Efficacy Of Cannabinoids Research Articles

Cannabis as medicine, aura and valebo - a new perspective on self-medication and medical support for chronic diseases

It is known from medical practise that patients and physicians can have positive experiences with little-researched and unapproved interventions. Under certain circumstances, effects even go beyond the placebo effect. Based on casuistics of chronic pain patients, the question of whether self-medication in the context of a good doctor-patient relationship can optimize the efficacy of cannabinoids and reduce dose and undesirable side effects is investigated. Using medicinal cannabis as an example, a new view on self-medication and medical support is proposed. The casuistics show that daily requirements (average of approximately 75 mg) for Δ9tetrahydocannabinol (THC) doses can be reduced. An unaccompanied and risky self-medication can be transformed into an effective therapy with significantly less medical cannabis. The approach consists of tracing the self-medication that has taken place to date and picking up the patient where he has "discovered" something for himself. The specific mode of action of cannabis in chronic diseases can be explained by mechanisms in the endocannabinoid system. Cannabinoids relieve patients in the context of stress, anxiety and depression, which are always involved in chronic diseases. In their physical as well as psychological sensations, patients are strengthened and eventually guided into self-efficacy. If the patient has "discovered" cannabis as medicine for himself and can draw on positive experiences, something very powerful can emerge. In addition to the specific effects demonstrated by studies, there are non-specific effects or contextual factors at work that tend to be neglected in evidence-based medicine. These non-specific effects include, above all, those factors through which a patient gives a (subjective) meaning to a specific intervention. A new view on self-medication and medical support in chronic diseases is needed.

Cannabinoids and Psychedelics for Neuropsychiatric Symptoms of Alzheimer's: Addressing Disparities Through Clinical Trials

AD and other forms of dementia are commonly associated with neuropsychiatric symptoms, including anxiety, agitation, and depression, all of which can lead to more rapid cognitive decline and a poor quality of life for both caregivers and patients.There are currently no FDA approved medications to treat neuropsychiatric symptoms associated with dementia. Instead, current treatment options include off-label use of psychotropic medications that are associated with well-established risks. Alternative therapeutic options include cannabinoids and psychedelics. This session will focus on discussing the safety and efficacy of cannabinoids in treating anxiety and agitation associated with Alzheimer's dementia, as well as the safety and efficacy of psychedelics in treating depression in older adults with dementia.The history of medicinal cannabis use dates back as far as 4000BC. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, activates cannabinoid receptors (mainly CB1 and CB2 receptors), producing anxiolytic and antidepressant effects while also reducing reduce brain inflammation. Cannabidiol (CBD), the major non-intoxicating component of cannabis, possesses low affinity to CB1 and CB2 receptors. CBD modulates systems outside of the endocannabinoid system, producing antioxidant and antipsychotic effects. Both THC and CBD have shown evidence of therapeutic effects on anxiety and pain. We will discuss three studies evaluating the use of cannabinoids as potential forms of treatment for agitation and anxiety in dementia.Psychedelics are also being introduced as potential mental health treatments. Past research has shown psychedelics can produce long-term anxiolytic and antidepressant effects after a single administration. A pilot trial at Johns Hopkins is examining the safety and efficacy of psilocybin treatment for participants with mild cognitive impairment (MCI) and depressive symptoms. The study hypothesizes that the psilocybin treatment will be associated with a significant reduction in depressive symptoms.Overall, these trials collectively guide research towards furthering our understanding of the pathology of Alzheimer's dementia and other forms of dementia and improving the quality of life for older adults and their caregivers.

Cannabis in Parkinson's Disease - the patient's perspective versus clinical trials: a systematic literature review.

Cannabis and cannabinoids are often considered in the treatment of Parkinson's Disease (PD). The purpose of this paper was to perform a systematic review of the available data on cannabis treatment. We aimed to assess randomised trials as well as surveys among patients. We identified 569 papers on PD and cannabinoid treatment. Of these, there were only seven papers featuring randomised trials on the effects of different cannabinoids on PD. The results of these trials did not support the efficacy of cannabinoids in the treatment of motor signs of PD. Based on the available data, we conclude that there is currently insufficient data to support the administration of cannabinoids to PD patients. Larger, randomised studies of cannabis use in PD should be conducted.

Dorsal Column Stimulation and Cannabinoids in the Treatment of Chronic Nociceptive and Neuropathic Pain: a Review of the Clinical and Pre-clinical Data.

