Introduction

The current overdose crisis is a critical public health issue worldwide. In 2015, approximately 450,000 people died as a result of drug use, with one-third to one-half due to overdose deaths, most of which were attributable to opioids.1 In the European Union, there were 8200 deaths caused by illicit drug use in 2017, and 90% of these were from opioids.2 In Canada, more than 11 people have died due to opioid overdoses each day since 2015, while many more individuals are hospitalized or seek care at emergency departments for opioid poisioning.3,4 The United States has the highest rate of overdose deaths, with more than 130 people dying each day from overdoses involving opioids.5,6 There is an urgent need to identify strategies that address the root causes of the overdose crisis, which include structural barriers to care, mental health and addictions, poverty, stigma, and their intersections.7-10 There is also a need to move beyond understanding cause and effect to addressing possible interventions for the overdose crisis. Identifying such approaches will require a consideration of frameworks beyond those of the health care sector.11 Despite being recognized in North America as a public health crisis spanning multiple sectors, there is a lack of multidisciplinary knowledge syntheses on the overdose crisis.

It is important to take a broad perspective on different types of legal approaches and government policies that may impact the overdose crisis. Changes to existing legal approaches and government policies related to illegal substances and drug use show that innovations may have far-reaching effects.12 Laws can affect which substances are most readily available to people and the relative purity of illegal substances.12,13 Consequently, new legal approaches may have a substantial impact if they shift use to a safer drug supply; for example, the use of prescription hydromorphone rather than procurement of illegal opioids with a high chance of contamination by fentanyl can significantly mitigate potential harms. Such legal measures can include decriminalization of drug possession or legalization of "hard" drugs (eg, heroin or cocaine).

Other legal approaches and government policies that do not directly target the overdose crisis may unintentionally affect overdose risk and other harms related to substance use. For example, some studies suggest that the legalization of recreational cannabis is associated with a reduction in opioid overdose rates.15 Additional legal options include enacting a Good Samaritan law that grants prosecutorial immunity for simple possession to people who seek help during a drug overdose; introducing therapeutic court programs (also known as specialty courts, drug courts, or dissuasion commissions) where drug possession is handled in the legal system through referral to addiction treatment programs; implementing involuntary confinement in medical care for individuals with substance use disorders; and pursuing murder prosecutions for drug dealers in cases of overdose deaths.16

It is also critical to consider the unintended, and sometimes adverse, consequences of policies enacted to address public health and safety. For instance, laws that restrict substance use may place barriers on individuals who need care but are reluctant to seek it due to fear of prosecution, stigma, or other negative consequences.12 Prescription drug monitoring programs may lead to inadvertent harms, as individuals who no longer have access to prescription opioids may seek illicit and contaminated substances.17

To address this topic, we gathered a team of researchers and decision-makers with expertise spanning the policy, health care, law enforcement, and legal systems to determine the most important review question to be answered using knowledge synthesis. We used an integrated knowledge translation approach. Each of the team members identified topics most relevant to them, which were then compiled into a list. The list was reviewed by the team, and each potential topic was discussed, merged, or refined, by consensus. Team members then anonymously voted for their priority topic, and the review question that received the most votes was chosen. Thus, we will undertake a scoping review on the different legal approaches and government policies that address the overdose epidemic. For the purpose of the protocol and review, the term "legal approaches and government policies" will be used to describe the variety of approaches that have been taken internationally through judiciary mechanisms as well as government measures, including legislative options and changes to health and social policy.

In the current crisis, evidence suggests that contamination of the illegal drug supply by high-potency opioid analogues, such as fentanyl, has been a main contributor to high overdose and death rates.14 Given the critical role of opioids within the current overdose crisis, a decision was made to limit the scope of this review to studies where the legal approach or government policy directly addressed opioids (both prescription or illegally obtained/manufactured) or where the consequences of the legal approach or government policy could directly or indirectly be associated with opioid use-related harms or outcomes. Limiting the scope to opioids will also make the review more manageable to conduct.

