Качество жизни пациентов, получающих лекарственный каннабис: систематический обзор и метаанализ результатов первичных исследований 2015-2025.

Introduction

Globally, chronic health conditions place a significant burden on individuals, health systems, and society more broadly, with chronic pain being the leading cause of disability worldwide [ 1 ]. The identification of cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), as analgesics in 1940 ignited interest in using a cannabis-based medicine as adjunctive treatment for the symptomatic relief of chronic pain [ 2 ]. However, most United Nations countries criminalised the consumption of cannabis in the 1960’s [ 3 ], consequently limiting research in this area. The past few decades have seen a resurgence of research on cannabis therapy, particularly after the discovery of the endocannabinoid system in the 1990’s and its important role in regulating mood and emotional responses [ 4 ]. Medicinal Cannabis (MC) began to be posited as a potential alternative to opioids associated with increasing incidence of adverse events [ 5 ], including hospitalization and death from overdose [ 6 ]. To enable MC research and build an evidence base for its therapeutic efficacy [ 7 ], many countries have since revised their policies and introduced legislation to allow the use of cannabis for research and medicinal purposes, starting with Canada in 2001 [ 8 ], and most recently, Ukraine in 2024 [ 9 ].

Patient-reported outcomes and the importance of health-related quality of life

A patient-reported outcome (PRO) is any report coming directly from patients, without interpretation by physicians or others, about how the patient feels in relation to their health condition and its therapy [ 10 ]. PROs are particularly important endpoints to include in clinical studies of patients with chronic conditions where the primary aim is to palliate symptoms [ 11 ]. A validated PRO measure (PROM) is a standardised questionnaire that allows comparisons between treatment groups, and within groups and individuals over time. PROMs can measure symptom burden, aspects of functioning, and health-related quality of life (HRQL). In this review, HRQL is defined as a “ multidimensional construct encompassing perceptions of the impacts – positive and negative - of a disease or its treatment on physical , emotional , social , and cognitive functions , as well as somatic discomfort and other symptoms ” [ 12 ]. There are other definitions of HRQL, for example, “ the value assigned to the duration of survival as modified by the impairment , functional states , perception and social opportunities that are influenced by disease , injury , treatment , or policy ” [ 13 ]. Optimal HRQL is universally valued as an important outcome across all health conditions, making it an important endpoint in clinical research. Considering the various ways of conceptualising HRQL, definitions will depend on the research context. It is important for researchers to be aware that HRQL is often defined, measured, and reported in different ways, and to be explicit about the specific meaning and context of HRQL in their studies [ 14 ]. Having a clear definition helps inform the selection of appropriate HRQL measures and improve scientific rigor. This is particularly important considering HRQL results can differ within the same group of patients depending on the PROM used to measure HRQL [ 14 ].

Previous HRQL evidence for MC

Two systematic reviews of HRQL in patients treated with MC have been published covering studies from inception to April 2015: Goldenberg et al. 2017 [ 15 ], and Whiting et al. 2015 [ 16 ]. Between them, they looked at 14 conditions including chemotherapy-induced nausea and vomiting, chronic pain, multiple sclerosis spasticity, depression, inflammatory bowel disease, anxiety, and sleep disorder. Goldenberg et al. found small HRQL improvements in patients with pain, multiple sclerosis, and inflammatory bowel disease [ 15 ]. Moderate-quality evidence supported MC for treating chronic pain and spasticity, but only low-quality evidence for chemotherapy-induced nausea and vomiting, appetite, sleep disorders, and Tourette syndrome [ 16 ]. In meta-analyses, overall effect sizes (Cohen’s d) were small and non-significant: 0.05 for HRQL [ 15 ] compared with controls, and 0.35 for HRQL [ 15 ] in pre- and post-therapy observational studies. However, analyses included all available data without categorising results by follow-up period. For example, HRQL assessed two weeks after MC therapy was combined with studies reporting HRQL following many months of therapy [ 15 ]. Notably, half of studies included within both reviews used synthetic cannabinoids rather than cannabinoids extracted from the cannabis plant (presumably due to historical legal and access restrictions). Since then, more countries have supported MC research and production, and non-synthetic MC formulations, and methods of administration have been further refined. Furthermore, access to MC often relies on the judgement and clinical justification of a prescribing doctor, which may cover a wider range of health conditions than previously reviewed.

Objectives and research aims

This review analysed all new evidence since 2015 assessing patients’ HRQL before and after receiving MC treatment. The research aims were to: (1) determine how HRQL was defined in studies of patients being prescribed MC, and identify which PROMs were used for HRQL assessment and the rationale for choosing them; (2) assess the quality and completeness of HRQL reporting in MC research; and (3) through meta-analyses, determine any short-, medium-, and long-term HRQL improvements in patients receiving MC.

Methods

Literature searches

This systematic review was prospectively registered with PROSPERO (CRD42022306778) [ 17 ] and followed guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [ 18 ]. Bibliographic databases were searched (MEDLINE, Web of Science, PsycINFO, EMBASE, AMED - Allied and Complimentary Medicine, Scopus, and Cinahl) for studies published since 1 January 2015 until 8 April 2025 using MeSH terms “medical marijuana” or “Cannabis” and “quality of life” or “patient-reported outcome measures”. See Online Resource 1 for example of search strategy used in MEDLINE. Electronic searches were supplemented by a search of reference lists of eligible studies.

Inclusion criteria

Two reviewers screened studies independently. Randomised and non-randomised controlled trials and longitudinal observational studies with pre-treatment baseline, including cohort studies and case series were included. Only studies of adults (over 18 years) with any diagnosed health condition using MC (prescribed or approved by a medical practitioner) for symptom management, using validated generic or disease-specific multi-item PROMs to assess HRQL at baseline (before therapy) and follow-up (greater than 2-weeks) were included. MC was defined as a non-synthetic pharmaceutical cannabinoid product. Cannabinoid products may constitute one or more of any cannabinoid, including the major cannabinoids; delta-9-tetrahydrocannabinol (THC), and cannabidiol (CBD), and/or minor cannabinoids, for example, cannabichromene (CBC), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerol monomethyl ether (CBGM), cannabinol (CBN), cannabitriol (CBT), tetrahydrocannabutol (THCB), and tetrahydrocannabiorcol (THCC), and many more. Randomised and non-randomised clinical trial comparators included usual care, placebo or no treatment. Observational cohort and case series did not require a control group.

Studies with children and adolescents under 18 years, adults unable to self-report (i.e. assessments by proxy), cross-sectional studies, healthy participants, studies looking at synthetic cannabinoids, and studies not assessing HRQL with validated PROMs were excluded.

Published studies were limited to English language, full text (not conference abstracts), and primary research (not reviews, systematic reviews, meta-analyses, or commentary).

Outcomes

Results for overall HRQL were extracted according to predefined time periods: short-term (2 weeks to 3-months), medium term (between 3-months and 12-months), and long-term (12-months or longer), following Cochrane guidelines for systematic reviews in back pain, [ 19 ] and time periods reported in similar reviews of chronic health interventions [ 20 , 21 ]. As patient treatment typically involves a titration period, acute HRQL assessments (within 2 weeks of commencing treatment) were excluded [ 22 ]. Changes of patient-reported HRQL from baseline to last available follow-up within the predefined time periods were extracted.

Data extraction

Standardised data extraction forms developed on the Covidence platform [ 23 ] were piloted on a small sample of papers ( n = 5) and adapted as necessary. To minimise bias and errors, data extraction involved two independent reviewers. Disagreements were resolved through discussion until consensus was reached or referred to a third reviewer where necessary.

The following information was extracted from included studies: First author; year of publication; country; study design; aim; sample size; health condition(s); MC treatment type; comparison group; HRQL definitions; justification for measuring HRQL; HRQL PROM; assessment timepoints; HRQL results (means; medians; standard deviations; IQR; effect sizes; confidence intervals; statistical tests; odds ratios); and study limitations.

Quality assessment

The completeness of reporting for included studies was scored formally by two reviewers independently following criteria outlined in the STROBE Checklist for reporting observational studies [ 24 ], and CONSORT-PRO checklist for reporting PROs in randomised controlled trials (RCT) [ 25 ], using data extraction templates managed on the Covidence platform [ 23 ]. Existing tools for completeness of reporting quantitative clinical study designs inadequately address key issues for PRO assessment. Therefore, this review assessed the completeness of PRO reporting, specifically. The quality of completeness assessment data extraction template combined CONSORT and STROBE items of similar content and integrated the 14 CONSORT-PRO extension items. To standardise scores across both RCTs and observational studies, items that were RCT-specific were replaced with corresponding STROBE items for observational studies (e.g. CONSORT items 20–22 regarding discussion topics, were replaced with STROBE items 19–21). As typically done with the CONSORT and STROBE checklists, total reporting completeness scores using the revised PRO reporting checklist were calculated as a percentage of total possible score. The final revised PRO reporting checklist of 18 items and criteria are included in Online Resource 2. Additionally, Risk of Bias (RoB) was assessed separately for RCTs included in the meta-analysis using the revised Cochrane Tool; RoB 2, designed specifically for RCTs and for assisting the interpretation of meta-analyses [ 26 ].

PRO reporting completeness and RoB 2 was scored by two reviewers independently. Each criterion was scored, and inter-assessor consistency cross-checked with discrepancies discussed until consensus reached.

Analysis

A narrative summary included study characteristics, i.e., study design and aims, population size, geographical location, year, baseline population characteristics, HRQL definition, justification for assessment and PROMs used. Where data was not reported in a format suitable for pooling (e.g. missing measures of variability) or datasets unavailable, study findings were synthesised using descriptive text and tables. Meta-analyses were run separately for studies reporting between group differences and within group differences and for different follow-up time periods (short-, medium-, and long-term). Where multiple studies were conducted on the same participants, analyses for each follow-up time period included data from one report only, selected by highest participant number. A random-effects model with effect size assumed to have a distribution within the population was used to estimate summary measures of effect. Medians and IQR were converted to means and SD using R package (estmeansd) [ 27 ]. For within group analyses, estimates of standard deviation of difference scores and standard error of effect sizes assumed a correlation between repeated measures of r = 0.5 [ 28 ]. In studies reporting HRQL from multiple PROMs and/or scales, results from one total or utility score were used where possible, chosen as the most comparable with those reported by other included studies. When multiple domain scores were reported instead of a single HRQL score, previously established domain correlations were used when calculating overall effect size of study (e.g. r = 0.62 for SF-36 physical and mental composite scores) [ 29 ]. To reduce possible bias from erroneous data, we crossed-checked all statistical information available for determining study effect sizes, including t tests and reported p-values, and where relevant, chose the most conservative estimation for inclusion in meta-analyses. Effect size (Cohen’s d) and variation of effect size were calculated in Microsoft Excel spreadsheets, and meta-analyses conducted with IBM SPSS Statistics 28.0 program. As a sensitivity analysis, meta-analyses with high heterogeneity ( τ 2 > 0.1) were re-run without outliers (Cohen’s d > 1.5) and reported separately.

Results

The search yielded 16,674 studies minus duplications. Title, abstract and full text screening resulted in 64 studies of 43,847 patient participants included in our analysis. Results from the search are summarized in the PRISMA diagram (Fig. 1 ). Most studies were observational cohort studies ( n = 38, 59.4%), with the remaining being case series ( n = 13, 20.3%), RCTs using parallel ( n = 9, 14.1%) or crossover ( n = 3, 4.7%) designs, and one non-randomised experimental study (1.5%). An overview of included studies is provided in Online Resource 3. The number of studies conducted in each country is represented in Fig. 2 alongside a map of countries and regions where MC is legal. Apart from south African regions and Sri Lanka, the distribution of studies was largely representative of countries where MC is legal. A third of included studies were conducted in the United Kingdom ( n = 22, 34%), with 19 collecting data through the United Kingdom Medical Cannabis Registry. The health conditions of participant groups studied included Chronic Pain ( n = 12) [ 6 , 30 – 40 ], Multiple Sclerosis ( n = 8) [ 41 – 48 ], Cancer ( n = 5) [ 49 – 53 ], Anxiety disorder ( n = 4) [ 54 – 57 ], Inflammatory Bowel Disease (includes Crohn’s disease and Ulcerative colitis) ( n = 4) [ 58 – 61 ], Epilepsy ( n = 3) [ 62 – 64 ], Fibromyalgia ( n = 3) [ 65 – 67 ], Arthritis ( n = 2) [ 68 , 69 ], Sleep disorder ( n = 2) [ 70 , 71 ], Chronic neuropathic pain ( n = 2) [ 72 ], HIV ( n = 2) [ 72 , 73 ], Post Traumatic Stress Disorder ( n = 1) [ 74 ], Primary Headache Disorder ( n = 1) [ 75 ], Hypertension ( n = 1) [ 76 ], or any condition eligible for MC ( n = 16) [ 77 – 91 ]. Online Resource 4 lists health conditions of all participants treated with MC in this review (including studies recruiting patients with any condition eligible for MC).

Fig. 1 PRISMA flow diagram of studies through the review process

Fig. 2 A Countries and regions where MC is legal and B Bubble plot distribution of studies assessing HRQL in MC patients globally

How HRQL is defined, justified and evaluated

Although 51 of the 64 studies (80%) mentioned HRQL (or quality of life) in the title or abstract, and 34 (53%) reported HRQL as their primary outcome, only five (8%) studies provided a definition of HRQL (Table 1 ) [ 38 , 76 , 80 , 83 , 85 ]. References for HRQL definitions were provided by four of the five studies and sourced from Osoba et al. [ 12 ] and the US Centres for Disease Control and Prevention [ 92 ]. A reason or justification for including HRQL as an endpoint was provided in 39 (61%) studies. PROMs used to assess HRQL and the methods for reporting HRQL varied across studies. Most studies ( n = 51; 80%) provided references for PROMs (Table 1 ). Of the 52 (81%) studies using generic HRQL PROMS, the most frequently used was the EuroQol Group EQ-5D-5L [ 93 ], ( n = 31, 48%) or earlier version EQ-5D-3 L ( n = 1, 1.5%), reporting five domain scores and a single utility index ( n = 24, 37%), score from the visual analogue scale presented at the end of the PROM ( n = 5, 8%), or five domain scores only ( n = 2, 3%). Another frequently used generic PROM was the RAND SF-36 [ 94 ] ( n = 14, 22%) or shorter version, SF-12 ( n = 2, 3%), typically reporting two composite summary scores, physical and psychological ( n = 6, 9%), 8 domain scores ( n = 7, 11%), or a total score ( n = 2, 3%) (Table 1 ). Twelve studies (19%) used condition-specific HRQL PROMs; most frequently, the Multiple Sclerosis Quality of Life [ 95 ], (MSQoL-54; n = 3, 5%); and variants of the Quality of Life in Epilepsy scale [ 96 ], QOLIE-89, QOLIE-31P, and QOLIE-10 ( n = 3) (Table 1 ). One study utilised four PROMs covering pain, sleep, and mood and collectively referred to them as measuring HRQL [ 40 ]. Table 1 displays characteristics of all included studies and a summary of significant or clinically important PRO findings.

