Potential Treatment for Overdose with Synthetic Cannabinoids

Meredith, Grant; DeLollis, Michael; Shad, Mujeeb U.

doi:10.1159/000506635

Cited by 5 publications

(5 citation statements)

References 5 publications

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“…CB1 receptor antagonists, such as rimonabant and CBD, might be valuable candidates for reversing the acute psychotic effects of SCs (Meredith et al 2020 ). Both drugs reduced activity in the mesolimbic cortex in animals (Alonso et al 1999 ; Roser et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

et al. 2021

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Background Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles of SCs are extremely scarce. Aim The current study was designed to assess the psychotomimetic effects of a moderate dose of JWH-018. Methods Twenty-four healthy participants (10 males, 14 females) entered a placebo-controlled, double blind, within-subjects trial and inhaled vapour of placebo or 75μg/kg bodyweight JWH-018. To ascertain a minimum level of intoxication, a booster dose of JWH-018 was administered on an as-needed basis. The average dose of JWH-018 administered was 5.52 mg. Subjective high, dissociative states (CADSS), psychedelic symptoms (Bowdle), mood (POMS) and cannabis reinforcement (SCRQ) were assessed within a 4.5-h time window after drug administration. Results JWH-018 caused psychedelic effects, such as altered internal and external perception, and dissociative effects, such as amnesia, derealisation and depersonalisation and induced feelings of confusion. Conclusion Overall, these findings suggest that a moderate dose of JWH-018 induces pronounced psychotomimetic symptoms in healthy participants with no history of mental illness, which confirms that SCs pose a serious risk for public health.

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Section: Discussionmentioning

confidence: 99%

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

et al. 2021

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“…Recently, many studies have indicated that prophylactic treatment with CB1 receptor antagonists can block cannabimimetic effects both in animals and humans. Therefore, single-use CB1 receptor inverse agonists could perhaps provide an acceptable temporary single-dose antidote [53,54]. Nonetheless, a never-ending effort is devoted to evaluating the effectiveness of drugs usually employed in Emergency Departments (EDs) for the treatment of NPS-induced adverse effects, with the goal of identifying novel, effective, antidotal therapeutic strategies to be adopted in the critical management of SCs intoxicated patients.…”

Section: Discussionmentioning

confidence: 99%

Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?

Marchetti

Bilel

Tirri

et al. 2023

IJMS

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JWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. SCs-based products are responsible for several intoxications in humans. Cardiac toxicity is among the main side effects observed in emergency departments: SCs intake induces harmful effects such as hypertension, tachycardia, chest pain, arrhythmias, myocardial infarction, breathing impairment, and dyspnea. This study aims to investigate how cardio-respiratory and vascular JWH-018 (6 mg/kg) responses can be modulated by antidotes already in clinical use. The tested antidotes are amiodarone (5 mg/kg), atropine (5 mg/kg), nifedipine (1 mg/kg), and propranolol (2 mg/kg). The detection of heart rate, breath rate, arterial oxygen saturation (SpO2), and pulse distention are provided by a non-invasive apparatus (Mouse Ox Plus) in awake and freely moving CD-1 male mice. Tachyarrhythmia events are also evaluated. Results show that while all tested antidotes reduce tachycardia and tachyarrhythmic events and improve breathing functions, only atropine completely reverts the heart rate and pulse distension. These data may suggest that cardiorespiratory mechanisms of JWH-018-induced tachyarrhythmia involve sympathetic, cholinergic, and ion channel modulation. Current findings also provide valuable impetus to identify potential antidotal intervention to support physicians in the treatment of intoxicated patients in emergency clinical settings.

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“…Recently, the recreational misuse of SCBs has become a global health problem, causing frequent emergencies [7]. Mepirapim has also been reported to cause serious side effects [17].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, their adverse effects are difficult to predict [5]. Indeed, there have been many reports of psychological side effects such as anxiety, depression and paranoia, as well as physical side effects such as tachycardia, hypertension, seizures and even death in SCB users [6,7].…”

Section: Introductionmentioning

confidence: 99%

Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents

et al. 2022

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Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potential of Mepirapim through an intravenous self-administration test and a conditioned place preference test in rodents. Moreover, to determine whether the pharmacological effects of Mepirapim are mediated by cannabinoid receptors, we investigated whether Mepirapim treatment induces cannabinoid tetrad symptoms in mice. Lastly, to identify Mepirapim induced neurochemical maladaptation in the brains of mice, we performed microdialysis, western blots and neurotransmitter enzyme-linked immunosorbent assays. In the results, Mepirapim supported the maintenance of intravenous self-administration and the development of conditioned place preference. As a molecular mechanism of Mepirapim addiction, we identified a decrease in GABAeric signalling and an increase in dopaminergic signalling in the brain reward circuit. Finally, by confirming the Mepirapim-induced expression of cannabinoid tetrad symptoms, we confirmed that Mepirapim acts pharmacologically through cannabinoid receptor one. Taken together, we found that Mepirapim induces addiction-related behaviours through neurochemical maladaptation in the brain. On the basis of these findings, we propose the strict regulation of recreational abuse of Mepirapim.

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Potential Treatment for Overdose with Synthetic Cannabinoids

Cited by 5 publications

References 5 publications

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?

Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents

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