Multidimensional behavioral effects of marijuana

Kelly Thomas H., Richard W. Foltin, Cleeve S. Emurian and Marian W. Fischman: Multidimensional Behavioral Effects of Marijuana. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 885–902.

1. 1. Five groups of three healthy adult male volunteers (n = 15), all reporting occasional, controlled marijuana use, gave written consent and participated in residential studies lasting 6 to 15 days.

2. 2. Subjects smoked marijuana cigarettes (0 1.3 2.3 or 2.7% THC, w/w) at 0945, 1330, 1700 and 2030 every day, and each subject received both active and placebo marijuana cigarettes in 2–5 consecutive day phases, with placebo and active doses presented in an alternating fashion.

3. 3. In comparison with placebo, active marijuana produced a variety of effects on measures of human behavior, including in food consumption and errors on psychomotor tasks, in bouts of tobacco-cigarette smoking and verbal interactions and in rates of task performance, time spent under social conditions or social cooperation.

4. 4. Dimensions of human behavior were differentially sensitive to the effects of smoked marijuana.

5. 5. The simultaneous measurement of multiple dimensions of human behavior is a useful procedure for determining dose potency following marijuana administration.

Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms

Khan, René s., Farooq Amin, Peter Powchik, Peter Knott, Marvin Goldstein, Seth Apter, Ben Kerman, Stacey Jaff and Michael Davidson: Increments in Plasma Homovanillic Acid Concentrations after Neuroleptic Discontinuation are Associated with Worsening of Schizophrenic Symptoms. Prog. NeuroPsychopharmacol. & Biol. Psychiat. 1990, : 879–884.

1. 1. Thirty-two male schizophrenic patients participated in this study.

2. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation.

3. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS).

4. 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline.

5. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly.

6. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

Subjective neuroleptic response and treatment outcome under open and double-blind conditions — A preliminary report

Pi Edmond, John Sramek, Tram Johnson, John Herrera, Chris Heh, Jerome Costa, Neal Cutler and Jambur Ananth: Subjective Neuroleptic Response and Treatment Outcome Under Open and Double-Blind Conditions: A Preliminary Report. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 921–928.

1. 1. A patient's early subjective response to a neuroleptic was recorded in 17 schizophrenic patients following a fixed dose of neuroleptic under both open and double-blind placebo-controlled conditions.

2. 2. High correlations were found between a patient's subjective response at 2.5, 24 and 48 hours after the initial dose, suggesting that the timing of the initial subjective response rating is not critical.

3. 3. The relationship between the psychiatric improvement and subjective response was not significant under double-blind conditions (r = 0.004), while the relationship under the open condition showed a trend towards significance comparable to earlier reports (r = 0.32).

4. 4. The findings question the usefulness of applying early subjective response to a neuroleptic to predict clinical improvement.

Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment

Wiesel, Frits-Axel: Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 871–881.

1. 1. Determination of regional glucose metabolism has been considered to be a tool to elucidate the mechanisms of action of neuroleptics.

2. 2. D₂-dopamine antagonists seem to increase glucose consumption in dopamine innervated areas.

3. 3. Studies in humans do not give results in complete accordance with animal findings.

4. 4. In patients neuroleptic compounds and dopamin agonists probably increase and decrease striatal metabolism respectively.

5. 5. Changes in metabolism, especially in the right hemisphere may be coupled with improvement of the patients.

6. 6. Future research must be based on protocols specially designed for the study of drug effects.

Biphasic actions of pentobarbital on synaptic transmission

1. 1. The effects of pentobarbital were studied on synaptic transmission in the rat hippocampal slice preparation.

2. 2. Low concentrations of pentobarbital (0.04–0.1 mM) produced an increase in the Schaffer collateral to CA 1 evoked EPSP and population field potential amplitudes.

3. 3. Higher concentrations of pentobarbital (0.2–1.0 mM) produced depression of field potential amplitudes.

4. 4. Pentobarbital altered synaptic transmission by affecting both pre- and post-synaptic functions.

5. 5. Analysis of input/output curves suggest the presynaptic site is most sensitive.