Table 1 Study characteristics, HRQL reporting, and summary of findings of included studies References Health condition MC composition Total N (% male) Mean age (SD or range) Follow-up [Recruitment dates] Study design HRQL assessment justified? HRQL definition? [citation?] HRQL PROM(s) [citation?] Summary of HRQL findings Aiewtrakoon et al. [ 71 ] Insomnia CBD 45 (33) 45.96 (11.7) 2-w [Sep 2021–Apr 2023] RCT - crossover No No EQ-5D-5L [no] Improved HRQL compared with placebo at 2-weeks (index score) Arkell et al. [ 77 ] Any condition THC: CBD 3148 (46.4) 55.9 (18.7) 20-m [Dec 2018–May 2022] Case series Yes No SF-36 [yes] Improved HRQL at 12-months (across all 8 domains). Aungsumart et al. [ 46 ] Multiple Sclerosis spasticity THC: CBD 7 (42.8) 41.3 (1.8) 12-w [Nov 2019–Jun 2020] Cohort study Yes No EQ-5D-5L [no] No change in HRQL at 12-weeks (index score) ‡ Bapir et al. [ 34 ] Chronic Pain CBD/THC/ THC: CBD 1254 (54.1) 45.7 (14.4) 3-m 6-m [Dec 2021–Jan 2022] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Barre et al. [ 73 ] HIV CBD 79 (69.6) 55.97 (12.8) 12-w [May 2022–Oct 2022] RCT - parallel Yes No SF-36 [yes] No change in HRQL compared with placebo at 12-weeks (physical and mental composite summary scores). Of 8 domains, only physical functioning improved Bar-Sela et al. [ 50 ] Cancer THC: CBD 34 (41) 63 (nr) 3-m [‘ 2 years ’] Non-randomised experimental No No QLQ-30 [yes] No change in HRQL at 3- months (global QoL). Improved insomnia and appetite (QLQ-C30 domains) Brett et al. [ 62 ] Epilepsy CBD 17 (50) 34.6 (18–64) 2.5-m 5-m [Aug 2017–Jun 2019] Cohort study Yes No QOLIE-31P [yes] Improved HRQL at 5-months (total score) Capano et al. [ 40 ] Chronic Pain CBD 97 (32) 56.2 (39–70) 8-w [Sep 2018–Dec 2018] Cohort study No No PHQ-4, PDI, PSQI, PEG [no] Improved HRQL at 8-weeks (sleep and pain PROMs only). No improvement in PHQ-4 or PDI Chaves et al. [ 67 ] Fibromyalgia THC 18 (0) 51.9 (nr) 8-w [Sep 2019–Nov 2019] RCT - parallel Yes No FIQ [yes] Improved HRQL compared with placebo at 8-weeks (total score) ‡ Datta et al. [ 33 ] Chronic Pain CBD/THC/ THC: CBD 1139 (54) 47 (14.1) 3-m 6-m 12-m [Dec 2019–Jan 2023] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 12-months (index score) ‡ Dickinson et al. [ 30 ] Chronic Pain (Hypermobility-associated) THC: CBD 161 (19.3) 37.42 (10.5) 3-m 6-m 18-m [Dec 2019–Dec 2023] Case series No No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 18-months (index score) Dujic et al. [ 76 ] Hypertension CBD 64 (57.8) 54.4 (8.9) 5-w [Dec 2021–Apr 2022] RCT - crossover Yes Yes [No] SF-36 [yes] No change in HRQL compared with placebo at 5-weeks (VAS presented after SF-36). Of 8 domains, only fatigue and psychological well-being improved Eibach et al. [ 72 ] HIV-Associated Neuropathic Pain CBDV 32 (97) 50.31 (9) 3-w [Jan 2017–Jan 2019] RCT - crossover Yes No SF-36 [yes] No change in HRQL compared with placebo at 3-weeks (across all 8 domains). † Ergisi et al. [ 78 ] Any condition THC: CBD 312 (55.1) 44.8 (15.4) 3-m 6-m [Dec 2019–nr] Case series Yes No EQ-5D-5L [no] Improved HRQL at 3- and 6-months (index score) † Erridge et al. [ 79 ] Any condition THC: CBD 129 (51.2) 46.23 (14.5) 3-m [Dec 2019–nr] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3-months (VAS) ‡ Francis et al. [ 68 ] Inflammatory Arthritis-associated Chronic Pain THC: CBD 82 (50) 47.61 (14.3) 3-m 6-m 12-m [Dec 2019–Jan 2023] Case series No No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 12-months (index score) ‡ Francis et al. [ 69 ] Osteoarthritis-related Chronic Pain THC: CBD 77 (52) 60.04 (14.3) 3-m 6-m 12-m [Dec 2019–Jan 2022] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Gaston et al. [ 64 ] Epilepsy CBD 53 (50.9) nr 12-m [nr] Cohort study Yes No QOLIE-89 [yes] Improved HRQL at 12-months (total score). Gruber et al. [ 91 ] Any condition THC: CBD 11 (55) 48.91 (15.1) 3-m [nr] Cohort study No No SF-36 [yes] Improved HRQL at 3-months (fatigue domain only) Gruber et al. [ 39 ] Chronic Pain THC: CBD 37 (44) 54.87 (14.0) 3-m 6-m [nr] Cohort study Yes No SF-36 [yes] Improved HRQL at 3- and 6-months (fatigue, pain and general health domains only) Gulbransen et al. [ 90 ] Any condition CBD 397 (46.1) 51.48 (19.1) 3-w [Dec 2017–Dec 2018] Cohort study No No EQ-5D-5L [yes] Improved HRQL at 3-weeks (VAS) Gupta et al. [ 58 ] Inflammatory Bowel Disease THC: CBD 116 (81) 39 (9.1) 3-m 6-m 18-m [Dec 2019–Dec 2023] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 18-months (index score) Hardy et al. [ 52 ] Advanced Cancer CBD 144 (52.8) 64.6 (12.8) 28-days [Feb 2019–Nov 2021] RCT - parallel No No QLQ-C15 [yes] No change in HRQL compared with placebo at 28-days (global QoL) Haroutounian et al. [ 6 ] Chronic Pain THC: CBD 206 (61.7) 51.2 (15.4) 6-m [Jun 2010–Jan 2013] Cohort study No No S-TOPS [yes] Improved HRQL at 6-months (all except physical disability domains) Haupts et al. [ 48 ] Multiple Sclerosis spasticity THC: CBD 241 (42) 49.1 3-m [nr] RCT - parallel Yes No EQ-5D-5L SF-36 [no] No change in HRQL compared with placebo at 3-months (EQ-5D index score and across SF-36 domains) Haupts et al. [ 42 ] Multiple Sclerosis spasticity THC: CBD 54 (39) 51.4 (11.1) 12-w [Dec 2021–Jan 2023] Cohort study No No MFHW [yes] No change in HRQL at 12-weeks (total score) Hershkovich et al. [ 66 ] Fibromyalgia THC: CBD 30 (0) 46 (5) 1-month [nr] Cohort study Yes No WHOQOL-BREF [yes] Improved HRQL at 1-month (pain, sleep, physical, and psychological domains only) Irving et al. [ 61 ] Inflammatory Bowel Disease (Ulcerative colitis) CBD 60 (79) 43.77 (13.9) 10-w [nr] RCT - parallel No No IBDQ [no] Improved HRQL compared with placebo at 10-weeks (total score) ‡ Kawka et al. [ 32 ] Chronic Pain THC: CBD 110 (49.1) 52.1 (15.4) 3-m 6-m [Dec 2019–nr] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3-months (index score) Kelley et al. [ 81 ] Any condition THC: CBD 103 (39.8) nr (18–65+) 30-days [nr] Cohort study Yes No SF-36 [no] Improved HRQL at 30-days (across all domains). Lamonarca et al. [ 63 ] Epilepsy CBD 44 (34) 35 (10) 3-m 6-m [nr] Cohort study Yes No QOLIE-10 [yes] Improved HRQL at 3- and 6-months (total score) Lent et al. [ 83 ] Any condition THC: CBD 438 (33.6) 46.4 (15.6) 3-m [Sep 2020–Jun 2023] Cohort study Yes Yes [Yes] SF-36 [yes] Improved HRQL at 3-months (across all domains) # Li et al. [ 54 ] Generalised Anxiety Disorder THC: CBD 120 (61.7) 39.38 (12.48) 3-m 6-m 12-m [Dec 2019–nr] Case series No No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 12-months (index score) Lucas et al. [ 89 ] Any condition CBD/THC/ THC: CBD 1145 (42.4) 51.2 (15.4) 3-m 6-m [nr] Cohort study No No WHOQOL-BREF [yes] Improved HRQL at 3- and 6-months (across all 4 domains) Lynskey et al. [ 82 ] Any condition THC: CBD 198 (47) 72.2 3-m [Aug 2020–Apr 2023] Cohort study yes no EQ-5D-5L [yes] Improved HRQL at 3-months (index score) Markova et al. [ 47 ] Multiple Sclerosis spasticity THC: CBD 191 (29.8) 51.3 (10.2) 12-w [nr] RCT - parallel Yes No SF-36 [no] No change in HRQL compared with placebo at 12-weeks (general health domain) Meng et al. [ 88 ] Chronic Pain THC: CBD 757 (38.3) nr (18–65+) 3-m 6-m 12-m [Sep 2015–Jul 2018] Cohort study Yes No EQ-5D-3 L [yes] Improved HRQL at 3-, 6- and 12-months (EQ-5D VAS) # Murphy et al. [ 55 ] General Anxiety Disorder THC: CBD 302 (69.5) 38.06 (11.7) 3-m 6-m 12-m [Dec 2019–Jan 2023] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 12-months (index score) Murphy et al. [ 41 ] Multiple Sclerosis THC: CBD 141 (48.9) 45.89 (11.1) 3-m 6-m [Dec 2019–Aug 2022] Cohort study Yes No EQ-5D-5L MSQoL-54 [yes] Improved HRQL at 3 and 6 months (EQ-5D index score and MSQoL-54 physical and mental composite summary scores) Naftali et al. [ 59 ] Inflammatory Bowel Disease (Crohn’s Disease) THC: CBD 56 (33) 34.5 (11) 8-w [2013–2018] RCT - parallel No No SF-36 [yes] Improved HRQL compared with placebo at 8-weeks (total score) Naftali et al. [ 60 ] Inflammatory Bowel Disease (Ulcerative colitis) THC 32 (56) 32 (10.86) 8-w [nr] RCT - parallel Yes No SF-36 [yes] Improved HRQL compared with placebo at 8-weeks (total score) Nathan et al. [ 51 ] Cancer THC: CBD 83 (58) nr (65–81+) 3-m [Jan 2018–Dec 2018] Cohort study No No ESAS [no] No change in HRQL at 3-months (across all domains) Nicholas et al. [ 75 ] Headache Disorder THC: CBD 97 (57) 37.9 (11.1) 3-m 6-m [Dec 2019–Feb 2022] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Palmieri et al. [ 87 ] Any condition THC 20 (60) 40.7 (nr) 3-m [nr] Cohort study No No SF-36 [yes] Improved HRQL at 3-months (across 6 domains) No change in role limitations and emotional state domains Peterson et al. [ 38 ] Chronic Pain THC: CBD 181 (47) 41.21 (12.9) 6-w [‘ Summer and Autumn ’2020] Cohort study Yes Yes [Yes] EQ-5D-5L [yes] Improved HRQL at 6-weeks (index score) Worsening in self-care domain # Rifkin-Zybutz et al. [ 57 ] Anxiety disorder THC: CBD 202 (68.6) 37 (11.5) 3-m 6-m [Dec 2019–nr] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Russo et al. [ 45 ] Multiple Sclerosis (Neuropathic Pain) THC: CBD 20 (40) 46 (5.8) 1-month [nr] Cohort study No No MSQoL-54 [no] Improved HRQL at 1-month (physical and mental composite summary scores) Russo et al. [ 44 ] Multiple Sclerosis spasticity THC: CBD 61 (nr) 42 (8.9) 1-m 6-m [Jan 2014–Dec 2014] Cohort study No No MSQoL-54 [yes] Deterioration of HRQL at 1-month (physical composite summary score) Improved HRQL at 6-months (mental composite summary scores) Safakish et al. [ 37 ] Chronic Pain THC: CBD 751 (43) 49.6 (14.3) 3-m 6-m 12-m [Oct 2015–Mar 2019] Cohort study Yes No SF-12 [yes] Improved HRQL over 12-months (physical and mental composite summary scores) Schloss et al. [ 53 ] Cancer (Glioma) THC: CBD 83 (51) 53.3 (12.6) 12-w [Nov 2018–Dec 2019] RCT - parallel No No FACT-Br [yes] No change in HRQL at 12-weeks (total score) Improved sleep and physical wellbeing domains Sridharan et al. [ 65 ] Fibromyalgia THC: CBD 148 (19.6) 47.2 (13.5) 3-m 6-m 12-m [Dec 2019–Jan 2023] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3-, 6- and 12-months (index score) Stienrut et al. [ 84 ] Any condition THC: CBD 21,284 (52.5) 54.1 (15.3) 3-m [Sep 2019–Oct 2020] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3-months (index score). Sultan et al. 2024 [ 74 ] Post-Traumatic Stress Disorder THC 58 (66) 39.2 (8.9) 3-m 6-m [Aug 2020–Apr 2023] Cohort study No No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (EQ-5D VAS) ‡ Tait et al. [ 35 ] Chronic Pain THC: CBD 761 (47.3) 46.8 (15.4) 3-m 6-m [Dec 2019–Jan 2022] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) No improvements at 6 months using MC flower *Tait et al. [ 85 ] Any condition CBD/ THC: CBD 2327 (37.2) 51 (15.4) 3-m [Nov 2020–Dec 2021] Cohort study Yes Yes [Yes] EQ-5D-5L QLQ-C30 [yes] Improved HRQL at 3- months (EQ-5D index score and QLQ-C30 summary score) *Tait et al. 2025 [ 80 ] Any condition CBD/ THC: CBD 2353 (37.2) 50.4 (15.4) 9-m 12-m [Nov 2020–Mar 2023] Cohort study Yes Yes [Yes] EQ-5D-5L QLQ-C30 [no] Improved HRQL at 9- and 12-months (EQ-5D index score and QLQ-C30 summary score) Ueberall et al. [ 31 ] Chronic Pain THC: CBD 800 (43) 46.3 (9.7) 12-w [Mar 2017–Dec 2017] Case series Yes No SF-12 [yes] Improved HRQL at 12-weeks (physical and mental composite summary scores) Deterioration only in patients with nociceptive pain Varadpande et al. [ 49 ] Cancer Pain THC: CBD 168 (60.7) 54.2 (14.6) 3-m 6-m [Dec 2019–Dec 2023] Case series No No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Vermersch et al. [ 43 ] Multiple Sclerosis spasticity THC: CBD 433 (44.8) 50.4 (10.4) 3-m [Aug 2013–Oct 2015] Cohort study No No EQ-5D-5L [no] Improved HRQL at 3-months (EQ-5D VAS) Vickery et al. [ 97 ] Any condition CBD/THC/ THC: CBD 3961 (46) 56.1 (19.2) 3-m 24-m [Dec 2018–Apr 2022] Cohort study No No SF-36 [yes] Improved HRQL at 3-, 12-, and 24- months (physical and mental composite summary scores) Vigano et al., 2023 [ 86 ] Any condition THC: CBD 2991 (49.8) 50.9 (18–96) 3-m 9-m 12-m [May 2015–Oct 2018] Cohort study No No EQ-5D-5L [yes] Improved HRQL at 3- and 12-months (global QoL) Vivek et al. [ 70 ] Insomnia THC: CBD 61 (72) 41.3 (13.0) 3-m 6-m [Dec 2019–Feb 2022] Case series Yes No EQ-5D-5L [yes] Improved HRQL at 3- and 6-months (index score) Ware et al. [ 36 ] Chronic Pain THC: CBD 431 (51.6) 45.5 (19–82) 6-m 12-m [Jan 2004–Apr 2008] Cohort study No No SF-36 [no] Improved HRQL compared with control group at 6- and 12-months (physical composite summary score). No change in mental composite summary score # Warner-Levy et al. [ 56 ] Generalised Anxiety Disorder THC: CBD 302 (69.5) 38.06 (11.7) 3-m 6-m 12-m [Dec 2019–Jan 2023] Cohort study Yes No EQ-5D-5L [yes] Improved HRQL at 3-, 6-, and 12-months (index score) * Papers report HRQL from same study cohort (2353 patients in QUEST study) but at different follow-up assessment timepoints ( n = 2) # Papers report HRQL from same study cohort (302 patients with anxiety on UK Medical cannabis Registry) at same follow-up assessment timepoints ( n = 4) ‡ Papers report HRQL from same study cohort (1254 patients with chronic pain on UK Medical cannabis Registry) at overlapping follow-up assessment timepoints ( n = 7) † Papers report HRQL from same study cohort (312 patients with any condition on UK Medical cannabis Registry) at overlapping follow-up assessment timepoints ( n = 2) CBD, cannabidiol (only); CBDV, cannabidivarin; EQ-5D-3 L, EuroQol quality of life − 5 dimensions-3 levels; EQ-5D-5L, EuroQol quality of life − 5 dimensions-5 levels; ESAS, Edmonton Symptom Assessment Score; FACT-Br, Functional Assessment of Cancer Therapy – Brain; FIQ, Fibromyalgia Impact Questionnaire; HRQL, health-related quality of life; IBDQ, Inflammatory bowel disease questionnaire; m, months; MC, medicinal cannabis; MFHW, Marburg questionnaire on habitual health; MSQoL-54, Multiple Sclerosis Quality of Life-54 items; nr, not reported; PDI, Pain Disability Index; PEG, 3-item scale assessing Pain Intensity and Interference; PHQ-4, Patient Health Questionnaire-4 items; PROM, patient-reported outcome measure; PSQI, Pittsburgh Sleep Quality Index; QLQ-C30, Quality of Life Questionnaire - Cancer 30 items; QLQ-C15, Quality of Life Questionnaire - Cancer 15 items for use in palliative care; QoL, quality of life; QOLIE-89, Quality Of Life In Epilepsy-89 items; QOLIE-31-P, Quality Of Life In Epilepsy-31items-plus 8 distress-related items; QOLIE-10, Quality Of Life In Epilepsy-10 items; RCT, randomised controlled trial; ref, reference; SD, standard deviation; SF-36, Short Form Health Survey − 36 items; SF-12, Short Form Health Survey − 12 items; S-TOPS, Treatment Outcomes in Pain Survey-Short Form; THC, delta-9-tetrahydrocannabinol (only); THC: CBD, combination of THC and CBD; VAS, visual analogue Scale w, weeks; WHOQOL-BREF, World Health Organisation Quality of Life Abbreviated Assessment

