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Cureus Jul 2020Marijuana is one of the most abused substances in the world. Marijuana is getting legalized around the world. So, it is crucial to understand its effect on our mental... (Review)
Review
Marijuana is one of the most abused substances in the world. Marijuana is getting legalized around the world. So, it is crucial to understand its effect on our mental health. Its impact on the schizophrenia spectrum needs our special attention. Even though marijuana has been around for a long time, its exact effects are still unknown. Schizophrenia is a chronic illness affecting approximately 20 million people worldwide. Schizophrenia and cannabis seem to have a close relationship, and we want to explore this. We want to know if marijuana is causing, exacerbating, or treating schizophrenia. This systematic review explores this question. We searched online resources like PubMed, PubMed Central, Cochrane Library, and Google Scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on cannabis and schizophrenia/ psychosis. We included human studies published in peer-reviewed journals in the English language in the last five years. After reviewing 96 initial results of our search, we excluded 25 duplicates, 29 abstracts, and 18 irrelevant articles. We did a quality assessment for the remaining 24 studies using various quality assessment tools. After the quality assessment, we found 12 articles were of low quality and excluded those. We included the remaining 12 final studies in our systematic review. Out of these 12 studies, five were traditional reviews, two systematic reviews, two meta-analysis, and three observational studies. Six of the articles were on cannabis's effect on just schizophrenia or psychotic disorder. The other six included schizophrenia plus other psychiatric or neurological illnesses. Ten of the studies had data supporting the causative link between cannabis and schizophrenia. Eight records had data supporting the exacerbating effect of marijuana. Six studies had data supporting the therapeutic effect of the cannabidiol (CBD) component of cannabis. From the current data, we can conclude that the tetrahydrocannabinol (THC) component of cannabis can be the main culprit causing psychosis and schizophrenia in the at-risk population. THC can also be the one exacerbating symptoms and causing an adverse prognosis in already diagnosed patients. Even though CBD shows therapeutic effects and THC opposing effects, the data is minimal and low safety and efficacy warrants more research. The relation between cannabis and schizophrenia needs further investigation. We need more case-control studies and clinical trials with a larger population to get conclusive data.
PubMed: 32839678
DOI: 10.7759/cureus.9309 -
BMJ Supportive & Palliative Care Mar 2020There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the beneficial and adverse effects of cannabis/cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults.
METHODS
Systematic review and meta-analysis to identify randomised controlled trials of cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults to determine the effect on pain intensity (primary outcome) and adverse effects, including dropouts. Searches included Embase, MEDLINE, PsycINFO, Web of Science, ClinicalTrials.gov, Cochrane and grey literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
We identified 2805 unique records, of which six randomised controlled trials were included in this systematic review (n=1460 participants). Five studies were included in the meta-analysis (1442 participants). All had a low risk of bias. There was no difference between cannabinoids and placebo for the difference in the change in average Numeric Rating Scale pain scores (mean difference -0.21 (-0.48 to 0.07, p=0.14)); this remained when only phase III studies were meta-analysed: mean difference -0.02 (-0.21 to 0.16, p=0.80). Cannabinoids had a higher risk of adverse events when compared with placebo, especially somnolence (OR 2.69 (1.54 to 4.71), p<0.001) and dizziness (OR 1.58 (0.99 to 2.51), p=0.05). No treatment-related deaths were reported. Dropouts and mortality rates were high.
CONCLUSIONS
Studies with a low risk of bias showed that for adults with advanced cancer, the addition of cannabinoids to opioids did not reduce cancer pain.
TRIAL REGISTRATION NUMBER
CRD42018107662.
