Assessment of cognitive and psychomotor impairment, subjective effects, and blood THC concentrations following acute administration of oral and vaporized cannabis

2021 ◽  
pp. 026988112110215
Author(s):  
Tory R Spindle ◽  
Erin L Martin ◽  
Megan Grabenauer ◽  
Thomas Woodward ◽  
Michael A Milburn ◽  
...  
Keyword(s):  
Psychomotor Performance ◽  
Subjective Effects ◽  
Drug Effects ◽  
Driving Under The Influence ◽  
Acute Administration ◽  
Performance Tests ◽  
Double Blind ◽  
Routes Of Administration ◽  
Psychomotor Impairment ◽  
Novel Biomarkers

Background: Cannabis legalization is expanding, but there are no established methods for detecting cannabis impairment. Aim: Characterize the acute impairing effects of oral and vaporized cannabis using various performance tests. Methods: Participants ( N = 20, 10 men/10 women) who were infrequent cannabis users ingested cannabis brownies (0, 10, and 25 mg Δ-9-tetrahydrocannabinol, THC) and inhaled vaporized cannabis (0, 5, and 20 mg THC) in six double-blind outpatient sessions. Cognitive/psychomotor impairment was assessed with a battery of computerized tasks sensitive to cannabis effects, a novel test (the DRiving Under the Influence of Drugs, DRUID®), and field sobriety tests. Blood THC concentrations and subjective drug effects were evaluated. Results: Low oral/vaporized doses did not impair cognitive/psychomotor performance relative to placebo but produced positive subjective effects. High oral/vaporized doses impaired cognitive/psychomotor performance and increased positive and negative subjective effects. The DRUID® was the most sensitive test to cannabis impairment, as it detected significant differences between placebo and active doses within both routes of administration. Women displayed more impairment on the DRUID® than men at the high vaporized dose only. Field sobriety tests showed little sensitivity to cannabis-induced impairment. Blood THC concentrations were far lower after cannabis ingestion versus inhalation. After inhalation, blood THC concentrations typically returned to baseline well before pharmacodynamic effects subsided. Conclusions: Standard approaches for identifying impairment due to cannabis exposure (i.e. blood THC and field sobriety tests) have severe limitations. There is a need to identify novel biomarkers of cannabis exposure and/or behavioral tests like the DRUID® that can reliably and accurately detect cannabis impairment at the roadside and in the workplace.

Evaluation of betahistine for the prevention of seasickness: Effect on vestibular function, psychomotor performance and efficacy at sea

2003 ◽  
Vol 13 (2-3) ◽  
pp. 103-111 ◽  
Author(s):  
Carlos R. Gordon ◽  
Ilana Doweck ◽  
Zohar Nachum ◽  
Adi Gonen ◽  
Orna Spitzer ◽  
...  
Keyword(s):  
Side Effects ◽  
Psychomotor Performance ◽  
Vestibular Function ◽  
Placebo Treatment ◽  
Crossover Design ◽  
Performance Tests ◽  
Double Blind ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex ◽  
Sinusoidal Harmonic Acceleration

Betahistine was evaluated for the prevention of seasickness in a laboratory and sea study. The effect of 48 mg betahistine on the vestibulo-ocular reflex (VOR) and on psychomotor performance was evaluated in twelve young healthy subjects in a double-blind, placebo controlled, randomized, crossover design. The vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. Psychomotor performance was assessed by both computerized and paper and pencil test batteries. No significant differences in VOR gain or phase were found between betahistine and placebo treatment for any of the frequencies tested. No significant differences were found between treatments for any of the psychomotor performance tests or other possible side effects. The effect of 48 mg betahistine on seasickness severity was evaluated in 83 subjects during a voyage in rough seas. Betahistine had a borderline non-statistically significant effect on the prevention of seasickness in comparison with placebo (p = 0.053), with no notable side effects. Although our results are insufficient to recommend betahistine as an anti-seasickness drug, further studies are required to determine its possible effectiveness in less provocative motion sickness situations.

scholarly journals Safety pharmacology of acute MDMA administration in healthy subjects

2017 ◽  
Vol 31 (5) ◽  
pp. 576-588 ◽  
Author(s):  
Patrick Vizeli ◽  
Matthias E Liechti
Keyword(s):  
Body Temperature ◽  
Adverse Effects ◽  
Healthy Subjects ◽  
Drug Effect ◽  
Subjective Effects ◽  
Drug Effects ◽  
Medical Setting ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety Pharmacology