The main objective of this review is to appraise the literature on the role of spinal cord stimulation (SCS), cannabinoid therapy, as well as SCS and cannabinoid combination therapy for the management of chronic neuropathic and nociceptive pain. Current research suggests that SCS reduces pain and increases functional status in carefully selected patients with minimal side effects. As cannabinoid-based medications become a topic of increasing interest in pain management, data remains limited regarding the clinical efficacy of cannabinoids for pain relief. Furthermore, from a mechanistic perspective, although various pain treatment modalities utilize overlapping pain-signaling pathways, clarifying whether cannabinoids work synergistically with SCS via shared mechanisms remains to be determined. In considering secondary outcomes, the current literature suggests cannabinoids improve quality of life, specifically sleep quality, and that SCS decreases opioid consumption, increases functional capacity, and decreases long-term healthcare costs. These findings, along with the high safety profiles of SCS and cannabinoids overall, incentivize further exploration of cannabinoids as an adjunctive therapy to SCS in the treatment of neuropathic and nociceptive pain.

The Use of Cannabinoids for Insomnia in Daily Life: Naturalistic Study.

BackgroundInsomnia is a prevalent condition that presents itself at both the symptom and diagnostic levels. Although insomnia is one of the main reasons individuals seek medicinal cannabis, little is known about the profile of cannabinoid use or the perceived benefit of the use of cannabinoids in daily life.ObjectiveWe conducted a retrospective study of medicinal cannabis users to investigate the use profile and perceived efficacy of cannabinoids for the management of insomnia.MethodsData were collected using the Strainprint app, which allows medicinal cannabis users to log conditions and symptoms, track cannabis use, and monitor symptom severity pre- and postcannabis use. Our analyses examined 991 medicinal cannabis users with insomnia across 24,189 tracked cannabis use sessions. Sessions were analyzed, and both descriptive statistics and linear mixed-effects modeling were completed to examine use patterns and perceived efficacy.ResultsOverall, cannabinoids were perceived to be efficacious across all genders and ages, and no significant differences were found among product forms, ingestion methods, or gender groups. Although all strain categories were perceived as efficacious, predominant indica strains were found to reduce insomnia symptomology more than cannabidiol (CBD) strains (estimated mean difference 0.59, SE 0.11; 95% CI 0.36-0.81; adjusted P<.001) and predominant sativa strains (estimated mean difference 0.74, SE 0.16; 95% CI 0.43-1.06; adjusted P<.001). Indica hybrid strains also presented a greater reduction in insomnia symptomology than CBD strains (mean difference 0.52, SE 0.12; 95% CI 0.29-0.74; adjusted P<.001) and predominant sativa strains (mean difference 0.67, SE 0.16; 95% CI 0.34-1.00; adjusted P=.002).ConclusionsMedicinal cannabis users perceive a significant improvement in insomnia with cannabinoid use, and this study suggests a possible advantage with the use of predominant indica strains compared with predominant sativa strains and exclusively CBD in this population. This study emphasizes the need for randomized placebo-controlled trials assessing the efficacy and safety profile of cannabinoids for the treatment of insomnia.

Cannabinoids in the Treatment of Epilepsy: A Review

Cannabinoids have been studied for their role in the treatment of epilepsy for many years. The U.S. Food and Drug Administration (FDA) approved them for the treatment of some refractory syndromes in 2018. Cannabidiol and tetrahydrocannabinol are the most commonly studied cannabinoids and have been studied in great depth vis-à-vis their pharmacokinetics and pharmacodynamics. Studies have shown the efficacy of cannabinoids in the treatment of refractory epilepsy. A substantial amount of research has been performed exploring the interactions between cannabinoids and other conventional antiseizure medications. The exact mechanisms by which cannabinoids exert their effects on seizure control remain unclear and research into these mechanisms continues in great earnest. Cognitive changes from cannabinoids are constantly being studied and add to potential benefits from the use of these compounds. Cultural and social misconceptions and roadblocks about the use of cannabinoids persist and represent an ongoing obstacle to increasing research and therapeutic use of these compounds. This review focuses on all these aspects and of the use of these cannabinoids in the treatment of epilepsy and seeks to offer a fairly comprehensive description of the facets of cannabinoid therapy for refractory epilepsy.

Cannabinoids efficacy in vanishing white matter disease: A case report

An oromucosal spray formulation (Sativex®) containing delta-9-tetrahydrocannabinol and cannabidiol (THC-CBD) is indicated to treat unresponsive severe spasticity in Multiple Sclerosis. A lot of clinical trials are underway demonstrating a potential role as supplemental therapy in various neurological conditions, in particular addressing pain and spasticity in adults and children.