Quality and completeness of PRO reporting

When evaluating all 64 included studies for completeness of reporting using the composite STROBE and CONSORT-PRO criteria, 40/64 (63%) studies met 75% or more of PRO reporting criteria either fully or partially, and one study failed to meet more than 50% of criteria (Online Resource 5). Figure 3 displays the degree to which each PRO reporting criterion was met across all included studies. All studies reported recruitment procedures, baseline characteristics, and described PRO or HRQL domains. More than half of studies failed to describe sample size calculations or attempts to minimise bias. Looking specifically at the 52 observational studies, 32 (62%) reported no attempts to address bias (i.e., have high risk of bias).

Fig. 3 Completeness of PRO reporting for included studies ( n = 64) displayed as % of criteria met

None of the 12 RCTs showed high risk of bias on any of the RoB 2 tool criteria and all were evaluated as having low risk of bias in measurement of the outcome (Fig. 4 ). Ratings for each RCT against RoB 2 items are presented in Online Resource 6, and overall RoB rating added to Fig. 5 .

Fig. 4 Risk of Bias graph: review of ratings for each RoB 2 criteria presented as percentage across 8 RCTs included in meta-analysis

Meta-analyses by study design

Short-term between group differences

Of the 12 studies comparing between group differences (cannabinoid treatment group vs. placebo or controls), eight reported sufficient data to be included in a meta-analysis (Fig. 5 ). Of excluded studies, one did not report any measure of variability (standard deviations, IQR, or confidence intervals), one reported improvement from baseline but provided post-treatment HRQL scores only, one simply stated the difference was not significant, and one study reported > 30% improvement responder rates across multiple domains. The eight included studies were all RCTs, either parallel ( n = 7) or crossover ( n = 1), with treatment periods ranging from 4-weeks to 3-months (short-term). Between group effect sizes ranged from − 0.03 to 1.74, with an overall effect size of 0.30 (95% CI: 0.03 to 0.57; p = 0.03; τ 2 = 0.09) favouring cannabinoids. Only two studies found statistically significant HRQL improvements. Across conditions, subgroup analyses by MC composition revealed THC interventions (d = 1.30; 95%CI: 0.68 to 1.92; p < 0.001) were more effective for improving HRQL than CBD alone (d = 0.07; 95%CI: -0.13 to 0.27; p = 0.47). Meta-analysis was conducted after removing the outlier with effect size greater than ± 1.5 (i.e., Chaves 2020), revealing a small overall effect size of 0.15 (95%CI: 0.01 to 0.30; p = 0.04; τ 2 = 0.00). Further subgroup analyses by health condition found MC least effective for improving HRQL in HIV-associated neuropathic pain and hypertension, with larger HRQL improvements in studies of fibromyalgia and Inflammatory Bowel Disease (d = 0.57;95%CI: 0.24 to 0.90; p < 0.001).

Fig. 5 Meta-Analysis Results from RCTs ( n = 9) assessing short-term HRQL after MC (2-weeks to 3-months)

CBD, cannabidiol; CBDV, cannabidivarin; EQ-5D-5L, EuroQol quality of life − 5 dimensions-5 levels; FIQ, Fibromyalgia Impact Questionnaire; HRQL, health-related quality of life; IBDQ, Inflammatory bowel disease questionnaire; PROM, patient-reported outcome measure; QLQ-C15, Quality of Life Questionnaire - Cancer 15 items for use in palliative care; RCT, randomised controlled trial; SF-36, Short Form Health Survey − 36 items; THC, delta-9 tetrahydrocannabinol; VAS, visual analogue Scale.

Short-term within group differences

Of the 46 studies evaluating short-term within group differences (pre- and post-cannabinoid treatment), 29 reported sufficient data and were eligible for meta-analysis (Fig. 6 ). Of the 17 excluded studies, 10 assessed participants from an already included study, and seven did not report a measure of variability or usable test statistic. The 29 included studies were all observational, either cohort ( n = 24) or case series ( n = 5), with treatment periods ranging from 3-weeks to 3-months (short-term). 79% ( n = 23) of studies found significant improvements in HRQL over the first 3-months of MC therapy. Within group effect sizes ranged from − 2.12 to 2.98, with an overall effect size of 0.43 (95% CI: 0.19 to 0.67; p < 0.001; τ 2 = 0.40) favouring cannabinoids. As with RCTs, meta-analysis was also conducted after removing outliers with effect sizes greater than ± 1.5 (i.e., Russo 2016b, and Hershkovich 2023), maintaining an overall moderate effect size of 0.43 (95%CI 0.34 to 0.51; p < 0.001; τ 2 = 0.03). Further subgroup analyses revealed similar HRQL improvements in studies investigating CBD only (d = 0.48; 95%CI: 0.36 to 0.60; p < 0.001) and those investigating various THC: CBD combinations (d = 0.41; 95%CI: 0.31 to 0.51; p < 0.001). Analyses by health condition revealed largest HRQL improvements for PTSD, anxiety, chronic pain (d = 0.45; 95%CI: 0.35 to 0.55; p < 0.001), and studies across any health condition (d = 0.48; 95%CI: 0.37 to 0.60; p < 0.001). Studies investigating headache, cancer (d = 0.24; 95%CI: -1.74 to 0.66; p = 0.252), and multiple sclerosis (d = 0.38; 95%CI: -0.21 to 0.96; p = 0.204) found no significant changes in HRQL. Short-term HRQL changes from baseline were most variable in studies of patients with multiple sclerosis, where an equal number of studies reported improved HRQL or no change.

Fig. 6 Meta-analysis of short-term (3-weeks to 3-months) results from cohort and case series studies ( n = 29) of HRQL after MC

CBD, cannabidiol; EQ-5D-5L, EuroQol quality of life − 5 dimensions-5 levels; HRQL, health-related quality of life; MC, medicinal cannabis; MFHW, Marburg questionnaire on habitual health; MSQoL-54, Multiple Sclerosis Quality of Life-54 items; PDI, Pain Disability Index; PEG, 3-item scale assessing Pain Intensity and Interference; PHQ-4, Patient Health Questionnaire-4 items; PROM, patient-reported outcome measure; PSQI, Pittsburgh Sleep Quality Index; QOLIE-31-P, Quality Of Life In Epilepsy-31items-plus 8 distress-related items; SF-36, Short Form Health Survey − 36 items; SF-12, Short Form Health Survey − 12 items; THC, delta-9 tetrahydrocannabinol; VAS, visual analogue Scale; WHOQOL-BREF, World Health Organisation Quality of Life Abbreviated Assessment.

Medium-term within group differences

Of the 30 studies evaluating medium-term within group differences (pre- and post-cannabinoid treatment), 19 were included in meta-analysis (Fig. 7 ). Of the 11 excluded studies, nine assessed participants from an already included study, and two did not report a measure of variability or usable test statistic. The 19 included studies were all observational, either cohort ( n = 14) or case series ( n = 5), with treatment assessment periods of 5-months ( n = 1), 6-months ( n = 16), or 9-months ( n = 2). 95% ( n = 18) of studies reported significantly improved HRQL. Within group effect sizes ranged from 0.24 to 2.03, with an overall effect size of 0.74 (95% CI: 0.52 to 0.96; p < 0.001; τ 2 = 0.21) favouring cannabinoids. A few outliers with effect sizes greater than 1.5 influenced overall effect size. Meta-analysis was conducted after removing outliers with effect sizes greater than ± 1.5 (i.e., Brett 2024, Murphy 2024b, and Ergasi 2023), revealing an overall moderate effect size of 0.54 (95%CI: 0.45 to 0.64; p < 0.001; τ 2 = 0.02). Further subgroup analyses revealed greater HRQL improvement over the medium term in studies investigating various THC: CBD combinations (d = 0.56; 95%CI: 0.46 to 0.66; p < 0.001) compared with THC only (d = 0.47; 95%CI: 0.05 to 0.89; p = 0.029). Larger HRQL improvements were seen across studies assessing patients with headache, multiple sclerosis, PTSD, chronic pain (d = 0.48; 95%CI: 0.35 to 0.62; p < 0.001) and any condition (d = 0.64; 95%CI: 0.58 to 0.71; p < 0.001).

Fig. 7 Meta-analysis of medium-term (5–9 months) results from cohort and case series studies ( n = 19) of HRQL after MC

CBD, cannabidiol; EQ-5D-5L, EuroQol quality of life − 5 dimensions-5 levels; HRQL, health-related quality of life; IBD, Inflammatory Bowel Disease; MC, medicinal cannabis; MSQoL-54, Multiple Sclerosis Quality of Life-54 items; PROM, patient-reported outcome measure; QOLIE-31-P, Quality Of Life In Epilepsy-31items-plus 8 distress-related items; SF-36, Short Form Health Survey − 36 items; SF-12, Short Form Health Survey − 12 items; S-TOPS, Treatment Outcomes in Pain Survey-Short Form; THC, delta-9 tetrahydrocannabinol; VAS, visual analogue Scale.

Long-term within group differences

Of the 17 studies evaluating long-term within group differences (pre- and post-cannabinoid treatment), five were excluded because they assessed participants from an already included study, leaving 12 studies with sufficient data to include in meta-analysis (Fig. 8 ). Included studies were all observational, either cohort ( n = 9) or case series ( n = 3), with treatment assessment periods of 12-months ( n = 9), 18-months ( n = 1), 20.7-months ( n = 1), or 24-months ( n = 1). Within group effect sizes ranged from 0.30 to 0.78, with an overall effect size of 0.53 (95% CI: 0.42 to 0.64; p < 0.001; τ 2 = 0.03) favouring cannabinoids. All studies found significant improvement in HRQL from 12-months. Further subgroup analyses found the largest HRQL improvements across studies investigating any health condition (d = 0.67; 95%CI: 0.55 to 0.80; p < 0.001), chronic pain (d = 0.47; 95%CI: 0.29 to 0.66; p < 0.001), and anxiety.