As the literature for legal approaches and government policies is heterogeneous and dispersed throughout the health, legal, and social sciences literature, we determined that a scoping review is the appropriate approach to answer our review questions. A preliminary search of MEDLINE, Open Science Framework (OSF), the Cochrane Database of Systematic Reviews, the Campbell Collaboration, PROSPERO, and Google Scholar found no existing knowledge syntheses on this topic.

This scoping review will serve as a comprehensive source of information for policy-makers and individuals working at the forefront of the overdose crisis to identify legal approaches and government policies already in place or those that have been recently implemented worldwide. It may also be used to inform the development of evidence-based legal approaches and government policies that can be implemented to mitigate the effects of the ongoing overdose crisis.

Review questions

i. What literature exists on the different legal approaches and government policies that have been implemented internationally resulting in an intended or unintended effect on the current overdose epidemic?

ii. What literature exists that documents the beneficial, harmful, and unintended effects of different legal approaches and government policies on opioid use-related harms and mortality?

Inclusion criteria

Concept

The scope of this review encompasses legal or policy approaches at a governmental or regulatory level that relate directly or indirectly to opioids, and intentionally or unintentionally affect an opioid use-related harm. A legal approach or government policy is an action taken at the international (ie, United Nations), federal, state/province, or municipal levels. This can include actions that are legislative (eg, prescription drug monitoring programs) or regulatory (eg, changing the scheduling of a prescription drug). It also includes actions taken by other regulatory bodies (eg, health authorities, other agencies that govern the conduct of health professionals). A legal or policy approach can have intended effects (eg, reducing opioid prescribing rates) or unintended effects (eg, increasing illicit drug overdose rates). An opioid use-related harm is a negative result of opioid use and may include diverse outcomes including overdose, death, crime, or infectious diseases spread through injection drug use.

Context

The context for this review is global, and will include legal approaches and government policies from countries of any income levels.

Types of sources

This review will consider any research article or policy document. We will include empirical, quantitative, or qualitative studies, as well as other research that aims to i) compare legal approaches and government policies in different jurisdictions; ii) analyze codes, rules, acts, laws, or guidelines; or iii) present the consequences of implementation of policies or laws, or effects on society. Studies published in English from 2000 onward will be included. The publication date limit was imposed to attempt to capture studies that focus on a time period with comparable contextual factors to the present (ie, increased rates of opioid prescriptions, fentanyl contamination of illicit drugs).3,14 Commentaries and letters to the editor will be excluded, as they are not considered studies as defined above. Conference abstracts will be excluded, as they are often ongoing studies without finalized data; however, excluded conference abstracts will be used to search for full study reports that have not already been included.

Methods

This review will follow the JBI methodology for scoping reviews.18

Search strategy

An initial limited search of MEDLINE (Ovid) and Academic Search Complete (EBSCO) was undertaken to identify articles that met the inclusion criteria, along with papers that were identified by the review team as relevant. The titles and abstracts of these studies, along with articles already identified by the research team, were used to identify keywords and the indexing terms in each database. The keywords and index terms were used to create a search strategy that will be translated to all databases. A simplified version of the search was developed for legal databases. A full MEDLINE search is presented in Appendix I. The final step in the search strategy is to review the reference lists of all included studies, as well as to use Google Scholar to review citing papers to locate additional studies.

Information sources

We will search health sciences databases (MEDLINE [Ovid], Embase [Ovid], PsycINFO [EBSCO], CINAHL Complete [EBSCO], Native Health Database), legal databases (Legal Periodicals & Books [EBSCO], LegalTrac [GALE], HeinOnline), and social sciences databases (PAIS Index [ProQuest], Sociology Collection [ProQuest], Academic Search Complete [EBSCO], JSTOR Collection, and Project Muse) to ensure comprehensive identification of studies across disciplines. To reduce publication bias, we will conduct an extensive gray literature search to find non-commercially published literature. We will also search conference proceedings (PapersFirst [WorldCat], Web of Science Conference Proceedings Citation Index: Science, and Conference Proceedings Citation Index: Social Science & Humanities), government and non-governmental organizations reports (De Libris, EU Bookshop, EUR-Lex, WHO Library Database, National Information Center on Health Services Research, United Nations Offices on Drugs and Crime Website, RAND Corporation Website), gray literature databases (OpenGrey, Grey Literature Report), and other databases and search engines (DoPHER, Google).

