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Brain Sciences Apr 2024This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical... (Review)
Review
This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.
PubMed: 38672008
DOI: 10.3390/brainsci14040356 -
JAMA Psychiatry Sep 2023Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment improves abstinence but is not routinely offered in community settings, particularly to those not seeking to quit smoking immediately.
OBJECTIVE
To determine the effectiveness of an 18-month pharmacotherapy and behavioral smoking cessation intervention incorporating weight management and support for physical activity in adults with serious mental illness interested in quitting smoking within 1 or 6 months.
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized clinical trial conducted from July 25, 2016, to March 20, 2020, at 4 community health programs. Adults with serious mental illness who smoked tobacco daily were included in the study. Participants were randomly assigned to intervention or control, stratified by willingness to try to quit immediately (within 1 month) or within 6 months. Assessors were masked to group assignment.
INTERVENTIONS
Pharmacotherapy, primarily varenicline, dual-form nicotine replacement, or their combination; tailored individual and group counseling for motivational enhancement; smoking cessation and relapse prevention; weight management counseling; and support for physical activity. Controls received quitline referrals.
MAIN OUTCOME AND MEASURES
The primary outcome was biochemically validated, 7-day point-prevalence tobacco abstinence at 18 months.
RESULTS
Of the 298 individuals screened for study inclusion, 192 enrolled (mean [SD] age, 49.6 [11.7] years; 97 women [50.5%]) and were randomly assigned to intervention (97 [50.5%]) or control (95 [49.5%]) groups. Participants self-identified with the following race and ethnicity categories: 93 Black or African American (48.4%), 6 Hispanic or Latino (3.1%), 90 White (46.9%), and 9 other (4.7%). A total of 82 participants (42.7%) had a schizophrenia spectrum disorder, 62 (32.3%) had bipolar disorder, and 48 (25.0%) had major depressive disorder; 119 participants (62%) reported interest in quitting immediately (within 1 month). Primary outcome data were collected in 183 participants (95.3%). At 18 months, 26.4% of participants (observed count, 27 of 97 [27.8%]) in the intervention group and 5.7% of participants (observed count, 6 of 95 [6.3%]) in the control group achieved abstinence (adjusted odds ratio [OR], 5.9; 95% CI, 2.3-15.4; P < .001). Readiness to quit within 1 month did not statistically significantly modify the intervention's effect on abstinence. The intervention group did not have significantly greater weight gain than the control group (mean weight change difference, 1.6 kg; 95% CI, -1.5 to 4.7 kg).
CONCLUSIONS AND RELEVANCE
Findings of this randomized clinical trial showed that in persons with serious mental illness who are interested in quitting smoking within 6 months, an 18-month intervention with first-line pharmacotherapy and tailored behavioral support for smoking cessation and weight management increased tobacco abstinence without significant weight gain.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02424188.
Topics: Adult; Humans; Female; Middle Aged; Tobacco Use Cessation; Smoking Cessation; Depressive Disorder, Major; Tobacco Use Cessation Devices; Weight Gain
PubMed: 37378972
DOI: 10.1001/jamapsychiatry.2023.1691 -
PloS One 2024Alcohol Use Disorder (AUD) is a major cause of premature death, disability and suffering. Available treatments are of modest efficacy and under-prescribed so there is a...
A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study.
BACKGROUND
Alcohol Use Disorder (AUD) is a major cause of premature death, disability and suffering. Available treatments are of modest efficacy and under-prescribed so there is a pressing need for a well-tolerated and effective treatment option for AUD. Dopamine is hypothesized to be involved in the development of alcohol dependence. To challenge the low-dopamine hypothesis of addiction, this randomized, double-blind, placebo-controlled, 13-week, multicentre clinical trial with four parallel arms is designed to evaluate the efficacy of two substances raising dopamine levels, varenicline and bupropion, alone and in combination vs. placebo on alcohol consumption in AUD. Varenicline, a partial agonist at brain nicotinic acetylcholine receptors increases dopamine release, whereas bupropion is a centrally-acting, norepinephrine-dopamine reuptake inhibitor. Varenicline is previously shown to reduce alcohol intake in individuals with AUD. We hypothesize that the effect size of a combination of two drugs affecting dopamine levels in the brain will exceed that of approved AUD therapies.
METHODS
Consenting individuals with AUD will be recruited via media advertisements. Those fulfilling the eligibility criteria (N = 380) will be randomized to one of four interventions (n = 95 per arm). Treatment will comprise one week of titration (varenicline 0.5‒2 mg; bupropion SR 150‒300 mg) plus 12 weeks at steady state. Efficacy will be evaluated using two primary endpoints of alcohol consumption: Heavy Drinking Days and blood levels of phosphatidylethanol. Secondary objectives, exploratory and subgroup analyses will be also performed. The modified Intention-to-Treat and Per Protocol datasets will be evaluated using Analysis of Covariance. Last patient out is estimated to occur in December, 2022.
