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National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12.

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The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research.

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Appendix BStudy Approach

In response to its charge, the committee developed a process defined by discrete actions building toward an evidence base that would eventually inform the committee's findings and conclusions. This process is depicted in Figure B-1.

FIGURE B-1. Summary of the committee's process.

FIGURE B-1

Summary of the committee's process.

The following sections detail the process by which the committee came to their conclusions about the weight of evidence regarding the association between cannabis and specific health endpoints. The steps include the literature search, the refinement of the specific health endpoints of medical and public health importance to be assessed, the identification and assessment of relevant literature (including published systematic reviews and primary literature), and the development of consistent and specific language to describe the integration of the literature to reflect the weight of evidence.

LITERATURE SEARCH

A professional research librarian worked with the committee to conduct the literature searches used to identify relevant research. Six searches were conducted. An initial search (Search 1) of Medline, Embase, and the Cochrane Database of Systematic Reviews found 19,189 total articles reporting on associations between cannabis exposure and health endpoints. Search 1 included articles that were published between January 1999 and June 2016 and that included a cannabis search term and search terms relevant to health effects of interest in at least one of several search fields (e.g., title, abstract, subject heading). A partial review of the search results found a large number of irrelevant documents. For this reason, a second and more limited search strategy was developed.

Search 2 involved the same databases as Search 1 but used different search terms to identify articles associated with specific health endpoints, and it excluded articles with specific terms (e.g., “animal,” “spice”) in the title or abstract. Search 2 produced 2,092 articles between 1999 and the 2016. The substantial reduction in articles indicated that the more limited search strategy caused relevant research to be excluded; consequently, a third and broader search strategy was developed.

Search 3 of the same databases produced 7,198 total articles reporting on associations between cannabis exposure and any health endpoint. This search included articles published between 1999 and 2016, excluded articles with specific terms (e.g., “mice,” “spice”) in the title or abstract, and limited articles by study design (e.g., clinical trial, observational study, systematic review).

The results of Search 2 and Search 3 were combined, and three additional searches were conducted in order to address potential gaps in the overall search results. Search 4 identified 1,396 articles in the PsycINFO database, filling gaps in the committee's collection of literature on the effects of cannabis exposure on mental health and psychosocial endpoints. Using the search term “Nabilone” (a synthetic cannabinoid), Search 5 identified 33 articles in Medline, Embase, and the Cochrane Database of Systematic Reviews that previous searches had not included. Search 6 identified 389 articles and brought the literature up to date by extending the date of publication parameter to August 2, 2016, and including articles published electronically ahead of print. The terms and strategies used in these searches are provided on page 419 of this appendix. In addition to these six searches, committee members also reviewed their personal libraries, and added potentially relevant articles from these collections to the combined search results.

The results from searches 2 through 6 were combined to create a master library containing 10,759 unique articles, including 1,488 articles initially categorized as systematic reviews. These articles were then sorted into seven major health endpoint topic areas: injury and mortality; cardiovascular and respiratory symptoms and conditions; cancer, immune function, and infections; mental health symptoms and conditions; prenatal, perinatal, and postnatal health effects; psychosocial health effects; and therapeutic health effects.1 Upon further reflection and review of the available literature, the committee decided to separate the original cardiovascular and respiratory topic area into two individual research topics, as well as to separate out two additional research topics—problem cannabis use, and cannabis use and abuse of other substances—from the original mental health topic area. This final list of topic areas was subsequently divided into the 11 health endpoint topic areas covered in the chapters that comprise parts II and III of the report. Within each of these topic areas the committee identified specific research questions relating to health endpoints of medical and public health importance that would be the focus of the report. They based this list on their public health and medical expertise, their knowledge of the cannabis literature, input from the sponsors at the first meeting, and other key reviews about the health effects of cannabis. This process, which reduced the total number of articles to be reviewed by the committee, was necessary to make the scope of the report manageable, but it may have resulted in the exclusion of certain health outcomes of interest to health professionals, researchers, policy makers, or the public. Below, Box B-1 lists the health topic areas and specific health endpoints selected for review by the committee.

Box Icon

BOX B-1

Health Topics and Prioritized Health Endpoints (listed in the order in which they appear in the report).

After filtering the original search results for articles relevant to the health endpoints of interest, 6,540 primary literature articles and 288 systematic reviews were left to be reviewed by the committee. Given the large number of potentially relevant articles, the committee decided to begin by reviewing the identified systematic reviews. To accomplish this, the committee modified previously developed approaches for evaluating the quality of the systematic reviews and primary literature. These approaches are described in the systematic review: identification and quality review, “Primary Literature: Identification and Quality Review,” and “Data Synthesis and Strength of Evidence Assessment” sections below.