Study selection

All identified studies will be uploaded into EndNote V9.1 (Clarivate Analytics, PA, USA) and duplicates will be removed. The references will then be uploaded to Rayyan (Qatar Computing Research Institute, Doha, Qatar) and any further identified duplicates will be removed. Due to the high number of expected results from our search, the titles and abstracts will first be screened by a single team member who will remove any that clearly do not include a legal approach, are not related to opioid use, or are clearly the wrong format (eg, commentary). When there is ambiguity, the team member will always choose to include studies for the next phase. The resulting titles and abstracts will be screened again independently and in duplicate by two team members using Rayyan. First, a pilot with 100 title and abstracts will be completed to test the inclusion criteria. The resulting full-text articles will then be reviewed independently and in duplicate by two team members using Rayyan. Again, a pilot with 50 full-text articles will be completed, and if this reveals a lack of consensus, the team members will meet to better clarify the inclusion criteria. Pilots of 50 articles will continue until at least 80% consensus has been reached. Any disagreements in screening and full-text review about the relevance of a particular study will be resolved through discussion until consensus is reached. When consensus cannot be reached, it will be reached through involvement of a third reviewer. The number of potential studies identified, number of abstracts reviewed, and number of full-text articles reviewed, as well as the number eliminated at each stage of the study selection process, will be documented. The results of the search and the study selection process will be reported narratively and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).19

Data extraction

A data extraction form will be created using REDCap (Vanderbilt University, TN, USA) electronic data capture tool. A draft of the fields for the data extraction form is included in Appendix II. Minimum data to be extracted from all sources include publication year, target substance, country, study population, conflicts of interest, type of legal approach/government policy, specific legal approach/government policy, and intended or unintended effects on the overdose epidemic or on opioid-related harms. Ten articles will be used in pilots to test the data extraction form. Once the data extraction form has been finalized, one team member will independently extract data from each article, and a second team member will independently verify the data extraction. Any disagreements will be discussed and resolved through consensus.

Data presentation

The results of the review will be presented as a narrative synthesis and in a tabular or diagrammatic form, depending on which is more appropriate to the objective of this review. Non-empirical sources will be presented in tabular form and will be mapped to the type of legal approach presented and country or region from where it is based. Empirical studies will be mapped to the type of legal approach, the specific legal approach, country/region, and outcomes, and will be presented in a table.

Acknowledgments

Members of the Overdose Crisis Knowledge Synthesis Working Group.

Funding

This work is supported in full by the Canadian Institutes of Health Research Opioid Crisis Knowledge Synthesis Grant #156786. The funder will have no role in content development.

Appendix I: Search strategy

Database: Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>

Search conducted April 24, 2018; all languages included

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1. analgesics, opioid/ (36,526)

2. (opioid? or algopan or biopan or cofapon or laudanon or laudan#m or laudopan or nepenthe or omnopon or opial or opon or oposal or pantopon or pantopone or papaveretum or pavon or tetrapon).tw,kw. (74,382)

3. Buprenorphine/ (4503)

4. (anorfin or belbuca or buprenorphine or buprenex or buprex or buprine or butrans or finibron or lepetan or norphin or pentorel or prefin or probuphine or subutex or temgesic or transtec).tw,kw. (5750)

5. "Buprenorphine, Naloxone Drug Combination"/ (194)

6. (bunavail or suboxone or zubsolv).tw,kw. (131)

7. Codeine/ (4316)

8. (codein? or codicaps or codipertussin or codyl or ardinex or isocodeine or methylmorphine or methyl morfine or methyl morphine or methylmorfine or pentuss or tussicalm).tw,kw. (4844)

9. Fentanyl/ (12,666)

10. (abstral or dur?gesic or epufen or fentanest or fenta#yl or fentora or fentalis or fentanex or instanyl or lazanda or leptanal or mezolar matrix or onsolis or pecfent or phentanyl or rapinyl or recuvyre or subsys or tany or transfenta or sublimaze).tw,kw. (16,971)

11. Heroin/ (5278)

12. (heroin? or acetomorphine or diacephine or diacetyl#lmorphine or diagesil or diamorf or diamorphine or diaphorin or morphacetin).tw,kw. (13,609)

