Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial.

Objective: To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike.

Tobacco Smoking and Brain Endogenous Opioid Release: More Than Nicotine Alone.

Introduction: The effects of smoking denicotinized (denic) and average nicotine (avnic) tobacco cigarettes were studied on brain mu opioid receptor binding by positron emission tomography with 11C carfentanil. The results indicated the importance of physiological and psychological effects induced by denic smoking.

Methods: Regional mu opioid binding potential (nondisplaceable binding potential, BPND) was measured in 20 adult male overnight abstinent chronic tobacco smokers.

Genetic Variation of the Mu Opioid Receptor (OPRM1) and Dopamine D2 Receptor (DRD2) is Related to Smoking Differences in Patients with Schizophrenia but not Bipolar Disorder.

It is not known why mentally ill persons smoke excessively. Inasmuch as endogenous opioid and dopaminergic systems are involved in smoking reinforcement, it is important to study mu opioid receptor (OPRM1) A118G (rs1799971), dopamine D2 receptor (DRD2) Taq1A (rs1800497) genotypes, and sex differences among patients with schizophrenia or bipolar disorder. Smokers and nonsmokers with schizophrenia (n=177) and bipolar disorder (n=113) were recruited and genotyped.

Cortisol in schizophrenia: No association with tobacco smoking, clinical symptoms or antipsychotic medication.

Cigarette smoking is associated with higher cortisol levels in healthy subjects. In schizophrenia this relationship is not clear. There are divergent results on the association between cortisol with smoking, clinical symptoms and medication in schizophrenia.

Nicotine-specific and non-specific effects of cigarette smoking on endogenous opioid mechanisms.

This study investigates differences in μ-opioid receptor mediated neurotransmission in healthy controls and overnight-abstinent smokers, and potential effects of the OPRM1 A118G genotype. It also examines the effects of smoking denicotinized (DN) and average nicotine (N) cigarettes on the μ-opioid system. Positron emission tomography with (11)C-carfentanil was used to determine regional brain μ-opioid receptor (MOR) availability (non-displaceable binding potential, BPND) in a sample of 19 male smokers and 22 nonsmoking control subjects.

Regional brain [(11)C]carfentanil binding following tobacco smoking.

Objective: To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking.

Methods: Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil.

Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious monkeys.

Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist, have a rapid antidepressant effect which lasts for up to 2 weeks. However, the neurobiological mechanism regarding this effect remains unclear. In the present study, the effects of subanesthetic doses of ketamine on serotonergic systems in conscious monkey brain were investigated.

Pro-inflammatory cytokine network in peripheral inflammation response to cerebral ischemia.

The key circulating pro-inflammatory cytokines and their interaction in peripheral inflammation after acute cerebral ischemia are poorly understood. CD40L, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-17 and TNF-α were determined using multi-ELISA kit in stroke patients within 72 h of an acute ischemic attack. Leukocyte mRNAs were determined using real-time polymerase chain reactions (PCR).

Tobacco smoking produces greater striatal dopamine release in G-allele carriers with mu opioid receptor A118G polymorphism.

Objective: To determine if carriers of the allelic expression of the G variant of the human mu opioid receptor (OPRM1) A118G polymorphism have greater increases in striatal dopamine (DA) release after tobacco smoking.

Methods: Nineteen of 20 genotyped male tobacco smokers, after overnight abstinence, smoked denicotinized (denic) and average nicotine (nic) containing tobacco cigarettes in a PET brain imaging study using [(11)C]raclopride.

Results: The right striatum had more free D(2) receptors than the left striatum pre- and post-tobacco smoking.

Denicotinized versus average nicotine tobacco cigarette smoking differentially releases striatal dopamine.

Introduction: Nicotine has long been recognized as a necessary but insufficient component of tobacco cigarettes to maintain a psychophysiological need to smoke. This study examined venous plasma concentrations effects of nicotine in cigarette smoking after overnight abstinence to release striatal dopamine (DA).

Methods: Twenty-two male smokers smoked either denicotinized (denic) or average nicotine (nic) cigarettes under single blind conditions.

Phencyclidine/schizophrenia: one view toward the past, the other to the future.

The history of the chemical synthesis and animal/human pharmacology of phencyclidine is documented. From its early use as a general anesthetic, chemical model of schizophrenia, and drug of abuse, phencyclidine has had a checkered history. Research with this agent and its chemical derivatives like ketamine have provided a solid foundation for just a beginning to understanding the neuropathology of schizophrenia.

