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Public Health in Practice (Oxford,... Dec 2023Compare financial barriers to the most effective smoking cessation medications - varenicline and combination nicotine replacement therapy (CNRT) across major insurance...
OBJECTIVES
Compare financial barriers to the most effective smoking cessation medications - varenicline and combination nicotine replacement therapy (CNRT) across major insurance categories and determine whether these financial barriers impact smoking cessation outcomes.
STUDY DESIGN
Longitudinal retrospective observational cohort study.
METHODS
Patients seen at Duke Smoking Cessation Program 05/2016 through 07/2021 were studied. Those prescribed varenicline or CNRT were determined to have financial barriers to access if they could not purchase the medication using insurance or their own funds. Outcomes were compared between Medicare, Medicaid, and private insurers. Abstinence was defined as self-reported 7-day smoking abstinence.
RESULTS
Patients with Medicare were 5.08 times more likely to face a financial barrier to highly effective smoking cessation medications compared to patients with private insurance (p<0.00001) and 2.81 times more likely compared to Medicaid (p<0.00001). Patients able to access these highly effective medications achieved a smoking abstinence rate that was 1.58 times higher than those who could not (p = 0.01).
CONCLUSIONS
Findings suggest Medicare coverage of the most effective smoking cessation medications is considerably worse than Medicaid or private insurance; inability to access these medications may lead to lower rates of smoking abstinence.
PubMed: 37766740
DOI: 10.1016/j.puhip.2023.100427 -
Frontiers in Pharmacology 2023Preclinical studies have identified glucagon-like peptide-1 receptor (GLP-1R) agonists, and the antismoking agents varenicline and bupropion as tentative agents for...
Preclinical studies have identified glucagon-like peptide-1 receptor (GLP-1R) agonists, and the antismoking agents varenicline and bupropion as tentative agents for treatment of alcohol use disorder (AUD). Combining different medications is a recent approach that has gained attention regarding heterogenous and difficult-to-treat diseases, like AUD. Successfully, this approach has been tested for the combination of varenicline and bupropion as it prevents relapse to alcohol drinking in rats. However, studies assessing the effects of the combination of semaglutide, an FDA-approved GLP-1R agonist for diabetes type II, and varenicline or bupropion to reduce alcohol intake in male and female rats remains to be conducted. Another approach to influence treatment outcome is to combine a medication with feeding interventions like high fat diet (HFD). While HFD reduces alcohol intake, the ability of the combination of HFD and semaglutide to alter alcohol drinking is unknown and thus the subject for a pilot study. Therefore, three intermittent alcohol drinking experiments were conducted to elucidate the effectiveness of these treatment combinations. We show that semaglutide, bupropion or HFD reduces alcohol intake in male as well as female rats. While various studies reveal beneficial effects of combinatorial pharmacotherapies for the treatment of AUD, we herein do not report any additive effects on alcohol intake by adding either varenicline or bupropion to semaglutide treatment. Neither does HFD exposure alter the ability of semaglutide to reduce alcohol intake. Although no additive effects by the combinatorial treatments are found, these findings collectively provide insight into possible monotherapeutical treatments for AUD.
PubMed: 37719854
DOI: 10.3389/fphar.2023.1180512 -
BMC Public Health Sep 2023Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these...
Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial.
BACKGROUND
Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months.
METHODS
A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily (N = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter.
DISCUSSION
Pragmatic trials are of particular value as they reflect the 'real world' impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy.
TRIAL REGISTRATION
NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022.
Topics: Humans; Nicotine; Smoking Cessation; Electronic Nicotine Delivery Systems; Vaping; New Zealand; Quality of Life; Varenicline; Tobacco Use Cessation Devices; Sodium Chloride, Dietary; Randomized Controlled Trials as Topic
PubMed: 37697327
DOI: 10.1186/s12889-023-16665-w -
The Cochrane Database of Systematic... Sep 2023Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies.
