-
The Medical Journal of Australia Apr 2023To review and synthesise the global evidence regarding the health effects of electronic cigarettes (e-cigarettes, vapes). (Review)
Review
OBJECTIVE
To review and synthesise the global evidence regarding the health effects of electronic cigarettes (e-cigarettes, vapes).
STUDY DESIGN
Umbrella review (based on major independent reviews, including the 2018 United States National Academies of Sciences, Engineering, and Medicine [NASEM] report) and top-up systematic review of published, peer-reviewed studies in humans examining the relationship of e-cigarette use to health outcomes published since the NASEM report.
DATA SOURCES
Umbrella review: eight major independent reviews published 2017-2021. Systematic review: PubMed, MEDLINE, Scopus, Web of Science, the Cochrane Library, and PsycINFO (articles published July 2017 - July 2020 and not included in NASEM review).
DATA SYNTHESIS
Four hundred eligible publications were included in our synthesis: 112 from the NASEM review, 189 from our top-up review search, and 99 further publications cited by other reviews. There is conclusive evidence linking e-cigarette use with poisoning, immediate inhalation toxicity (including seizures), and e-cigarette or vaping product use-associated lung injury (EVALI; largely but not exclusively for e-liquids containing tetrahydrocannabinol and vitamin E acetate), as well as for malfunctioning devices causing injuries and burns. Environmental effects include waste, fires, and generation of indoor airborne particulate matter (substantial to conclusive evidence). There is substantial evidence that nicotine e-cigarettes can cause dependence or addiction in non-smokers, and strong evidence that young non-smokers who use e-cigarettes are more likely than non-users to initiate smoking and to become regular smokers. There is limited evidence that freebase nicotine e-cigarettes used with clinical support are efficacious aids for smoking cessation. Evidence regarding effects on other clinical outcomes, including cardiovascular disease, cancer, development, and mental and reproductive health, is insufficient or unavailable.
CONCLUSION
E-cigarettes can be harmful to health, particularly for non-smokers and children, adolescents, and young adults. Their effects on many important health outcomes are uncertain. E-cigarettes may be beneficial for smokers who use them to completely and promptly quit smoking, but they are not currently approved smoking cessation aids. Better quality evidence is needed regarding the health impact of e-cigarette use, their safety and efficacy for smoking cessation, and effective regulation.
REGISTRATION
Systematic review: PROSPERO, CRD42020200673 (prospective).
Topics: Young Adult; Adolescent; Child; Humans; Electronic Nicotine Delivery Systems; Nicotine; Prospective Studies; Smoking; Smoking Cessation
PubMed: 36939271
DOI: 10.5694/mja2.51890 -
World Psychiatry : Official Journal of... Jun 2022People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a...
People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.
PubMed: 35524619
DOI: 10.1002/wps.20994 -
Acta Neuropathologica Communications Mar 2023In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified... (Review)
Review
In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified as A1, A1-like, or neuroinflammatory reactive astrocytes. In contrast to typical astrocytes, which promote neuronal survival, support synapses, and maintain blood-brain barrier integrity, these reactive astrocytes downregulate supportive functions and begin to secrete neurotoxic factors, complement components like C3, and chemokines like CXCL10, which may facilitate recruitment of immune cells across the BBB into the CNS. The proportion of pro-inflammatory reactive astrocytes increases with age through associated microglia activation, and these pro-inflammatory reactive astrocytes are particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
Topics: Humans; Astrocytes; Microglia; Central Nervous System; Blood-Brain Barrier; Chemokines; Neurotoxicity Syndromes
PubMed: 36915214
DOI: 10.1186/s40478-023-01526-9 -
Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
International Journal of Environmental... Mar 2020Following the recent electronic cigarette (e-cigarette) illness outbreak, the current review aimed to collect all related clinical cases for study and analysis and...
Following the recent electronic cigarette (e-cigarette) illness outbreak, the current review aimed to collect all related clinical cases for study and analysis and provide a critical synopsis of the proposed injury mechanism. Adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines, e-cigarette-related clinical cases were identified via Google Scholar and PubMed databases. Additionally, references of published case reports and previous review papers were manually searched, revealing 159 publications presenting e-cigarette-related case reports and 19 reports by the Centers for Disease Control and Prevention. 238 individual cases were identified; 53% traumatic injuries due to e-cigarette explosion or self-combustion, 24% respiratory cases, and 12% poisonings. Additional cases pertained to oral, cardiovascular, immunologic, hematologic, allergic reactions, infant complications, and altered medication levels. Case reports were mainly published between 2016-2019 (78%). The oldest case, a lipoid pneumonia, was published in 2012. The current review showed that e-cigarette-related health effects extend beyond the acute lung injury syndrome, including traumatic, thermal injuries and acute intoxications. Physicians should be aware of the distinct clinical presentations and be trained to respond and treat effectively. Regulators and public health authorities should address the regulatory gap regarding electronic nicotine delivery systems (ENDS) and novel tobacco products.