13. Hydrocodone/ (535)

14. (hydrocodon? or codinovo or dicodid or dihydrocodeinone or bekadid or dico or dicodid or dihydrocodeinone or dihydrocodone or hydrocodonum or hycodan or hycon or hydrocodeinonebitartrate or robidone).tw,kw. (947)

15. Hydromorphone/ (1163)

16. (hydromorphon? or biomorphyl or cofalaudid or dihydromorphinone or dihydromorphone or dilaudid or dolonovag or exalgo or hydal or hydromorphcontin or hydromorphinone hydrochloride or hydrostat ir or hymorphan or jurnista or laudaconum or novolaudon or opidol or pal#adon? or rexaphon or semcox or sophidone or laudacon or palladone).tw,kw. (1497)

17. Levorphanol/ (601)

18. (levorphanol or levorphan? or levodroman or levodromoran or levodromoran or lemoran or dromoran).tw,kw. (527)

19. Meperidine/ (5606)

20. (meperidine or algil or alodan or centralgin? or cluyer or demero? or dolantin? or dolargan or dolcontral or dolin or dolsin or dispadol or dolanquifa or dolantine or dolargan or dolcontral or dolenal or dolestie? or dolocontral or doloneurin or doloneurotrat or dolor or dolosa? or dolosan or dolvanol or endolate or isonipecain? or l#dol or pethidine or mefedina or mepadin or meperdol or meperid#n? or meperidol or mephedine or meperidine or mialgin or neomochin or opistan or pantalgin or petadin or petantin? or pethanol or pethidine? or petidin or phetidine or piridosal or sauteralgyl or simesalgina or supplosal or synlaudine).tw,kw. (5922)

21. Methadone/ (11,519)

22. (methadone or adanon or algidon or alglysin or algoxale or althose or amidon? or amidosan or anadon or butalgin or deamin or depridol or diaminon or dianone or dolafin or dolamid or dolesone or dolmed or dorex or dorexol or eptadone or fenadon or gobbidona or heptadon or ketalgin or mecodin or mepecton or mephenon or metadon or methaddict or metasedin or metadol or dolophine or biodone or methadose or methex or miadone or moheptan or pallidone or phenadon? or phymet or physepton? or polamidon or polamiv#t or pinadone or symoron or sinalgin or symoron or westadone).tw,kw. (12,694)

23. Morphine/ (36,706)

24. (anpec or morphine or morphia or (ms adj contin) or dur#morph or oramorphsr or epimorph or miro or morfin? or morphinium or morphium or opso or skenan).tw,kw. (47,374)

25. Morphine derivatives/ (2191)

26. Morphine?.tw,kw. (47,174)

27. Nalbuphine/ (640)

28. (bufigen or nalbuphin? or nubain or nalcryn or nalpain or nubain? or onfor).tw,kw. (875)

29. Opiate Alkaloids/ (142)

30. (opiate? Algopan or biopon or cofapon or laudanon or laudanum or laudopan or nepenthe or omnopon or opial or opon or oposal or pantopon? or papaveretum or pavon or tetrapon).tw,kw. (273)

31. Opium/ (1945)

32. opium.tw,kw. (2343)

33. Oxycodone/ (1905)

34. (oxycodone or dihydrohydroxycodeinone or dihydrone or dinarkon or eucodal? or oxiconum or oxycodeinon or oxycone or oxycont#n or pancodine or theocodin or bionin? or bolodorm or broncodal or broncodal or bucodal or cafacodal or cardanon or codenon or dihydrohydroxy#odeinone or dinarkon or endone or eubine or eucodalum or eu?din or eukodal or eumorphal or eurodamine or eutagenhydrocodal or hydroxycodeinoma or ludonal or medicodal or narcobasin# or narcosin or nargenol or narodal or nucodan or optonossicodone or oxanest or oxaydo or oxecta or oxicone or oxikon or oxy ir or oxycod or oxycodeinonhydrochloride or oxycodone hydrochloride or oxycodonhydrochlorid or oxycodyl or oxycontin or oxydose or oxyfast or oxygesic or oxyir or oxykon or oxynorm or paavinal or percolone or pronarcine or remoxy or rox#codone or sinthiodal or stupenal or supeudol or tebodal or tekodin or thecodin or xtampa or xtampza).tw,kw. (2879)