The committee identified articles as possibly being systematic reviews based on abstracts or keyword searches, and then they evaluated each of the identified articles for the presence of the key elements of a systematic review by asking the following questions:

1.

Does the article describe a search involving at least two databases?

2.

Does the article describe a search involving appropriate search terms?

3.

Does the article describe a search involving prespecified eligibility criteria?

4.

Does the article include a risk-of-bias discussion and/or quality assessment?

5.

Does the article include a meta-analysis or qualitative synthesis of findings?

6.

Does the article report on one or more health effects of cannabis on humans?

Articles that were deemed true systematic reviews using the above questions as a guideline were then assessed for quality based on five attributes adapted from other sources (Higgins et al., 2011). In their assessment of the quality of a systematic review, committee members considered the study eligibility criteria, how studies were identified and considered for inclusion, how data were collected and appraised by the authors, the methods by which study findings were selected and synthesized, and whether any conflict of interests were addressed. Box B-2 lists the specific questions committee members were asked to consider in the quality assessment.

Box Icon

BOX B-2

Quality Assessment Questions.

Based on the responses to these questions, the overall quality of the systematic review was rated as good, fair, or poor. To ensure the accuracy of quality assessments, all systematic reviews were rated independently by at least two committee members. Disagreements among committee members regarding the overall quality of a systematic review were resolved through deliberation or by the assessment of a third committee member. Only those systematic reviews rated as good or fair quality were used to inform the report's findings, conclusions, and recommendations.

PRIMARY LITERATURE: IDENTIFICATION AND QUALITY REVIEW

For those health endpoints addressed by more than one good- or fair-quality systematic review, the committee gave primacy to the most recently published systematic reviews (since 2011). Any deviations in this process are detailed in the chapter text. For every health endpoint with an associated good- or fair-quality systematic review, the committee also reviewed relevant primary literature published after the cutoff date of the literature search used in that systematic review. For endpoints not addressed by at least one good- or fair-quality systematic review, the committee reviewed all relevant primary literature published between January 1, 1999, and August 2, 2016.

Committee members first reviewed article abstracts to identify and remove editorials, opinion pieces, grey literature, and other documents that were not peer-reviewed cross-sectional studies, case-control studies, cohort studies, randomized controlled trials (RCTs), or nonsystematic literature reviews. During this preliminary review, committee members also assessed the relevance of the article to the health endpoint question.

In their in-depth review of the primary literature, committee members were guided by the Cochrane Quality Assessment for randomized controlled trials and the Newcastle–Ottawa Scale for cohort and case-control studies.2 For a depiction of the flow of articles through the search and selection process, see Figure B-2.

FIGURE B-2. Search and selection process flow chart.

FIGURE B-2

Search and selection process flow chart. NOTE: Totals within and across searches and health topic areas may not sum due to duplication of articles and hand-searching efforts.

DATA SYNTHESIS AND STRENGTH OF EVIDENCE ASSESSMENT

After completing the identification and quality-assessment process described above, the committee formulated its findings and conclusions. The committee employed two strategies to ensure that report conclusions and recommendations were based on the best available evidence and that the strength of the evidence informing the conclusions was explicitly articulated. First, the committee privileged evidence drawn from RCTs, followed by nonrandomized controlled trials, prospective controlled studies, and case-control studies. Case series and case studies were referenced only in the absence of higher-quality studies. Second, the committee developed a set of standardized terms to describe the strength of the evidence informing every conclusion. Informed by the reports of previous Institute of Medicine (IOM)3 committees, the committee developed standard language to categorize the weight of evidence regarding whether cannabis or cannabinoid use (for therapeutic purposes) is an effective or ineffective treatment for the prioritized health endpoints of interest, or whether cannabis or cannabinoid use (primarily for recreational purposes) is statistically associated with the prioritized health endpoints of interest. The weight of the evidence was determined during private deliberations of subgroups of the committee. This hierarchy of evidence does not imply the magnitude of the observed effect or the importance of the health effect from an individual or population standpoint. Instead, these terms reflect the quality, quantity, and consistency of the evidence supporting a conclusion. See Box B-3 for the terms and their descriptions.

Box Icon

BOX B-3

Weight-of-Evidence Categories.

DISCUSSION

The search strategies and processes described above were developed and adopted by the committee in order to adequately address a broad statement of task in a limited time frame, while adhering to the National Academies of Sciences, Engineering, and Medicine's high standards for the quality and rigor of committee reports. Some limitations to these strategies and processes are discussed below.

