Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of < 7 and > 7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis < 7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols > 7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain. (PsycInfo Database Record (c) 2025 APA, all rights reserved)
The 20% prevalence of chronic pain in the general population is a major health concern given the often profound associated impairment of daily activities, employment status, and health-related quality of life in sufferers. Resource utilization associated with chronic pain represents an enormous burden for healthcare systems. Although analgesia based on the World Health Organization's pain ladder continues to be the mainstay of chronic pain management, aside from chronic cancer pain or end-of-life care, prolonged use of non-steroidal anti-inflammatory drugs or opioids to manage chronic pain is rarely sustainable. As the endocannabinoid system is known to control pain at peripheral, spinal, and supraspinal levels, interest in medical use of cannabis is growing. A proprietary blend of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as the principal cannabinoids is formulated as an oromucosal spray (USAN name: nabiximols) and standardized to ensure quality, consistency and stability. This review examines evidence for THC:CBD oromucosal spray (nabiximols) in the management of chronic pain conditions. Cumulative evidence from clinical trials and an exploratory analysis of the German Pain e-Registry suggests that add-on THC:CBD oromucosal spray (nabiximols) may have a role in managing chronic neuropathic pain, although further precise clinical trials are required to draw definitive conclusions.
Indications of cannabis use are numerous although the indication to relief pain remains a major research interest and clinical application. Studies investigating the effect of herbal cannabis and cannabis-based medicine on neuropathic, non-neuropathic pain, acute pain and experimentally induced pain were reviewed. A search was performed in PubMed and Cochrane library for articles published in English between January 1, 2000 and May 8, 2020. The search terms used were related to cannabis and pain in adults. We identified 34 studies, of which 30 were randomized controlled clinical trials (RCTs). Varying effects were identified from the RCTs, and as expected more promising effects from non-RCTs. Cannabis-based medications were found most effective as an adjuvant therapy in refractory multiple sclerosis, and weak evidence was found to support the treatment of cancer pain especially in advanced stages. Chronic rheumatic pain showed promising results. Adverse events of cannabis-based treatment were found to be more frequent with tetrahydrocannabinol herbal strains compared to other cannabis-derived products.
OBJECTIVES: To determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events.
DATA SOURCES: A systematic search was performed in PubMed, ScienceDirect, ClincalTrials.gov, Scopus, Cochrane Library, and Embase from inception until June 2017.
STUDY SELECTION: Randomized controlled trials investigating the effects of cannabis or cannabinoids on pain reduction.
DATA EXTRACTION: Two reviewers extracted and assessed the quality of studies by means of Cochrane risk of bias. Standardized mean difference (SMD) was calculated. Random-effects model was undertaken to pool the treatment effects.
RESULTS: A total of 25 studies involving 2270 patients were included. We found that delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) (oromucosal route), THC (oromucosal route), and standardized dried cannabis (with THC; SCT; inhalation route) could reduce neuropathic pain score (SMD -0.41, 95% CI -0.7 to -0.1; -0.61, 95% CI -1.2 to -0.02; and -0.77, 95% CI -1.4 to -0.2; respectively). For nociceptive pain, only standardized cannabis extract (with THC; SCET) via oral route could reduce pain score (SMD -1.8, 95% C; -2.4 to -1.2). In cancer pain, THC/CBD via oromucosal route and THC via oral or oromucosal route could reduce pain score (SMD -0.7, 95% CI -1.2 to -0.2; and -2.1, 95% CI -2.8 to -1.4; respectively). No study was observed for THC/CBD via oral route or inhalation or THC via inhalation for cancer and nociceptive pain, SCET via oromucosal route or inhalation for neuropathic and cancer pain, THC via oromucosal route for nociceptive pain, and SCT via oromucosal or oral route for neuropathic, cancer, and nociceptive pain. Statistically significant increased risks of euphoria were observed in THC/CBD (oromucosal), THC (oromucosal), and SCT (inhalation).
CONCLUSION: The use of cannabis and cannabinoids via certain administration routes could reduce different types of pain. Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved.
