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Citation: Walsh, H., McNeill, A., Purssell, E. ORCID: 0000-0003-3748-0864 and Duaso, M. (2020). A systematic review and Bayesian meta‐ analysis of interventions which target or assess co‐‐ use of tobacco and cannabis in single or multi substance interventions. Addiction, 115(10), pp. 1800-1814. doi: 10.1111/add.14993

This is the accepted version of the paper.

This version of the publication may differ from the final published version.

Permanent repository link: https://openaccess.city.ac.uk/id/eprint/23622/

Link to published version: http://dx.doi.org/10.1111/add.14993

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doi: 10.1111/add.14993 as article this cite Please Record. of Version the and version this between differences cothethrough This article has been accepted for publication and undergone full peer review but has not been PROSPERO registration number: No declarations of completing interest Word count: College London, Maxwell Clerk James Building, 57 Road,Waterloo London SE1 8WA Dr Maria Duaso, Florence Nightingale Faculty of Nursing, andMidwifery Palliative Care, King’s College London, Maxwell Clerk James Building, 57 Road,Waterloo Lon Dr Edward Purssell, Florence Nightingale Faculty of Nursing, Midwifery and Care,Palliative King’s Neurosc Professor Ann McNeill, National Addictions Centre, Institute of Psychiatry, Psychology and London, ClerkJames Maxwell Building, 57 Waterloo Road, London SE1 8WA Hannah Walsh, Authors: multi which target or assess co systematicA review and Bayesian meta Maria 0000 Duaso (OrcidID: McNeillAnn0000 (OrcidID: Walsh0000 (OrcidID: Hannah - ience (IOPPN), Addictions Sciences Building, 4 Windsor Walk, Denmark Hill, London SE5 8BB substance interventions

4712, Florence Nightingale Faculty of Nursing, andMidwifery Palliative Care, King’s College pyediting,typesetting, topaginationleadproofreading may andprocess which Accepted Article

abstract311

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CRD42017071188 0002 0002 - 0002 - use use of tobacco and cannabis single in or - s from any authors - 4801 6223 This article This isprotected copyright. by Allrights reserved. - 1638

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analysis of interventions don don SE1 8WA

However, dual shown a clear effect Conclusions and acceptability. standardisation. of evidence was moderate, although measurement coof (0.25 [0.03, 0.4 versus RR=1.39 [0.75,2.74]) more effective than cannabis targeted interventions cannabison cessation ( 1. cessation ( interventions) delivered to co informative priors based on existing data of substance, 11 RCTs single (six multi five Results included studies were conducted. of same outcome measures in non mean change for tobacco cannabisand interventionreduction post separately. Narrative reporting measures: Prevention interventions were excluded. of tobacco cannabisand/or use requests for co Method outcomes. tobacco cannabisand/or use interventions of co Background and a Abstract 10

[0. - use on use quiton outcomes either for substance We soughtis mixed. to determine the e

68 Twenty Systematic withreview meta ,1.

risk risk ratio [ risk risk ratio for tobacco cannabisand cessation post intervention separately; standardised

87 S ingle and multi

- ], studies=9 5], studies =9) but not tobaccoon reduction (0.06 [ substance interventions targeting tobacco cannabisand appear feasible.

use data. use studies (12 RCTs and uncontrolled) 8 were included. Bayesian meta Uncontrolled

Accepted Article ims

on either on tobacco cannabisor cessation and reduction amongst co RR Tobacco cannabisand are cocommonly ] =1.4 Controlled Controlled and ). ). Subgroup analysis . . A significant intervention effect was observed cannabison reduction 8 - substance interventions addressing tobacco cannabisand/or -

[0. users (n= toup 1117) weak showed evidence for an effect cannabison studies targeting both cannabis and tobacco use indi

assessing use assessing ofpre andboth post intervention were included.

92,2.49 -

randomised clinical trials (non - analysis andanalysis narrative review, databasesusing five and author This article This isprotected copyright. by Allrights reserved. ], studies=8

uncontrolled intervention uncontrolled Bayesian Bayesian meta ,

delivered todelivered co sugg ) and no ested - - analysis was analysis used across four outcome use and cannabisof use requires

multi - users clear - used, and evidence thefor influence - substance interventions , -

- RCTs cannabison and tobacco use effect effect tobaccooncessation (RR= 0.11,0.23], studies = 9).

studies focussing on treatment )

and quality assessment of all RR= 2.19 RR= 2.19 [1.10, 4.36] cated feasibility - - analysis with substance -

users. users. fficacy of might might be have not Quality Quality

substance use treatments, efficacyoverall tends low, to be and abstinence rare Therapy (CBT) with contingency management (CM) Combining and pharmacotherapy interventions. Evidence latterthefor is incomplete and low quality (2 interventions is limited; only two Cochrane the most effective tobaccocessation method (2 Cochrane on Reviews the topic.pharmacotherapy Combining with behavioural support is likely to be A significant body of evidence exists on tobacco cessation interventions, as indicated by 82the cannabis use and its impact cessationon outcomes is concurrent use (17). whether co measure use of both substances interventions, little is known about the ofimpact co the influ interventions (16, cannabis17). Similarly, use is associated with higher nicotine cannabis use disorder (13,15), and influence to negatively outcomes of cannabistreatment use physiological and psychological level (14). Tobacc The relationship between tobacco cannabisand appears synergistic, operating on both a cessation attempts types all for of combustible andtobacco other cannabisand products. with risk of dependence and amongst which populations, and cohow evolving landscape for these two substances. It is of el and co use has been more frequent in other parts theof althoughworld, there are thatindicationsco tobacco cannabisand are commonly co in a time period,given concurrent. i.e. Globally, types of co Co consistently two to three times higher than amongst and early Africa (7). Although Tobacco is used by over 1.1people wor billion relationship between tobacco cannabisand use. but also potential aggregated harms (5), and years last have the seen few an increased focus theon not as established as that particular (2, 3). Cannabis use is also associated with significant harms, although the evidence base is required to address the significant use disparit Tobacco use theremains cause leading of preventable death and disease worldwide, and are frequently co Tobacco cannabisand are two theof commonlymost used psychoactive substances andworldwide Introduction - use may comprise both substances in cosame the product, i.e. may may ectronic devices used both to deliver

indications it may be increasing in the United Kingdom and(UK) in the United States (8 (US)

(6). (6). Cannabis prevalence appears stable in most of Europe Australasia, and though there are - administration is increasing in the US (13). ence of cannabis use tobacco on cessationmixed is change with increasing legalisation.

i - nterventions such as Motivational Enhancement Therapy (MET) administration may lead to poorer for outcomes tobaccocessation in comparison to

globally

-

Accepted Articleused but corarely Further Further research theofinto thenature relationship between tobacco and

tobacco prevalence is decreasing, for tobacco ,

nor typethe coof - treated in clinical interventions (1).

related harms (4). related Eachharms (4). substance poses distinct known harms - This article This isprotected copyright. by Allrights reserved. adminis tobacco/nicotine R eviews haveeviews been published, investigating psychosocial Co ldwide (6),ldwide cannabisand by an estimated 188 million y

2 - tered in Europe Australia, and whereas concurrent amongst people with co use of tobacco amon

) o use oseems to use be a in feature the development of . contrast,. By evidence the base for cannabis use important to understand Changing regulatory environments and a show - - use practised. use For example use on outcomes, since tobacco only user

warranted. use

some positive effects, but, as otherfor - and cannabis

use vary significantly; broadly speaking is is increasing in some regions (18 - 21

