Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids: A Systematic Review and Meta-Analysis

Bahji, Anees; Stephenson, Callum; Tyo, Richard; Hawken, Emily R.; Seitz, Dallas

doi:10.1016/j.biopsych.2021.02.561

Cited by 10 publications

(14 citation statements)

References 82 publications

(106 reference statements)

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“…We followed analytic approaches of previous NMAs for trials of treatments for psychiatric disorders, [40][41][42][43][44][45][46] employing the netmeta package from R Studio (version 3.5.1) software. 47,48 We graphed forest plots for each outcome measure (retention in treatment, dropouts, dropouts for adverse events, and total psychotic symptom rating score).…”

Section: Planned Methods Of Analysismentioning

confidence: 99%

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders

Yee

Bahji

Lolich

et al. 2022

J Clin Psychopharmacol

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BackgroundPsychotic disorders produce important morbidity and disability in children and adolescents. There have been few relevant treatment trials, encouraging assessment of research aimed at testing efficacy and safety of antipsychotics for juveniles. We aimed to compare the short- and long-term efficacy and safety of antipsychotics to treat psychotic disorders among children and adolescents.MethodsFour major bibliographic databases (PubMed, MEDLINE, PsycINFO, and EMBASE) were searched for clinical trials of antipsychotics in children or adolescents, from database inception to May 2021. We searched for clinical trials comparing antipsychotics with control conditions for juvenile psychosis based on blinded review by 2 independent investigators (C.S.Y. and M.L.). We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and applied the Cochrane risk-of-bias tool to appraise study quality. One reviewer (A.B.) performed data abstraction which was confirmed by 2 independent, blinded reviewers (C.S.Y. and M.L.). Primary outcomes were scores rating psychosis symptoms and dichotomized retention in treatment protocols versus dropouts because of adverse events. Effect sizes were pooled using frequentist random-effects network meta-analysis modeling to generate summary rate ratios (RRs) and Cohen d standardized mean differences.ResultsSystematic searching generated 1330 unique records. Of these, short-term (n = 15, for 6 [3–12] weeks) and long-term (n = 10, for 12 [6–60] months) treatment trials involved 2208 (39.2% females; median age, 15.3 years), and 1366 subjects (35.0% females; median age, 15.6 years), respectively. Short-term reduction of psychosis scores ranked clozapine (d = −1.35; 95% confidence interval [CI], −1.97 to −0.73]), molindone (−1.22; 95% CI, −1.68 to −0.75), olanzapine (−1.12; 95% CI, −1.44 to –0.81), and risperidone (−0.93; 95% CI, −1.22 to −0.63) as the most effective agents. In longer-term treatment, only lurasidone was effective. Clozapine (RR, 12.8) and haloperidol (RR, 5.15) led to more all-cause and adverse event-related dropouts. There were few trials/drug (1 each for aripiprazole, asenapine, lurasidone, molindone, paliperidone, and ziprasidone, short term; aripiprazole, clozapine, haloperidol, lurasidone, and molindone, long-term). Heterogeneity and inconsistency were high, especially in long-term trials, without evidence of publication bias.ConclusionsSome antipsychotics were effective and tolerated short term, but longer-term evidence was very limited. The overall paucity of trials and of adequate controls indicates that more well-designed randomized controlled trials are required for adequate assessment of antipsychotic drug treatment for juveniles.Systematic Review RegistrationPROSPERO CRD42021232937.

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Section: Planned Methods Of Analysismentioning

confidence: 99%

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders

Yee

Bahji

Lolich

et al. 2022

J Clin Psychopharmacol

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“…Cessation from long-term cannabinoid use often precipitates a specific set of symptoms known as cannabis withdrawal syndrome, and sleep disturbances are one of six diagnostic criteria for this condition (Bonnet and Preuss, 2017). A meta-analysis found that 47% of regular cannabis users exhibited cannabis withdrawal syndrome following discontinuation of use (Bahji et al , 2020). A systematic review of cannabis withdrawal and sleep notes that, while sleep disruption following withdrawal appears to be common across multiple studies, small sample sizes and the presence of confounding variables limit determination of the specific aspects of sleep that are affected (Gates et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

