Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications

Abstract

Background Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events. Methods We systematically reviewed (registered at PROSPERO: CRD42021229932) eight databases for randomized controlled trials (RCTs) of dronabinol, nabilone, cannabidiol and nabiximols for chronic pain, spasticity, nausea /vomiting, appetite, ALS, irritable bowel syndrome, MS, Chorea Huntington, epilepsy, dystonia, Parkinsonism, glaucoma, ADHD, anorexia nervosa, anxiety, dementia, depression, schizophrenia, PTSD, sleeping disorders, SUD and Tourette. Main outcomes and measures included patient-relevant/disease-specific outcomes, retention and adverse events. Data were calculated as standardized mean difference (SMD) and ORs with confidence intervals (CI) via random effects. Evidence quality was assessed by the Cochrane Risk of Bias and GRADE tools. Results In total, 152 RCTs (12,123 participants) were analysed according to the type of the cannabinoid, outcome and comparator used, resulting in 84 comparisons. Significant therapeutic effects of medical cannabinoids show a large variability in the grade of evidence that depends on the type of cannabinoid. CBD has a significant therapeutic effect for epilepsy (SMD − 0.5[CI − 0.62, − 0.38] high grade) and Parkinsonism (− 0.41[CI − 0.75, − 0.08] moderate grade). There is moderate evidence for dronabinol for chronic pain (− 0.31[CI − 0.46, − 0.15]), appetite (− 0.51[CI − 0.87, − 0.15]) and Tourette (− 1.01[CI − 1.58, − 0.44]) and moderate evidence for nabiximols on chronic pain (− 0.25[− 0.37, − 0.14]), spasticity (− 0.36[CI − 0.54, − 0.19]), sleep (− 0.24[CI − 0.35, − 0.14]) and SUDs (− 0.48[CI − 0.92, − 0.04]). All other significant therapeutic effects have either low, very low, or even no grade of evidence. Cannabinoids produce different adverse events, and there is low to moderate grade of evidence for this conclusion depending on the type of cannabinoid. Conclusions Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.

Cys-loop receptors on cannabinoids: All high?

“…The most frequently used Frontiers in Physiology frontiersin.org concomitant AEDs were clobazam (65%), valproate (57%), stiripentol (43%); 93% of patients were taking ≥2 AEDs at baseline and still experiencing a median of 13 convulsive seizures per 28 days (Devinsky et al, 2017;Scheffer et al, 2021;Jazz Pharmaceuticals, 2022). Additional types of epilepsy have been investigated as indicated by Bilbao and Spanagel, 2022 in clinical trials with promising results.…”

“…CBD was found most effective in seizures and moderately effective in parkinsonism. Sativex ® was found moderately effective in chronic pain and spasticity, followed by improving sleep and SUD’s (substance abuse disorders) ( Bahji et al, 2022 ; Bilbao and Spanagel, 2022 ). For all other indications, this meta-analysis ( Bilbao and Spanagel, 2022 ) reports low or very low evidence, but not all trials could be included due to methodological differences.…”

“…As can be gleaned from the large number of completed trials as reviewed recently ( Bilbao and Spanagel, 2022 ) and the growing body of literature, pCBs and selected sCBs have established their place in medical applications and can be expected to be used in many new indications in the near future. Presumably the effectiveness of various whole plant preparations will be confirmed in trials in the near future, as there is accumulating anecdotal evidence as well as from the literature for many indications.…”

“…Cannabinoids have shown to be of relevance in the treatment of chronic pain ( Johnson et al, 2010 , 2013 ; Portenoy et al, 2012 ; Johal et al, 2020 ; Bilbao and Spanagel, 2022 ; Henson et al, 2022 ).…”

“…Approved cannabinoid medications and their active ingredients, indications, and product types. Meta analysis findings from(Bilbao and Spanagel, 2022) are included for "high" and "moderate" evidence indications.…”