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4–8.2 h). The 125 mg dose of MDMA produced greater ‘good drug effect’ ratings than 75 mg. MDMA produced moderate and transient ‘bad drug effect’ ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.

scholarly journals Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

2019 ◽  
Vol 45 (3) ◽  
pp. 462-471 ◽  
Author(s):  
Friederike Holze ◽  
Patrick Vizeli ◽  
Felix Müller ◽  
Laura Ley ◽  
Raoul Duerig ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Mystical Experience ◽  
Subjective Effects ◽  
Plasma Concentrations ◽  
Drug Effects ◽  
Psychotherapy Research ◽  
Dose Finding ◽  
Controlled Study ◽  
Acute Effects ◽  
Double Blind

AbstractLysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and d-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and d-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), d-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than d-amphetamine, and d-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and d-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and d-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and d-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with d-amphetamine. d-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or d-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and d-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

scholarly journals A Framework for “Driving Under the Influence of Drugs” Policy for the Opioid Using Driver

2012 ◽  
Vol 3S;15 (3S;7) ◽  
pp. ES215-ES230
Author(s):  
Brian Wilhelmi
Keyword(s):  
Prescription Drugs ◽  
Opioid Analgesic ◽  
The United States ◽  
Driving Under The Influence ◽  
Steady Increase ◽  
Acute Administration ◽  
Opioid Use ◽  
Unique Challenge ◽  
Psychomotor Effects ◽  
Psychomotor Impairment

Background: Driving under the influence of drugs (DUID) is a term used to designate the action of driving an automobile after the consumption of drugs or medications other than alcohol that interfere with the capacity to operate a vehicle safely. Unlike recreational drugs, prescription medications pose a unique challenge to those attempting to harness their benefits yet protect the driving public. As studies demonstrate a steady increase in opioid use and abuse in the United States, these same constituencies must regulate a significant percentage of drivers who are under the influence of opioids. Objective: This article examines current DUID policy and attempts to present unified suggestions for improvement based on best scientific evidence of opioid-induced psychomotor impairment. Study Design: Literature Review Methods: A literature search was conducted regarding the epidemiology of opioid use and abuse, psychomotor effects of opioids, DUID, and state policy concerning DUID. A total of 23 epidemiological studies, 3 studies on acute psychomotor effects, 32 on chronic psychomotor effects, and selected pertinent law and policy were reviewed. Results: Current state law concerning DUID is variable and often relies on prosecutorial discretion to provide protection of the driving public and prosecution of the truly impaired. Limitations: The design of various studies included in this review imposes limitations on the epidemiological data extracted. Relationships between opioids and automobile accidents are commonly reviewed in retrospect. The data on opioid-induced psychomotor impairment and its effects on driving an automobile require further direct study to examine current inferences. Conclusions: A sizable percentage of the driving public has detectable levels of opioids within their bodies. The best available evidence demonstrates psychomotor impairment following acute administration of opioids or an increase in opioid dosage, but impairment diminishes with chronic, stable opioid usage. Policy makers must account for this evidence when balancing the benefit of pain relief against the need for public roadway protection when drafting DUID legislation. Key words: Driving under the influence of drugs, DUID, psychomotor impairment, opioids, regulation, automobile accident(s), driver impairment, prescription drugs, chronic opioid analgesic therapy, driving under the influence

Reduction in Pain Sensitivity from Pharmacological Elevation of Blood Pressure in Persons with Chronically Low Blood Pressure

2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pain Sensitivity ◽  
Pain Threshold ◽  
Pain Perception ◽  
Drug Effects ◽  
Pressure Effects ◽  
Double Blind ◽  
Low Blood Pressure ◽  
Present Trial

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.

