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The Journal of Urology Oct 2019With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility....
PURPOSE
With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility. We reviewed the literature regarding the effects of cannabis on male fertility.
MATERIALS AND METHODS
We performed a literature search using PubMed®/MEDLINE® to identify relevant studies of the effects of cannabis on male fertility. Relevant studies were identified and reviewed.
RESULTS
The strongest evidence of cannabis induced alterations in male fertility is in the category of semen parameters. Research supports a role for cannabis in reducing sperm count and concentration, inducing abnormalities in sperm morphology, reducing sperm motility and viability, and inhibiting capacitation and fertilizing capacity. Animal models demonstrate a role for cannabis in testicular atrophy, and reduced libido and sexual function but to our knowledge these results have not yet been replicated in human studies. Studies of hormonal changes suggest inconclusive effects on testosterone levels, lowered luteinizing hormone levels and unchanged follicle-stimulating hormone levels.
CONCLUSIONS
Current research suggests that cannabis may negatively impact male fertility. Further studies are needed to validate that robust findings in animal models will carry over into human experience. Clinicians should be aware of these potential effects when prescribing medical marijuana therapies to men of reproductive age, and they should consider the degree of cannabis use as a possible component of a complete male infertility workup.
Topics: Animals; Cell Survival; Disease Models, Animal; Fertility; Humans; Infertility, Male; Male; Medical Marijuana; Semen; Sperm Motility; Testis
PubMed: 30916627
DOI: 10.1097/JU.0000000000000248 -
Sleep Nov 2022As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers...
STUDY OBJECTIVES
As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers in their recommendations to patients, specifically focusing on dosing.
METHODS
We searched EMBASE, Medline, and Web of Science and identified 4550 studies for screening. Five hundred sixty-eight studies were selected for full-text review and 31 were included for analysis. Study results were considered positive based on improvements in sleep architecture or subjective sleep quality. Bias in randomized controlled trials was assessed using Cochrane Risk of Bias tool 2.0.
RESULTS
Sleep improvements were seen in 7 out of 19 randomized studies and in 7 out of 12 uncontrolled trials. There were no significant differences between the effects of tetrahydrocannabinol and cannabidiol. Cannabis showed most promise at improving sleep in patients with pain-related disorders, as compared to those with neurologic, psychiatric, or sleep disorders, and showed no significant effects on healthy participants' sleep. While subjective improvements in sleep quality were often observed, diagnostic testing showed no improvements in sleep architecture. Adverse events included headaches, sedation, and dizziness, and occurred more frequently at higher doses, though no serious adverse events were observed.
CONCLUSION
High-quality evidence to support cannabis use for sleep remains limited. Heterogeneity in cannabis types, doses, timing of administration, and sleep outcome measures limit the ability to make specific dosing recommendations.
Topics: Humans; Cannabis; Dronabinol; Cannabidiol; Cannabinoid Receptor Agonists; Sleep; Sleep Wake Disorders
PubMed: 36107800
DOI: 10.1093/sleep/zsac218 -
Obstetrics and Gynecology Feb 2022The endocannabinoid system is involved in pain perception and inflammation. Cannabis contains delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are...
OBJECTIVE
The endocannabinoid system is involved in pain perception and inflammation. Cannabis contains delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are cannabinoids that bind to endocannabinoid system receptors. A fatty acid amide called palmitoylethanolamide (PEA) enhances endogenous cannabinoids. Given that use of medical cannabis is increasing, we sought to characterize patterns of cannabis use for gynecologic pain and its effectiveness as an analgesic.
DATA SOURCES
We searched PubMed, EMBASE, Scopus, Cochrane, and ClinicalTrials.gov using terms for "woman," "cannabis," and "pain" or "pelvic pain" or "endometriosis" or "bladder pain" or "cancer." The search was restricted to English-language articles published between January 1990 and April 2021 and excluded animal studies.
METHODS OF STUDY SELECTION
The initial search yielded 5,189 articles with 3,822 unique citations. Studies were included if they evaluated nonpregnant adult women who used cannabinoids for gynecologic pain conditions (eg, chronic pelvic pain, vulvodynia, endometriosis, interstitial cystitis, malignancy). Study types included were randomized controlled trials (RCTs), cohort studies, and cross-sectional studies. Covidence systematic review software was used.