- ). ). Amongst single substance administration, or sequential use - gst cannabisgst users is use variation s

- (12).

occurring occurring substanceuse in have created how

or studies may notstudies

Cognitive Behaviour Cognitive

ly achieved ly (2 it is not known dependence, though co -

use may may influence a rapidly rapidly a is is associated

such as

efforts are

vailability vailability 3 4 ). ). - ). ). use

- 11)

potentially included articles. Discrepancies were resolved by discussion. repeated in January 2018 March and 2019. articles, full HW reviewed and searches All and initial screening of abstracts for were carriedreview out by HW 2017in July and particularly Spanish were included. 1990 was selected as older literature consistentis less in measurement, use treatment. Articles published from January 1990 to March2019 written in English, French and a combination of terms torelating tobacco and Search strategies were developed for each databasecontrolled using vocabulary and keywords using lists from included studies and cited literature reviews were also searched. databasesFive were used Identificationstudies of No limits were placed on age, setting, dual and multi pre and post treatment intervention. Controlled or uncontrolled, pilot orstudies offeasibility singl Studies were included if they published, or reported level of measuring, use of tobacco cannabisand Eligibility criteria Analyses statement, PRISMA (3 This systematic followedreview the Preferred Reporting Items for Systematic Reviews and Meta Method and to estim interventions which target bothtobacco cannabisuse,and or which assess in change use of both; This systematic seeksreview to investigate the natureand strength theof evidence base for Objectives targeting populations have been (3 reviewed single substance use interventions (1,14, 2 interventions, for sequential or simultaneous i Reviews of co of one substancecessation following of the other is importantto to substance single interventions either substance s dual interventions may have on co addressing co tobacco cessationcannabis in Despite commonlybeing co (2 Systematic of reviews digital interventions for cannabis use have identified a small reduction hared route of administration and withdrawal overlapping symptoms may act as cues to relapse of 5 - 2 7 ). ).

or addressing co

of cannabis. The Medline search strategy is shown in supplementary (S1). materials ate efficacythe of included oninterventions cessation reductionor both of substances. - - use have considered potentialthe for treatmentspharmacological in dual - use within single substance interventions, it is importantto investigate what impact substance use interventions were included. Prevention interventions were excluded. indicating indicating thatthe efficacy dual multi ofor

Accepted Article

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use for populations.all Embase - used, tobacco cannabis use and are corarely users 2 ). ). The protocolprior was registered

warrants - ; use. use. For cothose who 1

Web of Science may may be partly by explained co ), this is the first tosystematic review date of interventions duration This article This isprotected copyright. by Allrights reserved. 8 examination ). ). Although co nterventions and the relevant most evidence from

or type. intervention tobacco use treatment cannabisand cannabisand

;

Medline

(14, - administer administer tobacco and cannabis, - use interventions for African American -

2 substance interventions in comparison ;

8 PsychINFO - 2 9 consider - ). ). use, hence in addition to

Additionally, compensatory use to commencing the (3 review

; and

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treated. MD AM and reviewed ( 30

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CINAHL. ReferenceCINAHL.

Low rates of

the

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uninfor solutions was used in this casethe to maximise information, which would be diluted by an data, distribution. Solutions to this include using broad distributionsprior that effect have minimal on the interest. As this is the first of review this type nothere empirically existing is based prior factor Bayesian analyses is thatfor they require a prior probability di value,given complete in methods were performed on RCTs. Bayesianeleven meta and control condition. In RStudio for Criteria inclusion in the meta Meta extraction and foranalysis each the of used studies in metathe Where authors had provided raw data, of analysis the these data was carried out by HW and both then adapted. Data were extracted from each study datasetand by enteredHW and into a whole demographicssample were extracted by HW using a data extraction form which was piloted, Outcomecharacteris data, Data extraction dataset for andanalysis our the remainder provided analysed outcome data. whom provided data on two studies (3 not be usedthe as format was incompatible with ot thedata available or were unable to provide it, did fournot reply and provided one data couldwhich A total of 25 authors were contacted to threeup Oftimes. these, seven indicated did they nothave Contact with auth participants reporting co collected but not reported, authors were provide contactedseparate to data for this sub When the article indicated that tobacco and cannabis use measures pre and post intervention were measure of level of tobacco cannabisand postuse pre and intervention. studies also reported a fifth outcome dual of tobacco cannabisand cessation. cessation rate;cannabis cessation rate; tobacco rate;reduction cannabis reduction rate reduction in use. The outcomesprimary were change in use ofand tobacco cannabis, measured either by cessation or Outcome measures potential missing studies. Funnel plots, including trim andwhere fill indicated, were used to assess publication bias and carried out quality the reviews, and MD fivereviewed of these. use reporting (3 Relevant items from the Russell Standard fo The Cochrane ofRisk Bias assessment tool was used to evaluate the quality of included RCTs (3 Quality assessment

or use or of data f - analysis m ative ative prior distribution. formation about credible theparameter values, and consequently probability the of any and

5

may may be more appropriate for numbera smaller of studies ( ). ). Uncontrolled studies were reviewed using Law’s ReviewCritical Form (3 Accepted ArticleEach study therefore had potentially four outcome measures of interest: tobacco ors rom studiesthe tothemselves provide this (

- use at baseline. use baseline. at

tics studies of including location, studydesign, intervention content and -

analys (50)

meta 7 is is was a cessation or reduction outcome in an intervention - This article This isprotected copyright. by Allrights reserved. 4

9 ). ). Three authors provided theanonymised original - r tobacco were usedstudies to assess quality of tobacco analyses using analyses using Bayesian and traditional frequentis her data. Thirteen authors provided data, - analysis was analysis selected as it provides

- analysis was analysis checked by MD. 51,53 stribution for the parameter of ). The). oflatter these

51

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6 CSV file. CSV file. ). ). HW

two t 4

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of of

disorder or frequent cannabis usetimes per (>4 week). total number of participants, 11 substance use treatment settings; notably ofnone were these cannabis treatment Ofservices. the treatment settings including colleges and community settings. Only studiesfive were located within the UK, one from France and from Mostone Australia. participan studies Twelve st Characteristics studies of TABLE 1 Selected characteristics theof included studies are presented in table 1. FIGURE 1 on ofaverage 34.5% The were female. selection process is shown in 1. figure process, 20 studies were included. The total number o titles reviewed and 123 articles accessed for full A total of 6280 study titles were identified through the search process. Duplicates were removed, Included s Results Results of uncontrolled studies were extracted andreported are in 2. Figure Analysis of uncontrolled studies presented in supplementary material (S2). applied, as v measured using tau ( principles were applied across theall meta Sub deviation of the median were used as informativeweakly priors. was analysis carried out using again (i.e. frequency of use versus amount use). An of effectsi SMC was selected to forallow a variety of pre interventionof uselevels and measurement variation The standardised mean change (SMC) in use of each substance in eachcondition was calculated. The Reductionoutcomes deviation ( analysis. For informative priors, 1 was used risk as minimum the ratio, and as 4 the standard calculated using the The pooled risk ratio cessationfor in the intervention group compared to controlthe Cessation outcomes model carried As this is a relatively novel approach to meta - group by analysis intervention target was carried out s . out (3

udies udies were RCTs 7

51 , 3 tudies to allow forto allow comparison anda sensitivityas foranalysis the assumptions made in our ariance was not within available original study data. Code used for meta ). 8