5-Hydroxytryptophan attenuates somatic signs of nicotine withdrawal.

Abrupt nicotine cessation after chronic use disrupts monoaminergic systems and causes withdrawal signs/symptoms. In this study, the precursor of serotonin 5-hydroxytryptophan (5-HTP) relieved nicotine withdrawal signs. (-)-Nicotine bitartrate or equimolar sodium tartrate was infused into each rat via a s.

Dopamine D1/5 and D2/3 agonists differentially attenuate somatic signs of nicotine withdrawal in rats.

Abrupt tobacco/nicotine cessation after chronic use causes various withdrawal symptoms/signs. There is evidence that dysfunction of brain dopaminergic system might be responsible for some nicotine withdrawal symptoms. The hypothesis for the present study was that different dopaminergic agonists would relieve different nicotine withdrawal signs.

Muscarinic receptor occupancy and cognitive impairment: a PET study with [11C](+)3-MPB and scopolamine in conscious monkeys.

The muscarinic cholinergic receptor (mAChR) antagonist scopolamine was used to induce transient cognitive impairment in monkeys trained in a delayed matching to sample task. The temporal relationship between the occupancy level of central mAChRs and cognitive impairment was determined. Three conscious monkeys (Macaca mulatta) were subjected to positron emission tomography (PET) scans with the mAChR radioligand N-[(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB).

L-DOPA attenuates nicotine withdrawal-induced behaviors in rats.

There is some evidence that during nicotine abstinence brain dopamine levels are reduced. The hypothesis for the present study was that the precursor amino acid L-DOPA would relieve nicotine withdrawal-induced behaviors. Separate groups of adult male Sprague-Dawley rats were used.

Increased in vivo [11C]raclopride binding to brain dopamine receptors in amphetamine-treated rats.

The hypothesis that repeated daily doses of amphetamine increases the number of available dopamine D(2) receptors in vivo in rat striatum, and may enhance the response to subsequent amphetamine challenge doses, was examined. The in vivo binding potentials of [(11)C]raclopride, a D(2) receptor antagonist, were determined in male CD-1 rats under five conditions: (1) drug-naïve with saline challenge, (2) drug naïve with 5mg/kg amphetamine challenge, (3) amphetamine-dosed (five daily repeated s.c.

Taming the ketamine tiger. 1965.

Pharmacologic actions of CI-581, a chemical derivative of phencyclidine, were determined in 20 volunteers from a prison population. The results indicate that this drug is an effective analgesic and anesthetic agent in doses of 1.0 to 2.

Opioid modulation of oxytocin release.

Analgesia or anesthesia is frequently used for women in labor. A wide range of opioid analgesics with vastly different pharmacokinetics, potencies, and potential side effects can be considered by physicians and midwives for laboring patients requesting pain relief other than a labor epidural. The past 50 years have seen the use of the classic mu opioid agonist morphine and other opioids diminish markedly for several reasons, including availability of epidural anesthetics, side effects, formulary restrictions, and concern for neonatal respiratory depression.

Venous plasma nicotine correlates of hormonal effects of tobacco smoking.

The present study resolves some of the discrepancies in the literature by correlating the effects of tobacco smoking on hormone release with venous plasma nicotine levels. Cortisol, prolactin, and beta-endorphin concentrations were measured. Habitual male tobacco users smoked denicotinized (very low nicotine) and average nicotine cigarettes in the morning after overnight tobacco abstinence.

The effect of smoking on pain-related evoked potentials.

The effects of human tobacco smoking and nicotine on pain-related brain activities were investigated. EEG responses evoked by a painful laser beam (laser evoked potentials; LEPs), and the plasma nicotine concentration (PNC) were measured. There were two sessions, one after smoking (Smoking session), and the other in no smoking (Control session).

Tobacco smoking produces widespread dominant brain wave alpha frequency increases.

The major pharmacological ingredient in tobacco smoke is nicotine, a mild stimulant known to alter brain electrical activity. The objective of this study was to determine if tobacco smoking in humans produces localized or widespread neocortical dominant alpha electroencephalographic (EEG) frequency increases consistent with nicotine stimulation of the brainstem activating system in animals. Twenty-two male volunteer non-deprived tobacco smokers were studied.