Topics: Adult; Electronic Nicotine Delivery Systems; Female; Humans; Lung Injury; Male; Tobacco Products; United States; Vaping; Young Adult
PubMed: 32230711
DOI: 10.3390/ijerph17072248 -
Biomolecules Aug 2021Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide... (Review)
Review
Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide poisoning. Ongoing research into HBOT has shown that preconditioning for surgery is a potential new treatment application, which may reduce complication rates and hospital stay. In this review, the effect of HBOT on oxidative stress, inflammation and angiogenesis is investigated to better understand the potential mechanisms underlying preconditioning for surgery using HBOT. A systematic search was conducted to retrieve studies measuring markers of oxidative stress, inflammation, or angiogenesis in humans. Analysis of the included studies showed that HBOT-induced oxidative stress reduces the concentrations of pro-inflammatory acute phase proteins, interleukins and cytokines and increases growth factors and other pro-angiogenesis cytokines. Several articles only noted this surge after the first HBOT session or for a short duration after each session. The anti-inflammatory status following HBOT may be mediated by hyperoxia interfering with NF-κB and IκBα. Further research into the effect of HBOT on inflammation and angiogenesis is needed to determine the implications of these findings for clinical practice.
Topics: Biomarkers; Humans; Hyperbaric Oxygenation; Inflammation; Neovascularization, Pathologic; Oxidative Stress
PubMed: 34439876
DOI: 10.3390/biom11081210 -
The Cochrane Database of Systematic... Mar 2021Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most countries,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most countries, often repeated, and associated with suicide. Evidence assessing the effectiveness of interventions in the treatment of SH in children and adolescents is lacking, especially when compared with the evidence for psychosocial interventions in adults. This review therefore updates a previous Cochrane Review (last published in 2015) on the role of interventions for SH in children and adolescents.
OBJECTIVES
To assess the effects of psychosocial interventions or pharmacological agents or natural products for SH compared to comparison types of care (e.g. treatment-as-usual, routine psychiatric care, enhanced usual care, active comparator, placebo, alternative pharmacological treatment, or a combination of these) for children and adolescents (up to 18 years of age) who engage in SH.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialized Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic Reviews [CDSR]), together with MEDLINE, Ovid Embase, and PsycINFO (to 4 July 2020).
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing specific psychosocial interventions or pharmacological agents or natural products with treatment-as-usual (TAU), routine psychiatric care, enhanced usual care (EUC), active comparator, placebo, alternative pharmacological treatment, or a combination of these, in children and adolescents with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide.
DATA COLLECTION AND ANALYSIS
We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence internals (CIs). For continuous outcomes, we calculated the mean difference (MD) or standardised mean difference (SMD) and 95% CIs. The overall quality of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach.
MAIN RESULTS
We included data from 17 trials with a total of 2280 participants. Participants in these trials were predominately female (87.6%) with a mean age of 14.7 years (standard deviation (SD) 1.5 years). The trials included in this review investigated the effectiveness of various forms of psychosocial interventions. None of the included trials evaluated the effectiveness of pharmacological agents in this clinical population. There was a lower rate of SH repetition for DBT-A (30%) as compared to TAU, EUC, or alternative psychotherapy (43%) on repetition of SH at post-intervention in four trials (OR 0.46, 95% CI 0.26 to 0.82; N = 270; k = 4; high-certainty evidence). There may be no evidence of a difference for individual cognitive behavioural therapy (CBT)-based psychotherapy and TAU for repetition of SH at post-intervention (OR 0.93, 95% CI 0.12 to 7.24; N = 51; k = 2; low-certainty evidence). We are uncertain whether mentalisation based therapy for adolescents (MBT-A) reduces repetition of SH at post-intervention as compared to TAU (OR 0.70, 95% CI 0.06 to 8.46; N = 85; k = 2; very low-certainty evidence). Heterogeneity for this outcome was substantial ( I² = 68%). There is probably no evidence of a difference between family therapy and either TAU or EUC on repetition of SH at post-intervention (OR 1.00, 95% CI 0.49 to 2.07; N = 191; k = 2; moderate-certainty evidence). However, there was no evidence of a difference for compliance enhancement approaches on repetition of SH by the six-month follow-up assessment, for group-based psychotherapy at the six- or 12-month follow-up assessments, for a remote contact intervention (emergency cards) at the 12-month assessment, or for therapeutic assessment at the 12- or 24-month follow-up assessments.
AUTHORS' CONCLUSIONS
Given the moderate or very low quality of the available evidence, and the small number of trials identified, there is only uncertain evidence regarding a number of psychosocial interventions in children and adolescents who engage in SH. Further evaluation of DBT-A is warranted. Given the evidence for its benefit in adults who engage in SH, individual CBT-based psychotherapy should also be further developed and evaluated in children and adolescents.