Topics: Adult; Cancer Pain; Cannabinoids; Female; Humans; Male; Medical Marijuana; Middle Aged; Pain Management
PubMed: 31959586
DOI: 10.1136/bmjspcare-2019-002032 -
Pharmacotherapy Jun 2017Cannabinoid hyperemesis syndrome (CHS) has become more prevalent with increasing cannabis use. CHS is often resistant to standard antiemetics. The objective of this... (Review)
Review
Cannabinoid hyperemesis syndrome (CHS) has become more prevalent with increasing cannabis use. CHS is often resistant to standard antiemetics. The objective of this study is to review the current evidence for pharmacologic treatment of CHS. Medline, PsycINFO, DARE, OpenGrey, Google Scholar, and the Cochrane Library were searched from inception to February 2017. Articles were selected and reviewed independently. Evidence was graded using Oxford Center for Evidence-Based Medicine guidelines. The search resulted in 1262 articles with 63 of them eligible for inclusion (205 human subjects). There were 4 prospective level-2, 3 retrospective level-3 studies, 12 level-4 case series, and 44 level-5 case reports. Among level-2 studies (64 subjects), tricyclic antidepressants (TCAs) and lorazepam were discussed as effective long- and short-term treatments, respectively, in two studies. Ondansetron, promethazine, diphenhydramine, and opioids were also mentioned, but the authors did not comment on their efficacy. Among level-3 studies (43 subjects), one reported effective treatment with antiepileptics zonisamide and levetiracetam, but not TCAs. Another reported favorable response to morphine, ondansetron, and lorazepam but did not specify the actual number of patients receiving specific treatment. Among the level-4 case series (54 subjects), benzodiazepines, haloperidol, and capsaicin were reported as helpful. For level-5 case reports (44 subjects), benzodiazepines, metoclopramide, haloperidol, ondansetron, morphine, and capsaicin were reported as effective. Effective treatments mentioned only once included fentanyl, diazepam, promethazine, methadone, nabilone, levomepromazine, piritramide, and pantoprazole. Hot showers and baths were cited in all level-4 and -5 articles as universally effective. High-quality evidence for pharmacologic treatment of CHS is limited. Benzodiazepines, followed by haloperidol and capsaicin, were most frequently reported as effective for acute treatment, and TCAs for long-term treatment. As the prevalence of CHS increases, future prospective trials are greatly needed to evaluate and further define optimal pharmacologic treatment of patients with CHS.
Topics: Antiemetics; Benzodiazepines; Cannabinoids; Clinical Trials as Topic; Humans; Ondansetron; Treatment Outcome; Vomiting
PubMed: 28370228
DOI: 10.1002/phar.1931 -
Pain Jul 2021This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and... (Meta-Analysis)
Meta-Analysis
This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to identify important directions for future research. In service of these goals, this review (1) provides an overview of the endocannabinoid system and the pharmacology of cannabinoids and endocannabinoid system modulators, with specific relevance to animal models of pathological or injury-related persistent pain; (2) describes pharmacokinetics of cannabinoids in rodents and humans; and (3) highlights differences and discrepancies between preclinical and clinical studies in this area. Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.
Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Endocannabinoids; Pain; Pain Management; Receptors, Cannabinoid
PubMed: 33729211
DOI: 10.1097/j.pain.0000000000002268 -
Journal of Psychiatric Research Jan 2023Treatments for Adult ADHD include stimulants, two non-stimulant medications, as well as cognitive-behavioral therapy (CBT). These pharmacological agents are often... (Review)
Review
INTRODUCTION
Treatments for Adult ADHD include stimulants, two non-stimulant medications, as well as cognitive-behavioral therapy (CBT). These pharmacological agents are often associated with side effects, contributing to poor treatment adherence. Patients with ADHD have regularly stated that cannabis has helped improve their ADHD symptoms; however, scientific literature describing the effects of cannabis on symptoms of ADHD is scarce.
METHODS
We systematically searched MEDLINE, EMBASE, EMCARE, PsycINFO, Web of Science, Cochrane Library, and Clinicaltrials.gov. The searches included all publications in English up to June 27, 2022. We included both experimental and observational studies that assessed the effect of cannabis on ADHD symptomatology and neuropsychiatric outcomes. To synthesize our current understanding of the potential effects of cannabis use on ADHD symptoms and pathophysiology, and the effects of ADHD on cannabis use, data was extracted from each study regarding the characteristics of its population, methods used to assess both cannabis consumption and ADHD symptoms, and key findings.
