BACKGROUND: Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia.
OBJECTIVES: To determine the efficacy and safety of cannabinoids for the treatment of dementia.
SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates.
MAIN RESULTS: We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains. The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants). We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis. There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness.
AUTHORS' CONCLUSIONS: Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.
Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.
Cannabis and its pharmacologically active constituents, phytocannabinoids, have long been reported to have multiple medicinal benefits. One association often reported by users is sedation and subjective improvements in sleep. To further examine this association, we conducted a critical review of clinical studies examining the effects of cannabinoids on subjective and objective measures of sleep. PubMED, Web of Science, and Google Scholar were searched using terms and synonyms related to cannabinoids and sleep. Articles chosen included randomized controlled trials and open label studies. The Cochrane risk of bias tool was used to assess the quality of trials that compared cannabinoids with control interventions. The current literature focuses mostly on the use of tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in the treatment of chronic health conditions such as multiple sclerosis, posttraumatic stress disorder (PTSD), and chronic pain. Sleep is often a secondary, rather than primary outcome in these studies. Many of the reviewed studies suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease sleep onset latency. While many of the studies did show a positive effect on sleep, there are many limiting factors such as small sample sizes, examining sleep as a secondary outcome in the context of another illness, and relatively few studies using validated subjective or objective measurements. This review also identified several questions that should be addressed in future research. These questions include further elucidation of the dichotomy between the effects of THC and CBD, as well as identifying any long-term adverse effects of medicinal cannabinoid use. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients.
METHODS: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics 'Cannabis', 'Synthetic Cannabinoids', 'PTSD', and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD.
RESULTS: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep.
CONCLUSIONS: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.
This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 randomised controlled trials (RCTs) and 57 observational studies. Forty-eight studies examined neuropathic pain, 7 studies examined fibromyalgia, 1 rheumatoid arthritis, and 48 other CNCP (13 multiple sclerosis–related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, pooled event rates (PERs) for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo); significant effect for cannabinoids was found; number needed to treat to benefit was 24 (95% confidence interval [CI] 15-61); for 50% reduction in pain, PERs were 18.2% vs 14.4%; no significant difference was observed. Pooled change in pain intensity (standardised mean difference: −0.14, 95% CI −0.20 to −0.08) was equivalent to a 3 mm reduction on a 100 mm visual analogue scale greater than placebo groups. In RCTs, PERs for all-cause adverse events were 81.2% vs 66.2%; number needed to treat to harm: 6 (95% CI 5-8). There were no significant impacts on physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
INTRODUCTION: The incidence of posttraumatic stress disorder (PTSD) is common within the population and even more so among veterans. Current medication treatment is limited primarily to antidepressants. Such medicines have shown to produce low remission rates and may require 9 patients to be treated for 1 to have a response. Aside from the Veterans Affairs/Department of Defense guidelines, other guidelines do not recommend pharmacotherapy as a first-line option, particularly in the veteran population. Marijuana has been evaluated as an alternative and novel treatment option with 16 states legalizing its use for PTSD.
METHODS: A systematic search was conducted to evaluate the evidence for the use of marijuana for PTSD. Studies for the review were included based on a literature search from Ovid MEDLINE and Google Scholar.
RESULTS: Five studies were identified that evaluated the use of marijuana for PTSD. One trial was conducted in Israel and actively used marijuana. Three studies did not use marijuana in the treatment arm but instead evaluated the effects postuse. A retrospective chart review from New Mexico relied on patients to recall their change in PTSD symptoms when using marijuana. Three studies concluded there might be a benefit, but two discouraged its use. Although the two negative studies show a statistical difference in worse PTSD outcomes, clinical significance is unclear.
DISCUSSION: Conflicting data exist for the use of marijuana for PTSD; however, current evidence is limited to anecdotal experiences, case reports, and observational studies, making it difficult to make clinical recommendations.
We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD] 0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65), appetite (SMD 0.81 95% CI: [-1.14, 2.75]; P = 0.42), nausea/vomiting (SMD 0.21 [-0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07), or sleep problems (SMD -0.09 95% CI: [-0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD 0.20 [-0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.