Diagnosis and pharmacotherapy of conduct disorder

Lavin Michael R. and Arthur Rifkin: Diagnosis and Pharmacotherapy of Conduct Disorders. Prog. Neuro- Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 875–885.

1. 1. There are few double-blind, placebo-controlled studies of the drug treatment of conduct disorders in children and adolescents.

2. 2. The diagnosis of conduct disorders involves a persistent pattern of behavior in which the basic rights of others and standards of society are violated.

3. 3. There is frequent comorbidity associated with conduct disorders including attention-deficit hyperactivity disorder, oppositional defiant disorder, mood disorders and substance abuse.

4. 4. Childhood Conduct disorder is associated with a significant risk for adult psychopathology.

5. 5. A variety of treatment approaches may be employed to combat conduct disorders.

6. 6. The use of neuroleptics, lithium carbonate, stimulants and other agents is reviewed.

Can ECT-induced cognitive effects be altered pharmacologically?

Khan Arifulla, Mary Helen Mirolo, Hugh A. Mirolo and Sheree Miller: Can ECT-Induced Cognitive Effects be Altered Pharmacologically? Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 861–873.

1. 1. A systematic review of the literature revealed twelve clinical trials that evaluated nine different drugs, and used three different conceptual models to prevent, restore or treat ECT-induced cognitive deficits.

2. 2. This review indicated inconclusive results regarding clinical utility of any of the drugs.

3. 3. Major factors discussed include the complexities involved in the evaluation of ECT-induced cognitive deficits, and the techniques of evaluating changes in cognitive functions.

4. 4. Our conclusion is that future research should emphasize understanding the neural mechanisms related to ECT-induced cognitive deficits. We suggest several areas for future exploration.

Biological markers of depression: Who multi-center studies and future perspective

Tsukasa Koyama and Itaru Yamashita: Biological Markers of Depression; WHO Multi-Center Studies and Future Perspective. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 791–796.

1. 1. Dexamethasone suppresion test (DST), imipramine platelet binding and sleep EEG in depressed patients were studied by the network of WHO Collaborating Centers.

2. 2. DST and sleep EEG indicated abnormalities characteristic to depression, but imipramine platelet binding failed to show difference between depressed and normal subjects.

3. 3. 20 papers related to markers of depression were presented at the 17th Congress of CINP, Kyoto, 1990.

4. 4. They were introduced under 5 headings: 1) DST and its modifications, 2) serotonergic functions, 3) platelet studies, 4) ocular potentials and melatonin, and 5) brain imaging. There are reviewed here.

Opioid receptor affinities of kappa agonists, agonist/antagonists and antagonists in vitro and in vivo

1. 1. The CMS opioid receptors consist of a major triad: μ, δ and κ.

2. 2. The κ agonists presently available act as κ agonists, δ antagonists and μ₂ isoreceptor antagonists.

3. 3. Pure opiate antagonists possess a broad spectrum of activity at all 3 opioid receptor populations.

4. 4. The Ag/Ant analgesics also possess a broad spectrum of receptor affinities which awaits the definition of complex species differences in their actions.

5. 5. The design of more specific opioid agonists and antagonists will lead to a greater understanding of the many possible roles opioids serve within the CNS.

Neutrophil and monocyte phagocytosis in depressed patients

McAdams Catherine and Leonard Brian E.: Neutrophil and monocyte phagocytosis in depressed patients. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 971–984.

1. 1. Monocyte and neutrophil phagocytosis was investigated in a group of depressed patients during the active phase of their illness and following recovery. The results were compared with those obtained from a group of schizophrenia and manic patients and with age and sex matched controls. Neutrophil phagocytosis was reduced in all three patient groups during the active phase of the illness but returned to control values on recovery. Monocyte phagocytosis was however increased but while it returned to control values following recovery of the depressed patients, it remained raised in the manic and schizophrenic patients.

2. 2. T-cell replication in response to a mitogen challenge was also investigated in the depressed patients. This was found to be significantly reduced in the depressed patients during the active phase of the illness and remained reduced following their recovery.