, 4 , 6

Accepted 4 , Article

metafor metafor 9 54 , 5 - 55 9 - 62 (3 ). In all four). In all meta

9 ). package (5 -

4 Fourteen were fromstudies the US 5 % were daily % tobaccowere daily users, and had19% either cannabis use , 4 ,

7 bayesmeta , 4 , 8 0 This article This isprotected copyright. by Allrights reserved. , 5 ), then the

6 - analyses analyses using authors’ raw data. Heterogeneity was - - 5 - analyses, a conservative estimate of variance at 0.8 was analysis 8 ); . . The median of the effect size and the standard -

text review. textFollowing thereview. author data request and eight were pilot oreight and feasibility, (“uncontrolled”) bayesmeta , traditional frequentist analyses were also f participantsf 20within all studies was 1599,

ze was calculated then a Bayesian meta as specified in protocol, intentiontotreat

package (5

ts were recruited from non ,

two two from Switzerland, two from

0 ) for the Bayesian meta

- analyses is analyses is group was - - -

the other RCTs measured intervention versus no intervention. ( conducted. One RCT was excluded from metathe effi Although intervention format in the twelve RCTs varied, addressedall the same clinical question, i.e. Meta urinalysis without cutspecifying off points levels. cannabis for urine cotinine analysis. Methods used Methods toused tobaccoverify abstinencecarbon included monoxide testing andand/or saliva except one ( Of the dual six intervention studies, used all report as measures for tobacco cannabisand use at follow brief,All single session interventions as well as the single tobacco targeted intervention used self Biochemical verification about co used bothconcurrently, or co None of the dual studies reported any detailed measurement of co Type of co frequency of days used in past 30 was the (n=14). Measurement of cannabis use was more varied between frequency of use amountused;and Measurement of tobacco usestandard was relatively across studies,all most using cigarettes per day Frequency vs amount Outcome measurement across all studies exceptions ( and group format intervention employed behavioural components only, delivered F via pharmacological treatment, one of which studyinpatient was an Cannabis use interventions consisted mainly of behavioural interventions, with only two using interventionsall were individual. Only one dual intervention was an RCT. computer studies used contingency date for both substances, compared oneand simultaneous with sequential quit attempts of integration of these resourcesto coaddress resourcesexisting for both tobacco cannabisand behavioural tre interventions created new manuals for theof delivery co therapy (NRT) or medication such alongsidevarenicline as a behavioural component. Most dual Each dual intervention provided or offered pharmacotherapy in the form of nicotine repla (3 cannabis use Six studies were dual interventions targeting tobacco and cannabis Intervention content 5 8 9 ) as twothe conditions tested were simultaneous versus sequential , 4 cacy of intervention on change in use tobacco of cannabis,and therefore meta 4 - analyses analyses of RCTs , 4 , - 8 use - - delivered and delivered mobile 5 , use 4 62 6 4 (3 ( , 5 4

, 4 , ) used ) biochemical verification for cannabis cessation. 8 2 7 , , 4 , 6 40 ), (4 Accepted Article), 9

including including one which focussedon tobacco heavy alcoholand use one a of lengthy delivered culturallywhich adapted intervention. 7 - ).

4

).

3

The majority of multi the , 4 ,

management management in additional to other behavioural components; some used a 5 , 4 , - 9 administered, although two studies targeting cannabis use did ask ) , -

phone delivered interventions ( one targetedtobaccouse

to verify cannabisto verify abstinence were more varied; most used This article This isprotected copyright. by Allrights reserved.

most commonlymost used measure (n=8). biochemical verification for tobaccocessation, all and - use varied. Two usestudies varied. - substance interventions (MSI) were brief, with two - analysis andanalysis included in the narrative synthesis - use treatment, which were based on - (4 up. up. 7 )

and targetedsix multi 58 atment (4 - - 2 5 (3 use, i.e. whether use, i.e. participants , 4 , 9

acebook in both an individual 7 , 61, , 5

9 dual dual intervention whereas (60 ).

( 9 ). With one exception 5 The single tobacco single The use - ,62 8 6 - 2 62 ); seven targeted )

set theset same quit ),

although thealthough extent - analyses analyses were (4

- 4 substance use ).

(5 cement 8 ).

Most ( 62 - ), ),

p=0.00 tobacco reduction effect size estimate was 0.09, p=0.30 and cannabisfor the was 0.32,estimate Frequentist meta FIGURE 5 significant effect 0.25of [0.03, 0.45]. Heterogeneity was also high Meta FIGURE 4 df=8, p=0.5, I (studies = 9) showed no intervention effect 0.06at [ Meta Reduction outcomes in intervention target. indicated that I studies outcome, (RR= [1.10, 4.36]), whereas the intervention target. M However, for c multi difference; the pooled risk ratio cannabisfor targeted interventions was For tobaccocessation outcomes, subgroupintervention by analysis target showed very little Sub was 1.46 [1.03, 2.09], indicating almost no difference to Bayesian analysis outcomes. tobacco cessation risk ratio was 1.07 [0.76, 1.52], Forp=0.69. cannabiscessation, risk pooled Frequentist meta FIGURE 3 Heterogeneity across the nine stu ratio of 1.4 Meta FIGURE 2 (Q=8.57, ratio of 1. Meta Cessation outcomes TABLE 2 Each study measured two,three or outcomesfour as indicated in Measures used in meta - group group analysis - - - - - substance interventions 1.25 [0.53,2.94]. analysis of analysis cannabis cessation outcomes shown in 3Figure (studies=8) shows a pooled risk of analysis tobacco cessation outcomes 2Figure shown (studiesin = 9) showspooled a risk analysis of analysis cannabis red of analysis standardised mean change (SMC) in tobaccouse reduction shown as in 4Figure 1

. . This indicates no significant difference from Bayesian meta df=8, df=8, p=0.6; I

10 8

[ Interval [Credibility 2 CrI CrI =0.88). annabis cessation outcomes, subgroupanalyses did indicate a difference by 2

reducedto15% 26%and respectively, it suggesting may be explained by differences 0.9 - - analysis foranalysis cessation outcomes performed. Using was a random effects model, Accepted foranalysis reduction outcomes performed. Using was a random eff Article

2

,

ulti 2 1.39[0.75,2.74]). Heterogeneity of sub 2.

- =0.14). analyses 49 - cannabis targeted interventions mean estimate was simi substance interventions showed a significantly positive effect (RR= 2.19 ] indicating effecta ] small uction outcomes 5Figure shown (studiesin = 9) showed a small

(CrI) dies dies was moderate

0. 68 This article This isprotected copyright. by Allrights reserved. , 1. 87 ]. There was There ].

-

which may be 0.11, 0.23]. 0.11, 0.23]. Heterogeneity was high (Q=11.35, df=7, p=0.9, I little - group of analysis each substance

evidence of heterogeneity Table (Q=59.76, df=8,p=0.8, I clinically significant. - analysis outcomes. 2 1.10 [0.48, 2.85] and for .

2 =0.41 lar lar to the all ).

ects model,

(Q=45.55, 2 =0.93). ratio -

Outcomes of uncontrolled otherand studies of the outcomesfour Sensitivity analysis 0.54]. the studiesall outcome, at differences by intervention target. For cannabis targeted studies the mean estimate was similar to Similarly, for cannabis reduction outcomes, did subgroupanalysis n interventions estimate for cannabis targeted interventions was For tobacco reduction outcomes, subgrou Subgroup analysis

0.04 [0.13,0.169].

