“Purpose: This systemic review assesses currently available clinical information on which cannabinoids and what range of doses have been used to achieve positive effects in a diversity of medical context.

Methods: The data were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol guidelines. Inclusion criteria were articles that assessed administration of any cannabinoid to any clinical population, reported in the ClinicalTrials.gov or PubMed databases, that involved a comparison with other treatment or placebo and a result measurement to assess the effectiveness or ineffectiveness of the cannabinoid. Exclusion criteria were review or letter; articles not in the English language; not full-text articles; not a clinical trial, case report, case series, open-label trial, or pilot study; administration in animals, in vitro, or in healthy participants; cannabinoids administered in combination with other cannabinoids (except for cannabidiol [CBD] or tetrahydrocannabinol [THC]) or as whole cannabis extracts; no stated concentration; inhalation or smoke as a route of administration; and no results described. The articles were assessed by the risk of bias.

Finding: In total, 1668 articles were recovered, of which 55 studies met the inclusion criteria for 21 diseases. Positive effects were reported in clinical studies: 52% with THC (range, 0.01-0.5 mg/kg/d [0.62-31 mg/d]), 74% with CBD (range, 1-50 mg/kg/d [62-3100 mg/d]), 64% with THC-CBD (mean, 1:1.3 mg/kg/d [ratio, 1:1]), and 100% with tetrahydrocannabivarin (THCV) (0.2 mg/kg/d).

Implications: THC, CBD, and THCV can regulate activity in several pathologies. New studies of cannabinoids are highly encouraged because each patient is unique and requires a unique cannabinoid medication.”

https://pubmed.ncbi.nlm.nih.gov/36411116/

https://www.clinicaltherapeutics.com/article/S0149-2918(22)00349-6/fulltext

“Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines.

One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients’ lives.

This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities-and from a wider demographic profile-can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis.

We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.”

https://pubmed.ncbi.nlm.nih.gov/36405915/

“Cannabis has an excellent safety profile and is a historically established medicine. We hope that this paper will aid policymakers and prescribers understand the value of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation, which is ultimately harmful to patients, restricting access to medicines that could bring relief.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1027159/full

“Introduction: Oral medicinal cannabis (MC) has been increasingly prescribed for a wide range of clinical conditions since 2016. Despite an exponential rise in prescriptions and publications, high quality clinical efficacy and safety studies are lacking. The outcomes of a large Australian clinical electronic registry cohort are presented.

Methods: A prospective cannabis-naïve patient cohort prescribed oral MC participated in an ongoing longitudinal registry at a network of specialised clinics. Patient MC dose, safety and validated outcome data were collected regularly over two years and analysed.

Results: 3,961 patients (mean age 56.07 years [SD 19.08], 51.0% female) with multimorbidity (mean diagnoses 5.14 [SD 4.08]) and polypharmacy (mean 6.26 medications [SD 4.61]) were included in this analysis. Clinical indications were for: chronic pain (71.9%), psychiatric (15.4%), neurological (2.1%), and other diagnoses (10.7%). Median total oral daily dose was 10mg for Δ9-tetrahydrocannabinol (THC) and 22.5mg for cannabidiol (CBD). A stable dose was observed for over two years. 37.3% experienced treatment related adverse events. These were graded mild (67%), moderate (31%), severe (<2%, n = 23) and two (0.1%) serious adverse events. Statistically significant improvements at a p value of <0.001 across all outcomes were sustained for over two years, including: clinical global impression (CGI-E, +39%: CGI-I, +52%; p<0.001), pain interference and severity (BPI, 26.1% and 22.2%; p<0.001), mental health (DASS-21, depression 24.5%, anxiety 25.5%, stress 27.7%; p<0.001), insomnia (ISI, 35.0%; p<0.001), and health status (RAND SF36: physical function, 34.4%: emotional well-being, 37.3%; p<0.001). Mean number of concomitant medications did not significantly change over 2 years (p = 0.481).

Conclusions: Oral MC was demonstrated to be safe and well-tolerated for a sustained period in a large complex cohort of cannabis-naïve, multimorbid patients with polypharmacy. There was significant improvement (p<0.001) across all measured clinical outcomes over two years. Results are subject to limitations of Real World Data (RWD) for causation and generalisability. Future high quality randomised controlled trials are awaited”

https://pubmed.ncbi.nlm.nih.gov/36399463/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272241.