Altered sleep during spontaneous cannabinoid withdrawal in male mice

Missig

Mehta

Robbins

et al. 2022

Behavioural Pharmacology

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Cessation of cannabinoid use in humans often leads to a withdrawal state that includes sleep disruption. Despite important health implications, little is known about how cannabinoid abstention affects sleep architecture, in part because spontaneous cannabinoid withdrawal is difficult to model in animals. In concurrent work we report that repeated administration of the high-efficacy cannabinoid 1 (CB1) receptor agonist AM2389 to mice for 5 days led to heightened locomotor activity and paw tremor following treatment discontinuation, potentially indicative of spontaneous cannabinoid withdrawal. Here, we performed parallel studies to examine effects on sleep. Using implantable electroencephalography (EEG) and electromyography (EMG) telemetry we examined sleep and neurophysiological measures before, during, and after 5 days of twice-daily AM2389 injections. We report that AM2389 produces decreases in locomotor activity that wane with repeated treatment, whereas discontinuation produces rebound increases in activity that persist for several days. Likewise, AM2389 initially produces profound increases in slow-wave sleep (SWS) and decreases in rapid eye movement (REM) sleep, as well as consolidation of sleep. By the third AM2389 treatment, this pattern transitions to decreases in SWS and total time sleeping. This pattern persists following AM2389 discontinuation and is accompanied by emergence of sleep fragmentation. Double-labeling immunohistochemistry for hypocretin/ orexin (a sleep-regulating peptide) and c-Fos (a neuronal activity marker) in lateral hypothalamus revealed decreases in c-Fos/orexin+ cells following acute AM2389 and increases following discontinuation, aligning with the sleep changes. These findings indicate that AM2389 profoundly alters sleep in mice and suggest that sleep disruption following treatment cessation reflects spontaneous cannabinoid withdrawal. Behavioural

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“…Interrupted use of cannabis, the most commonly used illicit drug, likewise has been associated with withdrawal symptoms. By some estimates up to 30–70% of daily users, and 10–17% of all users, describe symptoms associated with spontaneous cannabis withdrawal (Copersino et al , 2006; Agrawal et al , 2008; Bahji et al , 2020). However, like nicotine or caffeine dependence, the predominant symptoms of cannabinoid abstinence such as nightmares, angry outbursts, and difficulty falling asleep are psychometric and, consequently, difficult to translate to animal models (Allsop et al , 2011).…”

Section: Introductionmentioning

confidence: 99%

Evidence for spontaneous cannabinoid withdrawal in mice

Paronis

Iliopoulos‐Tsoutsouvas

Papanastasiou

et al. 2021

Behavioural Pharmacology

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Although the behavioral effects of acute and chronic exposure to cannabinoids have been extensively studied in mice, spontaneous withdrawal following exposure to cannabinoids has not been well characterized in this species. To address this issue, different groups of mice were treated for 5 days with saline, 20–36 mg/kg/day of the CB partial agonist Δ9-tetrahydrocannabinol (Δ9-THC), or 0.06–0.1 mg/kg/day of the CB high-efficacy agonist AM2389. Initial studies assessed changes in observable behavior (paw tremors) that were scored from the recordings taken at 4 or 24 h after the last injection. Subsequently, radiotelemetry was used to continuously measure body temperature and locomotor activity before (baseline), during, and after the 5-day dosing regimens. Results show that increases in paw tremors occurred following 5-day exposure to AM2389 or Δ9-THC. In telemetry studies, acute AM2389 or THC decreased both temperature and activity. Rapid tolerance occurred to the hypothermic effects of the cannabinoids, whereas locomotor activity continued to be suppressed following each drug injection. In contrast, increases in locomotor activity were evident 12–72 h after discontinuing daily injections of either 0.06 or 0.1 mg/kg/day AM2389. Increases in locomotor activity were also noted in mice treated daily with 30 or 36, but not 20 mg/kg/day Δ9-THC; these effects were smaller and appeared later than effects seen in AM2389-treated mice. These results indicate that the discontinuation of daily treatment with a CB high-efficacy agonist will yield evidence of spontaneous withdrawal that may reflect prior dependence, and that the degree of cannabinoid dependence may vary in relation to the dose or efficacy of the agonist injected daily.

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Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids: A Systematic Review and Meta-Analysis

Abstract: IMPORTANCE Cannabis withdrawal syndrome (CWS)-a diagnostic indicator of cannabis use disorder-commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS.

Cited by 10 publications

References 82 publications

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders

Altered sleep during spontaneous cannabinoid withdrawal in male mice

Evidence for spontaneous cannabinoid withdrawal in mice

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