341 Acute effects of seltorexant, a selective orexin-2 antagonist (JNJ- 42847922), on driving after bedtime administration

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A136-A136
Author(s):  
S Brooks ◽  
R G J A Zuiker ◽  
G E Jacobs ◽  
I Kezic ◽  
A Savitz ◽  
...  
Keyword(s):  
Postural Stability ◽  
Driving Simulator ◽  
Motor Vehicle ◽  
Subjective Effects ◽  
Driving Ability ◽  
Post Dose ◽  
Double Blind ◽  
Increased Risk ◽  
Subjective Sleepiness ◽  
The Difference

Abstract Introduction Seltorexant (JNJ-42847922), a potent and selective antagonist of the human orexin-2 receptor, is being developed for the treatment of major depressive disorder. Seltorexant also has sleep-promoting properties. Investigating the effects of sleep-promoting medications on driving is important because some of these agents (e.g. GABAA receptor agonists) may be associated with increased risk of motor vehicle accidents. We evaluated the effect of seltorexant on driving after forced awakening at night, using a validated driving simulator. Methods This double-blind, placebo and active-controlled, randomized, 3-way cross-over study was conducted in 18 male and 18 female healthy subjects. All subjects received seltorexant 40 mg, zolpidem 10 mg, or placebo 15 minutes before bedtime. Eighteen subjects were awakened at 2- and 6-hours post-dose, and the other 18 at 4- and 8-hours post-dose. At those timepoints, pharmacokinetics, objective (standard deviation of the lateral position [SDLP]) and subjective effects (using Perceived Driving Quality and Effort Scales) on driving ability, postural stability and subjective sleepiness were assessed. Results For seltorexant, the SDLP difference from placebo (95% confidence interval) at 2-, 4-, 6- and 8-hours post-dose was 3.9 cm (1.26, 6.60), 0.9 cm (-1.08, 2.92), 1.1 cm (-0.42, 2.63), and 0.6 cm (-2.75, 1.55), respectively vs. 9.6 cm (6.97, 12.38), 6.6 cm (3.53, 9.60), 4.7 cm (1.46, 7.85), and 1.3cm (-1.16, 3.80), respectively for zolpidem. The difference from placebo was significant at 2-hours after taking seltorexant, while the difference from placebo was significant at 2, 4 and 6-hours after zolpidem. Subjective driving quality was decreased for both drugs at all time points and driving effort was increased up to 4-hours post-dose for both medications. Subjective sleepiness showed a significant increase compared to placebo 2- and 4-hours after administration of either drug. Postural stability was decreased up to 2-hours after administration of seltorexant, and up to 4-hours after administration of zolpidem. Conclusion Compared to zolpidem, objective effects on driving performance were more transient after seltorexant administration and largely normalized by 4–6 hours post-dose. Support (if any) This work was sponsored by Janssen R&D.

scholarly journals Effect of acute citalopram on self-referential emotional processing and social cognition in healthy volunteers

BJPsych Open ◽  
2020 ◽  
Vol 6 (6) ◽  
Author(s):  
Catherine Hobbs ◽  
Susannah E. Murphy ◽  
Lucy Wright ◽  
James Carson ◽  
Indra Van Assche ◽  
...  
Keyword(s):  
Social Cognition ◽  
Healthy Volunteers ◽  
Antidepressant Treatment ◽  
Affective Learning ◽  
The Self ◽  
Affective Processing ◽  
Antidepressant Effect ◽  
Acute Administration ◽  
Double Blind ◽  
Prosocial Behaviours

Background Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications. Aims To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour. Method Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours. Results Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group. Conclusions Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo

CNS Spectrums ◽  
2006 ◽  
Vol 11 (12) ◽  
pp. 956-965 ◽  
Author(s):  
Stefano Pallanti ◽  
Silvia Bernardi ◽  
Leonardo Quercioli ◽  
Concetta DeCaria ◽  
Eric Hollander
Keyword(s):  
Clinical Severity ◽  
Acute Administration ◽  
Double Blind ◽  
Pathological Gamblers ◽  
Healthy Control ◽  
Cortisol Responses ◽  
Gambling Severity ◽  
Prolactin Response ◽  
The Relationship

ABSTRACTObjectiveAcute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpi-perazine (m-CPP), that is used also as a street drug, has been reported to induce a “high” and craving response in various impulsive and sub-stance addiction disorders.IntroductionTo clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non substance addictions, we assessed behavioral (“high” and “craving”) and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed.MethodTwenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and “high” scales.ResultsPathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post–administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased “high” sensation after m-CPP administration compared with control.ConclusionThese results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of “high” might represent the path-way that leads to dyscontrolled behavior in patho-logical gamblers. Furthermore, the “high” feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behav-ioral and substance addictions.

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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