scholarly journals Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers

2021 ◽  
Author(s):  
Sunjeev K Kamboj ◽  
Hannah Zhao ◽  
Luzia Troebinger ◽  
Giulia Piazza ◽  
Emma Cawley ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Depressive Symptoms ◽  
Healthy Volunteers ◽  
Subjective Effects ◽  
Moderate Dose ◽  
Future Studies ◽  
Laughing Gas ◽  
Problematic Drug ◽  
Experimental Tool ◽  
Medical Air

Abstract Background Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity. Methods Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation. Results Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting. Conclusion To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.

Nitrous Oxide Intoxication: Subjective Effects in Healthy Young Men

1977 ◽  
Vol 9 (4) ◽  
pp. 317-328 ◽  
Author(s):  
Roland M. Atkinson ◽  
Pius Morozumi ◽  
J. DeWayne Green ◽  
John C. Kramer
Keyword(s):  
Nitrous Oxide ◽  
Subjective Effects ◽  
Young Men

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

2021 ◽  
Vol 13 (597) ◽  
pp. eabe1376
Author(s):  
Peter Nagele ◽  
Ben J. Palanca ◽  
Britt Gott ◽  
Frank Brown ◽  
Linda Barnes ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Depressive Symptoms ◽  
Major Depression ◽  
Rating Scale ◽  
Similar Efficacy ◽  
Comparable Efficacy ◽  
Crossover Fashion ◽  
Phase 2 ◽  
Treatment Resistant ◽  
Phase 2 Trial

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were −0.75 points on the HDRS-21 at 2 hours (P = 0.73), −1.41 points at 24 hours (P = 0.52), −4.35 points at week 1 (P = 0.05), and −5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were −0.87 points at 2 hours (P = 0.69), −1.93 points at 24 hours (P = 0.37), −2.44 points at week 1 (P = 0.25), and −7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

Nitrous oxide as a diazo transfer reagent: the synthesis of triazolopyridines

2021 ◽  
Author(s):  
Iris R. Landman ◽  
Farzaneh Fadaei-Tirani ◽  
Kay Severin
Keyword(s):  
Nitrous Oxide ◽  
Laughing Gas

Nitrous oxide (N2O, ‘laughing gas’) can be used as diazo transfer reagent for the synthesis of triazolopyridines.

scholarly journals Living With Bipolar Disorder in the Time of Covid-19: Biorhythms During the Severe Lockdown in Cagliari, Italy, and the Moderate Lockdown in Tunis, Tunisia

2021 ◽  
Vol 12 ◽  
Author(s):  
Mauro Giovanni Carta ◽  
Uta Ouali ◽  
Alessandra Perra ◽  
Azza Ben Cheikh Ahmed ◽  
Laura Boe ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Depressive Symptoms ◽  
Rating Scale ◽  
Biological Rhythms ◽  
Short Term ◽  
Female Age ◽  
Future Studies ◽  
Restrictive Measures ◽  
Depressive Episodes ◽  
Hamilton Rating Scale

Background: Restrictions during Covid-19 pandemic lockdown, in which rhythms of life have been compromised, can influence the course of bipolar disorder (BD). This study follows patients with bipolar disorder living in two geographically close cities (Cagliari and Tunis), but with different lockdown conditions: less severe in Tunis.Methods: Two cohorts were evaluated during lockdown (April 2020, t0) and 2 months later with lockdown lifted for a month (t1). Individuals were: over 18 years old without gender exclusion, BD I or II, in care for at least 1 year, received a clinical interview in the month before the start of the lockdown, stable clinically before the lockdown. The assessment was conducted by telephone by a psychiatrist or psychologist with good knowledge of patients. Diagnoses were made according to DSM-5 criteria. Depressive symptoms were collected through the Hamilton Rating Scale for Depression; cut-off 14 indicative of depressive episode. Circadian rhythms were measured using the BRIAN scale.Results: Forty individuals in Cagliari (70%female, age 48.57 ± 11.64) and 30 in Tunis (53.3% Female, age 41.8 ± 13.22) were recruited. In Cagliari at t0 45% had depressive episodes against none in Tunis, a similar difference appeared at t1. At t0 and t1 the Cagliari sample had more dysfunctional scores in the overall BRIAN scale and in the areas of sleep, activities and social rhythms; no differences were found in nutrition, both samples had predominantly nocturnal rhythm. In Cagliari at t0 and t1, the depressive sub-group showed more dysfunctional scores in the BRIAN areas sleep, activity, and nutrition. However, the differences in biological rhythms resulted, through ANCOVA analysis, independent of the co-presence of depressive symptoms.Discussion: A rigid lockdown could expose people with BD to depressive relapse through dysregulation of biological rhythms. The return to more functional rhythms did not appear 1 month after lockdown. The rekindling of the pandemic and the restoration of new restrictive measures will prevent, at least in the short term, the beneficial effect of a return to normality of the two cohorts.This was a limited exploratory study; future studies with larger samples and longer observational time are needed to verify the hypothesis.

Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers 

1999 ◽  
Vol 90 (3) ◽  
pp. 718-726 ◽  
Author(s):  
Matthew L. Black ◽  
Joanna L. Hill ◽  
James P. Zacny
Keyword(s):  
Healthy Volunteers ◽  
Dose Range ◽  
Subjective Effects ◽  
Cold Pressor Test ◽  
Drug Effects ◽  
Cold Pressor ◽  
Psychomotor Tests ◽  
Potency Ratio ◽  
Psychomotor Effects ◽  
Double Blinded

Background The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug. Methods Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test. Results Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects. Conclusions The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued.

Selective Performance Effects of Nitrous Oxide

1972 ◽  
Vol 14 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Robert J. Biersner
Keyword(s):  
Nitrous Oxide ◽  
Short Term Memory ◽  
Subjective Effects ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Wechsler Memory Scale ◽  
Hand Tool ◽  
Performance Effects

Twenty-one U.S. Navy divers were given several standard visual tests, the Purdue Peg-board, the Bennett Hand Tool Dexterity Test, and the Wechsler Memory Scale while breathing air or 30% nitrous oxide. The results showed that visual function, fine and gross motor performance, and long-term memory were normal under nitrous oxide, while learning and short-term memory were significantly impaired. The subjective effects of breathing nitrous oxide were similar to those experienced during compressed air narcosis. The selective impairment of short-term memory suggests that divers might be able to perform useful work at depths deeper than those currently authorized, provided the tasks were well learned and practiced.

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