Topics: Adolescent; Bias; Child; Cognitive Behavioral Therapy; Confidence Intervals; Depression; Dialectical Behavior Therapy; Family Therapy; Female; Humans; Male; Mentalization; Odds Ratio; Patient Compliance; Psychosocial Intervention; Psychotherapy; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Self-Injurious Behavior; Suicidal Ideation; Treatment Outcome
PubMed: 33677832
DOI: 10.1002/14651858.CD013667.pub2 -
Journal of Neurology Dec 2019The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to... (Meta-Analysis)
Meta-Analysis
The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to identify the most appropriate management strategies. In this review, possible pathogenetic mechanisms are also discussed. A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. 87 articles were included in this review, 29 case-control studies, 52 prospective/retrospective cohort studies and 2 randomised control trials, 1 cross sectional study, and 3 population-based studies. The prevalence of peripheral neuropathy amongst chronic alcohol abusers is 46.3% (CI 35.7- 57.3%) when confirmed via nerve conduction studies. Alcohol-related peripheral neuropathy generally presents as a progressive, predominantly sensory axonal length-dependent neuropathy. The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. At present, it is unclear what the pathogenetic mechanisms for the development of neuropathy amongst those who chronically abuse alcohol are, and therefore, it is unknown whether it is attributed to the direct toxic effects of ethanol or another currently unidentified factor. There is presently sparse data to support a particular management strategy in alcohol-related peripheral neuropathy, but the limited data available appears to support the use of vitamin supplementation, particularly of B-vitamin regimens inclusive of thiamine.
Topics: Alcoholic Neuropathy; Humans; Peripheral Nervous System Diseases
PubMed: 30467601
DOI: 10.1007/s00415-018-9123-1 -
JAMA Psychiatry Sep 2021Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.
OBJECTIVE
To estimate the association of time receiving OAT with mortality.
DATA SOURCES
The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.
STUDY SELECTION
All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included.
DATA EXTRACTION AND SYNTHESIS
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses.
MAIN OUTCOMES AND MEASURES
Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically.
RESULTS
Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.
Topics: Analgesics, Opioid; Cause of Death; Humans; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34076676
DOI: 10.1001/jamapsychiatry.2021.0976 -
The Lancet. Psychiatry Apr 2020Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 188 million people use cannabis yearly worldwide, and it has recently been legalised in 11 US states, Canada, and Uruguay for recreational use. The potential for increased cannabis use highlights the need to better understand its risks, including the acute induction of psychotic and other psychiatric symptoms. We aimed to investigate the effect of the cannabis constituent Δ-tetrahydrocannabinol (THC) alone and in combination with cannabidiol (CBD) compared with placebo on psychiatric symptoms in healthy people.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published in English between database inception and May 21, 2019, with a within-person, crossover design. Inclusion criteria were studies reporting symptoms using psychiatric scales (the Brief Psychiatric Rating Scale [BPRS] and the Positive and Negative Syndrome Scale [PANSS]) following the acute administration of intravenous, oral, or nasal THC, CBD, and placebo in healthy participants, and presenting data that allowed calculation of standardised mean change (SMC) scores for positive (including delusions and hallucinations), negative (such as blunted affect and amotivation), and general (including depression and anxiety) symptoms. We did a random-effects meta-analysis to assess the main outcomes of the effect sizes for total, positive, and negative PANSS and BPRS scores measured in healthy participants following THC administration versus placebo. Because the number of studies to do a meta-analysis on CBD's moderating effects was insufficient, this outcome was only systematically reviewed. This study is registered with PROSPERO, CRD42019136674.
FINDINGS
15 eligible studies involving the acute administration of THC and four studies on CBD plus THC administration were identified. Compared with placebo, THC significantly increased total symptom severity with a large effect size (assessed in nine studies, with ten independent samples, involving 196 participants: SMC 1·10 [95% CI 0·92-1·28], p<0·0001); positive symptom severity (assessed in 14 studies, with 15 independent samples, involving 324 participants: SMC 0·91 [95% CI 0·68-1·14], p<0·0001); and negative symptom severity with a large effect size (assessed in 12 studies, with 13 independent samples, involving 267 participants: SMC 0·78 [95% CI 0·59-0·97], p<0·0001). In the systematic review, of the four studies evaluating CBD's effects on THC-induced symptoms, only one identified a significant reduction in symptoms.
INTERPRETATION
A single THC administration induces psychotic, negative, and other psychiatric symptoms with large effect sizes. There is no consistent evidence that CBD induces symptoms or moderates the effects of THC. These findings highlight the potential risks associated with the use of cannabis and other cannabinoids that contain THC for recreational or therapeutic purposes.
FUNDING
UK Medical Research Council, Maudsley Charity, Brain and Behavior Research Foundation, Wellcome Trust, and the UK National Institute for Health Research.
Topics: Administration, Inhalation; Cannabidiol; Dronabinol; Drug Combinations; Drug Interactions; Hallucinogens; Humans; Marijuana Smoking; Psychoses, Substance-Induced
PubMed: 32197092
DOI: 10.1016/S2215-0366(20)30074-2