RESULTS
Our scoping review included a total of 39 studies. Only one study employed a randomized and placebo-controlled design to directly measure the effect of cannabis on ADHD, and no significant effect was observed for the study's primary outcome, the QbTest (Est = -0.17, 95% CI -0.40 to 0.07, p = 0.16). Most of the literature consists of cross-sectional studies that evaluate the association between ADHD severity and cannabis use. 15 studies addressed the neuropsychiatric effects of cannabis on ADHD by employing either a battery of neuropsychiatric tests or neuroimaging. The concentration and amount of THC and CBD used were not well measured in most of the studies. Although some studies indicated that cannabis improved ADHD symptoms, most studies indicated it worsened or had no effect on ADHD symptoms.
CONCLUSIONS
Given the current evidence, cannabis is not recommended for people with ADHD. Limitations of the literature include the absence of objective measurements for cannabis exposure and ADHD symptoms, heterogenous definitions, oversampling, and small sample sizes.
Topics: Adult; Humans; Attention Deficit Disorder with Hyperactivity; Cannabis; Cross-Sectional Studies; Central Nervous System Stimulants; Hallucinogens; Attention; Randomized Controlled Trials as Topic
PubMed: 36508935
DOI: 10.1016/j.jpsychires.2022.11.029 -
Canadian Journal of Psychiatry. Revue... May 2023Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on... (Review)
Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.
BACKGROUND
Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders.
OBJECTIVE
The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder.
METHODS
We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations.
RESULTS
Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results.
CONCLUSION
The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Cannabis; Marijuana Abuse; Canada; Anxiety; Substance-Related Disorders
PubMed: 35711159
DOI: 10.1177/07067437221099769 -
Neurotoxicology Sep 2019Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different... (Review)
Review
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different activity compared with the psychotomimetic THC. Most typically, CBD is reported to be used in some medical conditions, including chronic pain. Conversely, the main aim of this systematic review is to assess and summarise the available body of evidence relating to both efficacy and safety of CBD as a treatment for psychiatric disorders, alone and/or in combination with other treatments. Eligible studies included randomized controlled trials (RCT) assessing the effect of CBD in a range of psychopathological conditions, such as substance use; psychosis, anxiety, mood disturbances, and other psychiatric (e.g., cognitive impairment; sleep; personality; eating; obsessive-compulsive; post-traumatic stress/PTSD; dissociative; and somatic) disorders. For data gathering purposes, the PRISMA guidelines were followed. The initial search strategy identified some n = 1301 papers; n = 190 studies were included after the abstract's screening and n = 27 articles met the inclusion criteria. There is currently limited evidence regarding the safety and efficacy of CBD for the treatment of psychiatric disorders. However, available trials reported potential therapeutic effects for specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Further large-scale RCTs are required to better evaluate the efficacy of CBD in both acute and chronic illnesses, special categories, as well as to exclude any possible abuse liability.
Topics: Anxiety; Cannabidiol; Humans; Mental Disorders; Randomized Controlled Trials as Topic
PubMed: 31412258
DOI: 10.1016/j.neuro.2019.08.002 -
BMJ Open Aug 2022To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020.
STUDY SELECTION
Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up.
DATA EXTRACTION AND SYNTHESIS
A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence.
RESULTS
We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up (test for interaction p<0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared with other pain management options, such as opioids.
CONCLUSIONS
There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events.
Topics: Adult; Analgesics, Opioid; Cannabinoids; Child; Chronic Pain; Humans; Medical Marijuana
PubMed: 35926992
DOI: 10.1136/bmjopen-2021-054282 -
Frontiers in Pharmacology 2020Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a... (Review)
Review
Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of . One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD's therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.
PubMed: 33551817
DOI: 10.3389/fphar.2020.618184 -
Pharmacology, Biochemistry, and Behavior Sep 2023Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications.... (Review)
Review
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.
Topics: Humans; Cannabidiol; Cannabinoids; Cannabis; Hallucinogens; Attention Deficit Disorder with Hyperactivity; Dronabinol; Randomized Controlled Trials as Topic
PubMed: 37543051
DOI: 10.1016/j.pbb.2023.173607