35. Oxymorphone/ (480)

36. (oxymorphone or numorphan or opana or hydroxydihydromorphinone).tw,kw. (594)

37. Pentazocine/ (2210)

38. (pentazocin? or talwin or lexir or fortral or dolapent or fortal or fortalgesic or frotaline or fortwin or liticon or peltazon or pentafen or pentagon or pentalgina or perutagin or sosegon or sosigon or talioin or talwin).tw,kw. (3168)

39. Phenazocine/ (510)

40. (phenazocine or phenbenzorphan or phenethylazocine or narphen or prin#dol or xenagol).tw,kw. (81)

41. Phenoperidine/ (216)

42. (phenoperidine or operidine or lealgin or fenoperidine).tw,kw. (153)

43. Sufentanil/ (1704)

44. (sufentan#l or sufenta or sufentanilhameln or sufentanilratiopharm or fentathi#nyl or fentatinenil or zalviso).tw,kw. (2479)

45. Tramadol/ (2736)

46. (tramadol or tramadoc or tramadin or tramabeta or tramadorsch or tramadorsch or tramakd or tramaabz or tralgiol or tradonal or tradolpuren or tradolpuren or tradol or topalgic or tiral or theradol or takadol or tamolan or tandol or tarol or topalgic or trabar or trabilan or trabilin or topalgic or trabar or trabilan or trabilin or tradolan or tradonal or tralic or tramada or tramadex or tramadol or tramadolium chloride or tramagetic or tramagit or tramahexal or tramake or tramal or tramazac or tramed or tramol or tramundin or trasedal or trasik or trexol or tridol or trodon or trondon or unitral or urgendol or zamad#l or zodol or zumatran or omnidol or pengesic or penimadol or prontofort or prontofort or nobligan or newdorphin or nobligan or nonalges or mtwtramadol or mtw or mabron or melanate or mosepan or tramadol or jutadol or katrasic or kontram xl or contramal or calmador or calmol or conzip or dolana or dolika or dolmal or dolotral or dolzam or dromadol or eufindol or exopen or biokanol or biodalgic or bellatram or biodalgic or adamo? or amadol or adolonta or adamon or Amanda or analdol or andalpha or tramadoldolgit or tramadolhameln or tramadolor or tramadolratiopharm or tramadura or tramagetic or tramagit or tramake or tramal or tramex or tramundin or trasedal or radol or rofy or fyzolt or sefmal or sensitram or ultram or zamudol or zumalgic or zydol or zytram).tw,kw. (4663)

47. Opioid-Related Disorders/ or heroin dependence/ or morphine dependence/ or Opium Dependence/ (22,597)

48. Narcotics/ (15,884)

49. (narcotic? or stupefacient).tw,kw. (14,352)

50. Loperamide/ (1055)

51. (loperamide or imodium).tw,kw. (1587)

52. Mitragyna/ (132)

53. (mitragyna? or kratom or ketum).tw,kw. (303)

54. or/1-53 (18,8176)

55. legislation/ (1670)

56. lj.fs. (239,344)

57. (legislation or legislate or legislative).tw,kw. (38,505)

58. Legislation as Topic/ (15,749)

59. (amendment? or law?).tw,kw. (110,343)

60. (legal adj4 (construct^* or framework^* or approach^*)).tw,kw. (2535)

61. Legislation, Drug/ (9625)

62. (decriminali^* or criminal^* or legali^* or prohibition or depenal^*).tw,kw. (25,456)

63. government/ or federal government/ or government agencies/ or local government/ or state government/ (45,277)

64. Government Programs/ or state health plans/ (9048)

65. (govern^* or state health plan?).tw,kw. (172,992)

66. Government Regulation/ (19,990)

67. (regulation or regulate).tw,kw. (890188)

68. Policy/ or Health Policy/ or Public Policy/ or Policy Making/ (100,272)

69. (policy or policies).tw,kw. (209,106)