DISCUSSION
The COMB Study aims to evaluate the efficacy of the combination of varenicline and bupropion, two drugs affecting dopamine, on alcohol consumption, and to challenge the low-dopamine hypothesis of addiction. Study Code COMB-BO8, EudraCT 2018-000048-24, Version 3.2, Lidö & deBejczy, 2020-06-16; https://clinicaltrials.gov identifier NCT04167306.
Topics: Humans; Varenicline; Bupropion; Alcoholism; Nicotinic Agonists; Dopamine; Smoking Cessation; Benzazepines; Quinoxalines; Treatment Outcome; Alcohol Drinking; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38206930
DOI: 10.1371/journal.pone.0296118 -
Journal of Clinical Medicine Dec 2023Tobacco smoking has been a recognized risk factor for cardiovascular diseases (CVD). Smoking is a chronic relapsing disease and pharmacotherapy is a main component of... (Review)
Review
Tobacco smoking has been a recognized risk factor for cardiovascular diseases (CVD). Smoking is a chronic relapsing disease and pharmacotherapy is a main component of smoking cessation. Obstructive sleep apnea (OSA) and smoking both increase the risk of CVD and are associated with significant morbidity and mortality. There are few existing data examining how pharmacological treatment, such as nicotine replacement therapy (NRT), bupropion, and varenicline, affect smokers suffering with OSA and especially their cardiovascular effects. The aim of this review was to evaluate the effects of smoking cessation pharmacotherapy on OSA with a special emphasis on the cardiovascular system. Results: Only small studies have assessed the effect of NRTs on OSA. Nicotine gum administration showed an improvement in respiratory events but with no permanent results. No specific studies were found on the effect of bupropion on OSA, and a limited number evaluated varenicline's effects on sleep and specifically OSA. Varenicline administration in smokers suffering from OSA reduced the obstructive respiratory events, especially during REM. Studies on second-line medication (nortriptyline, clonidine, cytisine) are even more limited. There are still no studies evaluating the cardiovascular effects of smoking cessation medications on OSA patients. Conclusions: Sleep disturbances are common withdrawal effects during smoking cessation but could be also attributed to pharmacotherapy. Smokers should receive personalized treatment during their quitting attempts according to their individual needs and problems, including OSA. Future studies are needed in order to evaluate the efficacy and safety of smoking cessation medications in OSA patients.
PubMed: 38137639
DOI: 10.3390/jcm12247570 -
Journal of the American Pharmacists... Apr 2024Tobacco use remains a leading cause of death in the U.S. Varenicline is a preferred medication for tobacco cessation, and a prior report in the literature showed its use...
BACKGROUND
Tobacco use remains a leading cause of death in the U.S. Varenicline is a preferred medication for tobacco cessation, and a prior report in the literature showed its use fell dramatically after the voluntary recall of Chantix (name-brand varenicline) in July 2021.
OBJECTIVES
Working with data on prescriptions for varenicline and nicotine-replacement therapy (NRT), we studied use from 2018 to 2023 to determine if varenicline use had recovered or if there had been a compensatory increase in NRT use.
METHODS
Data are yearly from state employees and their dependents who were aged >18 years and were health-insurance beneficiaries of the Washington Public Employees Benefits Board from July 2018 through June 2023. Data include numbers of tobacco users and numbers of prescriptions filled.
RESULTS
The 5-year prevalence of tobacco use among 224,816 beneficiaries was 4.6%. The percentage of tobacco users who filled a prescription for varenicline fell from highs of 9.5% and 9.6% in the 2018-2019 and 2019-2020 year to lows of 5.3% and 6.4% in the 2021-2022 and 2022-2023 years. For nicotine replacement therapy, prescriptions rose modestly over the 5 years, from 4.5% in 2018-2019 to 6.0% in 2022-2023.
DISCUSSION
Varenicline use dropped after the voluntary recall of Chantix by Pfizer in mid-2021 and has not returned to pre-recall levels.
CONCLUSION
Pharmacists and other clinicians should address this drop, in addition to addressing longer-term challenges to increasing varenicline use; these include the requirement for a prescription and the black-box warning by the Food and Drug Administration, rescinded in 2016.
PubMed: 38649095
DOI: 10.1016/j.japh.2024.102102 -
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 -
Addiction (Abingdon, England) Sep 2023Treatment of depression-related psychological factors related to smoking behavior may improve rates of cessation among adults with major depressive disorder (MDD). This... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of combination behavioral activation for smoking cessation and varenicline for treating tobacco dependence among individuals with current or past major depressive disorder: A 2 × 2 factorial, randomized, placebo-controlled trial.