Accepted Article altering the variance in each analysis to made 0.2 no significant difference

0.17 0.17 [

- 0.14, 0.45] by and multi This article This isprotected copyright. by Allrights reserved. p analysis p by analysis intervention target made little difference; the

0.09[ - 0.16, 0.34] and multi for - substance interventions at 0.26 [0.03, ot show any meaningful - substance

to any

offered to people with a intervention target Our meta consideration, o Quality of evi by intervention target. 0.23]). Significant heterogeneity within reduction outcomes was not by explained subgroup analysis was observed on cannabis reduction (0.25 [0.03, 0.45]) buttobacco not reduction cannabis cessation, which heterogeneitymay explain found A sma in analysis. substance interventions appeared to have a greater impact than cannabistargeted interventions on negligible impact positive impact on cannabis cessation which significanceapproached (1.48 [0.92, novel analysis approach, Bayesian meta within intervention findings by using unpublis which have been delivered to co This is the first systematic andreview meta D funnel plots were very close to outcomes. original Plots are not this forshown reason. For reduction meta evidence of publication bias. was used to threeadd studies,the risk ratio reduced 1 from meta No evidence of asymmetry was seen when trim and fill was used on funnel ofplot tobacco cessation Publicationbias inconsistent. standardRussell for tobacco abstinence. In otherthe reporting studies of tobacco outcomes was Studies targeting tobacco, including the dual interventions showed higher concordance with the Russell Standard rates of biochemical verification amongst the uncontrolled studies compared t moderate Appraisalquality. of the uncontrolled studies indicates reasonable quality The ofRisk Bias summa Risk of bias summary Quality appraisal degreesmall of reduction in both substances. studies. Reduction outcomes are not presented as data were incomplete, but studiesall indicated a cessation, thatandcessation oftobacco both and The data suggest that a higher proportion of cannabispeople achieved cessation than tobacco TABLE 3 in order of size. sample Table iscussion - analysis (see supplementary material S5). However for cannabis cessation, when trim and fill 3

shows tobacc

- analysis of analysis tobacco cessation outcomes noshowed intervention effect,

dence is considered moderate,

verall theverall quality of evidence should not influence the of validity the findings

on tobaccoon cessation (

Accepted Article . . This - analysis, analysis, no evidence of publication bias was observed as estimates within o ando cannabis cessation for outcomes studiesall not included in meta

ry (supplementary materials S3) indicates that theoverall RCT studies are of

n SUD contrast

which found - s users. users. The has review reported a on

with a recent Cochrane Review ofrecent Review a tobacco Cochrane cessation treatment - 1.10 [0.68, 1.87] This article This isprotected copyright. by Allrights reserved. analysis of analysis RCTs to delivered co -

positive positive outcomes ( overall analysis tolook at interventions for tobacco cannabisor and although heterogeneity should be taken into

hed data

cannabis cannabis was relatively rare, even within dual on co ). ). Subgroup indicatedanalysis that multi .46 to 1.18 [0.8, 1.77], some suggesting - users provided by authors. a Using population 6 - 3 users showed a small ). ). Importantly, most of the ll interventionll effect o RCTs.

previously hidden previously 2.49] irrespective of ( 0.06 [ ,

including including high

); but a ); - 0.11, - analysis analysis .

-

reported only pre studies were excluded as they did not measure use bothof This has review also highlighted methodological issues with the literature. First, a numberlarge of address this prior tocommencing recruitment f than substance settings. misuse Motivation may be a barrier to recruitment; an intervention to must beto given the frame as sampling community settings appear more successful for recruitment the differences between tobacco cannabisand Feasibilityoutcomes. indicafindings outcome standards was high in the dual studies cessation, comparabl T addressing both tobacco cannabisand were identified interventions are any more or effectiveless than multi The from findings our meta absence of prior information. interpretation of th demonstrated one solution to this which is to fromuse priors the data itself. undertaking Bayesian analysis is the lack of informative prior distributions, here we have and distributionfull of the parameter in the o form are similar, their interpretation is very different; the Bayesian analysis giving both a point estimate This has analysis used both Bayesian and traditional methods of meta commonly used within tobacco interventions. reduction was not seen in our analysis, although reduction in comparison tocessation is less inte usersregular has been characterised as challenging, requiring multiple attempts (6 Our showedanalysis effecta small for cannabis reduction. Cannabis cessation or reduction amongst reporting onfully a range tobacco cessation interventions, may potential for interventions to have measured cannabisuse but not reported this, in especially process.review However, the numberlarge of authors who di by explained a non theeffect small we found for cannabis dependence found quality mixed evidence, ( evidence in that was review considered low quality (2 Cochrane of Review psychosocial Our meta use of the other substance post cessationcomparison in toconcurrent use. co may be effectiveless interventions also found no intervention effect tobaccofor cessation, cessation. systematicAn earlier review considering tobaccocessation outcomes within alcohol may partly explain the absence of effect, an in addition tothe influence of cannabison use tobacco interventions in our meta hese - use practised is required; for example, co rvention effects appear(2 small demonstrated - analysis of analysis cannabis cessation shows an effectintervention lower than that found in the

sence/absence of cannabis, of ratheruselevel than Accepted Article - e full posterior e distributionfull reporting bias, although there

e to our meta feas in in targeting cessation ibility

. . Evidence of asymmetry in the funnel plot for cannabis cessation may be - of substance use can addressoutcomes analysis did analysis not i - analysis doanalysis not clearly indicate whether substance single use

and suggest a greater impact cannabison cessation than tobacco

interventions for CUD (RR=2.55, [1.34, 4.83]) - analysis findings. analysis Notably, adherence to tobacco cessation 3 , 2 indicate 5 This article This isprotected copyright. by Allrights reserved. ), in with ), keeping our An effectfindings. on tobacco

nclude evidence (6 - adm 4)

a non

may or treatment appeared effective (6 . . In future interventions, greater attention to types of , e.g. inistration of tobacco cannabisand may increase we f a credible credible f interval.a

compensate for any limitation -

reporting bias. bias. reporting defining abstinencedefining re no obvious indications of such bias in the 4 , although not theincluded in meta - ). ). The Cochrane of Review pharmacotherapies substance use interventions. Dual studies RR 0.98, 0.64to 1.52) - substances based tobacco cessation treatment. This dn’t provide data cofor this potential bias. Analysis Analysis of f . - although brief interventions Biochemical testing may be Although theanalysis. results

pre and pre postand intervention

One of obstaclesthe to , which

The more logical , (

23 thealthough uture studies may may explain some of ), comparable), to 6 relating to 5 ). ). ) te that attention ,

and - users, the and - analysis the brief , or, .

impact on intervention effects is required further discussion of how socio these vary significantly worldwide (7 Most theof evidence was reviewed from the US domains may indicate the source of heterogeneity,the although were not planned in this review. intervention and biochemical verification of cessation. Further sen other sources ofinclude measurement,variability as discussed previously, differences in duration of Although h relevant (7 in cannabis potencythe in last few decades that indicatemore recentto data is likely be most whom only thirteen provided data. Older datasets were likely toless be available, increasing the risk of selection bias. Due totime constraints, only one author conductedscreening initial the process, potentially compensatory use. should be made available conclusions about the dual efficacyvs. interventions single of on use both of substances. This data post intervention theof substanceprimary was not available, and hopefully these will be developed. conclusions. Unfortunately, no RCTs which targetedco int account when considering the greater impact seen cannabison targeted studies. Future male. The lack of tobacco the meta This containsreview limitations and has only partially met its objectives. consensus development within the ( field cannabis reporting standards. Measurement of cannabis use requires fur measure tobacco benefituse would from adherence to these(3 guidelines cessation outcome reporting has been set out Standard;in Russell the cannabis studies which further challenge in reviewing studies, a development of ( CUD indicates that potency may play a sig Third, no within thisstudies reportedreview measuring cannabis type or potency. Literature substance, with successand varying of cessationor reduction either of substance. in joints. Specific patterns coof studies may under reduce Second, addressing these commonly used substances. useand in single multi availability of such data would forallow further investigation by secondary challenging on the basis of cost, erventions which target either but measure both can be added to datatheto expand theseon findings tofindings other countries. One studyformaterials a adapted specific population

potential measurement coof - analysis is smallanalysis 4 eterogeneity of intervention targets has been explored within the sub ). ).