3. 3. The results suggest that the changes in phagocytosis and T-cell replication are state and trait markers respectively of depression.

4. 4. A differential white blood cell count revealed that the neutrophil number was increased and the monocytes decreased, in the depressed patients during the active phase of the illness, but returned to normal values on recovery.

5. 5. The factor(s) responsible for the changes in these various aspects of the imune function is unknown. However, evidence is presented that the changes are not due to hypercortisolaemia or to the direct effects of the psychotropic medication on phagocytosis or T-cell replication.

Early serum levels of neuroleptics do not predict therapeutic response in Schizophrenia

Gaebel, Wolfgang, Bruno Müller-Oerlinghausen and Jürgen Schley: Early Serum Levels of Neuroleptics do not Predict Therapeutic Response in Schizoprenia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 891–900.

1. 1. Thirty-six acute schizophrenics were included in a 28-day open treatment study with the neuroleptic perazine.

2. 2. Peak serum levels of parent drug and its main inactive metabolite desmethyl-perazine were assessed 2 hours after an oral test dose given at the beginning of the study.

3. 3. Whereas peak levels of perazine were not significantly different in treatment responders and nonresponders, desmethylperazine was significantly higher in nonresponders.

4. 4. The ratio between desmethylperazine and perazine was not predictive of (non-)response to neuroleptic treatment in schizophrenia.

Behavioral and EEG responses to alcohol in nonalcoholic men with a family history of alcoholism

1. 1. Behavioral and EEG responses were examined in nonalcoholic males with (FH+) and without (FH-) a family history of alcoholism following the consumption of a placebo and real beer.

2. 2. FH+ subjects were less confident of being able to resist another drink following consumption of the placebo and reported higher taste ratings and feeling more intoxicated following ethanol consumption than FH- subjects.

3. 3. Both groups showed increases in EEG alpha activity (9–12Hz) following alcohol consumption.4. Alpha activity was positively associated with desire to drink in the FH+ group before and after consumption, but was positively associated with perceived intoxication in the FH- group only after consumption.

An experimental antidepressant increases rem sleep

1. 1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep.

2. 2. The design included a four-week drug administration period, proceeded and followed by a one week placebo period.

3. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance.

4. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants.

5. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related.

6. 6. Further, given that the only known action of the drug is its inhibitory effect on GABA-ergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation.

Topographic evoked potentials during backward masking in schizophrenics, patient controls and normal controls

1. 1. A backward masking task with simultaneous measurement of topographically mapped evoked potentials was performed by normal, schizophrenic, and patient control subjects.

2. 2. Behavioral results replicated previous studies demonstrating schizophrenic deficit and to a lesser extent patient control deficit in this task.

3. 3. Two competing theories of (A) defects in “gating” mechanisms or (B) failure in early stimulus “registration” processes were tested.

4. 4. Topographical evoked response maps Indicated a significant absence of a negative going wave in the 70–100 msec epoch in the schizophrenic group relative to both control groups.

5. 5. As the 70–100 msec negativitity attenuation occurred during target presentation, and well before mask onset, it was concluded that schizophrenic deficit in this task consists of a failure in Initial stimulus “registration” processes within the time allowed for stimulus availability.

6. 6. Such defective mechanisms may be significant in the pathogenesis of schizophrenia.

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system

Vécsei, László and Erik Widerlöv: Preclinical and Clinical Studies with Cysteamine and Pantethine Related to the Central Nervous System. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 835–862.

1. 1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues.

2. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation.

3. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactinsecreting adenomas) indications in clinical practice.

4. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine.

5. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine.

6. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.

Treatment of alcohol organic mental disorder with piracetam

1. 1. The paper presents an investigation of the efficiency of piracetam in alcohol organic mental disorder.

2. 2. A double blind placebo controlled study design was used to compare two dosages of the substance (2 × 3g versus 2 × 12g).

3. 3. The cognitive functions of the patients, especially short term memory and concentration, were assessed on the days 0, 7, 14, 28 and 42 using various psychological instruments.

4. 4. An analysis of 39 patients showed an improvement of cognitive functions in all three groups.