BACKGROUND AND AIMS
Treatment of depression-related psychological factors related to smoking behavior may improve rates of cessation among adults with major depressive disorder (MDD). This study measured the efficacy and safety of 12 weeks of behavioral activation for smoking cessation (BASC), varenicline and their combination.
DESIGN, SETTING, PARTICIPANTS
This study used a randomized, placebo-controlled, 2 × 2 factorial design comparing BASC versus standard behavioral treatment (ST) and varenicline versus placebo, taking place in research clinics at two urban universities in the United States. Participants comprised 300 hundred adult smokers with current or past MDD.
INTERVENTIONS
BASC integrated behavioral activation therapy and ST to increase engagement in rewarding activities by reducing avoidance, withdrawal and inactivity associated with depression. ST was based on the 2008 PHS Clinical Practice Guideline. Both treatments consisted of eight 45-min sessions delivered between weeks 1 and 12. Varenicline and placebo were administered for 12 weeks between weeks 2 and 14.
MEASUREMENTS
Primary outcomes were bioverified intent-to-treat (ITT) 7-day point-prevalence abstinence at 27 weeks and adverse events (AEs).
FINDINGS
No significant interaction was detected between behavioral treatment and pharmacotherapy at 27 weeks (χ = 0.19, P = 0.67). BASC and ST did not differ (χ = 0.43, P = 0.51). Significant differences in ITT abstinence rates (χ = 4.84, P = 0.03) emerged among pharmacotherapy arms (16.2% for varenicline, 7.5% for placebo), with results favoring varenicline over placebo (rate ratio = 2.16, 95% confidence interval = 1.08, 4.30). All significant differences in AE rates after start of medication were higher for placebo than varenicline.
CONCLUSION
A randomized trial in smokers with major depressive disorder found that varenicline improved smoking abstinence versus placebo at 27 weeks without elevating rates of adverse events. Behavioral activation for smoking cessation did not outperform standard behavioral treatment, with or without adjunctive varenicline therapy.
Topics: Adult; Humans; Varenicline; Tobacco Use Disorder; Smoking Cessation; Depressive Disorder, Major; Nicotinic Agonists; Benzazepines; Treatment Outcome; Quinoxalines
PubMed: 37069490
DOI: 10.1111/add.16209 -
Biomedicines Oct 2023Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major...
Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major hurdle. Varenicline is a medication used to aid smoking cessation, with anti-inflammatory and antioxidant effects. In this study, varenicline was investigated for its antiviral potential against DENV. This study provides evidence of the antiviral activity of varenicline against DENV, regardless of the virus serotype or cell type used. Varenicline demonstrated dose-dependent effects in reducing viral protein expression, infectivity, and virus yield in Vero and A549 cells infected with DENV-1 and DENV-2, with EC50 values ranging from 0.44 to 1.66 μM. Time-of-addition and removal experiments demonstrated that varenicline had a stronger inhibitory effect on the post-entry stage of DENV-2 replication than on the entry stage, as well as the preinfection and virus attachment stages. Furthermore, cell-based trans-cleavage assays indicated that varenicline dose-dependently inhibited the proteolytic activity of DENV-2 NS2B-NS3 protease. Docking models revealed the formation of hydrogen bonds and van der Waals forces between varenicline and specific residues in the DENV-1 and DENV-2 NS2B-NS3 proteases. These results highlight the antiviral activity and potential mechanism of varenicline against DENV, offering valuable insights for further research and development in the treatment of DENV infection.
PubMed: 37893127
DOI: 10.3390/biomedicines11102754 -
International Review of Neurobiology 2024Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in... (Review)
Review
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Sodium Oxybate; Baclofen; Drug Repositioning; Substance Withdrawal Syndrome; Alcohol Drinking
PubMed: 38555115
DOI: 10.1016/bs.irn.2024.02.002 -
Psychiatry Research Aug 2023Tobacco smoking is a significant determinant of preventable morbidity and mortality worldwide. It is now possible to modulate the activity of the neurocircuitry... (Review)
Review
Tobacco smoking is a significant determinant of preventable morbidity and mortality worldwide. It is now possible to modulate the activity of the neurocircuitry associated with nicotine dependence using repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive neurostimulation approach, which has recently demonstrated efficacy in clinical trials and received regulatory approval in the US and Canada. However there remains a paucity of replication studies and real-world patient effectiveness data as access to this intervention is extremely limited. There are a number of unique challenges related to the delivery of rTMS that need to be addressed prior to widespread adoption and implementation of this treatment modality for smoking cessation. In this paper, we review the accessibility, scientific, technological, economical, and social challenges that remain before this treatment can be translated into clinical practice. By addressing these remaining barriers and scientific challenges with rTMS for smoking cessation and delineating implementation strategies, we can greatly reduce the burden of tobacco-related disease worldwide.
PubMed: 37454610
DOI: 10.1016/j.psychres.2023.115340