646
更新日期:1980-01-01 00:00:00
abstract::The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption droppe...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245190
更新日期:1995-01-01 00:00:00
abstract:RATIONALE:Glucose administration may decrease desire to smoke in abstinent smokers. Moreover, glucose administration has been associated with improved performance on measures of attention in healthy humans but evidence remains modest. OBJECTIVE:The present study aimed to determine whether reported craving and nicotine...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00213-002-1035-0
更新日期:2002-05-01 00:00:00
abstract::The aim of the present study was to investigate the locomotor stimulant effects of the atypical antipsychotic agent, olanzapine, in mice depleted of their dopamine by reserpine and alpha-methyl-DL-p-tyrosine pretreatment. Olanzapine (0.5, 1 and 2 mg/kg) dose-dependently increased locomotor activity, which was complete...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050877
更新日期:1999-02-01 00:00:00
abstract::Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02246290
更新日期:1995-06-01 00:00:00
abstract::Three-hour sessions of differential reinforcement of low-rate behavior (DRL 45-s) in rats were used to investigate alprazolam, caffeine, and their interactions at the onset, peak and disappearance of serum alprazolam, while caffeine level remained constant. The dose-response curve (DRC) method of Pöch permitted an ext...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246346
更新日期:1996-07-01 00:00:00
abstract:RATIONALE:Clozapine is a unique antipsychotic with very low propensity to cause motor side effects. In contrast to most other antipsychotics that block more than 70% of dopamine D(2) receptors at therapeutic doses, clozapine occupies less than 70%. Furthermore, even at maximum occupancy, 70% is not exceeded. Several me...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-001-0967-0
更新日期:2002-02-01 00:00:00
abstract:RATIONALE:Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. OBJECTIVE:This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D(2) receptor agonist, influenced smoked cocaine self-administration, cardiovascular m...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00213-011-2231-6
更新日期:2011-08-01 00:00:00
abstract:INTRODUCTION:Non-medical use of prescription opioids such as the mu opioid receptor (MOP-r) agonist oxycodone is a growing problem in the USA and elsewhere. There is limited information about oxycodone's impact on diverse gene systems in the brain. OBJECTIVES:The current study was designed to examine how chronic oxyco...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4657-y
更新日期:2017-08-01 00:00:00
abstract::The effects of bilateral nucleus accumbens microinjections of d-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 micrograms) treated rats. Microinjections of DALA (2.5 microgra...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244999
更新日期:1994-05-01 00:00:00
abstract::The anti-withdrawal effect of clonidine was studied using quasi-morphine abstinence behaviour induced by dipropylacetate (DPA) in naive rats. Clonidine potently suppressed body shakes and locomotor activity (ID50 30 and 40 micrograms/kg IP respectively). Phenoxybenzamine and prazosine did not antagonize the anti-withd...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427276
更新日期:1983-01-01 00:00:00
abstract::The behavioral effects following intrastriatal MPP+, the neurotoxic metabolite of MPTP, were evaluated in mice. Bilateral injections of 10 micrograms MPP+ to mice previously trained in the shuttle box paradigm produced a 66% decrease in striatal dopamine and significant deficits in all measures of conditioned avoidanc...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00176480
更新日期:1987-01-01 00:00:00
abstract::The ventral tegmental area (VTA) evaluates salience of environmental stimuli and provides dopaminergic innervation to many brain areas affected by acute and chronic ethanol exposure. While primarily associated with rewarding and reinforcing stimuli, recent evidence indicates a role for the VTA in aversion as well. Eth...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-018-4875-y
更新日期:2018-06-01 00:00:00
abstract:RATIONALE:Current medications for attention-deficit/hyperactivity disorder (ADHD) include some single isomer compounds [dextroamphetamine (D: -amphetamine, dexedrine) and dexmethylphenidate (Focalin)] and some racemic compounds [methylphenidate and mixed-salts amphetamine (Adderall)]. Adderall, which contains approxima...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-004-2012-6
更新日期:2005-03-01 00:00:00
abstract:RATIONALE/OBJECTIVES:Previous research has shown that ecstasy users are impaired in thinking and reasoning. The present study sought to explore the possibility that syllogistic reasoning errors in ecstasy users were due to an inability to construct a model of the premises due to working memory limitations. METHODS:Twe...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-0006-7
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Caffeine has a well-established effect on reaction times (RTs) but the neurocognitive mechanisms underlying this are unclear. METHODS:In the present study, 15 female participants performed an oddball task after ingesting caffeine or a placebo, and electroencephalographic data were obtained. Single-trial P3b...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4790-7
更新日期:2018-03-01 00:00:00
abstract::Ro 15-4513, a partial inverse agonist at the benzodiazepine (BZ) receptor site was labelled with 11C and used for in vitro autoradiography on human post mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. The total radiochemical yield of [11C]Ro 15-4513 was 30-40% with an overall sy...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245279
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND AND RATIONALE:Nicotinic acetylcholine systems play major roles in cognitive function. Nicotine and a variety of nicotinic agonists improve attention, and nicotinic antagonist exposure impairs it. This study was conducted to investigate the effect of a novel nicotinic receptor agonist at α4β2 nicotinic recept...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2712-2
更新日期:2012-10-01 00:00:00
abstract::Serotonin(5-HT)-stimulated intracellular calcium(Ca) mobilization was measured in the platelets of depressed patients to assess 5-HT2 receptor function. The 5-HT-induced Ca response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancho...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02245204
更新日期:1994-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244125
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of ...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-017-4793-4
更新日期:2018-02-01 00:00:00
abstract::The effects of the benzomorphan antagonist Mr 2266 and the selective delta-antagonist ICI 154,129 on the body weight gain of 6-day-old suckling rat pups was observed. Mr 2266 significantly reduced body weight gain in these animals, though ICI 154,129 had no affect on this variable. These findings suggest that mu- and ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432046
更新日期:1984-01-01 00:00:00
abstract::After publication of this paper, the authors determined an error in the calculation of the norepinephrine standard concentrations for the HPLC calibration curves. ...
journal_title:Psychopharmacology
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00213-018-4996-3
更新日期:2018-09-01 00:00:00
abstract:RATIONALE:Prospective memory pervades our daily lives and failures can have detrimental consequences. This ability to execute delayed intentions may be impacted by stress, yet few studies have examined these effects. Moreover, as many cannabis users report using cannabis to cope with stress, it is important to understa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-019-5184-9
更新日期:2019-06-01 00:00:00
abstract:RATIONALE:The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. OBJECTIVE:This study established stimulus contro...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3271-x
更新日期:2014-02-01 00:00:00
abstract::Basal morning humoral (H)-endorphin blood levels were assessed in ten autistic patients, 12 chronic schizophrenic patients and 11 healthy control subjects. Four autistic patients and four schizophrenic patients were drug free for at least 6 months while all other psychiatric patients were under treatment with antidopa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427687
更新日期:1984-01-01 00:00:00
abstract:RATIONALE:Dronabinol (Δ(9)tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects. OBJECTIVES:Employing a within-subjects, double-...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1995-4
更新日期:2010-12-01 00:00:00
abstract:RATIONALE:Executive function impairment, as classically assessed using the Wisconsin Card Sort Test or intradimensional/extradimensional tests, is a key feature of schizophrenia but remains inadequately treated by existing therapies. Recently, however, erythropoietin has been shown to improve attentional set-shifting p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1990-9
更新日期:2010-12-01 00:00:00
abstract::The effect of the selective noradrenaline neurotoxin DSP4 on steady-state operant behaviour was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation, which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02180039
更新日期:1988-01-01 00:00:00