Fig. 8 Meta-analysis of long-term (12–24 months) HRQL results from cohort and case series studies ( n = 12) after MC therapy. CBD, cannabidiol; EQ-5D-5L, EuroQol quality of life − 5 dimensions-5 levels; HRQL, health-related quality of life; IBD, Inflammatory Bowel Disease; MC, medicinal cannabis; PROM, patient-reported outcome measure; QOLIE-89, Quality Of Life In Epilepsy-89 items; SF-36, Short Form Health Survey − 36 items; SF-12, Short Form Health Survey − 12 items; THC, delta-9 tetrahydrocannabinol; VAS, visual analogue Scale

Discussion

This systematic review with meta-analysis included all prospective studies between 2015 and 2025 reporting HRQL in patients treated with non-synthetic MC. The included studies are mostly representative of countries globally where MC is legal, apart from southeastern African countries where MC is legal, but no studies were identified.

Completeness of PRO reporting was adequate for most studies, however one study failed to meet more than 50% of reporting criteria. HRQL was rarely defined and a third of studies did not provide a rationale for assessing HRQL. Failing to define HRQL, justify its assessment, or provide a clear HRQL hypothesis suggests these studies may not have had a clear research objective regarding HRQL. PROs are increasingly being used in clinical studies [ 98 ], following recommendations from professional and clinical organisations, health agencies, and regulatory bodies [ 10 , 99 , 100 ]. It is important for researchers to be explicit about the meaning and context of HRQL in their studies to enable assessment of whether the chosen HRQL measure was fit-for-purpose [ 14 ]. We found vastly different short-term HRQL results across the six observational studies assessing patients with multiple sclerosis treated with THC: CBD. Although not directly assessed, this may partly be due to a lack of HRQL definitions and rationales for evaluating HRQL, and the use of different HRQL PROMs across these studies. Having a clear HRQL definition helps inform the selection of appropriate PROMs, improves scientific rigor, and helps contextualise any discrepancies in findings. This is particularly important considering different PROMs have previously been shown to produce discrepant HRQL results within the same group of patients [ 14 ].

Overall, our meta-analysis findings suggest that, compared with baseline, small to moderate HRQL improvements are apparent within 3 months of commencing MC, with moderate to large improvements between 5 and 9-months, and moderate levels long-term (12 to 24 months). However, HRQL did not improve for all conditions and improvements often varied depending on cannabinoids used. Findings across moderate- to high-quality RCTs indicated clinically meaningful short-term improvements in HRQL were mostly driven by studies of patients with irritable bowel disease or fibromyalgia. One study with HIV patients used a specific cannabinoid, Cannabidivarin (CBDV), not investigated by any other included studies, which focused on CBD and THC cannabinoids. The findings from this study suggest CBDV was not effective in this cohort for reducing pain or improving HRQL. Meta-analysis of short-term observational studies found moderate HRQL improvements overall, with similar findings across studies looking at CBD only and THC: CBD in combination. However, this was also dependent on health conditions treated, with no change seen across studies of patients with cancer or multiple sclerosis. Notably, the two observational studies providing extreme negative and positive effect sizes were also rated as having low completeness of PRO reporting. For example, Hershkovich et al. didn’t specify the type of variability reported in results, however, after due diligence and investigation, we determined it was most likely standard deviation and included it in the meta-analysis. Although doubts were raised about the accuracy of reporting (e.g. whether standard error was mistakenly reported as standard deviation), we assumed research findings in peer-reviewed publications were reported correctly. However, to reduce possible bias from erroneous data, we crossed-checked all statistical information available for determining study effect sizes, including t tests and reported p-values, and where relevant, chose the most conservative estimation for inclusion in meta-analyses.

Comparisons with previous review findings

In their review, Goldenberg et al. found no main effect of MC on HRQL [ 15 ]. Along with synthetic cannabinoids, they reviewed six studies that used cannabis (smoked or ingested) and seven that used non-synthetic pharmaceutical cannabinoids (Sativex). Regarding the six cannabis studies, they found no main effect on HRQL, however, three of the studies were cross-sectional without pre- and post-therapy comparisons, two were prospective with small sample sizes (13 and 37), with the one RCT reporting significant but small improvements in mental HRQL in patients with neuropathic pain [ 101 ]. Across the seven non-synthetic cannabinoid studies, six found no main effect of MC on HRQL, and one observational study of 276 multiple sclerosis patients found significant HRQL improvements when assessed with MSQoL-54, but no HRQL change when the same patients were assessed using EQ-5D-3 L [ 102 ]. We observed similar disparate HRQL findings across studies assessing HRQL in multiple sclerosis patients using different PROMs, further highlighting the need to clearly define HRQL in this context to inform PROM selection. Goldenberg et al. concluded that where HRQL improvements were reported, this was mainly attributed to pain reduction [ 15 ]. However, as summarised in Table 1 , we found that studies reported HRQL improvements in patients due not only to pain reduction, but also through resolving sleep, and physical and psychological issues [ 41 , 42 , 48 , 53 – 57 , 62 – 64 , 66 , 70 , 71 , 79 ].

Strengths and limitations

A strength of this review is that all studies reviewed used non-synthetic cannabinoids derived from the cannabis plant, reflective of current MC products available in countries where MC prescribing is legal. Further, studies followed participants across short-, medium-, and long-term follow-up with meta-analyses comparing studies with similar follow-up assessment periods. A further strength of the current review is the wide coverage of 77 health conditions treated with MC in included studies (Online resource 4). This contrasts with previous reviews of HRQL in MC that included studies of synthetic cannabinoids, had limited coverage of health conditions, and short follow-up periods [ 15 , 16 ].

Generally, meta-analysis of observational studies should be interpreted cautiously, particularly over medium- and long-term assessment periods, due to possible attrition bias [ 103 ]. This is a limitation of review findings because participants remaining in observational studies are more likely those who are benefitting from therapy, inflating positive findings. Across all studies included in this review, a quarter employed methods to reduce attrition bias including intention-to-treat analyses in RCTs [ 6 , 31 , 47 , 48 , 53 , 61 ], and applying the ‘baseline observation carried forward approach’ [ 104 ] for handling missing data in observational studies [ 30 , 33 , 49 , 54 – 56 , 58 , 65 , 68 , 69 ]. However, when reasons for missing data are unknown, imputing data may potentially introduce other biases. We found most included observational studies did not report any attempts to reduce or address bias in their studies.

Another limitation of interpreting results of within group meta-analysis is that the correlation between pre and post therapy scores was often not reported in studies, thus introducing biased effect size variance, and without a control group it is unknown whether the effect is due to therapy, placebo, or natural recovery [ 105 ]. To account for this, we applied recommended correlations where available for repeated measures (including for RCT-crossover trials) and for multiple outcomes (HRQL domains) reported by the same group [ 28 , 29 ]. This is in contrast to a previous meta-analysis that included multiple domains from one study alongside studies with single outcomes, inflating the overall effect size contributions from studies with multiple domains [ 15 ].

Conclusions

We found a main effect of improved HRQL in patients using MC across studies published over the past decade. Improvements were observed across multiple health conditions over short-, medium- and long-term follow-up. However, disparate findings between studies of patients with the same health condition were also observed, possibly due to using different HRQL measures. This conflicting evidence may be better understood when researchers communicate how HRQL is defined and assessed in the context of their study and provide a justification for PROM selection.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Supplementary Material 3

Supplementary Material 4

Supplementary Material 5

Supplementary Material 6

The original online version of this article was revised: Figure 5 and Supplementary information file (MOESM 6) areupdated.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Change history

3/13/2026

The original online version of this article was revised: Figure 5 and Supplementary information file (MOESM 6) areupdated.

Change history

3/25/2026

A Correction to this paper has been published: 10.1007/s11136-026-04216-w

Author contributions

Margaret-Ann Tait, Claudia Rutherford, Rachel Campbell, and Daniel SJ Costa contributed to the study concept and design. Margaret-Ann Tait performed literature search. Study screening and data extraction was performed by Margaret-Ann Tait and Louise Acret. Margaret-Ann Tait conducted meta-analyses. The first draft of the manuscript was written by Margaret-Ann Tait and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

Open Access funding enabled and organized by CAUL and its Member Institutions. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of interest

Financial interests: Louise Acret, Daniel SJ Costa, Rachel Campbell, and Kate White declare they have no financial interests. Margaret-Ann Tait and Claudia Rutherford have previously received research support from Little Green Pharma Ltd. Non-financial interests: none.

References

1. Vos T Abajobir AA Abate KH Abbafati C Abbas KM Abd-Allah F Abdulkader RS Abdulle AM Abebo TA Abera SF Aboyans V Abu-Raddad LJ Ackerman IN Adamu AA Adetokunboh O Afarideh M Afshin A Agarwal SK Aggarwal R Global, regional, and National incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990­-2016: A systematic analysis for the global burden of disease study 2016 The Lancet 2017 390 10100 1211 1259 10.1016/S0140-6736(17)32154-2 PMC5605509 28919117 Vos, T., Abajobir, A. A., Abate, K. H., Abbafati, C., Abbas, K. M., Abd-Allah, F., Abdulkader, R. S., Abdulle, A. M., Abebo, T. A., Abera, S. F., Aboyans, V., Abu-Raddad, L. J., Ackerman, I. N., Adamu, A. A., Adetokunboh, O., Afarideh, M., Afshin, A., Agarwal, S. K., Aggarwal, R., et al. (2017). Global, regional, and National incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the global burden of disease study 2016. The Lancet , 390 (10100), 1211–1259. 10.1016/S0140-6736(17)32154-2 10.1016/S0140-6736(17)32154-2 PMC5605509 28919117

2. Robson, P. (2005). Human studies of cannabinoids and medicinal cannabis. In R. G. Pertwee (Ed.), Cannabinoids. Handbook of experimental Pharmacology (Vol. 168, pp. 719–756). Springer. 10.1007/3-540-26573-2_25 16596794

3. Social Council of the United Nations. (1972). Single convention on narcotic drugs, 1961. https://www.unodc.org/pdf/convention_1961_en.pdf

4. de Melo Reis RA Isaac AR Freitas HR de Almeida MM Schuck PF Ferreira GC Andrade-da-Costa B Trevenzoli IH Quality of life and a surveillant endocannabinoid system Frontiers in Neuroscience 2021 15 747229 10.3389/fnins.2021.747229 34776851 PMC8581450 de Melo Reis, R. A., Isaac, A. R., Freitas, H. R., de Almeida, M. M., Schuck, P. F., Ferreira, G. C., Andrade-da-Costa, B., & Trevenzoli, I. H. (2021). Quality of life and a surveillant endocannabinoid system. Frontiers in Neuroscience , 15 , 747229. 10.3389/fnins.2021.747229 34776851 10.3389/fnins.2021.747229 PMC8581450

5. Gautam CS Pandey A Tahlan A Gautam SS Opioid use in palliative care/chronic pain: Ethical & legal perspectives in India [Review] Biomedicine (India) 2017 37 2 178 182 Gautam, C. S., Pandey, A., Tahlan, A., & Gautam, S. S. (2017). Opioid use in palliative care/chronic pain: Ethical & legal perspectives in India. Biomedicine , 37 (2), 178–182.

6. Haroutounian S Ratz Y Ginosar Y Furmanov K Saifi F Meidan R Davidson E The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain: A prospective open-label study The Clinical Journal of Pain 2016 32 12 1036 1043 10.1097/AJP.0000000000000364 26889611 Haroutounian, S., Ratz, Y., Ginosar, Y., Furmanov, K., Saifi, F., Meidan, R., & Davidson, E. (2016). The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain: A prospective open-label study. The Clinical Journal of Pain , 32 (12), 1036–1043. 10.1097/AJP.0000000000000364 26889611 10.1097/AJP.0000000000000364

7. Therapeutic Goods Administration. (2016). Final decisions and reasons for decisions by a delegate of the secretary to the department of health. https://www.tga.gov.au/sites/default/files/scheduling-delegates-final-decisions-cannabis-and-tetrahydrocannabinols-march-2016_0.pdf . Accessed 25 May 2025.

8. Shim M Nguyen H Grootendorst P Lessons from 20 years of medical cannabis use in Canada Plos One 2023 18 3 e0271079 10.1371/journal.pone.0271079 36952564 PMC10035846 Shim, M., Nguyen, H., & Grootendorst, P. (2023). Lessons from 20 years of medical cannabis use in Canada. Plos One , 18 (3), e0271079. 10.1371/journal.pone.0271079 36952564 10.1371/journal.pone.0271079 PMC10035846

9. Dysa, Y. (2024). Ukraine legalises cannabis for medical use. Reuters.

10. Food and Drug Administration. (2009). Patient reported outcome measures: Use in medical product development to support labelling claims. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims

11. Lipscomb J Gotay CC Snyder CF Patient-reported outcomes in cancer: A review of recent research and policy initiatives CA: A Cancer Journal for Clinicians 2007 57 5 278 300 10.3322/ca.57.5.278 17855485 Lipscomb, J., Gotay, C. C., & Snyder, C. F. (2007). Patient-reported outcomes in cancer: A review of recent research and policy initiatives. CA: A Cancer Journal for Clinicians , 57 (5), 278–300. 10.3322/ca.57.5.278 17855485 10.3322/CA.57.5.278

12. Osoba D Lessons learned from measuring health-related quality of life in oncology. [Review] Journal of Clinical Oncology 1994 12 3 608 616 10.1200/JCO.1994.12.3.608 8120561 Osoba, D. (1994). Lessons learned from measuring health-related quality of life in oncology. Journal of Clinical Oncology , 12 (3), 608–616. 10.1200/JCO.1994.12.3.608 8120561 10.1200/JCO.1994.12.3.608

13. Patrick DL Erickson P Health status andhealth policy: Quality of life in health care evaluation andresource allocation 1993 Oxford UniversityPress 314 Patrick, D. L., & Erickson, P. (1993). Health status and health policy: Quality of life in health care evaluation and resource allocation (p. 314). Oxford University Press.