BACKGROUND: Pain is the most frequent indication for which medical cannabis treatment is sought. OBJECTIVES: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects. METHODS: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted. RESULTS: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects. CONCLUSION: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Cannabis and its pharmacologically active constituents, phytocannabinoids, have long been reported to have multiple medicinal benefits. One association often reported by users is sedation and subjective improvements in sleep. To further examine this association, we conducted a critical review of clinical studies examining the effects of cannabinoids on subjective and objective measures of sleep. PubMED, Web of Science, and Google Scholar were searched using terms and synonyms related to cannabinoids and sleep. Articles chosen included randomized controlled trials and open label studies. The Cochrane risk of bias tool was used to assess the quality of trials that compared cannabinoids with control interventions. The current literature focuses mostly on the use of tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in the treatment of chronic health conditions such as multiple sclerosis, posttraumatic stress disorder (PTSD), and chronic pain. Sleep is often a secondary, rather than primary outcome in these studies. Many of the reviewed studies suggested that cannabinoids could improve sleep quality, decrease sleep disturbances, and decrease sleep onset latency. While many of the studies did show a positive effect on sleep, there are many limiting factors such as small sample sizes, examining sleep as a secondary outcome in the context of another illness, and relatively few studies using validated subjective or objective measurements. This review also identified several questions that should be addressed in future research. These questions include further elucidation of the dichotomy between the effects of THC and CBD, as well as identifying any long-term adverse effects of medicinal cannabinoid use. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Chronic pain states have resulted in an overreliance on opioid pain relievers, which can carry significant risks when used long term. As such, alternative pain treatments are increasingly desired. Although emerging research suggests that cannabinoids have therapeutic potential regarding pain, results from studies across pain populations have been inconsistent. To provide meta-analytic clarification regarding cannabis’s impact on subjective pain, we identified studies that assessed drug-induced pain modulations under cannabinoid and corresponding placebo conditions. A literature search yielded 25 peer-reviewed records that underwent data extraction. Baseline and end-point data were used to compute standardized effect size estimates (Cohen’s d) across cannabinoid administrations (k = 39) and placebo administrations (k = 26). Standardized effects were inverse-variance weighted and pooled across studies for meta-analytic comparison. Results revealed that cannabinoid administration produced a medium-to-large effect across included studies, Cohen’s d = −0.58, 95% confidence interval (CI) [−0.74, −0.43], while placebo administration produced a small-to-medium effect, Cohen’s d = −0.39, 95% CI [−0.52, −0.26]. Meta-regression revealed that cannabinoids, β = −0.43, 95% CI [−0.62, −0.24], p < .05, synthetic cannabinoids, β = −0.39, 95% CI [−0.65, −0.14], p < .05, and sample size, β = 0.01, 95% CI [0.00, 0.01], p < .05, were associated with marked pain reduction. These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted. Additionally, given demonstrated neurocognitive side effects associated with some constituent cannabinoids (i.e., THC), subsequent work may consider developing novel therapeutic agents that capitalize on cannabis’s analgesic properties without producing adverse effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND: The importance of medical cannabis and cannabis-based medicines for cancer pain management needs to be determined.
METHODS: A systematic literature search until December 2018 included CENTRAL, PubMed, SCOPUS and trial registers. Randomised controlled trials (RCTs) investigating medical cannabis and/or pharmaceutical cannabinoids for pain control in cancer patients with a study duration of at least 2 weeks and a sample size of at least 20 participants per study arm were included. Clinical outcomes comprised efficacy (pain intensity, patient impression of improvement, combined responder, sleep problems, psychological distress, opioid maintenance and breakthrough dosage), tolerability (dropout rate due to adverse events) and safety (nervous system, psychiatric and gastrointestinal side effects; serious adverse events). The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS: Five RCTs with oromucosal nabiximols or tetrahydrocannabinol (THC) including 1534 participants with moderate and severe pain despite opioid therapy were identified. Double blind period of the RCTs ranged between 2 and 5 weeks. Four studies with a parallel design and 1333 patients were available for meta-analysis. The quality of evidence was very low for all comparisons. Oromucosal nabiximols and THC did not differ from placebo in reducing pain, sleep problems, opioid dosages and in the frequency of combined responder, serious adverse events and psychiatric disorders side effects. The number of patients who reported to be much or very much improved was higher with oromucosal nabiximols and THC than with placebo (number needed to treat for an additional benefit 16; 95% confidence interval [CI] 8 to infinite). The dropout rates due to adverse events (number needed to treat for an additional harm [NNTH] 20; 95% CI 11-100), the frequency of nervous system (NNTH 10; 95% CI 7-25) and of gastrointestinal side effects (NNTH 11; 95% CI 7-33) was higher with oromucosal nabiximols and THC than with placebo.
CONCLUSIONS: Very low quality evidence suggests that oromucosal nabiximols and THC have no effect on pain, sleep problems and opioid consumption in patients with cancer pain with insufficient pain relief from opioids. The complete manuscript is written in English.
PURPOSE: This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology.
METHODS: A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology.
RESULTS: Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified.
CONCLUSIONS: There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.
Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of < 7 and > 7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis < 7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols > 7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain. (PsycInfo Database Record (c) 2025 APA, all rights reserved)