Accepted Article bias and -

report co

69 - substance intervention studies,and would strengthen the evidence base for ). ). Differences between frequency and amount of cannabis use presents a

, targeted provide in in future intervention studies, for allowing an investigation of potential

most studies primarily targeted cannabis - - use, including whether use, use, for when example asked about cannabis may ignore tobacco used 5 - - ) cultural influences pertaining to tobacco cannabisand use use may be associated w but self .

In detail detail and context use of behaviours (6 Evidence of potential compensat studies is a significant limitation, and should be taken into

adequate measurement of types coof Additionally, we contacted a nificant factor in experiencethe of adverse effects and the - nd This article This isprotected copyright. by Allrights reserved. report are measures 72 .

Increasing Increasing variety in routes of administration for both both concepts are subject to recall bias ( );

this

, though process process has begun concurrent coand/or - use could be included in the meta

ith higher levels of dependency on either p atterns ofcannabis both use coand of value large numberlarge of authors (n=25), of also also sitivity analyses acrosssitivity other , ory use of secondthe substance

and and (73) , and easily limits our limits ability to draw T ther discussion and . most 7 -

- he number of studies in

administered - use 5

analysis of analysis the role of co 68 ), and from a ofset ). ). Participants in limits thelimits transfer of participants - ob group analysis, however

7 tainable. tainable. The 0 - 71

wo (4 - ). ). Tobacco analyses; analyses; 6 may may

uld uld were ) changes

but - use

-

http://apps.who.int/iris/bitstream/10665/178574/1/9789240694606_eng.pdf?ua=1. taxes on tobacco. from: 2015. Available 6. Drug and Alcohol Dependence. 2016;166:6 5. effects of recreational cannabis Addiction. use? 2015;110:19 4. Prevention and Health Promotion, Office on andSmoking Health, 2014. Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Years of Progress: A Report theof Surgeon 3. systematic review of prevalencesmoking in addiction treatment. Addiction. 2016;111:220 2. spliffs, and cigarettes:mulled A systematic literature review. Addictive Behaviors. 2017;64:200 1. References in using RStudio. With thanks to the authors whodata provided this for review, and toPeven Kimberley for assistance Acknowledgements provided. that tobacco dependence measured is fully and that adequate tobaccocessation treatment is RCTs of dual interventions are required to address co collect details of type coof impa potential co for Outcomes outcomes amongst co cessation or cannabiscessation. Further researchto is required extricate potential reasons for poor on cannabis reduction but not on tobacco reduction treatment interventions targeting tobacco and/or cannabis use showed interventiona small effect Dual interventi Conclusions research using more intensive tobacco treatment is also interventions warranted. this toreview evaluate simultaneous versus sequential dual treatment Furtherwas inconclusive. different outcome to known whether delivering a tobacco intervention a alongside cannabis intervention results in a concurrently. As the theoretical our review, but most dual interventions adapted existing formaterials either substance closely related substances. The theoretical basis of intervention F more harmful methods of tobacco cannabisand prevail. use may requires administration tobacco, nicotine, cannabisand in its many forms may elicit changes in co uture research considershould the theoretical frame

Meier Meier E, Hatsukami DK. A review of the additive health risk of cannabis tobaccoand co W.Hall What has research over the p US Department of Health and Human TheServices. Health Consequences of Smoking Guydish J, Passalacqua E, Pagano A, Martinez C, L Schauer GL, Rosenberry ZR, Peters EN. Marijuana and tobaccoco World Health Organisation. WHO Report on Global the TobaccoEpidemic, 2015: raising scrutiny

ct of co of ct ons for tobacco cannabisand co and future intervention studies need

-

across populations,all including those from more deprived

Accepted the for account fully to measurement routine need cannabis and tobacco of use Article an - - users.

use in both tobacco and cannabis specific interventions. Interventions must must Interventions interventions. specific cannabis and tobacco both in use intervention which seek t - use practised, as as well

basis basis for This article This isprotected copyright. by Allrights reserved.

dual interventions dual is yetinterventions to developed,fully itbe is not

- General. AtlantaGeneral. (GA): US Department of Health and 12. ast two decades revealed abouttwo decadesast revealed the adverse health

- use have demonstrateduse have feasibility o integrate treatmentintegrate o of both. The study single in . fuller fuller to to take these complexities into account

- N use. use. Future dual intervention work required for addressing use of two o significant effect e T, Chun e J, An T, internationalal. Chun et details details of cannabis use. - 35. s w

as described by some studies in

- - administration in blunts, w use practises such co as as populations seen on

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M s should ensure eta

tobacco , - delivered delivered analysis of where - 30. . . This - 50

- - 11. use. use. -

Research. 2016;22(5): Non 26. reduce cannabis use: A systematic andreview meta 25. use disorder. Cochrane Database of Systematic Reviews. 2016(5). 24. Cochrane Database of Systematic2019(1). Reviews. 23. behavioural interventions for cessation.smoking Cochrane Database of Sys 22. 2020; 206. cessati 21. 291 smokers? Analysis from a multilarge et Doesal. cannabis use moderate cessatsmoking 20. nicotine addiction in adolescent Drugsmokers. and Alcohol Dependence. 2014;141:159 19. Representative Sample of US Adults. Journal of Clinical Psychiatry. 2018;79. ofRisk Cigarette Initiation,Smoking Persistence, andLongitudinal DataRelapse? From a 18. use: a systematicAddiction. review. 2012; 107. 17. Psychiatry. 2013;73:242 relapse in the human laboratory: robust impact tobaccoof cigarette statussmoking 16. United Kingdom. Drug and Alcohol Dependence. 2015;148:165 cigarette andsmoking cannabis dependence: a studylongitudinal of young cann 15. mechanisms 14. 2018;108:137Health. Cannabis Use Among Cigarette Smokers: United States, 2002 13. Drug and Alcohol Dependence. 2018;191:355 cigarette decliningsmoking in the United States? The impact cannabisof use status, 2002 12. American Journal of Drug and Alcohol 2019:1Abuse. disorders overall and by sociodemographic subgroups: a narrative andreview new findings. The 11. England andHome Wales. Office. London, UK; 2018. 10. Canberra, Australia; 2018. 9. Trends and Developments. Luxembourg: Publications Office of Europeanthe 2019.Union. 8. Nations Publications. 7.