14. Costa DSJ Mercieca-Bebber R Rutherford C Tait MA King MT How is quality of life defined and assessed in published research? Quality of Life Research 2021 30 8 2109 2121 10.1007/s11136-021-02826-0 33792834 Costa, D. S. J., Mercieca-Bebber, R., Rutherford, C., Tait, M. A., & King, M. T. (2021). How is quality of life defined and assessed in published research? Quality of Life Research , 30 (8), 2109–2121. 10.1007/s11136-021-02826-0 33792834 10.1007/s11136-021-02826-0

15. Goldenberg M Reid MW IsHak WW Danovitch I The impact of cannabis and cannabinoids for medical conditions on health-related quality of life: A systematic review and meta-analysis Drug and Alcohol Dependence 2017 174 80 90 10.1016/j.drugalcdep.2016.12.030 28319753 Goldenberg, M., Reid, M. W., IsHak, W. W., & Danovitch, I. (2017). The impact of cannabis and cannabinoids for medical conditions on health-related quality of life: A systematic review and meta-analysis. Drug and Alcohol Dependence , 174 , 80–90. 10.1016/j.drugalcdep.2016.12.030 28319753 10.1016/j.drugalcdep.2016.12.030

16. Whiting PF Wolff RF Deshpande S Di Nisio M Duffy S Hernandez AV Keurentjes JC Lang S Misso K Ryder S Schmidlkofer S Westwood M Kleijnen J Cannabinoids for medical use: A systematic review and meta-analysis Jama 2015 313 24 2456 2473 10.1001/jama.2015.6358 26103030 Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., Keurentjes, J. C., Lang, S., Misso, K., Ryder, S., Schmidlkofer, S., Westwood, M., & Kleijnen, J. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. Jama , 313 (24), 2456–2473. 10.1001/jama.2015.6358 26103030 10.1001/jama.2015.6358

17. Health-related quality of life in patients accessing medicinal cannabis for symptom management: Systematic review of primary research since 2015. (2024). PROSPERO. https://www.crd.york.ac.uk/PROSPERO/view/CRD42022306778

18. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S. (2021). The Prisma 2020 statement: An updated guideline for reporting systematic reviews. BMJ , 372 , n71. 10.1136/bmj.n71 PMC8005924 33782057

19. Furlan, A. D., Pennick, V., Bombardier, C., & van Tulder, M. & from the Editorial Board of the Cochrane Back Review Group. (2009). 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine , 34 (18), 1929–1941. 10.1097/BRS.0b013e3181b1c99f 19680101

20. Casey, M. B., Smart, K. M., Segurado, R., & Doody, C. (2020). Multidisciplinary-based rehabilitation (MBR) compared with active physical interventions for pain and disability in adults with chronic pain: A systematic review and meta-analysis. The Clinical Journal of Pain , 36 (11), 874–886. 10.1097/AJP.0000000000000871 32773436

21. Liu C Ferreira GE Shaheed A Chen C Harris Q Bailey IA Peul CS Koes WC Lin CWC Surgical versus non-surgical treatment for sciatica: Systematic review and meta-analysis of randomised controlled trials Bmj 2023 381 e070730 10.1136/bmj-2022-070730 37076169 PMC10498296 Liu, C., Ferreira, G. E., Shaheed, A., Chen, C., Harris, Q., Bailey, I. A., Peul, C. S., Koes, W. C., B., & Lin, C. W. C. (2023). Surgical versus non-surgical treatment for sciatica: Systematic review and meta-analysis of randomised controlled trials. Bmj , 381 , e070730. 10.1136/bmj-2022-070730 37076169 10.1136/bmj-2022-070730 PMC10498296

22. MacCallum CA Russo EB Practical considerations in medical cannabis administration and dosing European Journal of Internal Medicine 2018 49 12 19 10.1016/j.ejim.2018.01.004 29307505 MacCallum, C. A., & Russo, E. B. (2018). Practical considerations in medical cannabis administration and dosing. European Journal of Internal Medicine , 49 , 12–19. 10.1016/j.ejim.2018.01.004 29307505 10.1016/j.ejim.2018.01.004

23. Veritas Health Innovation. (2025). Covidence systematic review software [computer software]. Melbourne, Australia. Available at http://www.covidence.org/

24. von Elm E Altman D Egger M Pocock S Gøtzsche P Vandenbroucke J STROBE Initiative The strengthening the reporting of observational studies in epidemiology (strobe)statement: Guidelines for reporting observational studies Journal of Clinical Epidemiology 2008 61 4 344 349 10.1016/j.jclinepi.2007.11.008 18313558 von Elm, E., Altman, D., Egger, M., Pocock, S., Gøtzsche, P., Vandenbroucke, J., & STROBE Initiative. (2008). The strengthening the reporting of observational studies in epidemiology (strobe)statement: Guidelines for reporting observational studies. Journal of Clinical Epidemiology , 61 (4), 344–349. 18313558 10.1016/j.jclinepi.2007.11.008

25. Calvert M Brundage M Jacobsen PB Schünemann HJ Efficace F The consort patient-reported outcome (pro) extension: Implications for clinical trials and practice Health and Quality of Life Outcomes 2013 11 184 10.1186/1477-7525-11-184 24168680 PMC3842645 Calvert, M., Brundage, M., Jacobsen, P. B., Schünemann, H. J., & Efficace, F. (2013). The consort patient-reported outcome (pro) extension: Implications for clinical trials and practice. Health and Quality of Life Outcomes , 11 , 184. 10.1186/1477-7525-11-184 24168680 10.1186/1477-7525-11-184 PMC3842645

26. Sterne J Savović J Page M Elbers R Blencowe N Boutron I Cates C Cheng HY Corbett M Eldridge S Hernán M Hopewell S Hróbjartsson A Junqueira D Jüni P Kirkham J Lasserson T Li T McAleenan A Rob 2: A revised tool for assessing risk of bias in randomised trials Bmj 2019 366 l4898 10.1136/bmj.l4898 31462531 Sterne, J., Savović, J., Page, M., Elbers, R., Blencowe, N., Boutron, I., Cates, C., Cheng, H. Y., Corbett, M., Eldridge, S., Hernán, M., Hopewell, S., Hróbjartsson, A., Junqueira, D., Jüni, P., Kirkham, J., Lasserson, T., Li, T., McAleenan, A., et al. (2019). Rob 2: A revised tool for assessing risk of bias in randomised trials. Bmj , 366 , l4898. 31462531 10.1136/bmj.l4898

27. McGrath, S., Zhao, X., & Steele, R.. (2023). Estmeansd: Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. 10.32614/CRAN.package.estmeansd 10.1177/0962280219889080 PMC7390706 32292115

28. Balk, E. M., Earley, A., Patel, K., Trikalinos, T. A., & Dahabreh, I., J (2012). Empirical assessment of within-arm correlation imputation in trials of continuous outcomes. Methods research report (prepared by the tufts evidence-based practice center under contract no 290-2007-10055-i) Ahrq publication no 12(13)-ehc141-ef . Agency for Healthcare Research and Quality. 23326900

29. Farivar SS Cunningham WE Hays RD Correlated physical and mental health summary scores for the SF-36 and SF-12 Health Survey, V. 1 Health and Quality of Life Outcomes 2007 5 54 10.1186/1477-7525-5-54 17825096 PMC2065865 Farivar, S. S., Cunningham, W. E., & Hays, R. D. (2007). Correlated physical and mental health summary scores for the SF-36 and SF-12 Health Survey, V. 1. Health and Quality of Life Outcomes , 5 , 54. 10.1186/1477-7525-5-54 17825096 10.1186/1477-7525-5-54 PMC2065865

30. Dickinson M Erridge S Warner-Levy J Clarke E McLachlan K Coomber R Holden W Rucker JJ Platt MW Sodergren MH Uk medical cannabisregistry: An analysis of outcomes of medical cannabis therapy forhypermobility-associated chronic pain ACR Open Rheumatology 2025 10.1002/acr2.70024 40079426 PMC11905011 Dickinson, M., Erridge, S., Warner-Levy, J., Clarke, E., McLachlan, K., Coomber, R., Holden, W., Rucker, J. J., Platt, M. W., & Sodergren, M. H. (2025). UK medical cannabis registry: An analysis of outcomes of medical cannabis therapy for hypermobility-associated chronic pain. ACR Open Rheumatology . 10.1002/acr2.70024. e70024. 40079426 10.1002/acr2.70024 PMC11905011

31. Ueberall MA Essner U Mueller-Schwefe GHH Effectiveness and tolerability of thc:cbd oromucosal spray as add-on measure in patients with severe chronic pain: Analysis of 12-week open-label real-world data provided by the German pain e-registry J Pain Res 2019 12 1577 1604 10.2147/JPR.S192174 31190969 PMC6535492 Ueberall, M. A., Essner, U., & Mueller-Schwefe, G. H. H. (2019). Effectiveness and tolerability of thc:cbd oromucosal spray as add-on measure in patients with severe chronic pain: Analysis of 12-week open-label real-world data provided by the German pain e-registry. J Pain Res , 12 , 1577–1604. 10.2147/JPR.S192174 31190969 10.2147/JPR.S192174 PMC6535492

32. Kawka M Erridge S Holvey C Coomber R Usmani A Sajad M Platt MW Rucker JJ Sodergren MH Clinical outcome data of first cohort of chronic pain patients treated with cannabis-based Sublingual oils in the united kingdom: Analysis from the Uk medical cannabis registry Journal of Clinical Pharmacology 2021 61 12 1545 1554 10.1002/jcph.1961 34473850 PMC9292210 Kawka, M., Erridge, S., Holvey, C., Coomber, R., Usmani, A., Sajad, M., Platt, M. W., Rucker, J. J., & Sodergren, M. H. (2021). Clinical outcome data of first cohort of chronic pain patients treated with cannabis-based Sublingual oils in the United Kingdom: Analysis from the UK medical cannabis registry. Journal of Clinical Pharmacology , 61 (12), 1545–1554. 10.1002/jcph.1961 34473850 10.1002/jcph.1961 PMC9292210

33. Datta I Erridge S Holvey C Coomber R Guru R Holden W Darweish Medniuk A Sajad M Searle R Usmani A Varma S Rucker JJ Platt M Sodergren MH Uk medical cannabis registry: A clinical outcome analysis of medical cannabis therapy in chronic pain patients with and without co-morbid sleep impairment Pain Practice 2025 25 1 e13438 10.1111/papr.13438 39545361 PMC11683519 Datta, I., Erridge, S., Holvey, C., Coomber, R., Guru, R., Holden, W., Darweish Medniuk, A., Sajad, M., Searle, R., Usmani, A., Varma, S., Rucker, J. J., Platt, M., & Sodergren, M. H. (2025). UK medical cannabis registry: A clinical outcome analysis of medical cannabis therapy in chronic pain patients with and without co-morbid sleep impairment. Pain Practice , 25 (1), e13438. 10.1111/papr.13438 39545361 10.1111/papr.13438 PMC11683519

34. Bapir L Erridge S Nicholas M Pillai M Dalavaye N Holvey C Coomber R Hoare J Khan S Weatherall MW Rucker JJ Platt M Sodergren MH Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study Expert Review of Neurotherapeutics 2023 23 3 281 295 10.1080/14737175.2023.2181696 36803620 Bapir, L., Erridge, S., Nicholas, M., Pillai, M., Dalavaye, N., Holvey, C., Coomber, R., Hoare, J., Khan, S., Weatherall, M. W., Rucker, J. J., Platt, M., & Sodergren, M. H. (2023). Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study. Expert Review of Neurotherapeutics , 23 (3), 281–295. 10.1080/14737175.2023.2181696 36803620 10.1080/14737175.2023.2181696

35. Tait J Erridge S Holvey C Coomber R Usmani A Sajad M Hoare J Khan S Weatherall M Rucker JJ Platt M Sodergren MH Clinical outcome data of chronic pain patients treated with cannabis-based oils and dried flower from the Uk medical cannabis registry Expert Review of Neurotherapeutics 2023 23 4 413 423 10.1080/14737175.2023.2195551 37021592 Tait, J., Erridge, S., Holvey, C., Coomber, R., Usmani, A., Sajad, M., Hoare, J., Khan, S., Weatherall, M., Rucker, J. J., Platt, M., & Sodergren, M. H. (2023). Clinical outcome data of chronic pain patients treated with cannabis-based oils and dried flower from the UK medical cannabis registry. Expert Review of Neurotherapeutics , 23 (4), 413–423. 10.1080/14737175.2023.2195551 37021592 10.1080/14737175.2023.2195551

36. Ware MA Wang T Shapiro S Collet JP Cannabis for the management of pain: Assessment of safety study (compass) Journal of Pain 2015 16 12 1233 1242 10.1016/j.jpain.2015.07.014 26385201 Ware, M. A., Wang, T., Shapiro, S., & Collet, J. P. (2015). Cannabis for the management of pain: Assessment of safety study (compass). Journal of Pain , 16 (12), 1233–1242. 10.1016/j.jpain.2015.07.014 26385201 10.1016/j.jpain.2015.07.014

37. Safakish R Ko G Salimpour V Hendin B Sohanpal I Loheswaran G Yoon SYR Medical cannabis for the management of pain and quality of life in chronic pain patients: A prospective observational study Pain Medicine (Malden, Mass.) 2020 21 11 3073 3086 10.1093/PM/PNAA163 32556203 Safakish, R., Ko, G., Salimpour, V., Hendin, B., Sohanpal, I., Loheswaran, G., & Yoon, S. Y. R. (2020). Medical cannabis for the management of pain and quality of life in chronic pain patients: A prospective observational study. Pain Medicine , 21 (11), 3073–3086. 10.1093/PM/PNAA163 32556203 10.1093/pm/pnaa163

38. Peterson AM Le C Dautrich T Measuring the change in health-relatedquality of life in patients using marijuana for painrelief Medical Cannabis andCannabinoids 2021 10.1159/000517857 PMC8832252 35224431 Peterson, A. M., Le, C., & Dautrich, T. (2021). Measuring the change in health-related quality of life in patients using marijuana for pain relief. Medical Cannabis and Cannabinoids . 10.1159/000517857 10.1159/000517857 PMC8832252 35224431

39. Gruber SA Smith RT Dahlgren MK Lambros AM Sagar KA No pain, all gain? Interim analyses from a longitudinal, observational study examining the impact of medical cannabis treatment on chronic pain and related symptoms Experimental and Clinical Psychopharmacology 2021 29 2 147 156 10.1037/pha0000435 33764103 Gruber, S. A., Smith, R. T., Dahlgren, M. K., Lambros, A. M., & Sagar, K. A. (2021). No pain, all gain? Interim analyses from a longitudinal, observational study examining the impact of medical cannabis treatment on chronic pain and related symptoms. Experimental and Clinical Psychopharmacology , 29 (2), 147–156. 10.1037/pha0000435 33764103 10.1037/pha0000435

40. Capano A Weaver R Burkman E Evaluation of the effects of Cbd hemp extract on opioid use and quality of life indicators in chronic pain patients: A prospective cohort study Postgraduate Medicine 2020 132 1 56 61 10.1080/00325481.2019.1685298 31711352 Capano, A., Weaver, R., & Burkman, E. (2020). Evaluation of the effects of Cbd hemp extract on opioid use and quality of life indicators in chronic pain patients: A prospective cohort study. Postgraduate Medicine , 132 (1), 56–61. 10.1080/00325481.2019.1685298 31711352 10.1080/00325481.2019.1685298