First, the committee was not tasked to conduct a systematic review, which would have required a lengthy and robust series of processes. The committee did, however, adopt key features of that process: a comprehensive literature search, assessments by more than one person of the quality (risk of bias) of key literature and the conclusions, prespecification of the questions of interest before conclusions were formulated, standard language to allow comparisons between conclusions, and declarations of conflict of interest via the National Academies conflict of interest policies. Second, there is a possibility that some literature was missed because of the practical steps taken to narrow a very large literature to one that was manageable within the time frame available to the committee. Furthermore, very good research may not be reflected in this report because it did not directly address the health endpoint questions that the committee formulated.

SEARCH STRATEGIES

  • Search 2
  • Date: June 27, 2016
  • Total citations:
  • Systematic reviews: 541
  • Primary literature: 1,551
  • Total: 2,092

Databases (search engine): Medline (Ovid); Embase (Ovid); Cochrane (Ovid)

Note: Ovid command-line syntax is provided below. Terms immediately followed by a forward slash (/) are Medical Subject Headings (MESH headings from MEDLINE) or EMTREE terms (from the EMBASE controlled vocabulary). The fields searched by a .mp in Embase and Medline include title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, and unique identifier. The fields searched by a .mp in Cochrane include title, short title, abstract, full text, keywords, caption text.