Medical Cannabis in Palliative Psychiatry: Clinical Aspects of Affective Regulation and Legal Challenges

Millions of Americans use cannabis for medical purposes including but not limited to pain, nausea, mood changes and appetite stimulation. The use of cannabinoid in the palliative care setting is a relatively new trend. Given the fact that a patient receiving palliative care is not necessarily approaching death, the increasing need for palliative care as the American population ages, this literature review was compiled in order to examine the potential efficacy of cannabis in treating the mental health comorbidities of palliative care patients. We attempted to create the most comprehensive report on cannabinoid use in palliative psychiatry. It summarizes the most recently published science on cannabinoid use in palliative care patients and its impact on mood and anxiety symptoms. The mechanism of action of cannabinoids on their associated receptors was elucidated, as were the pharmacological roles that specific molecules in cannabinoids, like cannabidiolic acid and terpenes, play in cannabinoids’ overall efficacy. The legal impediments to widespread cannabis use were also explored. While the potential efficacy of cannabinoids has proven to be mixed, more research is necessary to ensure that a potentially vital resource in treating palliative care patients does not go underutilized.

P12.07 The potential of cannabinoids to improve quality of life in glioma patients: A meta-analysis in patients with neurological and oncological disease

Abstract BACKGROUND Gliomas are primary brain tumors with a dismal prognosis. Reducing symptoms and maintaining quality of life (QoL) are main treatment aims in glioma patients. Mental well-being is an important subdomain of QoL. Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety or depression. Glioma patients frequently report unprescribed cannabinoid use for these reasons. We performed a meta-analysis of the current evidence on cannabinoid efficacy on QoL and mental well-being to identify its added value in treatment of glioma patients. MATERIAL AND METHODS We performed a systematic PubMed, Embase and Web of Science search according to the PRISMA guidelines on September 22nd and 23rd, 2020. The effects of any dose of tetrahydrocannabinol (THC) or cannabidiol (CBD) on both general QoL and mental well-being were evaluated. The intervention had to be given for at least a week to establish a steady-state concentration. Effect size was calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane’s Risk of Bias tool 2.0. RESULTS We retrieved no publications on cannabinoids use and QoL in glioma and, therefore, we expanded the search to cannabinoid use in other cancer types and chronic central nervous system (CNS) diseases. Sixteen studies were identified: four in cancer and twelve in CNS disease. Meta-analysis showed no effect of cannabinoids on general QoL (twelve studies in 1,740 patients; g = -0.02, 95% CI -0.11 to 0.07, p = 0.65) and mental well-being (twelve studies in 1,587 patients; g = -0.00, 95% CI -0.15 to 0.14, p = 0.96). Risk of bias was low in five studies, raised some concern in one study and was high in ten studies, mainly due to possible unblinding of patients after psychoactive adverse effects. CONCLUSION No studies on the effects of cannabinoids on QoL in glioma patients have been reported. A pooled analysis of studies in oncological patients and patients with CNS disease showed no effect of cannabinoids on QoL or mental well-being. However, studies were clinically heterogeneous and only one small study investigated monotherapy CBD with undecided results. As many glioma patients currently use cannabinoids, and monotherapy CBD has not been sufficiently investigated, future studies are necessary to evaluate its value in this specific population. SUPPORT/DISCLOSURE This meta-analysis has been funded by The Anita Veldman Foundation (CCA-2019-2-21).

Efficacy of Cannabinoids on Spasticity and Chronic Pain in a Patient with Co-occurrence of Multiple Sclerosis and Neurofibromatosis Type 1.

Chronic pain is a possible complication of several neurological conditions and may show a poor response to standard drugs, thus affecting quality of life.Oromucosal cannabinoid sprays are routinely used in multiple sclerosis spasticity.Cannabinoids may be also effective against neurogenic pain in neurofibromatosis type 1.

Efficacy of cannabinoids in fibromyalgia: a literature review

Fibromyalgia is a chronic disease of unclear etiology, involving a neural oversensitization and impaired pain modulation, in addition to a clinical deficiency of the endocannabinoid system. Fibromyalgia is associated with a number of somatic and psychological disorders and hence multiple pharmacological approaches have been used, including opioids, antidepressants, antiepileptics, and more recently medical cannabis. This narrative review comprises a review of the current literature on the efficacy of cannabinoids in fibromyalgia. The studies describe a possible influence of cannabis on pain control in patients with fibromyalgia, with positive effects on quality of life and sleep. The use of cannabis seems to be beneficial in patients with fibromyalgia; however, more robust studies are still needed to establish is actual efficacy in pain management, quality of life and improvement of associated symptoms.