41. Murphy M Kaur V Bui HL Yang T Erridge S Holvey C Coomber R Rucker JJ Weatherall MW Sodergren MH Clinical outcome analysis of patients with multiple sclerosis - analysis from the Uk medical cannabis registry Multiple Sclerosis and Related Disorders 2024 87 105665 10.1016/j.msard.2024.105665 38728958 Murphy, M., Kaur, V., Bui, H. L., Yang, T., Erridge, S., Holvey, C., Coomber, R., Rucker, J. J., Weatherall, M. W., & Sodergren, M. H. (2024). Clinical outcome analysis of patients with multiple sclerosis - analysis from the UK medical cannabis registry. Multiple Sclerosis and Related Disorders , 87 , 105665. 10.1016/j.msard.2024.105665 38728958 10.1016/j.msard.2024.105665

42. Haupts MR Essner U Maurer M Patient-reported benefits from nabiximols treatment in multiple sclerosis-related spasticity exceed conventional measures Neurodegenerative Disease Management 2024 14 1 11EP 20 10.2217/nmt-2023-0040 38318862 PMC11238742 Haupts, M. R., Essner, U., & Maurer, M. (2024). Patient-reported benefits from nabiximols treatment in multiple sclerosis-related spasticity exceed conventional measures. Neurodegenerative Disease Management , 14 (1), 11–20. 10.2217/nmt-2023-0040 38318862 10.2217/nmt-2023-0040 PMC11238742

43. Vermersch P Trojano M Tetrahydrocannabinol:Cannabidiol oromucosal spray for multiple sclerosis-related resistant spasticity in daily practice European Neurology 2016 76 5–6 216 226 10.1159/000449413 27732980 Vermersch, P., & Trojano, M. (2016). Tetrahydrocannabinol: Cannabidiol oromucosal spray for multiple sclerosis-related resistant spasticity in daily practice. European Neurology , 76 (5–6), 216–226. 10.1159/000449413 27732980 10.1159/000449413

44. Russo M De Luca R Torrisi M Rifici C Sessa E Bramanti P Naro A Calabro RS Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study European Review for Medical and Pharmacological Sciences 2016 20 14 3127 3133 27460745 Russo, M., De Luca, R., Torrisi, M., Rifici, C., Sessa, E., Bramanti, P., Naro, A., & Calabro, R. S. (2016). Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study. European Review for Medical and Pharmacological Sciences , 20 (14), 3127–3133. 27460745

45. Russo M Naro A Leo A Sessa E D’Aleo G Bramanti P Calabro RS Evaluating sativex r in neuropathic pain management: A clinical and neurophysiological assessment in multiple sclerosis Pain Medicine 2016 17 6 1145 1154 10.1093/pm/pnv080 26764336 Russo, M., Naro, A., Leo, A., Sessa, E., D’Aleo, G., Bramanti, P., & Calabro, R. S. (2016). Evaluating sativex r in neuropathic pain management: A clinical and neurophysiological assessment in multiple sclerosis. Pain Medicine , 17 (6), 1145–1154. 10.1093/pm/pnv080 26764336 10.1093/pm/pnv080

46. Aungsumart S Pongsuthimanus N Apiwattanakul M A pilot study of the government pharmaceutical organization (gpo) cannabis extract for multiple sclerosis (ms) spasticity treatment in Thailand Journal of the Medical Association of Thailand 2021 104 3 460 465 10.35755/jmedassocthai.2021.03.11919 Aungsumart, S., Pongsuthimanus, N., & Apiwattanakul, M. (2021). A pilot study of the government pharmaceutical organization (gpo) cannabis extract for multiple sclerosis (ms) spasticity treatment in Thailand. Journal of the Medical Association of Thailand , 104 (3), 460–465. 10.35755/jmedassocthai.2021.03.11919

47. Markova J Essner U Akmaz B Marinelli M Trompke C Lentschat A Vila C Sativex as add-on therapy vs. Further optimized first-line antispastics (savant) in resistant multiple sclerosis spasticity: A double-blind, placebo-controlled randomised clinical trial International Journal of Neuroscience 2019 129 2 119 128 10.1080/00207454.2018.1481066 29792372 Markova, J., Essner, U., Akmaz, B., Marinelli, M., Trompke, C., Lentschat, A., & Vila, C. (2019). Sativex as add-on therapy vs. Further optimized first-line antispastics (savant) in resistant multiple sclerosis spasticity: A double-blind, placebo-controlled randomised clinical trial. International Journal of Neuroscience , 129 (2), 119–128. 10.1080/00207454.2018.1481066 29792372 10.1080/00207454.2018.1481066

48. Haupts M Vila C Jonas A Witte K Alvarez-Ossorio L Influence of previous failed antispasticity therapy on the efficacy and tolerability of thc:cbd oromucosal spray for multiple sclerosis spasticity European Neurology 2016 75 5–6 236 243 10.1159/000445943 27160412 Haupts, M., Vila, C., Jonas, A., Witte, K., & Alvarez-Ossorio, L. (2016). Influence of previous failed antispasticity therapy on the efficacy and tolerability of thc:cbd oromucosal spray for multiple sclerosis spasticity. European Neurology , 75 (5–6), 236–243. 10.1159/000445943 27160412 10.1159/000445943

49. Varadpande, M., Erridge, S., Aggarwal, A., Cowley, I., Evans, L., Clarke, E., McLachlan, K., Coomber, R., Rucker, J. J., Platt, M. W., Khan, S., & Sodergren, M. (2025). UK medical cannabis registry: An analysis of clinical outcomes of medicinal cannabis therapy for cancer pain. Journal of Pain & Palliative Care Pharmacotherapy , 39 (2): 174–194. 10.1080/15360288.2025.2457101 10.1080/15360288.2025.2457101 39921589

50. Bar-Sela G Tauber D Mitnik I Sheinman-Yuffe H Bishara-Frolova T Aharon-Peretz J Cannabis-related cognitive impairment: A prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study Anti-Cancer Drugs 2019 30 1 91 97 10.1097/CAD.0000000000000685 30540595 Bar-Sela, G., Tauber, D., Mitnik, I., Sheinman-Yuffe, H., Bishara-Frolova, T., & Aharon-Peretz, J. (2019). Cannabis-related cognitive impairment: A prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study. Anti-Cancer Drugs , 30 (1), 91–97. 10.1097/CAD.0000000000000685 30540595 10.1097/CAD.0000000000000685

51. Nathan R Mupamombe CT Elibol J Case AA Smith D Hyland A Attwood K Hansen ED Assessing efficacy and use patterns of medical cannabis for symptom management in elderly cancer patients The American Journal of Hospice & Palliative Care 2023 40 4 368 373 10.1177/10499091221110217 35749740 Nathan, R., Mupamombe, C. T., Elibol, J., Case, A. A., Smith, D., Hyland, A., Attwood, K., & Hansen, E. D. (2023). Assessing efficacy and use patterns of medical cannabis for symptom management in elderly cancer patients. The American Journal of Hospice & Palliative Care , 40 (4), 368–373. 10.1177/10499091221110217 35749740 10.1177/10499091221110217

52. Hardy J Greer R Huggett G Kearney A Gurgenci T Good P Phase Iib randomized, placebo-controlled, dose-escalating, double-blind study of Cannabidiol oil for the relief of symptoms in advanced cancer (medcan1-cbd) Journal of Clinical Oncology 2023 41 7 1444 1452 10.1200/JCO.22.01632 36409969 Hardy, J., Greer, R., Huggett, G., Kearney, A., Gurgenci, T., & Good, P. (2023). Phase Iib randomized, placebo-controlled, dose-escalating, double-blind study of Cannabidiol oil for the relief of symptoms in advanced cancer (medcan1-cbd). Journal of Clinical Oncology , 41 (7), 1444–1452. 10.1200/JCO.22.01632 36409969 10.1200/JCO.22.01632

53. Schloss J Lacey J Sinclair J Steel A Sughrue M Sibbritt D Teo C A phase 2 randomised clinical trialassessing the tolerability of two different ratios of medicinalcannabis in patients with high grade gliomas Frontiers in Oncology 2021 10.3389/fonc.2021.649555 34094937 PMC8176855 Schloss, J., Lacey, J., Sinclair, J., Steel, A., Sughrue, M., Sibbritt, D., & Teo, C. (2021). A phase 2 randomised clinical trial assessing the tolerability of two different ratios of medicinal cannabis in patients with high grade gliomas. Frontiers in Oncology . 10.3389/fonc.2021.649555 34094937 10.3389/fonc.2021.649555 PMC8176855

54. Li A Erridge S Holvey C Coomber R Barros D Bhoskar U Crews M Donnelly L Imran M Korb L Mwimba G Sachdeva-Mohan S Rucker JJ Sodergren MH Uk medical cannabis registry: A case series analyzing clinical outcomes of medical cannabis therapy for generalized anxiety disorder patients International Clinical Psychopharmacology 2024 39 6 350EP 360 10.1097/YIC.0000000000000536 38299624 PMC11424060 Li, A., Erridge, S., Holvey, C., Coomber, R., Barros, D., Bhoskar, U., Crews, M., Donnelly, L., Imran, M., Korb, L., Mwimba, G., Sachdeva-Mohan, S., Rucker, J. J., & Sodergren, M. H. (2024). Uk medical cannabis registry: A case series analyzing clinical outcomes of medical cannabis therapy for generalized anxiety disorder patients. International Clinical Psychopharmacology , 39 (6), 350–360. 10.1097/YIC.0000000000000536 38299624 10.1097/YIC.0000000000000536 PMC11424060

55. Murphy M Erridge S Holvey C Coomber R Rucker JJ Sodergren MH A cohort study comparing the effects of medical cannabis for anxiety patients with and without comorbid sleep disturbance Neuropsychopharmacology Reports 2024 44 1 129EP 142 10.1002/npr2.12407 38155535 PMC10932782 Murphy, M., Erridge, S., Holvey, C., Coomber, R., Rucker, J. J., & Sodergren, M. H. (2024). A cohort study comparing the effects of medical cannabis for anxiety patients with and without comorbid sleep disturbance. Neuropsychopharmacology Reports , 44 (1), 129–142. 10.1002/npr2.12407 38155535 10.1002/npr2.12407 PMC10932782

56. Warner-Levy J Erridge S Clarke E McLachlan K Coomber R Asghar M Bexley K Bhoskar U Crews M De Angelis A Imran M Kamal F Korb L Mwimba G Sachdeva-Mohan S Shaya G Rucker JJ Sodergren MH Uk medical cannabis registry: A cohort study of patients prescribed cannabis-based oils and dried flower for generalised anxiety disorder Expert Review of Neurotherapeutics 2024 24 12 1193EP 1202 10.1080/14737175.2024.2423634 39526700 Warner-Levy, J., Erridge, S., Clarke, E., McLachlan, K., Coomber, R., Asghar, M., Bexley, K., Bhoskar, U., Crews, M., De Angelis, A., Imran, M., Kamal, F., Korb, L., Mwimba, G., Sachdeva-Mohan, S., Shaya, G., Rucker, J. J., & Sodergren, M. H. (2024). Uk medical cannabis registry: A cohort study of patients prescribed cannabis-based oils and dried flower for generalised anxiety disorder. Expert Review of Neurotherapeutics , 24 (12), 1193–1202. 10.1080/14737175.2024.2423634 39526700 10.1080/14737175.2024.2423634

57. Rifkin-Zybutz R Erridge S Holvey C Coomber R Gaffney J Lawn W Barros D Bhoskar U Mwimba G Praveen K Symeon C Sachdeva-Mohan S Rucker JJ Sodergren MH Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the united kingdom: A cohort study from the Uk medical cannabis registry Psychopharmacology (Berl) 2023 240 8 1735 1745 10.1007/s00213-023-06399-3 37314478 PMC10349732 Rifkin-Zybutz, R., Erridge, S., Holvey, C., Coomber, R., Gaffney, J., Lawn, W., Barros, D., Bhoskar, U., Mwimba, G., Praveen, K., Symeon, C., Sachdeva-Mohan, S., Rucker, J. J., & Sodergren, M. H. (2023). Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the united kingdom: A cohort study from the UK medical cannabis registry. Psychopharmacology , 240 (8), 1735–1745. 10.1007/s00213-023-06399-3 37314478 10.1007/s00213-023-06399-3 PMC10349732

58. Gupta A Erridge S Graf V Kelada M Bapir L Jesuraj N Warner-Levy J Clarke E McLachlan K Coomber R Rucker JJ Platt MW Sodergren MH Uk medical cannabis registry: An updated analysis of clinical outcomes of cannabis-based medicinal products for inflammatory bowel disease Expert Review of Gastroenterology and Hepatology 2024 18 12 829EP 838 10.1080/17474124.2024.2443574 39689344 Gupta, A., Erridge, S., Graf, V., Kelada, M., Bapir, L., Jesuraj, N., Warner-Levy, J., Clarke, E., McLachlan, K., Coomber, R., Rucker, J. J., Platt, M. W., & Sodergren, M. H. (2024). Uk medical cannabis registry: An updated analysis of clinical outcomes of cannabis-based medicinal products for inflammatory bowel disease. Expert Review of Gastroenterology and Hepatology , 18 (12), 829–838. 10.1080/17474124.2024.2443574 39689344 10.1080/17474124.2024.2443574

59. Naftali T Bar-Lev Schleider L Almog S Meiri D Konikoff FM Oral cbd-rich cannabis induces clinical but not endoscopic response in patients with crohn’s disease, a randomised controlled trial Journal of Crohn’s & Colitis 2021 15 11 1799 1806 10.1093/ecco-jcc/jjab069 33858011 Naftali, T., Bar-Lev Schleider, L., Almog, S., Meiri, D., & Konikoff, F. M. (2021). Oral cbd-rich cannabis induces clinical but not endoscopic response in patients with Crohn’s disease, a randomised controlled trial. Journal of Crohn’s & Colitis , 15 (11), 1799–1806. 10.1093/ecco-jcc/jjab069 10.1093/ecco-jcc/jjab069 33858011

60. Naftali T Bar-Lev Schleider L Scklerovsky Benjaminov F Konikoff FM Matalon ST Ringel Y Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial PLoS ONE [Electronic Resource] 2021 16 2 e0246871 10.1371/journal.pone.0246871 33571293 PMC7877751 Naftali, T., Bar-Lev Schleider, L., Scklerovsky Benjaminov, F., Konikoff, F. M., Matalon, S. T., & Ringel, Y. (2021). Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial. PLoS ONE [Electronic Resource] , 16 (2), e0246871. 10.1371/journal.pone.0246871 33571293 10.1371/journal.pone.0246871 PMC7877751