Search No.Search Syntax
Beneficial
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
1410 not 13
15Rats/ or rats.ti,ab.
16Mice/ or mice.ti,ab.
17animals/ or animals.ti,ab.
18or/15–17
1914 not 18
20Therapeutics/
21“therapeutic use”.mp.
22benefits.mp.
23treatment.mp.
24therapy.mp.
25Palliative Care/ or palliation.mp.
26“Quality of Life”/
27or/20–26
2819 and 27
29Nausea/ or nausea.mp.
30Vomiting/
31vomiting.mp.
32or/28–30
3328 and 31
34limit 32 to (abstracts and English language and humans and yr=“1999–Current”)
35Analgesia/ or Analgesia.mp.
3628 and 35
37limit 36 to (English language and humans and yr=“1999–Current”)
38Anxiety/ or anxiety relief.mp. or Anxiety Disorders/
3928 and 38
40limit 39 to (English language and humans and yr=“1999–Current”)
41irritable bowel syndrome.mp. or Irritable Bowel Syndrome/
4228 and 41
43limit 42 to (English language and humans and yr=“1999–Current”)
44improved sexual function.mp. or Sexual Behavior/
45sexual function.mp.
46or/44–45
4728 and 46
48limit 47 to (English language and humans and yr=“1999–Current”)
49Interpersonal Relations/ or social relationships.mp.
5028 and 57
51limit 50 to (English language and humans and yr=“1999–Current”)
52increased appetite.mp. or Appetite/ or Eating/
53wasting.mp. or Wasting Syndrome/
54or/52–53 28 and 54
55limit 54 to (English language and humans and yr=“1999–Current”)
56Substance-Related Disorders/ or addiction.mp.
5728 and 56
58limit 57 to (English language and humans and yr=“1999–Current”)
59intraocular pressure.mp. or Intraocular Pressure/
6028 and 59
61limit 60 to (English language and humans and yr=“1999–Current”)
62PTSD.mp. or Stress Disorders, posttraumatic/
63trauma.mp.
64or/62–63
6528 and 64
66limit 65 to (English language and humans and yr=“1999–Current”)
67Premenstrual Syndrome/ or Premenstrual Dysphoric Disorder/ or premenstrual.mp.
6828 and 67
69limit 68 to (English language and humans and yr=“1999–Current”)
70Epilepsy/ or seizure control.mp. or Seizures/
7128 and 70
72limit 71 to (English language and humans and yr=“1999–Current”)
73sleep disorders.mp. or Sleep Wake Disorders/
74insomnia.mp. or “Sleep Initiation and Maintenance Disorders”/
75or/73–74
7628 and 75
77limit 76 to (English language and humans and yr=“1999–Current”)
78Muscle Spasticity/ or Spasticity.mp.
79Pain/
80Multiple Sclerosis/
81or/78–80
8228 and 81
83limit 82 to (English language and humans and yr=“1999–Current”)
84cancer treatment.mp.
85cancer prevention.mp.
86or/84–85
8728 and 86
88limit 87 to (English language and humans and yr=“1999–Current”)
89brain injury.mp. or Brain Injuries/
9028 and 89
91limit 90 to (English language and humans and yr=“1999–Current”)
9234 or 37 or 40 or 43 or 48 or 51 or 55 or 58 or 61 or 66 or 69 or 72 or 77 or 83 or 88 or 91
93limit 92 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
9434 or 37 or 40 or 43 or 48 or 51 or 55 or 58 or 61 or 66 or 69 or 72 or 77 or 83 or 88 or 91
95limit 94 to (meta-analysis or systematic reviews)
Cancer
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
14Rats/ or rats.ti,ab.
15Mice/ or mice.ti,ab.
16animals/ or animals.ti,ab.
17or/14–16
1810 not 13
19cancer.mp. or Neoplasms/
20lung cancer.mp. or Lung Neoplasms/
21Esophageal Neoplasms/ or Pharyngeal Neoplasms/ or Laryngeal Neoplasms/ or “Head and Neck Neoplasms”/ or upper aerodigestive tract cancer.mp. or Mouth Neoplasms/
22testicular cancer.mp. or Testicular Neoplasms/
23childhood cancer.mp.
24immune system.mp. or Immune System/
25Immunity/
26immunity.mp.
27or/19–26
2818 and 27
2928 not 17
30limit 29 to (human and English language and yr=“1999–Current”)
31limit 30 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
32limit 30 to (meta analysis or systematic reviews)
Cardiovascular
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11Cardiovascular Abnormalities/ or Cardiovascular Diseases/ or cardiovascular.mp.
12cerebrovascular.mp. or Cerebrovascular Disorders/
13Peripheral Vascular Diseases/ or peripheral vascular.mp.
14heart attack.mp. or Myocardial Infarction/
15Stroke/ or stroke risk.mp.
16thromboangiitis obliterans.mp. or Thromboangiitis Obliterans/
17spice.ti,ab.
18K2.ti,ab.
19or/17–18
2010 not 19
21Rats/ or rats.ti,ab.
22Mice/ or mice.ti,ab.
23animals/ or animals.ti,ab.
24or/21–23
25or/11–16
2620 and 25
2726 not 24
2827
29limit 28 to (English language and humans and yr=“1999–Current”)
30limit 29 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
31limit 29 to (meta analysis or systematic reviews)
Injury
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
14Rats/ or rats.ti,ab.
15Mice/ or mice.ti,ab.
16animals/ or animals.ti,ab.
17or/14–16
18injury.mp. or “Wounds and Injuries”/
1910 and 18
2019 not 13
2120 not 17
2221
23limit 22 to (English language and humans and yr=“1999–Current”)
24Accidents, Traffic/ or motor vehicle accident.mp.
25motor vehicle crash.mp.
26or/24–25
2710 and 26
2827 not 13
2928 not 17
3029
31limit 30 to (English language and humans and yr=“1999–Current”)
32all-cause death.mp.
33Death/
34or/32–33
3510 and 34
3635 not 13
3736 not 17
3837
39limit 38 to (English language and humans and yr=“1999–Current”)
40Drug Overdose/
41overdose death.mp.
42or/40–41
4310 and 42
4443 not 13
4544 not 17
4645
47limit 46 to (English language and humans and yr=“1999–Current”)
48limit 23 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
49limit 31 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
50limit 39 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
51limit 47 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
52limit 23 to (meta analysis or systematic reviews)
53limit 31 to (meta analysis or systematic reviews)
54limit 39 to (meta analysis or systematic reviews)
55limit 47 to (meta analysis or systematic reviews)
Mental Health
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
14Rats/ or rats.ti,ab.
15Mice/ or mice.ti,ab.
16animals/ or animals.ti,ab.
17or/14–16
1810 not 13
19mental disease/ or mental health/
2018 and 19
2120 not 17
2221
23limit 22 to (human and English language and yr=“1999–Current”)
24limit 23 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
25limit 24 to (journal and article)
26limit 24 to (meta analysis or “systematic review”)
27limit 26 to (journal and (article or review))
28cannabis addiction/
29drug abuse/ or drug misuse/
30cannabis dependence.mp.
31or/28–30
3218 and 31
3332 not 17
3433
35limit 34 to (human and english language and yr=“1999–Current”)