OBJECTIVES
To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco.
SEARCH METHODS
We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE.
MAIN RESULTS
Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2).
AUTHORS' CONCLUSIONS
The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.
Topics: Adult; Female; Humans; Pregnancy; Bupropion; Electronic Nicotine Delivery Systems; Network Meta-Analysis; Nicotine; Nortriptyline; Smoking Cessation; Varenicline
PubMed: 37696529
DOI: 10.1002/14651858.CD015226.pub2 -
American Journal of Translational... 2023Nabiximols is used for treating various symptoms associated with multiple sclerosis (MS). Nabiximols is also being investigated as a potential treatment medication for...
OBJECTIVE
Nabiximols is used for treating various symptoms associated with multiple sclerosis (MS). Nabiximols is also being investigated as a potential treatment medication for individuals with cannabis use disorder (CUD). A variety of investigations have shown that, at low doses, nabiximols is overall well tolerated for MS treatment. However, due to tolerance, the management of CUD would likely require much higher doses of nabiximols to be effective. The effects of high doses of nabiximols on clinical laboratory tests remain unclear. Therefore, we investigated the sub-chronic effects of high doses of nabiximols on liver function, renal function, and other routine blood tests in this prospective study.
METHODS
We performed a secondary analysis of various blood markers results collected during a double-blind, placebo-controlled randomized clinical trial (Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence, NCT01747850, https://clinicaltrials.gov/ct2/show/record/NCT01747850). This trial tested the impact of the 12-week administration of nabiximols with a maximum daily dose of up to 113.4 mg THC/105 mg CBD.
RESULTS
The measurements of the various biomarkers were in the normal range during the 12-week time frame. The results indicate an overall good tolerability of high-dose nabiximols on the blood markers measured.
CONCLUSION
Our preliminary results suggest that high doses of nabiximols might be well tolerated by individuals with CUD.
PubMed: 37692969
DOI: No ID Found -
Annals of Clinical and Translational... Jan 2024The natural history of Friedreich ataxia is being investigated in a multi-center longitudinal study designated the Friedreich ataxia Clinical Outcome Measures Study...
OBJECTIVE
The natural history of Friedreich ataxia is being investigated in a multi-center longitudinal study designated the Friedreich ataxia Clinical Outcome Measures Study (FACOMS). To understand the utility of this study in analysis of clinical trials, we performed a propensity-matched comparison of data from the open-label MOXIe extension (omaveloxolone) to that from FACOMS.
METHODS
MOXIe extension patients were matched to FACOMS patients using logistic regression to estimate propensity scores based on multiple covariates: sex, baseline age, age of onset, baseline modified Friedreich Ataxia Rating scale (mFARS) score, and baseline gait score. The change from baseline in mFARS at Year 3 for the MOXIe extension patients compared to the matched FACOMS patients was analyzed as the primary efficacy endpoint using mixed model repeated measures analysis.
RESULTS
Data from the MOXIe extension show that omaveloxolone provided persistent benefit over 3 years when compared to an untreated, matched cohort from FACOMS. At each year, in all analysis populations, patients in the MOXIe extension experienced a smaller change from baseline in mFARS score than matched FACOMS patients. In the primary pooled population (136 patients in each group) by Year 3, patients in the FACOMS matched set progressed 6.6 points whereas patients treated with omaveloxolone in MOXIe extension progressed 3 points (difference = -3.6; nominal p value = 0.0001).
INTERPRETATION
These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity-matched analysis may contribute to understanding of effects of therapeutic agents. This demonstrates the direct value of natural history studies in clinical trial evaluations.