61. Irving PM Iqbal T Nwokolo C Subramanian S Bloom S Prasad N Hart A Murray C Lindsay JO Taylor A Barron R Wright S A randomized, double-blind, placebo-controlled, parallel-group, pilot study of cannabidiol-rich botanical extract in the symptomatic treatment of ulcerative colitis Inflammatory Bowel Diseases 2018 24 4 714 724 10.1093/ibd/izy002 29538683 Irving, P. M., Iqbal, T., Nwokolo, C., Subramanian, S., Bloom, S., Prasad, N., Hart, A., Murray, C., Lindsay, J. O., Taylor, A., Barron, R., & Wright, S. (2018). A randomized, double-blind, placebo-controlled, parallel-group, pilot study of cannabidiol-rich botanical extract in the symptomatic treatment of ulcerative colitis. Inflammatory Bowel Diseases , 24 (4), 714–724. 10.1093/ibd/izy002 29538683 10.1093/ibd/izy002

62. Brett BA Conroy M Doshi H Lowe MX Kalcheff-Korn S Jackson H An observational time-series study on the behavioral effects of adjunctive artisanal Cannabidiol use by adults with treatment resistant epilepsies BMC Neurology 2024 24 1 141 10.1186/s12883-024-03646-8 38671370 PMC11046917 Brett, B. A., Conroy, M., Doshi, H., Lowe, M. X., Kalcheff-Korn, S., & Jackson, H. (2024). An observational time-series study on the behavioral effects of adjunctive artisanal Cannabidiol use by adults with treatment resistant epilepsies. BMC Neurology , 24 (1), 141. 10.1186/s12883-024-03646-8 38671370 10.1186/s12883-024-03646-8 PMC11046917

63. Lamonarca J Mintz I Bayarres L Kochen S Oddo S Psychiatric comorbidities before and after Cannabidiol treatment in adult patients with drug resistant focal epilepsy Epilepsy and Behavior 2024 160 110032 10.1016/j.yebeh.2024.110032 39433001 Lamonarca, J., Mintz, I., Bayarres, L., Kochen, S., & Oddo, S. (2024). Psychiatric comorbidities before and after Cannabidiol treatment in adult patients with drug resistant focal epilepsy. Epilepsy and Behavior , 160 , 110032. 10.1016/j.yebeh.2024.110032 39433001 10.1016/j.yebeh.2024.110032

64. Gaston TE Szaflarski M Hansen B Bebin EM Szaflarski JP Quality of life in adults enrolled in an open-label study of Cannabidiol (cbd) for treatment-resistant epilepsy Epilepsy and Behavior 2019 95 10 17 10.1016/j.yebeh.2019.03.035 31003195 Gaston, T. E., Szaflarski, M., Hansen, B., Bebin, E. M., & Szaflarski, J. P. (2019). Quality of life in adults enrolled in an open-label study of Cannabidiol (cbd) for treatment-resistant epilepsy. Epilepsy and Behavior , 95 , 10–17. 10.1016/j.yebeh.2019.03.035 31003195 10.1016/j.yebeh.2019.03.035

65. Sridharan S Erridge S Holvey C Coomber R Holden W Rucker JJ Platt M Sodergren MH Comparison of cannabis-based medicinal product formulations for fibromyalgia: A cohort study Journal of Pain and Palliative Care Pharmacotherapy 2024 10.1080/15360288.2024.2414073 39417761 Sridharan, S., Erridge, S., Holvey, C., Coomber, R., Holden, W., Rucker, J. J., Platt, M., & Sodergren, M. H. (2024). Comparison of cannabis-based medicinal product formulations for fibromyalgia: A cohort study. Journal of Pain and Palliative Care Pharmacotherapy . 10.1080/15360288.2024.2414073 39417761 10.1080/15360288.2024.2414073

66. Hershkovich O Hayun Y Oscar N Shtein A Lotan R The role of cannabis in treatment-resistant fibromyalgia women Pain Practice : the official Journal of World Institute of Pain 2023 23 2 180 184 10.1111/papr.13179 36333278 PMC10100523 Hershkovich, O., Hayun, Y., Oscar, N., Shtein, A., & Lotan, R. (2023). The role of cannabis in treatment-resistant fibromyalgia women. Pain Practice , 23 (2), 180–184. 10.1111/papr.13179 36333278 10.1111/papr.13179 PMC10100523

67. Chaves C Bittencourt PCT Pelegrini A Ingestion of a thc-rich cannabis oil in people with fibromyalgia: A randomized, double-blind, placebo-controlled clinical trial Pain Medicine (United States) 2020 21 10 2212 2218 10.1093/PM/PNAA303 PMC7593796 33118602 Chaves, C., Bittencourt, P. C. T., & Pelegrini, A. (2020). Ingestion of a thc-rich cannabis oil in people with fibromyalgia: A randomized, double-blind, placebo-controlled clinical trial. Pain Medicine , 21 (10), 2212–2218. 10.1093/PM/PNAA303 10.1093/pm/pnaa303 PMC7593796 33118602

68. Francis A Erridge S Holvey C Coomber R Guru R Darweish Medniuk A Sajad M Searle R Usmani A Varma S Rucker J Platt M Holden W Sodergren MH Assessment of clinical outcomes in patients with inflammatory arthritis: Analysis from the Uk medical cannabis registry International Clinical Psychopharmacology 2024 10.1097/YIC.0000000000000556 38976497 PMC12122089 Francis, A., Erridge, S., Holvey, C., Coomber, R., Guru, R., Darweish Medniuk, A., Sajad, M., Searle, R., Usmani, A., Varma, S., Rucker, J., Platt, M., Holden, W., & Sodergren, M. H. (2024). Assessment of clinical outcomes in patients with inflammatory arthritis: Analysis from the UK medical cannabis registry. International Clinical Psychopharmacology . 10.1097/YIC.0000000000000556 38976497 10.1097/YIC.0000000000000556 PMC12122089

69. Francis A Erridge S Holvey C Coomber R Holden W Rucker J Platt M Sodergren M Assessment of clinical outcomes in patients with osteoarthritis: Analysis from the Uk medical cannabis registry Journal of Pain and Palliative Care Pharmacotherapy 2024 38 2 103 116 10.1080/15360288.2024.2340076 38669060 Francis, A., Erridge, S., Holvey, C., Coomber, R., Holden, W., Rucker, J., Platt, M., & Sodergren, M. (2024). Assessment of clinical outcomes in patients with osteoarthritis: Analysis from the UK medical cannabis registry. Journal of Pain and Palliative Care Pharmacotherapy , 38 (2), 103–116. 38669060 10.1080/15360288.2024.2340076

70. Vivek K Karagozlu Z Erridge S Holvey C Coomber R Rucker JJ Weatherall MW Sodergren MH Ukmedical cannabis registry: Assessment of clinical outcomes inpatients with insomnia Brain andBehavior 2024 10.1002/brb3.3410 PMC10858318 38337193 Vivek, K., Karagozlu, Z., Erridge, S., Holvey, C., Coomber, R., Rucker, J. J., Weatherall, M. W., & Sodergren, M. H. (2024). Uk medical cannabis registry: Assessment of clinical outcomes in patients with insomnia. Brain and Behavior . 10.1002/brb3.3410. e3410. 10.1002/brb3.3410 PMC10858318 38337193

71. Aiewtrakoon C Efficacy and safety of Cannabidiol oil on chronic insomnia: The first randomized, double-blind, placebo-controlled, crossover, pilot study in Thailand Journal of the Medical Association of Thailand 2024 107 3 160EP 170 10.35755/jmedassocthai.2024.3.13952 Aiewtrakoon, C. (2024). Efficacy and safety of Cannabidiol oil on chronic insomnia: The first randomized, double-blind, placebo-controlled, crossover, pilot study in Thailand. Journal of the Medical Association of Thailand , 107 (3), 160–170. 10.35755/jmedassocthai.2024.3.13952

72. Eibach L Scheffel S Cardebring M Lettau M Ozgur Celik M Morguet A Roehle R Stein C Cannabidivarin for hiv-associated neuropathic pain: A randomized, blinded, controlled clinical trial Clinical Pharmacology & Therapeutics 2021 109 4 1055 1062 10.1002/cpt.2016 32770831 Eibach, L., Scheffel, S., Cardebring, M., Lettau, M., Ozgur Celik, M., Morguet, A., Roehle, R., & Stein, C. (2021). Cannabidivarin for HIV-associated neuropathic pain: A randomized, blinded, controlled clinical trial. Clinical Pharmacology & Therapeutics , 109 (4), 1055–1062. 10.1002/cpt.2016 32770831 10.1002/cpt.2016

73. Barre T Couton C Mourad A Carrieri P Protopopescu C Klein H De Dieuleveult B Hocqueloux L Mollet L Prazuck T Limited impact of Cannabidiol on health-related quality of life of people with long-term controlled hiv: A double-blind, randomized, controlled trial Open Forum Infectious Diseases 2024 11 9 ofae492 10.1093/ofid/ofae492 39296339 PMC11409882 Barre, T., Couton, C., Mourad, A., Carrieri, P., Protopopescu, C., Klein, H., De Dieuleveult, B., Hocqueloux, L., Mollet, L., & Prazuck, T. (2024). Limited impact of Cannabidiol on health-related quality of life of people with long-term controlled hiv: A double-blind, randomized, controlled trial. Open Forum Infectious Diseases , 11 (9), ofae492. 10.1093/ofid/ofae492 39296339 10.1093/ofid/ofae492 PMC11409882

74. Sultan W Madiedo A Moreno-Sanz G Controlled inhalation of tetrahydrocannabinol-predominant cannabis Flos mitigates severity of post-traumatic stress disorder symptoms and improves quality of sleep and general mood in cannabis-experienced Uk civilians: A real-world, observational study Medical Cannabis and Cannabinoids 2024 7 1 149EP 159 10.1159/000540978 39474239 PMC11521486 Sultan, W., Madiedo, A., & Moreno-Sanz, G. (2024). Controlled inhalation of tetrahydrocannabinol-predominant cannabis Flos mitigates severity of post-traumatic stress disorder symptoms and improves quality of sleep and general mood in cannabis-experienced UK civilians: A real-world, observational study. Medical Cannabis and Cannabinoids , 7 (1), 149–159. 10.1159/000540978 39474239 10.1159/000540978 PMC11521486

75. Nicholas M Erridge S Bapir L Pillai M Dalavaye N Holvey C Coomber R Rucker JJ Weatherall MW Sodergren MH Uk medical cannabis registry: Assessment of clinical outcomes in patients with headache disorders Expert Review of Neurotherapeutics 2023 23 1 85 96 10.1080/14737175.2023.2174017 36722292 Nicholas, M., Erridge, S., Bapir, L., Pillai, M., Dalavaye, N., Holvey, C., Coomber, R., Rucker, J. J., Weatherall, M. W., & Sodergren, M. H. (2023). Uk medical cannabis registry: Assessment of clinical outcomes in patients with headache disorders. Expert Review of Neurotherapeutics , 23 (1), 85–96. 10.1080/14737175.2023.2174017 36722292 10.1080/14737175.2023.2174017

76. Dujic G Kumric M Vrdoljak J Sutlovic D Dujic Z Bozic J Chronic Cannabidiol administration mitigates excessive daytime sleepiness and fatigue in patients with primary hypertension: Insights from a randomized crossover trial Cannabis and Cannabinoid Research 2024 10.1089/can.2024.0028 39187263 Dujic, G., Kumric, M., Vrdoljak, J., Sutlovic, D., Dujic, Z., & Bozic, J. (2024). Chronic Cannabidiol administration mitigates excessive daytime sleepiness and fatigue in patients with primary hypertension: Insights from a randomized crossover trial. Cannabis and Cannabinoid Research . 10.1089/can.2024.0028 39187263 10.1089/can.2024.0028

77. Arkell TR Downey LA Hayley AC Roth S Assessment of medical cannabis and health-related quality of life JAMA Network Open 2023 6 5 e2312522 10.1001/jamanetworkopen.2023.12522 37159196 PMC10170337 Arkell, T. R., Downey, L. A., Hayley, A. C., & Roth, S. (2023). Assessment of medical cannabis and health-related quality of life. JAMA Network Open , 6 (5), e2312522. 10.1001/jamanetworkopen.2023.12522 37159196 10.1001/jamanetworkopen.2023.12522 PMC10170337

78. Ergisi M Erridge S Harris M Kawka M Nimalan D Salazar O Loupasaki K Ali R Holvey C Coomber R Usmani A Sajad M Beri S Hoare J Khan SA Weatherall MW Platt M Rucker JJ Sodergren MH An updated analysis of clinical outcome measures across patients from the Uk medical cannabis registry Cannabis and Cannabinoid Research 2023 8 3 557 566 10.1089/can.2021.0145 35073160 Ergisi, M., Erridge, S., Harris, M., Kawka, M., Nimalan, D., Salazar, O., Loupasaki, K., Ali, R., Holvey, C., Coomber, R., Usmani, A., Sajad, M., Beri, S., Hoare, J., Khan, S. A., Weatherall, M. W., Platt, M., Rucker, J. J., & Sodergren, M. H. (2023). An updated analysis of clinical outcome measures across patients from the Uk medical cannabis registry. Cannabis and Cannabinoid Research , 8 (3), 557–566. 10.1089/can.2021.0145 35073160 10.1089/can.2021.0145

79. Erridge S Salazar O Kawka M Holvey C Coomber R Usmani A Sajad M Beri S Hoare J Khan S Weatherall MW Platt M Rucker JJ Sodergren MH An initial analysis of the Uk medical cannabis registry: Outcomes analysis of first 129 patients Neuropsychopharmacology Reports 2021 41 3 362 370 10.1002/npr2.12183 33988306 PMC8411316 Erridge, S., Salazar, O., Kawka, M., Holvey, C., Coomber, R., Usmani, A., Sajad, M., Beri, S., Hoare, J., Khan, S., Weatherall, M. W., Platt, M., Rucker, J. J., & Sodergren, M. H. (2021). An initial analysis of the Uk medical cannabis registry: Outcomes analysis of first 129 patients. Neuropsychopharmacology Reports , 41 (3), 362–370. 10.1002/npr2.12183 33988306 10.1002/npr2.12183 PMC8411316