36limit 35 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
37limit 36 to (journal and article)
38limit 35 to (meta analysis or “systematic review”)
39limit 38 to (journal and (article or review))
40alcohol abuse/
41tobacco dependence/ or tobacco consumption/
42“tobacco use”/
43drug abuse/
44drug dependence/
45or/40–44
4618 and 45
4746 not 17
4847
49limit 48 to (human and English language and yr=“1999–Current”)
50limit 49 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
51limit 50 to (journal and article)
52limit 49 to (meta analysis or “systematic review”)
53limit 52 to (journal and (article or review))
54schizophrenia/
55psychosis/
56psychotic disorder.mp.
57or/54–56
5818 and 57
5958 not 17
6059
61limit 60 to (human and English language and yr=“1999–Current”)
62limit 61 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
63limit 62 to (journal and article)
64limit 61 to (meta analysis or “systematic review”)
65limit 64 to (journal and (article or review))
66depression/
6718 and 66
6867 not 17
6968
70limit 69 to (human and English language and yr=“1999–Current”)
71limit 70 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
72limit 71 to (journal and article)
73limit 70 to (meta analysis or “systematic review”)
74limit 73 to (journal and (article or review))
75suicide/
7618 and 75
7776 not 17
7877
79limit 78 to (human and English language and yr=“1999–Current”)
80limit 78 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
81limit 80 to (journal and article)
82limit 79 to (meta analysis or “systematic review”)
83limit 82 to (journal and (article or review))
84anxiety/
8518 and 84
8685 not 17
8786
88limit 87 to (human and English language and yr=“1999–Current”)
89limit 88 to (clinical trial or randomized controlled trial or controlled clinical trial or multicenter study or phase 1 clinical trial or phase 2 clinical trial or phase 3 clinical trial or phase 4 clinical trial)
90limit 89 to (journal and article)
91limit 88 to (meta analysis or “systematic review”)
92limit 91 to (journal and (article or review))
Pregnancy
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
14Rats/ or rats.ti,ab.
15Mice/ or mice.ti,ab.
16animals/ or animals.ti,ab.
17or/14–16
1810 not 13
19pregnancy outcomes.mp. or pregnancy outcome/
20low birthweight.mp. or low birth weight/
21premature labor/ or pre term delivery.mp.
22birth defects.mp.
23stillbirth/
24miscarriage.mp. or spontaneous abortion/
25neonatal mortality.mp. or newborn mortality/
26physical growth.mp. or growth/
2718 and 19
2827 not 17
2928
30limit 29 to (human and english language)
3118 and 20
3231 not 17
3332
34limit 33 to (human and English language and yr=“1999–Current”)
3518 and 21
3635 not 17
3736
38limit 37 to (human and English language and yr=“1999–Current”)
3918 and 22
4039 not 17
4140
42limit 41 to (human and English language and yr=“1999–Current”)
43or/23–25
4418 and 43
4518 and 43
4645 not 17
4746
4846
49limit 48 to (human and English language and yr=“1999–Current”)
5018 and 26
5150 not 17
5251
53limit 52 to (human and English language and yr=“1999–Current”)
54limit 30 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
55limit 30 to (meta analysis or systematic reviews)
56limit 34 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
57limit 34 to (meta analysis or systematic reviews)
58limit 38 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
59limit 38 to (meta analysis or systematic reviews)
60limit 42 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
61limit 42 to (meta analysis or systematic reviews)
62limit 49 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
63limit 49 to (meta analysis or systematic reviews)
64limit 53 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
65limit 53 to (meta analysis or systematic reviews)
66breast feeding.mp. or Breast Feeding/
6718 and 66
6867 not 17
6968
70limit 69 to (English language and humans and yr=“1999–Current”)
71Pregnancy/
7271 and 18
7372 not 17
7473
75limit 74 to (English language and humans and yr=“1999–Current”)
76limit 70 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
78limit 70 to (meta analysis or systematic reviews)
80limit 75 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
82limit 75 to (meta analysis or systematic reviews)
Psychosocial
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
14Rats/ or rats.ti,ab.
15Mice/ or mice.ti,ab.
16animals/ or animals.ti,ab.
17or/14–16
1810 not 13
19psychosocial.mp. or Social Adjustment/
20psychosocial effects.mp.
21or/19–20
2221 and 18
2322 not 17
24limit 23 to (English language and humans and yr=“1999–Current”)
25cognitive development.mp.
26Cognition/
27Achievement/ or academic achievement.mp.
28or/25–27
2928 and 18
3029 not 17
3130
32limit 31 to (English language and humans and yr=“1999–Current”)
33cognitive impairment.mp. or Cognition Disorders/
3433 and 18
3534 not 17
36limit 35 to (English language and humans and yr=“1999–Current”)
37Employment/
38Income/
39or/37–38
4039 and 18
4140 not 17
42limit 41 to (English language and humans and yr=“1999–Current”)
43Interpersonal Relations/ or social relationships.mp.
4443 and 18
4544 not 17
4645
47limit 46 to (English language and humans and yr=“1999–Current”)
48Social Behavior/ or social roles.mp.
4948 and 18
5049 not 17
51limit 50 to (English language and humans and yr=“1999–Current”)
5224 or 32 or 36 or 42 or 47 or 51
53limit 52 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
5424 or 32 or 36 or 42 or 47 or 51
55limit 54 to (meta analysis or systematic reviews)
Respiratory
1marijuana.mp. or cannabis/
2cannabis.mp.
3cannabinoids.mp. or cannabinoid/
4tetrahydrocannabinol.mp. or tetrahydrocannabinol/
5dronabinol.mp. or dronabinol/
6cannabidiol.mp. or cannabidiol/
7cannabinol.mp. or cannabinol/
8THC.mp.
9marinol.mp.
10or/1–9
11spice.ti,ab.
12K2.ti,ab.
13or/11–12
1410 not 13
15Rats/ or rats.ti,ab.
16Mice/ or mice.ti,ab.
17animals/ or animals.ti,ab.
18or/15–17
19pulmonary.mp. or Pulmonary Disease, Chronic Obstructive/
20lung disease.mp. or Lung Diseases/ or Respiratory Tract Diseases/ or respiratory disease.mp. or COPD.mp.
21or/19–20
2221 and 14
2322 not 18
2423
25limit 24 to (human and English language and yr=“1999–Current”)
26limit 25 to (meta analysis or systematic reviews)
27limit 25 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
  • Search 3
  • Date: July 6, 2016
  • Total citations:
  • Systematic Reviews: 912
  • Primary Literature: 6,286
  • Total: 7,198