- - 296. Clinical Clinical Settings: Findings from a Systematic Review and Meta on outcome? An observational cohort studycare. Drug in primary and alcohol dependence. Hoch E, Preuss UW, Ferri M, Simon InterventionsR. Digital for Problematic Cannabis in Users Olmos A, Tirado Gates PJ, Sabioni P, Copeland J, Le Foll B, Gowing Nielsen S, Gowing L, Sabioni P, Foll B. PharmacotherapiesLe for cannabis dependence. Stead P,LF, Koilpillai Fanshawe TR, Lancaster T. Combined pharmacotherapy and Voci S, L,Zawertailo Balianus D,Masood Is cannabisSelby P. Z, use associated with tobacco Rabin Rubinstein ML, Rait MA, Frequent Prochaska JJ. marijuana use is a Weinberger AH, Platt J, Copeland J, Goodwin RD. Is Cannabis Assoc Use Peters EN, Budney KM. AJ, ClinicalCarroll correlates of co Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD, Predictors al. et of marijuana Hindocha C, Shaban ND,Freeman TP, Das Gale G,RK, Schafer G, Associations al. et between Rabin RA, George TP. A review of co Goodwin RD, Pacek LR, Copeland J, Moeller SJ, Dierker L, Pacek LR, Copeland J, Dierker L, DS,Hasin Shm Office of National Statistics. Drug Misuse: fromFindings the 2017/18 Survey forCrime Australian Institu European Monitoring Centre for Drugs Drugand Addiction. European Drug Report 2019: United Nations Office on Drugs World andDr Crime.

to highexplain rates of co

AcceptedRA, Ashare RL, Schnoll PM,RA, Cinciripini Hawk LW, Lerman C, Tyndale RF, George TP. Article

- 233 42. ulewitz ulewitz D, Sarvet AL. Time trends in US cannabis use and cannabis use - - 8. Muñoz Farré J, M, Torrens M. The efficacy computerizedof interventions to te of Health and Welfare. Alcohol, tobacco& other drugs in Australia.

-

42.

- center Thetrial. American Journal on Addictions. 2016; 25(4): - use. The use. AmericanThe Journal on Addictions. 2015;24:105 This article This isprotected copyright. by Allrights reserved. CO,Cunningham SS,Martins RD. Goodwin Among whom is - morbid tobacco cannabisand use disorders: possible - 60.

ion outcomes in treatment -

ana - 21. lysis. lysis. Addictive Behaviors. 2018;79:52

L. L. Psychosocial interventions for cannabis ug Report 2019. Vienna, Austria: United - 2014. 2014. American Journal of Public - 71. Weinberger A,Weinberger et Trendsal. in Daily

- occurring occurring cannabis and tobacco -

Analysis. EuropeanAnalysis. Addiction ssociated with greater tematic Reviews. tematic2016. Reviews.

- seeking tobaccoseeking iated With Increased abis abis users in the . . Biological - 62. -

2015. 2015.

- - 60. 16.

tobacco cessation outcomes in young adults. Journal Substanceof Abuse Treatment. 2018;94:69 47. Tribe. Addictive Behaviors Reports. 2016;3:21 results of culturally adapted evidence 46. 2013;21:46 receiving treatment for marijuana dependence. Experimental and clinical psychopharmacology. 45. 2011;119:194 and tobacco cessationsmoking among heavy alcohol Drugdrinkers. and Alcohol Dependence. 44. young Controlled Trial in Primary Care. Annals of Family Medicine. 2017;15(2):131 Young Users 41. treatments for marijuana dependence. Addictive Behaviors. 2007;32(6):1220 40. Substance Abuse Treatment. 2013;44(2):231 multiple substance use intervention among young men with and without booster Journal sessions. of 39. Adults. Plos One. 2011;6(3). Exercise Training Reduces Cannabis Craving and inUse Non 38. 2018;50(1):12 varenicline for treating co 37. quantitative studies. McMaster 1998. University 36. for a common standard. Addiction. 2005;100:299 35. Collaboration’s tool for risk ofassessing bias in randomised tri 34. PROSPERO: International prospective register of systematic 2017.reviews interventions which address use of both tobacco cannabi and 33. Reviews and Meta 32. Americans. Psychology of Addictive Behaviours. 2017;31(8):922 psychosocial and pharmacological treatments for cannabis and tobacco use among African 31. clinical psychopharmacology. 2018. cannabis co 30. adults: a systematic of review their co 29. tobacco: Addiction. a 2012;107(7):1221review. 28. a meta 27.

cannabis users. Addiction. 2008;103:1809 - analysis. analysis. Drug and Alcohol Dependence. 2013;133(2):295 Vogel Vogel EA, Rubinstein ML, Prochaska JJ, Ramo betweenAssociations DE. marijuana use a Venner KL, BL,Greenfield KJ, Hagler Simmons J, D,Lupee Homer Pete Metrik J, NS,Spillane Leventhal AM, Kahler CW, Metrik J, NS,Spillane et Marijuanaal. use Laporte C, Vaillant Kadden RM, Litt MD, Kabela G,Gmel Gaume J, Bertho Buchowski MS, Meade NN, Charboneau E, Park S, MS,Dietrich Cowan Aerobic RL, al. et Adams TR, Arnsten JH, Y,Ning S. Nahvi Feasibility and preliminary effectiveness of Law M, Stewart D, Pollock N, Letts L, Bosch J, M. Westmorland West R, Hajek P, SteadL,Stapleton OutcomeJ. criteria in cessationsmoking trials: proposal JPT,Higgins Altman DG, Gøtzsche PC, Jüni P, Moher D,Oxman AD, et Theal. Cochrane Walsh H, Duaso M, A. McNeill A systematic review of behavioural and pharmacological Moher D, Liberati A, Tetzlaff J, Altman DG, The Preferred PG. Report Montgomery L, Robinson Seaman C, EL, Haeny AM. A scopi McClure EA, Tomko RL Ramo DE,Liu H, Prochaska Tobacco JJ. marijuana and use among adolescents and young Agrawal A, Budney AJ, Lynskey MT. The co Tait RJ, Spijkerman R, InternetRiper H. and computerbased interventions for cannabis use: - - 54. use: Druguse: substitution, quit interest, and cessation preferences. Experimental and - rs EN, Petry NM, DM,Lapaglia KM. Reynolds Delay B, Carroll discounting in adults A A Brief Intervent - - 200. 8.

Accepted Article -

Analyses: Analyses: The PRISMA Statement. PLoS Medicine. 2009;6(7):e1000097. - - occurring occurring cannabis and tobacco use. Journal of Psychoactive Drugs. Roussel Roussel H, B,Pereira Blanc O,B,Eschalier Kinouani S, et Cannabis andal.

ion to Reduce Consumption Their (CANABIC): A Cluster Randomized , Salazar , CA, Akbar SA, Squeglia LM, Herrmann E, et Tobacco al. and let let N, J,Flueckiger Daeppen J

- Cormier E,Cormier - - based substance use disorder treatment with a Southwest use. use. Clinical psychology review. 2012;32(2):105 This article This isprotected copyright. by Allrights reserved. - 40. - 7.

- Petry NM. Abstinence ratesbehavioral following 33.

-

18. - 303. - occurring use and occurring use ofmisuse cannabis and

- Treatment Cannabis Seeking s. s. In: Research NIoH, editor. als. British Medical Journal. 2011;343. - B. B. Effectiveness of a brief integrative - 43. - 304. ng review ng andreview meta

Critical reviewCritical form for E, et Pilot outcomeal.