70. (administrative adj2 (law? or sanction? or violation?)).tw,kw. (209)

71. Criminal Law/ (5268)

72. (criminal adj justice).tw,kw. (3385)

73. Jurisprudence/ (29,460)

74. (jurisprudence or (legal adj (status or aspect? or obligation?)) or (court adj decision?) or litigation? or judicial).tw,kw. (18,926)

75. Supreme Court Decisions/ (3658)

76. (supreme adj court).tw,kw. (3718)

77. Practice Guidelines as Topic/ (103,452)

78. (guideline? adj2 (develop^* or publication)).tw,kw. (11,296)

79. ((prescribing adj2 standard?) or reschedul^*).tw,kw. (550)

80. or/55-79 (1,733,305)

81. Drug Overdose/pc [Prevention & Control] (768)

82. overdose?.tw. (16,478)

83. ((therapeutic or specialty or drug) adj5 court).tw,kw. (349)

84. (dissuasion adj5 commission?).tw,kw. (0)

85. ((drug or opioid?) adj8 (sentencing or sentence? or prosecution? or criminal charge?)).tw,kw. (188)

86. Crime/ or Criminals/ or Drug Trafficking/ or Prescription Drug Diversion/ or Prescription drug misuse/ (19,168)

87. (crime? or criminal or possession or trafficking or ((drug or opioid) adj2 (trade? or dealing? or smuggling? or misuse or diversion? or manufacturing or distribution)) or (controlled substance adj2 diversion?)).tw,kw. (88,407)

88. ((murder adj8 overdose) or (mandatory adj3 minimum?)).tw,kw. (63)

89. (good adj2 Samaritan).tw,kw. (399)

90. (prosecutorial adj2 immunity).tw,kw. (0)

91. (medical adj3 amnesty).tw,kw. (35)

92. Harm Reduction/ (2393)

93. (harm adj2 (reduction or minimi#ation)).tw,kw. (3678)

94. Naloxone/ (18,055)

95. (naloxone or narcan or narcanti or nalone).tw,kw. (22,088)

96. Opiate Substitution Treatment/ (2104)

97. ((opioid or opiate) adj (substitution or replacement)).tw,kw. (885)

98. (heroin assisted adj treatment).tw,kw. (93)

99. Needle-Exchange Programs/ (1565)

100. (safe injection adj5 site^*).tw,kw. (25)

101. ((safe or supervised) adj2 consumption).tw,kw. (419)

102. (((syringe or needle) adj (exchange or distribution or program? or access)) or (supervised adj inject^*) or NSP).tw,kw. (4086)

103. involuntary treatment/ or involuntary treatment, psychiatric/ (12)

104. (involuntary adj3 (confine^* or treatment? or commitment?)).tw,kw. (998)

105. legal commitment.tw,kw. (18)

106. Substance Abuse Treatment Centers/ (5020)

107. (rehab or rehabilitation or (drug adj2 (centre or center))).tw,kw. (141,890)

108. ((drug adj2 (dehabituation or abuse treatment)) or (residential adj2 drug treatment)).tw,kw. (1164)

109. mandatory programs/ or mandatory reporting/ or mandatory testing/ (6332)

110. (mandatory adj2 (program^* or reporting or screening or testing)).tw,kw. (2329)

111. Social Control Policies/ (774)

112. (social adj2 control?).tw,kw. (2818)

113. Coercion/ (4266)

114. coercion.tw,kw. (2822)

115. Law Enforcement/ (3223)

116. (police or policing).tw,kw. (12,798)

117. LEAD.tw,kw. (522,282)

118. Prisons/ or Prisoners/ (20,795)

119. (incarcerat^* or prison^*or inmate? or correctional or penal or penitentiary or postincarceration).tw,kw. (13,836)

120. ((restorative adj2 (justice or conferenc^* or board? or circle? or system?)) or sentencing circle? or community court? or (victim offender adj2 (dialogue or conferencing or reconciliation)) or ((family group or community accountability) adj2 coferen^*) or community restorative board? or community justice committee? or referral order panel? or peacemaking circle?).tw,kw. (501)