Databases (search engine): Medline (Ovid); Embase (Ovid); Cochrane (Ovid)

Note: Ovid command-line syntax is provided below. Terms immediately followed by a forward slash (/) are Medical Subject Headings (MESH headings from MEDLINE) or EMTREE terms (from the EMBASE controlled vocabulary). The fields searched by a .mp in Embase and Medline include title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, and unique identifier. The fields searched by a .mp in Cochrane include title, short title, abstract, full text, keywords, caption text.

Search No.Search Syntax
1Cannabis/
2Marijuana Smoking/
3Marijuana Abuse/
4Medical Marijuana/
5Cannabinoids/
6Dronabinol/
7(cannabis or marijuana or cannabinoid or dronabinol or marinol). ti,ab.
8THC.ti,ab
9or/1–8
10k2.ti,ab.
11spice.ti,ab.
12or/10–11
139 not 12
14Mice/ or mice.ti,ab.
15Rats/ or rats.ti,ab.
16or/14–15
1713 not 16
1817
19limit 18 to (English language and humans)
20limit 19 to (classical article or clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or comparative study or controlled clinical trial or evaluation studies or guideline or journal article or multicenter study or observational study or practice guideline or pragmatic clinical trial or randomized controlled trial or validation studies)
21limit 19 to (addresses or autobiography or bibliography or biography or case reports or clinical conference or comment or congresses or consensus development conference or consensus development conference, NIH or “corrected and republished article” or dataset or dictionary or directory or duplicate publication or editorial or english abstract or festschrift or government publications or historical article or in vitro or interactive tutorial or interview or introductory journal article or lectures or legal cases or legislation or letter or meta analysis or news or newspaper article or overall or patient education handout or periodical index or personal narratives or portraits or published erratum or research support, non us gov't or retracted publication or “retraction of publication” or “review” or “scientific integrity review” or systematic reviews or technical report or video-audio media or webcasts)
2220 not 21
23limit 22 to yr=1999-current
24limit 19 to (meta analysis or “review” or systematic reviews)
25limit 19 to (addresses or autobiography or bibliography or biography or case reports or clinical conference or comment or congresses or consensus development conference or consensus development conference, NIH or “corrected and republished article” or dataset or dictionary or directory or duplicate publication or editorial or english abstract or festschrift or government publications or historical article or in vitro or interactive tutorial or interview or introductory journal article or lectures or legal cases or legislation or letter or news or newspaper article or overall or patient education handout or periodical index or personal narratives or portraits or published erratum or research support, non us gov't or retracted publication or “retraction of publication” or “scientific integrity review” or technical report or video-audio media or webcasts)
2624 not 25
27limit 26 to yr=1999-current
  • Search 4
  • Date: July 8, 2016
  • Total citations:
  • Systematic Reviews: 20
  • Primary Literature: 1,376
  • Total: 1,396

Database (search engine): PsycINFO (ProQuest)

Note: Terms with SU in front of them are Subject Headings taken from the Thesaurus of Psychological Index Terms.