80. Tait MA Costa DSJ Campbell R Warne LN Norman R Schug S Rutherford C Improvements inhealth-related quality of life are maintained long-term in patientsprescribed medicinal cannabis in australia: The quest initiative12-month follow-up observational study Plos One 2025 10.1371/journal.pone.0320756 40173146 PMC11964238 Tait, M. A., Costa, D. S. J., Campbell, R., Warne, L. N., Norman, R., Schug, S., & Rutherford, C. (2025). Improvements in health-related quality of life are maintained long-term in patients prescribed medicinal cannabis in australia: The quest initiative 12-month follow-up observational study. Plos One . 10.1371/journal.pone.0320756. e0320756. 40173146 10.1371/journal.pone.0320756 PMC11964238

81. Kelley MD Obaid M Miller EM Bowie M Heeter ZS Observational analysis of the influence of medical marijuana use on quality of life in patients Medical Cannabis and Cannabinoids 2024 7 1 44EP 50 10.1159/000536591 38500669 PMC10948168 Kelley, M. D., Obaid, M., Miller, E. M., Bowie, M., & Heeter, Z. S. (2024). Observational analysis of the influence of medical marijuana use on quality of life in patients. Medical Cannabis and Cannabinoids , 7 (1), 44–50. 10.1159/000536591 38500669 10.1159/000536591 PMC10948168

82. Lynskey MT Thurgur H Athanasiou-Fragkouli A Schlag AK Nutt DJ Prescribed medical cannabis use among older individuals: Patient characteristics and improvements in well-being: Findings from t21 Drugs and Aging 2024 41 6 521EP 530 10.1007/s40266-024-01123-y 38880841 Lynskey, M. T., Thurgur, H., Athanasiou-Fragkouli, A., Schlag, A. K., & Nutt, D. J. (2024). Prescribed medical cannabis use among older individuals: Patient characteristics and improvements in well-being: Findings from t21. Drugs and Aging , 41 (6), 521–530. 10.1007/s40266-024-01123-y 38880841 10.1007/s40266-024-01123-y

83. Lent MR McCalmont TR Short MM Dugosh KL Changes in health-related quality of life over the first three months of medical marijuana use J Cannabis Res 2024 6 1 36 10.1186/s42238-024-00245-9 39256884 PMC11389276 Lent, M. R., McCalmont, T. R., Short, M. M., & Dugosh, K. L. (2024). Changes in health-related quality of life over the first three months of medical marijuana use. Journal of Cannabis Research , 6 (1), 36. 10.1186/s42238-024-00245-9 39256884 10.1186/s42238-024-00245-9 PMC11389276

84. Stienrut P Pongpirul K Phutrakool P Savigamin C Sermsaksasithorn P Chanhom O Jeamjumrus P Pongchaichanon P Nootim P Soisamrong M Chuthaputti A Wanaratna K Thaneerat T Medical cannabis prescription practices and quality of life in Thai patients: A nationwide prospective observational cohort study Medical Cannabis and Cannabinoids 2024 7 1 125EP 137 10.1159/000540153 39144529 PMC11324265 Stienrut, P., Pongpirul, K., Phutrakool, P., Savigamin, C., Sermsaksasithorn, P., Chanhom, O., Jeamjumrus, P., Pongchaichanon, P., Nootim, P., Soisamrong, M., Chuthaputti, A., Wanaratna, K., & Thaneerat, T. (2024). Medical cannabis prescription practices and quality of life in Thai patients: A nationwide prospective observational cohort study. Medical Cannabis and Cannabinoids , 7 (1), 125–137. 10.1159/000540153 39144529 10.1159/000540153 PMC11324265

85. Tait MA Costa DSJ Campbell R Norman R Warne LN Schug S Rutherford C Health-related quality of life in patients accessing medicinal cannabis in australia: The quest initiative results of a 3-month follow-up observational study Plos One 2023 18 9 e0290549 10.1371/journal.pone.0290549 37672515 PMC10482296 Tait, M. A., Costa, D. S. J., Campbell, R., Norman, R., Warne, L. N., Schug, S., & Rutherford, C. (2023). Health-related quality of life in patients accessing medicinal cannabis in Australia: The quest initiative results of a 3-month follow-up observational study. Plos One , 18 (9), e0290549. 10.1371/journal.pone.0290549 37672515 10.1371/journal.pone.0290549 PMC10482296

86. Vigano A Moride Y Hachem Y Canac-Marquis M Gamaoun R Kalaba M Martel MO Perez J Néron A Beaulieu P Desroches J Ware M The Quebec cannabis registry: Investigating the safety and effectiveness of medical cannabis Cannabis and Cannabinoid Research 2022 8 6 1106 1116 10.1089/can.2022.0041 36579921 PMC10714117 Vigano, A., Moride, Y., Hachem, Y., Canac-Marquis, M., Gamaoun, R., Kalaba, M., Martel, M. O., Perez, J., Néron, A., Beaulieu, P., Desroches, J., & Ware, M. (2022). The Quebec cannabis registry: Investigating the safety and effectiveness of medical cannabis. Cannabis and Cannabinoid Research , 8 (6), 1106–1116. 10.1089/can.2022.0041 36579921 10.1089/can.2022.0041 PMC10714117

87. Palmieri B Laurino C Vadala M Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis Galenical Preparation (bedrocan) International Journal of Pharmacy Practice 2019 27 3 264 270 10.1111/ijpp.12514 30768819 PMC6593769 Palmieri, B., Laurino, C., & Vadala, M. (2019). Spontaneous, anecdotal, retrospective, open-label study on the efficacy, safety and tolerability of cannabis galenical preparation (bedrocan). International Journal of Pharmacy Practice , 27 (3), 264–270. 10.1111/ijpp.12514 30768819 10.1111/ijpp.12514 PMC6593769

88. Meng H Page MG Ajrawat P Deshpande A Samman B Dominicis M Ladha KS Fiorellino J Huang A Kotteeswaran Y McClaren-Blades A Kotra LP Clarke H Patient-reported outcomes in those consuming medical cannabis: A prospective longitudinal observational study in chronic pain patients Canadian Journal of Anesthesia 2021 68 5 633 644 10.1007/s12630-020-01903-1 33469735 Meng, H., Page, M. G., Ajrawat, P., Deshpande, A., Samman, B., Dominicis, M., Ladha, K. S., Fiorellino, J., Huang, A., Kotteeswaran, Y., McClaren-Blades, A., Kotra, L. P., & Clarke, H. (2021). Patient-reported outcomes in those consuming medical cannabis: A prospective longitudinal observational study in chronic pain patients. Canadian Journal of Anesthesia , 68 (5), 633–644. 10.1007/s12630-020-01903-1 33469735 10.1007/s12630-020-01903-1

89. Lucas P Boyd S Milloy MJ Walsh Z Cannabis significantly reduces the use of prescription opioids and improves quality of life in authorized patients: Results of a large prospective study Pain Medicine (Malden, Mass.) 2021 22 3 727 739 10.1093/pm/pnaa396 33367882 PMC7971472 Lucas, P., Boyd, S., Milloy, M. J., & Walsh, Z. (2021). Cannabis significantly reduces the use of prescription opioids and improves quality of life in authorized patients: Results of a large prospective study. Pain Medicine , 22 (3), 727–739. 10.1093/pm/pnaa396 33367882 10.1093/pm/pnaa396 PMC7971472

90. Gulbransen G Xu W Arroll B Cannabidiol prescription in clinicalpractice: An audit on the first 400 patients in newzealand BJGP Open 2020 10.3399/bjgpopen20X101010 32019776 PMC7330185 Gulbransen, G., Xu, W., & Arroll, B. (2020). Cannabidiol prescription in clinical practice: An audit on the first 400 patients in New Zealand. BJGP Open . 10.3399/bjgpopen20X101010 32019776 10.3399/bjgpopen20X101010 PMC7330185

91. Gruber, S. A., Sagar, K. A., Dahlgren, M. K., Racine, M. T., Smith, R. T., & Lukas, S. E. (2016). Splendor in the grass? A pilot study assessing the impact of medical marijuana on executive function. Frontiers in Pharmacology . 10.3389/fphar.2016.00355 10.3389/fphar.2016.00355 PMC5062916 27790138

92. National Center for Chronic Disease Prevention and Health Promotion. (2022). Health-related quality of life. https://archive.cdc.gov/www_cdc_gov/hrqol/index.htm . Accessed Aug 2025.

93. Herdman M Gudex C Lloyd A Janssen M Kind P Parkin D Bonsel G Badia X Development and preliminary testing of the new five-level version of eq-5d (eq-5d-5l) Quality of Life Research 2011 20 10 1727 1736 10.1007/s11136-011-9903-x 21479777 PMC3220807 Herdman, M., Gudex, C., Lloyd, A., Janssen, M., Kind, P., Parkin, D., Bonsel, G., & Badia, X. (2011). Development and preliminary testing of the new five-level version of eq-5d (eq-5d-5l). Quality of Life Research , 20 (10), 1727–1736. 10.1007/s11136-011-9903-x 21479777 10.1007/s11136-011-9903-x PMC3220807

94. Hays RD Morales LS The rand-36 measure of health-related quality of life Annals of Medicine 2001 33 5 350 357 10.3109/07853890109002089 11491194 Hays, R. D., & Morales, L. S. (2001). The rand-36 measure of health-related quality of life. Annals of Medicine , 33 (5), 350–357. 10.3109/07853890109002089 11491194 10.3109/07853890109002089

95. Vickrey BG Hays RD Harooni R Myers LW Ellison GW A health-related quality of life measure for multiple sclerosis Quality of Life Research 1995 4 3 187 206 10.1007/bf02260859 7613530 Vickrey, B. G., Hays, R. D., Harooni, R., Myers, L. W., & Ellison, G. W. (1995). A health-related quality of life measure for multiple sclerosis. Quality of Life Research , 4 (3), 187–206. 10.1007/bf02260859 7613530 10.1007/BF02260859

96. Devinsky O Vickrey BG Cramer J Perrine K Hermann B Meador K Hays RD Development of the quality of life in epilepsy inventory Epilepsia 1995 36 11 1089 1104 10.1111/j.1528-1157.1995.tb00467.x 7588453 Devinsky, O., Vickrey, B. G., Cramer, J., Perrine, K., Hermann, B., Meador, K., & Hays, R. D. (1995). Development of the quality of life in epilepsy inventory. Epilepsia , 36 (11), 1089–1104. 10.1111/j.1528-1157.1995.tb00467.x 7588453 10.1111/j.1528-1157.1995.tb00467.x

97. Vickery AW Roth S Ernenwein T Kennedy J Washer P A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years Plos One 2022 17 11 e0272241 10.1371/journal.pone.0272241 36399463 PMC9674134 Vickery, A. W., Roth, S., Ernenwein, T., Kennedy, J., & Washer, P. (2022). A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years. Plos One , 17 (11), e0272241. 10.1371/journal.pone.0272241 36399463 10.1371/journal.pone.0272241 PMC9674134

98. Mercieca-Bebber R Williams D Tait MA Roydhouse J Busija L Sundaram CS Wilson M Langford A Rutherford C Roberts N King M Vodicka E Devine B Trials with patient-reported outcomes registered on the Australian new Zealand clinical trials registry (anzctr) Quality of Life Research 2018 27 10 2581 2591 10.1007/s11136-018-1921-5 29915979 Mercieca-Bebber, R., Williams, D., Tait, M. A., Roydhouse, J., Busija, L., Sundaram, C. S., Wilson, M., Langford, A., Rutherford, C., Roberts, N., King, M., Vodicka, E., & Devine, B. (2018). Trials with patient-reported outcomes registered on the Australian new Zealand clinical trials registry (anzctr). Quality of Life Research , 27 (10), 2581–2591. 10.1007/s11136-018-1921-5 29915979 10.1007/s11136-018-1921-5

99. European Medicines Agency. (2016). Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man: The use of patient-reported outcome (pro) measures in oncology studies . European Medicines Agency London.

100. NHS Digital. (2025). Patient reported outcome measures (proms). https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/patient-reported-outcome-measures-proms . Accessed 3 Sep 2025.

101. Ware MA Wang T Shapiro S Robinson A Ducruet T Huynh T Gamsa A Bennett GJ Collet JP Smoked cannabis for chronic neuropathic pain: A randomized controlled trial Cmaj 2010 182 14 E694 701 10.1503/cmaj.091414 20805210 PMC2950205 Ware, M. A., Wang, T., Shapiro, S., Robinson, A., Ducruet, T., Huynh, T., Gamsa, A., Bennett, G. J., & Collet, J. P. (2010). Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. CMAJ , 182 (14), E694–E701. 10.1503/cmaj.091414 20805210 10.1503/cmaj.091414 PMC2950205

102. Flachenecker P Henze T Zettl UK Nabiximols (thc/cbd oromucosal spray, sativex?) in clinical practice - results of a multicenter, non-interventional study (move 2) in patients with multiple sclerosis spasticity European Neurology 2014 71 5–6 271 279 10.1159/000357427 24525548 Flachenecker, P., Henze, T., & Zettl, U. K. (2014). Nabiximols (thc/cbd oromucosal spray, sativex?) in clinical practice - results of a multicenter, non-interventional study (move 2) in patients with multiple sclerosis spasticity. European Neurology , 71 (5–6), 271–279. 10.1159/000357427 24525548 10.1159/000357427

103. Nunan D Aronson J Bankhead C Catalogue of bias: Attrition bias BMJ Evidence-Based Medicine 2018 23 1 21 22 10.1136/ebmed-2017-110883 29367321 Nunan, D., Aronson, J., & Bankhead, C. (2018). Catalogue of bias: Attrition bias. BMJ Evidence-Based Medicine , 23 (1), 21–22. 10.1136/ebmed-2017-110883 29367321 10.1136/ebmed-2017-110883

104. Liu-Seifert H Zhang S D’Souza D Skljarevski V A closer look at the baseline-observation-carried-forward (bocf) Patient Preference and Adherence 2010 4 11 16 10.2147/ppa.s8135 20165594 PMC2819899 Liu-Seifert, H., Zhang, S., D’Souza, D., & Skljarevski, V. (2010). A closer look at the baseline-observation-carried-forward (bocf). Patient Preference and Adherence , 4 , 11–16. 10.2147/ppa.s8135 20165594 10.2147/ppa.s8135 PMC2819899

105. Cuijpers P Weitz E Cristea IA Twisk J Pre-post effect sizes should be avoided in meta-analyses Epidemiology and Psychiatric Sciences 2017 26 4 364 368 10.1017/s2045796016000809 27790968 PMC6998624 Cuijpers, P., Weitz, E., Cristea, I. A., & Twisk, J. (2017). Pre-post effect sizes should be avoided in meta-analyses. Epidemiology and Psychiatric Sciences , 26 (4), 364–368. 10.1017/s2045796016000809 27790968 10.1017/S2045796016000809 PMC6998624