- ing Items ing for Systematic 9. - 36. intervention among

- 21. - analysis of - Dependent

nd - 73.

and 2013;8.Policy. demand analysis, program description, and acceptability. Substance Abuse Treatment Prevention Development of an integrative cessation program for co 66. efficacy for quitting. Addictive Behaviors. 2018;76:45 barriers for cannabis cessation: Relations tocanna 65. reduce cigarette smoking? Drug and Alcohol Dependence. 2008;96:263 64. 2016;11:CD010274. treatment for recoveryor from substance use disorders. Cochrane Database Systematic Reviews. 63. smokers of cannabis and tobacco. and Drug alcohol2015;34:4 review. 62. Alcohol Dependence. 2015;155:134 computer 61. study. The American Journal on Addictions. 2013;22:233 therapy and 60. cigarette smoking. Addictive Behaviors. 2018;79:86 contingency management as an adjunctive treatment cofor 59. Abuse Treatment. 2019;98:39 simultaneous treatment approaches to cannabis anduse disorder tobacco use. Journal of Substance 58. 2008;22:107 mandated students is it or just getting caught that Psychology works? of Addictive Behaviors. 57. a multi drug consumption and perceptions of drug 56. appropriately quantified. International Journal of Epidemiology. 2008;37:1158 55. heterogeneity may mislead. BMC Medical Research Methodology. 2008;8:79. 54. of the Entropy.Likelihood. 2017;19(10). 53. 2018. 25(1): 178 meta 52. fro Available 51. Statistical Computing, Vienna, Austria. 2017. 50. withdrawal in humans: an open 49. intervention. Alcoholism, clinical and research.experimental 2007;31:1380 interventions for mandated students:college sleeper effects of in an 48.

- analysis, and power from analysis a Bayesian perspective. - site cluster randomized trial. Addiction. 2004;99 Becker Jy, Hungerbuehler I, Berg O, Szamrovicz M, A,Haubensack Kormann A, al. et Zvolensky MJ, Paulus DJ, Garey L, Manning Hogan K, JBD, Buckner Perceived al. JD, et McCambridge J, Jenkins DoRJ. brief interve D,Apollonio Philipps R, Bero L. Interventions for tobacco use cessation in people in Becker J, Haug S, Kraemer T, Schaub of MP. Feasibility a group cessation program cofor Lee DC, Budney AJ, BrunetteMF, Hughes JR, Etter J Hill KP, Toto LH, Lukas SE, RD, Weiss Trksak GH, Rodolico behavioralJM, Cognitive al. et Beckham JC, Adkisson KA, Hertzberg J, Kimbrel NA, Budney AJ, Stephens RS, Mo al. et Lee DC, DD,Walker Hughes JR, BrunetteMF, Sche White HR, Mun EY, TJ. Morgan Do brief personalized feedback interventions work for McCambridge J, Strang TheJ. efficacy of single JPT.Higgins Commentary: Heterogeneity in meta Rücker G, Schwarzer G, Carpenter JR, SchumacherUndue reli M. A,Gelman Simpson D, Betancourt M. The Only Prior Can Be Often Understood in the Context Kruschke, andK. J. T. The M. Liddell. Bayesian New Statistics: Hypothesis testing, estimation, Rover BayesianC. random R Core Team. R: A language and environment for statistical computing. R Foundation for Winstock AR, Lea T, Copeland Lithium J. carbonate in management the of cannabis White HR, Mun EY, Pugh L, TJ. MorganLong - assisted intervention - the nicotine transdermal patch dual for nicotine and cannabis dependence: a pilot m: 16. https://arxiv.org/abs/1711.08683 -

Accepted Article206.

50.

- 46. - simultaneously targeting cannabis and tobacco use. Drug and

label study. label Journal of Psychopharmacology

- effects meta - 40.

This article This isprotected copyright. by Allrights reserved. - related risk and harm among young people: results from

- analysis using the bayesmeta R package. 2017. .

bis use problems, bis use withdrawal symptoms, and self - ntions which target alcohol consumption also - 92. term effects of brief substance use - 51. -

session motivational interviewing in reducing :39 - - smokers smokers

8. - rer E, Stanger C,Sequential al. et and analysis should be expected and -

- 52. F, Stanger Outcomes C. F, from a - morbid cannabis use disorder and

Psychonomic Bulletin & Review. of cigarettes and cannabis: - pers 18 - 70. - ance on I 26. on personal feedback -

91. . . 2009;23:84

-

60. 2

in in assessing - 93.

bile bile - -

Intention to Quit. Frontiers in Psychiatry. 2016;7:104. Global Over 75. Psychological Medicine. 2018:1 cannabis potency first and 74. DJ, Rehm J, Gual, TheA. Standard Joint DrugUnit. & Alcohol Dependence. 2017. 176: 109 73. cannabis use disorder. Drug and Alcohol Dependence. 2019;194:500 outcome domains and measures used in psychosocialand pharmacological treatment trials for 72. Lancet Psychiatry. 2018;5:e8. 71. Psychologicaltrial. Medicine. 2017:1 psychotomimetic eff 70. with severity of cannabis dependence. Psychological Medicine. 2015;45:3181 69. devil is in the Drugdetails. and Alcohol Dependence. 2003;70:131 68. 2017;112:1830 administered tobacco cannand 67.

Hindocha C, Freeman TP, Ferris JA, Lynskey MT, No Winstock AR. Smoke without Tobacco: A Freeman TP, van der Pol P, Kuijpers W,J, DasWisselink RK, Rigter Casajuana Kögel C, Balcells Lee DC, S Hindocha C, Norberg MM, Tomko RL. theSolving problem of cannabis quantification. The Hindocha C, Freeman TP, JX,Xia Shaban AcuteNDC, Curran memory andHV. Freeman T Strain versus EC. Single multiple drug focus in substance abuse clinical trials research: The Walsh H, Hindocha C, Duaso M. Commentary on et Popova (2017):al. Co‐used co‐and view of Cannabis and Tobacco Routes Administration of and Their Association with - 1. chlienz NJ, Peters EN, Dworkin TurkRH, DC, EC,Strain et Systematical. of review Accepted Article P, Winstock the Examining AR. profile of high ects of cannabis and tobacco both ‘joint’ and individually: a placebo - time admissions time toadmissions drug treatment: a 16

- abis abis (marijuana) require further Addiction.investigation. 7.

- Olivero MM, López - 12. This article This isprotected copyright. by Allrights reserved.

- Pelayo H,Pelayo Miquel L, Teixidó L, J,Colom Nutt - potency cannabis and its association - 4. - year year study in the Netherlands. - 17.

S, in Changes al. et - 9.

- controlled - 116.

Table 2011( Buchowski 2019Lee ( 2015Lee ( Hill2013 ( ( Adams (5 Beckham2018 ( Becker2015 37 62 9 ) ) )

1

Study

Characteristics of includedstudies 38 2018 )

60 58 61

) ) )

Tobacco & substance Cannabis cannabis Target

Switzerland Location USA USA USA USA USA USA

treatmentwith Withinsubject Studydesign medication cross Pilotstudy Feasibility historical control Single Pilot Pilot RCT - over;

criteria CUD for + TUD days/past7; +veurine 45/past90 days; daily week andweek smoked for 40/past90 day use;C criteria CUD, for non Age18 Age18=, has CUD, T Age18+, meet DSM Age18+;meet DSM lessthan 10CPD in treatmentseeking, dailyTuse inpast smoker; weeklyC Inclusioncriteria Age18+;C use 5 Age18+; usepast 5 days Age18+;C use pastyear T smoker pastyear smoker - C testC 70;has CUD; daily T

Accepted- Article

MET,CBT, CM, NRT MET,CBT, CM, NRT ART,CM, CBT, NRT GT, IT,NRT + V Intervention IT, CBT, IT, NRT MAT,SCC, V CAIT, AE

Historical trial Comparison/ Sequential (crossover MAT,SCC cessation control design) This article is protected copyright.rights by All reserved. data - - - -