SearchSearch Syntax
Systematic Reviews + Meta Analysis((SU(“Cannabinoids” OR “Cannabis” OR “Marijuana Usage” OR “Marijuana”) OR TI,AB(cannabis OR marijuana OR cannabinoid OR dronabinol) NOT TI,AB(“K-2” OR spice)) AND peer(yes) AND (la.exact(“ENG”))) AND (me.exact((“Systematic Review” OR “Meta Analysis”) NOT (“Empirical Study” OR “Quantitative Study” OR “Interview” OR “Longitudinal Study” OR “Followup Study” OR “Prospective Study” OR “Literature Review” OR “Treatment Outcome/Clinical Trial” OR “Qualitative Study” OR “Brain Imaging” OR “Clinical Case Study” OR “Retrospective Study” OR “Mathematical Model” OR “Twin Study” OR “Focus Group” OR “Field Study” OR “Experimental Replication” OR “Scientific Simulation” OR “Nonclinical Case Study”)) AND rtype. exact((“Journal” OR “Peer-reviewed Journal” OR “Journal Article”) NOT (“Comment/reply” OR “Editorial” OR “Letter” OR “Erratum/ correction” OR “Review-book” OR “Column/opinion” OR “Abstract Collection” OR “Reprint” OR “Review-media” OR “Obituary”)) AND po.exact((“Male” OR “Human” OR “Female” OR “Outpatient” OR “Inpatient”) NOT “Animal”) AND pd(19990101-20161231) AND PEER(yes))
Peer-reviewed Literature(SU(“Cannabinoids” OR “Cannabis” OR “Marijuana Usage” OR “Marijuana”) OR TI(cannabis OR marijuana OR cannabinoid OR dronabinol) NOT TI,AB(“K-2” OR spice)) AND peer(yes) AND (la. exact(“ENG”) AND me.exact((“Empirical Study” OR “Quantitative Study” OR “Longitudinal Study” OR “Followup Study” OR “Prospective Study” OR “Treatment Outcome/Clinical Trial” OR “Clinical Case Study” OR “Twin Study”) NOT (“Interview” OR “Literature Review” OR “Qualitative Study” OR “Brain Imaging” OR “Mathematical Model” OR “Systematic Review” OR “Meta Analysis” OR “Field Study” OR “Focus Group”)) AND rtype.exact((“Journal” OR “Peer-reviewed Journal” OR “Journal Article”) NOT (“Comment/ reply” OR “Editorial” OR “Letter” OR “Erratum/correction” OR “Review-book” OR “Column/opinion” OR “Abstract Collection” OR “Reprint” OR “Review-media” OR “Obituary”))) AND pd(19990101-20160601)
  • Search 5
  • Date: July 15, 2016
  • Total citations:
  • Systematic Reviews: 10
  • Primary Literature: 23
  • Total: 33

Database (search engine): Medline (Ovid); Embase (Ovid); Cochrane (Ovid)

Note: Ovid command-line syntax is provided below. Terms immediately followed by a forward slash (/) are Medical Subject Headings (MESH headings from MEDLINE) or EMTREE terms (from the EMBASE controlled vocabulary). The fields searched by a .mp in Embase and Medline include title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, and unique identifier. The fields searched by a .mp in Cochrane include title, short title, abstract, full text, keywords, caption text.

Search No.Search Syntax
1nabilone.mp
2spice.ti,ab.
3K2.ti,ab.
4or/2–3
51 not 4
6Rats/ or rats.ti,ab.
7Mice/ or mice.ti,ab.
8animals/ or animals.ti,ab.
9or/6–8
105 not 9
11limit 10 to (English language and yr=“1999-Current”)
12limit 11 to (clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or observational study or randomized controlled trial)
13limit 11 to (meta-analysis or systematic reviews)
  • Search 6
  • Date: August 2, 2016

Search Parameters: Published June 30, 2016–August 2, 2016

  • Total citations:
  • Systematic Reviews: 32
  • Primary Literature: 357
  • Total: 389

Database (search engine): Embase (Ovid)

Note: The Medline search was duplicated in PubMed to ensure that all e-pub and non-indexed / in-process citations were captured.