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

Synthetic Cannabinoids Induce Autophagy and Mitochondrial Apoptotic Pathways in Human Glioblastoma Cells Independently of Deficiency in TP53 or PTEN Tumor Suppressors.

Simple SummaryGlioblastomas (GBMs) are aggressive brain tumors with frequent genetic defects in TP53 and PTEN tumor suppressor genes, which render tumors refractory to standard chemotherapeutics. Natural and synthetic cannabinoids showed antitumor activity in glioma cells and animal glioma models. Due to differences in the expression of cannabinoid type 2 receptors (CB2), which are abundant in GBMs but absent from a healthy brain, we tested synthetic cannabinoids for their ability to kill numerous glioma cells. We performed multiple biochemical analyses to determine which cell death pathways are activated in human glioma cells. We demonstrate high susceptibility of human glioblastoma cells to synthetic cannabinoids, despite genetic defects contributing to apoptosis resistance, which makes cannabinoids promising anti-glioma therapeutics.Glioblastomas (GBMs) are aggressive brain tumors with frequent genetic alterations in TP53 and PTEN tumor suppressor genes rendering resistance to standard chemotherapeutics. Cannabinoid type 1 and 2 (CB1/CB2) receptor expression in GBMs and antitumor activity of cannabinoids in glioma cells and animal models, raised promises for a targeted treatment of these tumors. The susceptibility of human glioma cells to CB2-agonists and their mechanism of action are not fully elucidated. We determined CB1 and CB2 expression in 14 low-grade and 21 high-grade tumor biopsies, GBM-derived primary cultures and established cell lines. The non-selective CB receptor agonist WIN55,212-2 (but not its inactive enantiomer) or the CB2-selective agonist JWH133 induced apoptosis in patient-derived glioma cultures and five established glioma cell lines despite p53 and/or PTEN deficiency. Growth inhibitory efficacy of cannabinoids correlated with CB1/CB2 expression (EC50 WIN55,212-2: 7.36–15.70 µM, JWH133: 12.15–143.20 µM). Treatment with WIN55,212-2 or JWH133 led to activation of the apoptotic mitochondrial pathway and DNA fragmentation. Synthetic cannabinoid action was associated with the induction of autophagy and knockdown of autophagy genes augmented cannabinoid-induced apoptotic cell death. The high susceptibility of human glioblastoma cells to synthetic cannabinoids, despite genetic defects contributing to apoptosis resistance, makes cannabinoids promising anti-glioma therapeutics.

The effect of cannabidiol on canine neoplastic cell proliferation and mitogen-activated protein kinase activation during autophagy and apoptosis.

Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (eg, p38, JNK, AKT and mTOR) potentially involved in the response to treatment with CBD. CBD significantly reduced canine cancer cell proliferation far better than CBDA across five canine neoplastic cell lines when treated with concentrations ranging from 2.5 to 10μg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti-proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signalling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy. In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.

The Role of Cannabinoids as Anticancer Agents in Pediatric Oncology.

Simple SummaryThe endocannabinoid system (ECS) is a complex signaling pathway system involved in the regulation of multiple functions in both normal tissues and cancer. Δ9-tetrahydrocannabinol and cannabidiol are plant-derived cannabinoids that possess some efficacy against adult cancer, in part via modulation of the ECS, and may be less toxic agents compared to other treatments used in oncology. To date, there are minimal studies that have investigated these drugs in the pediatric cancer setting. Indeed, there are currently no preclinical or clinical studies examining the effects of cannabinoids in pediatric brain cancer, although there is some evidence that they can alleviate symptoms associated with childhood cancer therapy, such as vomiting and nausea. Given there is accumulating evidence that cannabis use during adolescence is associated with poor mental and cognitive health, there is a present and urgent need to investigate the safety and efficacy of cannabinoids in pediatric oncology to provide guidance to families and physicians.Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer. In recent years, the medical use of cannabis has been approved in different countries for a variety of human conditions. However, the use of these compounds, specifically as anticancer agents, remains controversial. Studies have shown that cannabinoids do have anticancer activity in different tumor types such as breast cancer, melanoma, lymphoma and adult brain cancer. Specifically, phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been shown to induce apoptosis and inhibit proliferation of adult cancer cells, as well as modulate angiogenesis and metastasis. Despite increasing evidence that cannabinoids elicit antitumor effects in adult cancers, there is minimal data available on their effects in children or in pediatric cancers despite public and clinical demand for information. Here we describe a comprehensive and critical review of what is known about the effects of cannabinoids on pediatric cancers, highlight current gaps in knowledge and identify the critical issues that need addressing before considering these promising but controversial drugs for use in pediatric oncology.