4 weeks4 weeks8 months months follow Length weeks weeks weeks up 24 12 10 of 6 6

-

intervention Durationof 4+4weeks 5 12weeks 12weeks 10weeks 2 weeks2 weeks6 - 6 weeks6

co Sample sizeof - 67 32 12 77 users 6 6 5

Attrition sample) (whole 14% 35% 44% 42% 24% rate 0% 0%

(4 White2007 ( Venner2016 (44 Metrik2011 2004(5 McCambridge (3 Gmel2013 (4 Vogel2018 (4 Winstock2009 (4 Peters2013 ( McClure2014 2008( McCambridge ( Kadden2007 ( Laporte2017 46 42 40 41 9 7 9 5 8 ) ) ) ) ) ) ) ) ) )

43 6 ) )

substance Tobacco Multi

-

Switzerland Australia France USA USA USA USA USA USA USA UK UK

trialfor safety double Cluster medication medication Inpatient + utility+ Parallel Pilot RCT; RCT RCT RCT RCT RCT RCT RCT RCT - blind RCT

DSMdiagnosis ofSUD, jointper month over 1 receivingintervention 18+, Conscriptsto military wk;per current useC Age18 Age18+;met criteria service,interested in mandated to for CUD for inpast year Age18+, meet DSM Age15 Studentsreporting Age18+;10+ CPD; Age15 treatmentseeking tribalenrolment, Age16 currentdrug use criteria CUD for heavy drinker 18+,students

dependence metcriteria C for treatment weekly; - weekly 25;CPD,1 x3 - - year 21;useC 3x 25,C use1 - 19;useC

receive

Accepted Article

or CMor or MET + CBT CaseMor MET+CBT IT incl.IT alcohol; NRT CBTor CBT+CM or MICRA (culturally CMCMor CBT+ reinforcement adaptedMI + NAC, CM,NAC, IT community approach OG,CBT + CM + BMI BMI MI BI BI Li

‘Educationas Placebo,CM, intervention intervention Usualcare SCadvice feedback website Written IT, IT, NRT This article is protected copyright.rights by All reserved. usual’ Each Each ASU DIA IT - -

8 weeks8 months months months months months months months weeks weeks weeks weeks 15 24 26 12 12 12 13 14 12 6 6

Singlesession Singlesession Singlesession 12weeks 12weeks sessions 4 weeks8 weeks9 20mins 1 week 1 16

weeks 1 hr 1 - 20

230 254 265 114 240 26 57 19 13 91 68 3

Not givenNot 10.5% 29.2% 55.7% 5.5% 15% 21% 15% 13% 28% 19% 17%

abstinence; RCT: Randomisedcontrolled trial; SC: treatment(for opioid use); MET: Motivation Enhancement Therapy;MotivationalMI: Interviewing; NAC:N DrugDIA: informationand advice; DSM: Diagnostic and Statistical Manual;OGT: Online group; GT:Group therapy; IT: Individua Computer Key: (5 White2008 7

) AE;Aerobic Exercise; ART: Abstinence ReinforcementTherapy; ASU: Assessment ofsubstance use; BI: BriefIntervention; BMI: B

- assisted IndividualTherapy; CaseM: Case Management; CBT:Cognitiv USA

Smokingcessation; SCC: Standard clinical care; T:tobacco; V: Varenicline RCT

mandated toreceive 18+,students treatment eBehaviour Therapy; CM: Contingency management; CPD: cigarettes per day; CUD: cannabis usedisorder;; Accepted Article Immediatewritten feedback - acetylcysteine; NRT: Nicotinereplacement therapy; PPA: point prevalence

feedback Delayed written This article is protected copyright.rights by All reserved. ltherapy; Li: Lithium carbo

riefMotivational Interviewing; C: cannabis;CAIT: months 7

Singlesession nate;MAT: Medication assisted

14

4.8%

pastin30 Table participants of Total number ( 2018 Vogel ( White 2008 ( White 2007 ( Metrik 2011 ( 2004 McCambridge ( Gmel 2013 ( 2013 Peters ( 2014 McClure ( 2008 McCambridge ( 2007 Kadden ( Laporte 2017 56 43 ) )

2

Outcome measures used eachfor RCT includedin meta

39 47 57 48 45 44 40 ) 41 ) 42

) ) )

)

) ) )

Accepted Article Biochemicallyverified (BV) or self(BV) cessation cessation Tobacco Tobacco 1117 (SR) BV BV SR SR SR SR SR SR SR - -

- reported

Biochemicallyor verified(BV) Cannabis cessation Cannabis cessation self - reported(SR) 1095 BV BV SR SR SR SR SR SR - - -

This article is protected copyright.rights by All reserved.

-

analysis.CPD =cigarettes perday, past30 days = days useof days used in past past days used in cigarettes per per cigarettes per cigarettes reduction Tobacco Tobacco week week 1068 CPD CPD CPD CPD CPD CPD 28 - -

Cannabis Cannabis reduction frequency of frequency in use of frequency frequency of use use of frequency month per joints joints per day per joints past past 30 days past 30 past 30 days past 30 days past past month past month per week 1103 - -

days

use in use

15 15 months 13 months 14 months 12 months 7 7 months 26 weeks 12 weeks 6 months 6 months 12 12 weeks 8 8 weeks follow follow up Length of of Length

Table T=tobacco, C=cannabis, MSI = multi = MSI C=cannabis, T=tobacco, n Venner 2016( Beckham Buchowski 2011 ( Adams 2018 ( Hill ( 2013 Winstock 2009 (4 Lee 2015 ( Lee 2019 ( Becker 2015 (

3

Outcomes tobaccoof and cannabis cessation withinstudies Study

2018 ( 60 61 58 ) ) )

61 37 46 59 ) )

Accepted Article)

9 38 ) )

)

T&C T&C T&C T&C T&C T&C - MSI substance intervention substance C C

Target

127 13 32 67 77 3 5 6 6 7

Sample size

8 months 8 months 6 months 6 10weeks 12weeks 12weeks 12weeks

4 weeks 4 weeks 8 This article is protected copyright.rights by All reserved. Length of follow- -

up

excluded from meta 4 (7.8) 4 1 (20)1 n quit tobacco and 5 0 0 0 0 0 0 -

cannabis, (%) 4 (12.5)4 (17.6)6 (10.4)8 3 (100)3 - 21

n quit tobacco, analysis 0 0 0 0 0

(%)

;

15(19.5) 7 (20.6)7 14(44) 1 (20)1 (23)3 1(14)

31 n quit cannabis, 0 0 0

(%)

Figure 1 Accepted Article :PRISMA diagram showing search andreview process

This article is protected copyright.rights by All reserved.

targeted bothsubstances group/totalin group;intervention target shown in brackets afterstudy name;CrI Credibility= Interval. NB not all studies ‘Intervention’Key: = numberwho quitin intervention group/totalin group;‘con Heterogeneity:Q=11.35, df=7,p=0.9, I Figure targeted bothsubstances group/totalin group;intervention target shown in brackets afterstudy name;CrI ‘Intervention’Key: = numberwho quitin intervention group/totalin group;‘control’ = number whoquit controlin Heterogeneity Figure 2 3

Tobaccocessation Cannabis cessation Accepted Article:Q=8.57, df=

8, p=0.6,I 2 2 =0.14,n=1050 =0.41,n=1028

This article is protected copyright.rights by All reserved. trol’ = number whoquit controlin

= Credibility= Interval. NB notall studies

Heterogeneity:Q=59.76, valuep = 0.8, I Figure Heterogeneity:Q= Figure 4 5

Tobaccoreduction Cannabisreduction

Accepted Article45.55,p value= 0.5, I

2 2 = 0.93,= n=1103 =0.88, n=1068 This article is protected copyright.rights by All reserved.