121. Cultural Competency/ (4462)

122. (cultural adj2 (competenc^* or safety)).tw,kw. (2956)

123. Child Protective Services/ (206)

124. ((child protective adj3 service^*) or (child welfare adj3 agenc^*)).tw,kw. (1064)

125. child welfare/ or child advocacy/ or child custody/ (25,166)

126. ((child or adolescent or juvenile or youth) adj2 (welfare or well being or protection or protective)).tw,kw. (6422)

127. (child adj2 advocac?).tw,kw. (230)

128. (child adj2 (support or custody)).tw,kw. (1146)

129. Drug monitoring/ (18,412)

130. ((drug or prescription or opioid) adj2 monitoring).tw,kw. (11,297)

131. (prior adj authori#ation).tw,kw. (462)

132. prescriptions/ or drug prescriptions/ or inappropriate prescribing/ (29,616)

133. (prescribing? or prescription? or prescribe).tw,kw. (113,106)

134. Drug Approval/ (13,099)

135. (drug adj2 approv^*).tw,kw. (8686)

136. "Drug and Narcotic Control"/ (8298)

137. ((drug or narcotic or opioid or opiate) adj5 (control? or regulation?)).tw,kw. (20,724)

138. Cannabis/ (7861)

139. (cannabi? or bhang? or ganja? or hashish? or hemp? or mari#uana?).tw,kw. (24,787)

140. Medical Marijuana/ (627)

141. "marijuana use"/ or marijuana smoking/ (4171)

142. cannabinoids/ or cannabidiol/ or cannabinol/ or dronabinol/ (12,250)

143. (cannabinoid? or cannabidiol or cannabinol or dronabinol or marinol or THC or tetrahydrocannabinol).tw,kw. (21,786)

144. Street drugs/ (9888)

145. ((recreational or street or illicit or illegal) adj2 drug?).tw,kw. (14,145)

146. Designer drugs/ (1356)

147. ((designer or customized) adj2 drug?).tw,kw. (1290)

148. Crack Cocaine/ (1335)

149. crack.tw,kw. (7534)

150. Cocaine/ or Cocaine Smoking/ or Cocaine-Related Disorders/ (27,769)

151. cocain?.tw,kw. (35,341)

152. Amphetamine/ (12,255)

153. (amfetamine? or amphetamine?).tw,kw. (23,860)

154. Dextroamphetamine/ (6840)

155. (Dextroamphetamine or curban or dexamfetamine or dexamphetamine or Dexedrine or dextro amphetamine or dextrostat or oxydess or d amphetamine).tw,kw. (5827)

156. Methamphetamine/ (8408)

157. (methamphetamine? or crank or crystal or ice or speed or meth).tw,kw. (365,116)

158. "n methyl 3,4 methylenedioxyamphetamine"/ (3699)

159. ("n methyl 3,4 methylenedioxyamphetamine" or ecstasy or MDMA).tw,kw. (5407)

160. "3,4-Methylenedioxyamphetamine"/ (880)

161. ("3-Methylmethcathinone" or 3-MMC or 3-mephedrone).tw,kw. (139)

162. (ketamine or cal#psol or kalipsol or ketalar or ketanest or ketaset).tw,kw. (16,274)

163. (hallucinogenic or hallucinogens or psychedeli^* or ((psychotomimetic or psychodysleptic) adj2 (drug? or agent?))).tw,kw. (3563)

164. (me#calin? or peyote or peyotine or peyoti).tw,kw. (825)

165. Psiloc#bin?.tw,kw. (594)

166. (Dimethyltryptamine or DMT).tw,kw. (2226)

167. Ayahuasca.tw,kw. (200)

168. (Phencyclidine or PCP or angel dust or sernyl or serylan or syclan).tw,kw. (13,262)

169. (LSD or Lysergic Acid Diethylamide or lysrgide).tw,kw. (5558)

170. salvia.tw,kw. (3816)

171. or/81-170 (1,562,014)

172. 54 and 80 and 171 (8379)

173. exp Animals/ not (exp Animals/ and exp Humans/) (4,448,859)

174. 172 not 173 (6435)

175. limit 174 to yr="2000 -Current" (4806)

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Appendix II: Draft data extraction form

References