Topics: Humans; Friedreich Ataxia; Longitudinal Studies; Outcome Assessment, Health Care; Triterpenes; Male; Female; Clinical Trials as Topic
PubMed: 37691319
DOI: 10.1002/acn3.51897 -
JAMA Network Open Sep 2023Adaptive pharmacotherapy, ie, starting a medication regimen and then modifying that regimen based on patient response, is common in many medical domains but is not... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Adaptive pharmacotherapy, ie, starting a medication regimen and then modifying that regimen based on patient response, is common in many medical domains but is not common in smoking cessation. Recently, studies have found that adaptive treatment using precessation nicotine patches is efficacious for smoking cessation; however, adaptive treatment using precessation varenicline and adaptive treatment in clinical practice settings have not been fully assessed.
OBJECTIVE
To determine whether adaptive pharmacotherapy leads to higher smoking abstinence rates than standard pharmacotherapy in a clinical practice setting.
DESIGN, SETTING, AND PARTICIPANTS
This double-blinded stratified placebo-controlled randomized clinical trial compared adaptive treatment with standard treatment for smoking cessation. The study was conducted at a university health system in Durham, North Carolina, from February 2018 to May 2020 and was stopped early due to COVID-19. Data were analyzed as intent-to-treat from May 24, 2021, to February 27, 2022.
INTERVENTIONS
Participants were allowed to choose varenicline or nicotine patches and were then randomized to adaptive or nonadaptive (standard) treatment. Participants started on their chosen medication (adaptive) or placebo (standard) 4 weeks before their target quit day. Two weeks later, participants were assessed for treatment response. Adaptive participants who did not decrease daily cigarettes smoked by at least 50% (nonresponders) received bupropion in addition to their chosen medication. Participants in the adaptative treatment group who did decrease daily cigarettes smoked by at least 50% (responders) and participants in the standard treatment group received additional placebo bupropion. Participants in the standard treatment group received varenicline starting 1 week before the target quit date or nicotine patches starting on the target quit day. All participants received brief behavioral support.
MAIN OUTCOME AND MEASURES
The main outcome was biochemically verified 30-day continuous smoking abstinence 12 weeks after their target quit smoking day. Other measures included demographic characteristics, smoking history, and repeated smoking assessments.
RESULTS
Of the planned 300 participants, a total of 188 participants (mean [SD] age, 49.1 [12.5] years; 102 [54%] female) were enrolled before the trial was stopped because of the COVID-19 pandemic. A total of 127 participants chose to use varenicline, including 64 randomized to adaptive treatment and 63 randomized to standard treatment, and 61 participants chose to use nicotine patches, including 31 randomized to adaptive treatment and 30 randomized to standard treatment. At baseline, participants smoked a mean (SD) of 15.4 (7.3) cigarettes per day. At 12 weeks after the target quit day, biochemically verified 30-day continuous smoking abstinence was observed in 23 of 95 participants (24%) in the adaptive treatment group and 8 of 93 participants (9%) in the standard treatment (odds ratio [OR], 3.38; 95% CI, 1.43-7.99; P = .004); among participants who used varenicline, 30-day continuous abstinence was 18 participants (28%) in the adaptive treatment group, and 5 participants (8%) in the standard treatment group (OR, 4.54; 95% CI, 1.57-13.15); among participants who used nicotine patches, 30-day continuous abstinence was 5 participants (16%) in the adaptive treatment group and 3 participants (10%) in the standard treatment group (OR, 1.73; 95% CI, 0.38-7.99). Sleep problems were more common for participants in the varenicline adaptive treatment group than in the varenicline standard treatment group (rate ratio, 1.74; 95% CI, 1.18-2.58; P = .03).
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that adaptive pharmacotherapy was efficacious for smoking cessation treatment in a practice setting.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02501265.
Topics: Female; Humans; Middle Aged; Male; Smoking Cessation; Varenicline; Bupropion; Nicotine; Pandemics; COVID-19; Tobacco Use Cessation Devices
PubMed: 37682573
DOI: 10.1001/jamanetworkopen.2023.32214 -
ENeuro Sep 2023Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic....
Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic. Reversible gene therapy using long-lived chemogenetic approaches is an appealing option. We used the genetically activated chloride channel PSAM-GlyR to examine pain pathways in mice. Using recombinant AAV9-based delivery to sensory neurons, we found a reversal of acute pain behavior and diminished neuronal activity using and GCaMP imaging on activation of PSAM-GlyR with varenicline. A significant reduction in inflammatory heat hyperalgesia and oxaliplatin-induced cold allodynia was also observed. Importantly, there was no impairment of motor coordination, but innocuous von Frey sensation was inhibited. We generated a transgenic mouse that expresses a CAG-driven FLExed PSAM-GlyR downstream of the locus that requires Cre recombinase to enable the expression of PSAM-GlyR and tdTomato. We used Na1.8 Cre to examine the role of predominantly nociceptive Na1.8+ neurons in cancer-induced bone pain (CIBP) and neuropathic pain caused by chronic constriction injury (CCI). Varenicline activation of PSAM-GlyR in Na1.8-positive neurons reversed CCI-driven mechanical, thermal, and cold sensitivity. Additionally, varenicline treatment of mice with CIBP expressing PSAM-GlyR in Na1.8+ sensory neurons reversed cancer pain as assessed by weight-bearing. Moreover, when these mice were subjected to acute pain assays, an elevation in withdrawal thresholds to noxious mechanical and thermal stimuli was detected, but innocuous mechanical sensations remained unaffected. These studies confirm the utility of PSAM-GlyR chemogenetic silencing in chronic pain states for mechanistic analysis and potential future therapeutic use.
Topics: Mice; Animals; Cancer Pain; Acute Pain; Varenicline; Sensory Receptor Cells; Hyperalgesia; Mice, Transgenic; Neoplasms; Ganglia, Spinal
PubMed: 37679042
DOI: 10.1523/ENEURO.0151-23.2023 -
Neuropsychopharmacology Reports Dec 2023Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking...
AIMS
Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking cessation is of great importance not only for individual smokers but also for social health. Regarding current cessation therapies, the effectiveness of nicotine replacement is limited, and the cost of varenicline medication is considerable. Thus, a method for screening smokers who are responsive to cessation therapy based on the therapeutic effectiveness is required. Peripheral biomarkers reflecting smoking dependence status are necessary to establish a method for achieving effective cessation therapy.
METHODS
Methylation status of smokers' blood DNA was evaluated focusing on SHATI/NAT8L, an addiction-related gene. Eight CpG sites in SHATI/NAT8L were quantified by pyrosequencing.
RESULTS
There was no difference in the methylation status of this gene between smokers (n = 129) and non-smokers (n = 129) at all CpG sites. No correlations between the methylation status of SHATI/NAT8L and indicators of smoking dependence were found.
CONCLUSIONS
Although the present study found no significance in the DNA methylation of SHATI/NAT8L among smokers, the exploration of predictable peripheral biomarkers for the effectiveness of smoking cessation therapy is required.
Topics: Humans; DNA Methylation; Smokers; Smoking Cessation; Tobacco Use Cessation Devices; Biomarkers; Tobacco Products; Acetyltransferases
PubMed: 37668111
DOI: 10.1002/npr2.12373 -
BMJ (Clinical Research Ed.) Aug 2023To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational... (Review)
Review
OBJECTIVE
To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).
DESIGN
Umbrella review.
DATA SOURCES
PubMed, PsychInfo, Embase, up to 9 February 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.
RESULTS
101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).
CONCLUSIONS
Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.
STUDY REGISTRATION
PROSPERO CRD42018093045.
FUNDING
None.
Topics: Adolescent; Adult; Female; Humans; Infant, Newborn; Pregnancy; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Hallucinogens; Randomized Controlled Trials as Topic; Risk Assessment; Sleepiness; Systematic Reviews as Topic; Meta-Analysis as Topic; Observational Studies as Topic
PubMed: 37648266
DOI: 10.1136/bmj-2022-072348