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

Search No.Search Syntax
1Cannabis/
2Marijuana Smoking/
3Marijuana Abuse/
4Medical Marijuana/
5Cannabinoids/
6Dronabinol/
7(cannabis or marijuana or cannabinoid or dronabinol or marinol). ti,ab.
8nabilone.ti,ab.
9or/1–8
10k2.ti,ab.
11spice.ti,ab.
12or/10–11
139 not 12
14Mice/ or mice.ti,ab.
15Rats/ or rats.ti,ab.
16or/14–15
1713 not 16
1817
19limit 18 to (English language and humans)
20limit 19 to (classical article or clinical study or clinical trial, all or clinical trial, phase I or clinical trial, phase II or clinical trial, phase III or clinical trial, phase IV or clinical trial or comparative study or controlled clinical trial or evaluation studies or guideline or journal article or multicenter study or observational study or practice guideline or pragmatic clinical trial or randomized controlled trial or validation studies)
21limit 19 to (addresses or autobiography or bibliography or biography or case reports or clinical conference or comment or congresses or consensus development conference or consensus development conference, NIH or “corrected and republished article” or dataset or dictionary or directory or duplicate publication or editorial or Dnglish abstract or festschrift or government publications or historical article or in vitro or interactive tutorial or interview or introductory journal article or lectures or legal cases or legislation or letter or meta analysis or news or newspaper article or overall or patient education handout or periodical index or personal narratives or portraits or published erratum or research support, non us gov't or retracted publication or “retraction of publication” or “review” or “scientific integrity review” or systematic reviews or technical report or video-audio media or webcasts)
2220 not 21
23limit 22 to ed=20160630-20160901
24limit 19 to (meta-analysis or “review” or systematic reviews)
25limit 19 to (addresses or autobiography or bibliography or biography or case reports or clinical conference or comment or congresses or consensus development conference or consensus development conference, NIH or “corrected and republished article” or dataset or dictionary or directory or duplicate publication or editorial or English abstract or festschrift or government publications or historical article or in vitro or interactive tutorial or interview or introductory journal article or lectures or legal cases or legislation or letter or news or newspaper article or overall or patient education handout or periodical index or personal narratives or portraits or published erratum or research support, non us gov't or retracted publication or “retraction of publication” or “scientific integrity review” or technical report or video-audio media or webcasts)
2624 not 25
27limit 26 to ed=20160630-20160901
Embase (Ovid)
1major clinical study/
2clinical article/
3case report/
4clinical trial/
5controlled clinical trial/
6phase 1 clinical trial/
7phase 2 clinical trial/
8phase 3 clinical trial/
9phase 4 clinical trial/
10randomized controlled trial/
11double blind procedure/
12single blind procedure/
13crossover procedure/
14multicenter study/
15controlled study/
16“clinical trial (topic)”/
17“controlled clinical trial (topic)”/
18“phase 1 clinical trial (topic)”/
19“phase 2 clinical trial (topic)”/
20“phase 3 clinical trial (topic)”/
21“phase 4 clinical trial (topic)”/
22“randomized controlled trial (topic)”/
23“multicenter study (topic)”/
24cannabis/
25cannabis addiction/ or medical cannabis/ or “cannabis use”/ or cannabis smoking/ or cannabis derivative/
26cannabinoid/
27dronabinol/
28nabilone/
29(Cannabis or marijuana or cannabinoid or dronabinol or nabilone or marinol).ti,ab.
30or/24–29
31k2.ti,ab.
32spice.ti,ab.
33or/31–32
3430 not 33
35Mice/ or mice.ti,ab.
36Rats/ or rats.ti,ab.
37or/35–36
3834 not 37
39or/1–23
4038 and 39
41limit 40 to (journal and article)
42limit 40 to (book or book series or chapter or conference abstract or conference paper or conference proceeding or “conference review” or editorial or erratum or letter or note or “review” or short survey or trade journal)
4341 not 42
44case report/
4543 not 44
4645
47limit 46 to (human and English language)
48limit 47 to yr=“2016–Current”
49limit 48 to dd=20160630-20161231
50meta analysis/
51“meta analysis (topic)”/
52“meta analysis (topic)”/
53“systematic review (topic)”/
54or/50–53
5538 and 54
56limit 55 to (journal and (article or review))
5756
58limit 57 to (human and English language)
5958
60limit 59 to yr=“2016–Current”
61limit 60 to dd=20160630-20161231

REFERENCES

  • Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA., Cochrane Bias Methods Group, and the Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343(d5928) [PMC free article: PMC3196245] [PubMed: 22008217] [CrossRef]
  • Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2011. [November 28, 2016]. http://www​.ohri.ca/programs​/clinical_epidemiology/oxford.asp.

Footnotes

1

The organization of Search 2 results involved different search terms and tools than the organization of Search 3 results. Search 2 topic groups were developed using unique search terms, online databases (Medline, Embase, Cochrane Database of Systematic Reviews), and Ovid search functions. Search 3 topics groups were developed using unique search terms, the Search 3 EndNote library, and the EndNote full-text keyword search function.

2

The Cochrane Risk Assessment Tool was designed to assess for a risk of bias consequent to flaws in the design, conduct, analysis, and reporting of randomized trials (Higgins, 2011). The Newcastle–Ottawa Scale (NOS) was designed to assess the quality of nonrandomized trials to be included in a systematic review. The NOS assesses studies along three dimensions: selection of study groups, comparability of study groups, and determination of endpoints and exposures (Wells et al., 2011).

3

As of March 2016, the Health and Medicine Division continues the consensus studies and convening activities previously carried out by the Institute of Medicine (IOM).

Copyright 2017 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK425758

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