5. 5. Patients receiving drug treatment showed earlier responses than patients receiving placebo; differences between the three investigational groups were not statistically significant.

6. 6. The results achieved make the effect of piracetam appear somewhat questionable.

The effects of antidepressant drugs on adenylyl cyclase linked beta adrenergic binding sites on mouse astrocytes in primary cultures

1. 1) It has been widely reported that the chronic administration of antidepressant drugs induces a down regulation of beta receptors in the brains of experimental animals with a time course that parallels the therapeutic improvement seen in depressed patients given these drugs. It has been tacitly assumed that these beta receptors are located on neurons.

2. 2) All classes of antidepressant drugs tested, various monoamine uptake inhibitors, a monoamine oxidase inhibitor, or novel drugs lacking either of these actions, reduced the retention of dihydroalprenolol by intact astrocytes in primary cultures. The drug concentrations altering this retention by astrocytes (K_i) are in the same range as those reported by other investigators using homogenates of glioma cells or whole brain.

3. 3) The isoproterenol-induced stimulation of cyclic AMP formation by astrocytes in primary cultures is reduced acutely by the antidepressants amitriptyline, tranylcypromine and doxepin. Following washout of the antidepressant drug, isoproterenol stimulation of adenylyl cyclase is reduced in astrocytes exposed in culture to amitriptyline or tranylcypromine for 12–14 days or longer but is not altered in astrocytes exposed to the antidepressants for only 5 days.

4. 4) This indicates that the chronic exposure of astrocytes in culture to antidepressant drugs, down regulates astrocyte beta receptors with a time course that parallels the beta down regulation seen in vivo in animal brain homogenates and the therapeutic improvement seen in depressed patients. The possible functional aspects of drug astrocyte interactions must be considered in any hypothesis concerning drug-brain interactions.

Variation in evoked potential measures over the menstrual cycle: A pilot study

Nancy Kluck, Scan J. O'Connor, Victor M. Hesselbrock, Allan Tasman and Donald Maier, Lance Bauer: Variation in Evoked Potential Measures Over the Menstrual Cycle: A Pilot Study. Prog. Neuro. Psychopharmacol. Biol. Psychiat. 1992. 16(6): 901–911.

1. 1. The P3 component of a visual event related potential (ERP) was studied for five consecutive weeks in six women with normal menstrual cycles. Serum concentrations of luteinizing hormone (LH), estradiol (E2) and progesterone were studied during the same period.

2. 2. Increases in P3 amplitude, although nonsignificant, were noted in the week preceding onset of menses.

3. 3. No significant changes in reaction times to target/nontarget stimuli were noted over the same time period.

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.

Benzodiazepine effects on flicker sensitivity: Role of stimulus frequency and size

Maddock Richard J., Evanne J. Casson, Lori A. Lott, Cameron S. Carter, and Chris A. Johnson: Benzodiazepine effects on flicker sensitivity: Role of stimulus frequency and size. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 955–970.

1. 1. Benzodiazepines (BZDs) impair sensitivity to temporally modulated visual stimuli (flicker). Critical flicker-fusion frequency (CFF) is commonly used as a measure of this effect, but it only measures sensitivity to a narrow range of frequencies, usually above 25 Hz. Are other frequencies more sensitive to the effects of BZDs?

2. 2. Flicker sensitivity at 1, 2, 4, 8, 16, and 32 Hz was measured for 1° and 5° stimuli before and 50 to 100 minutes after triazolam (0.25 mg), lorazepam (1.0 mg) and placebo. Drug effects on CFF were also measured.

3. 3. Both BZDs significantly impaired overall flicker sensitivity. Triazolam produced 50% more impairment than lorazepam. CFF was significantly impaired by triazolam. BZD effects did not vary with stimulus size.

4. 4. Significantly greater BZD-induced impairment of flicker sensitivity occurred at 16 Hz than at 1, 2, 4, or 32 Hz.

5. 5. The magnitude of BZD effects on flicker sensitivity vary with the temporal frequency of the stimulus. BZD effects are greatest for 8–16 Hz stimuli.