Pharmacotherapeutic Considerations for Use of Cannabinoids to Relieve Symptoms of Nausea and Vomiting Induced by Chemotherapy.

Patients suffering from malignant diseases receive very often highly emetogenic chemotherapy as part of their treatment.With the aim of assessing the efficacy of cannabinoids in treating chemotherapy-induced nausea and vomiting (CINV), we searched the literature published until April 2020 in Medline/PubMed, Embase, the Cochrane Controlled Trials Register, and in specific web pages. Randomized clinical trials comparing cannabinoids efficacy in managing CINV with that of placebo reported absence of vomit-ing (3 trials, 168 patients) and absence of nausea and vomiting (3 trials, 288 participants). In comparison with patients receiving other antiemetics, patients receiving cannabinoids reported no nausea (5 trials, 258 participants), no vomiting (4 trials, 209 participants), and absence of both (4 trials, 414 patients). Across all trials, cannabinoids were more effective in relieving the symptoms of nausea and vomiting induced by cytotoxic therapy than placebo was and slightly better than conventional antiemetics. A retrospective review com-paring nabilone, dronabinol, delta-9-THC, and delta 8-THC with other antiemetics used to manage CINV in pediatric patients showed that these drugs could also be used as adjuvant antiemetics. Cancer patients on highly emetogenic chemotherapy but with insufficiently effective standard antiemetic therapy can be given cannabis preparations containing similar amounts of tetrahydrocannabinol and can-nabidiol, which should be received in strict compliance with the professional guidelines for the treatment of CINV.

Successful Treatment of Super-Refractory Status Epilepticus With Cannabis Oil in a Patient With Neuronal Ceroid Lipofuscinosis

Herein we describe a case of a 25-year-old man diagnosed with the “variant late infantile-onset” neuronal ceroid lipofuscinosis (NCL) who has a novel mutation in the CLN6 gene located on chromosome 15. The patient developed seizures at the age of 10 years along with progressive symptoms of ataxia, spasticity, cognitive decline and visual difficulties. At the age of 25 years, the seizures were drug-resistant, and the patient was put in an anesthesia-induced coma until the use of cannabis oil in combination with Food and Drug Administration (FDA)-approved anti-seizure drugs proved to be lifesaving. Treatment for NCL currently consists of symptomatic relief of seizures, and supportive therapies for associated symptoms of behavior, language and visual difficulties. Although limited, recent data on the efficacy of cannabinoids for treatment-resistant epilepsy have been published. Since cannabis oil is not currently FDA approved for most formulations, its use in drug-resistant epilepsy is anecdotal and remains highly controversial. J Neurol Res. 2020;10(6):245-247 doi: https://doi.org/10.14740/jnr626

Cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis.

Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder. We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder. We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥18years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I2 statistic. A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤4weeks of follow-up (mean difference -1.89 [95% confidence interval {CI} -2.68 to -1.10]; n=176) and at 8 weeks of follow-up (mean difference -2.41 [95% CI -3.36 to -1.46]; n=166). One double-blind crossover RCT (n=32) reported that, compared with amitriptyline, nabilone-a synthetic analogue to tetrahydrocannabinol (THC)-improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference -3.25 [95% CI -5.26 to -1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01-0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n=9), THC reduced sleep-onset latency compared with placebo at 10mg, 20mg and 30mg doses (mean difference -43.00min [95% CI -82.76 to -3.24], -62.00 [95% CI -103.60 to -20.40] and -54.00 [95% CI -103.93 to -4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias. Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder. PROSPERO registration number, CRD42020161043.

Efficacy of cannabinoids for treating paediatric spasticity in cerebral palsy or traumatic brain injury: what is the evidence?

This commentary is on the original article by Fairhurst et al. on pages 1031–1039 of this issue.

Analgesic efficacy of cannabinoids for acute pain management after surgery: a systematic review and meta-analysis

BackgroundEvidence regarding the role of cannabinoids in managing acute postoperative pain is conflicting. The purpose of this systematic review and meta-analysis was to determine the analgesic efficacy of perioperative cannabinoid...