TABULATION, INTEGRATION, AND RESULTS
Fifty-nine studies were considered for full review, and 16 met inclusion criteria. Prevalence of cannabis use ranged from 13% to 27%. Most women ingested or inhaled cannabis and used cannabis multiple times per week, with dosages of THC and CBD up to 70 mg and 2,000 mg, respectively. Sixty-one to 95.5% reported pain relief. All six prospective cohort studies and one RCT of PEA-combination medications reported significant pain relief, and the average decrease in pain after 3 months of treatment was 3.35±1.39 on the 10-point visual analog scale. However, one fatty acid amide enzyme inhibitor RCT did not show pain reduction.
CONCLUSION
Survey data showed that most women reported that cannabis improved pain from numerous gynecologic conditions. Cohort studies and an RCT using PEA-combination medications reported pain reduction. However, interpretation of the studies is limited due to varying cannabis formulations, delivery methods, and dosages that preclude a definitive statement about cannabis for gynecologic pain relief.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42021248057.
Topics: Female; Genital Diseases, Female; Humans; Medical Marijuana; Pain Management
PubMed: 35104069
DOI: 10.1097/AOG.0000000000004656 -
Cannabis and Cannabinoid Research Oct 2023Parkinson's disease (PD) is a serious neurodegenerative condition impacting many individuals worldwide. There is a need for new non-invasive treatments of PD.... (Review)
Review
Parkinson's disease (PD) is a serious neurodegenerative condition impacting many individuals worldwide. There is a need for new non-invasive treatments of PD. Cannabinoids in the form of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) may offer utility as treatment, and our objective was hence to conduct a systematic review regarding the clinical evidence for the efficacy and safety of cannabinoids in treating PD. Screening, data extraction, and quality assessments were all conducted by multiple reviewers, with discrepancies resolved by consensus. After conducting searches in 4 different databases, 673 articles were screened. Thirteen articles were deemed eligible for inclusion in this review. It was shown that cannabis, CBD, and nabilone (a synthetic form of THC) were capable of consistently improving motor symptoms more than a placebo. All treatments improved various non-motor symptoms, particularly with cannabis improving pain intensity, and CBD improving psychiatric symptoms in a dose-dependent manner. Adverse effects were usually minor, and, in the case of CBD, rare (except at very high doses). Cannabinoids have been shown to safely offer important potential in treating motor symptoms in PD and some non-motor symptoms. More large-scale randomized control trials for specific forms of cannabinoid treatments are required to determine their overall efficacy.
Topics: Humans; Cannabinoids; Parkinson Disease; Cannabidiol; Cannabis; Drug-Related Side Effects and Adverse Reactions; Hallucinogens
PubMed: 37253174
DOI: 10.1089/can.2023.0023 -
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 -
Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
Animal Health Research Reviews Jun 2022Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize... (Review)
Review
Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis ( = 4), with epilepsy ( = 1), and with behavioral disorders ( = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg twice daily ( = 4), orally ( = 5), during 4 or 6 weeks ( = 3), and compared CBD with placebo ( = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis ( = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy ( = 1) and the aggressive behavior of dogs ( = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.
Topics: Animals; Cannabidiol; Cannabis; Dog Diseases; Dogs; Epilepsy; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 35703023
DOI: 10.1017/S1466252321000189 -
Pain Jul 2021Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised...
Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of <7 and >7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis <7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols >7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.
Topics: Analgesics; Cannabinoids; Cannabis; Chronic Pain; Humans
PubMed: 32804836
DOI: 10.1097/j.pain.0000000000001929 -
Pain Physician Sep 2017The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.
OBJECTIVES
This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.
STUDY DESIGN
A systematic review and meta-analysis.
METHODS
An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.
RESULTS
The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.
LIMITATIONS
Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.
CONCLUSIONS
The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.
Topics: Cannabidiol; Cannabis; Chronic Pain; Dronabinol; Drug Combinations; Humans; Medical Marijuana; Neuralgia; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28934780
DOI: No ID Found -
BMJ Open Jul 2021To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.
DESIGN
Systematic review.
DATA SOURCES
CENTRAL, EMBASE and MEDLINE.
MAIN OUTCOMES AND MEASURES
Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.
STUDY SELECTION CRITERIA AND METHODS
We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome.
RESULTS
Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) -3.4 milligram morphine equivalent (MME); 95% CI (CI) -12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD -0.18 cm; 95% CI -0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD -0.22 cm; 95% CI -0.4 to -0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD -1%; 95% CI -4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD -22.5 MME; 95% CI -43.06 to -1.97).
CONCLUSION
Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.CRD42018091098.
Topics: Analgesics, Opioid; Cannabinoids; Chronic Pain; Humans; Medical Marijuana; Observational Studies as Topic; Randomized Controlled Trials as Topic; Vomiting
PubMed: 34321302
DOI: 10.1136/bmjopen-2020-047717