Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

“Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.”

https://pubmed.ncbi.nlm.nih.gov/35459926/

Recreational cannabis legalizations associated with reductions in prescription drug utilization among Medicaid enrollees

“The potential substitution of cannabis for prescription medication has attracted a substantial amount of attention within the context of medical cannabis laws (MCLs). However, much less is known about the association between recreational cannabis laws (RCLs) and prescription drug use. With recent evidence supporting substitution of cannabis for prescription drugs following MCLs, it is reasonable to ask what effect RCLs may have on those outcomes. We use quarterly data for all Medicaid prescriptions from 2011 to 2019 to investigate the effect of state-level RCLs on prescription drug utilization. We estimate this effect with a series of two-way fixed effects event study models. We find significant reductions in the volume of prescriptions within the drug classes that align with the medical indications for pain, depression, anxiety, sleep, psychosis, and seizures. Our results suggest substitution away from prescription drugs and potential cost savings for state Medicaid programs.”

https://pubmed.ncbi.nlm.nih.gov/35429072/

Measuring the Change in Health-Related Quality of Life in Patients Using Marijuana for Pain Relief

“Current evidence suggests that cannabinoids are safe with minimal side effects and are effective in managing chronic pain. Data also show that medical marijuana (MM) may improve quality of life (QoL) among patients. However, there are little data showing the health-related QoL (HRQoL) benefit in MM patients using it for pain. The purpose of this study was to determine if there is a relationship between HRQol and MM use in patients using it to relieve pain.

Results

1,762 people responded to the screening request, and 1,393 (79%) met screening criteria. Of those, 353 (25.3%) agreed to participate and 51% completed all 4 surveys, for a final sample of 181 with 85 male and 95 female and one nonbinary subject. The average age was 41.21 (SD = 12.9) years, with no difference between genders. The adjusted HRQoL score improved from 0.722 to 0.747 (p = 0.011) from survey 2 to survey 4, as did the self-reported pain and health scores. The EQ-5D subscales revealed no change in mobility or usual activities, significant improvement in anxiety and pain, and a significant worsening in self-care.

Conclusion

The results show a significant improvement in HRQoL among patients using MM for pain. The EQ-5D subscales validated the pain improvement and also showed an improvement in anxiety. However, the decline in the self-care subscale may have tempered the overall improvement in HRQoL, and further research into which aspects of self-care are impacted by MM use in this population is warranted. Overall, there is a positive relationship between MM use and HRQoL in patients using it for pain.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832252/

The Efficacy of Cannabis in Reducing Back Pain: A Systematic Review

“Objective: To critically analyze the evidence and efficacy of cannabis to treat surgical and nonsurgical back pain via a Systematic Review.

Methods: We conducted a systematic review to investigate the efficacy of cannabis to treat non-surgical and surgical back pain. A literature search was performed with MEDLINE and Embase databases. Only RCTs and prospective cohort studies with concurrent control were included in this study. Risk of bias and quality grading was assessed for each included study.

Results: Database searches returned 1738 non-duplicated results. An initial screening excluded 1716 results. Twenty-two full text articles were assessed for eligibility. Four articles ultimately met pre-determined eligibility and were included in the study. Two studies addressed post-SCI pain while other two studies addressed low back pain. No studies specifically examined the use of cannabis for surgical back pain. The type of cannabis varied between study and included THC, dronabinol, and Nabilone. A total of 110 patients were included in the four studies reviewed. In each study, there was a quantifiable advantage of cannabis therapy for alleviating back pain. There were no serious adverse effects reported.

Conclusions: In all articles, cannabis was shown to be effective to treat back pain with an acceptable side effect profile. However, long-term follow up is lacking. As medicinal cannabis is being used more commonly for analgesic effect and patients are “self-prescribing” cannabis for back pain, additional studies are needed for healthcare providers to confidently recommend cannabis therapy for back pain.”

https://pubmed.ncbi.nlm.nih.gov/35128969/

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Chronic Back Pain

“This study investigates whether the use of medical cannabis (MC) in patients with chronic back pain is associated with a decreased opioid prescription.

Results

Patients who started at less than 15 MME/day and patients who started at greater than 15 MME/day decreased from 15.1 to 11.0 (n = 186, p < 0.01), 3.5 to 2­­­.1 (n = 134, p < 0.01), and 44.9 to 33.9 (n = 52, p < 0.01), respectively. Pain and disability scores were improved at follow-up as well.

Conclusion

MC use reduces opioid prescription for patients with chronic back pain and improves pain and disability scores.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860705/

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Osteoarthritis

“Osteoarthritis (OA) can result in significant pain, requiring pain management with opioids. Medical cannabis (MC) has the potential to be an alternative to opioids for chronic pain conditions. This study investigates whether MC used in the management of OA-related chronic pain can reduce opioid utilization.

Results

Average MME/day decreased from 18.2 to 9.8 (n=40, p<0.05). The percentage of patients who dropped to 0 MME/day was 37.5%. VAS scores decreased significantly at three and six months, and Global Physical Health score increased significantly by three months.

Conclusions

MC reduces opioid prescription for patients with chronic OA pain and improves pain and quality of life.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873278/

[Cannabinoids reduce opioid use in older patients with pain : Retrospective three-year analysis of data from a general practice]

“Background: Relevant data for the prescription and therapeutic effects of medical cannabinoids (CAM) are still missing in everyday medicine especially for elderly and geriatric patients.

Aim of the study: Documentation of prescription (duration, age) of CAM (dronabinol, nabiximols, cannabinoid extracts) and co-medicated opioids in a doctor’s office specializing in pain.

Methods: Analysis of the consumption of opioids (morphine equivalent) and CAM (THC equivalent) for age and gender.

Results: In all, 178 patients with chronic pain were treated for a period of 366 days (median; range 31-2590 days). Median age was 72 years (26-96 years); 115 were women (64.8%). Of these, 34 were younger than 65 years, 42 were 65-80 years and 40 were more than 80 years old. Of the 63 men, 29 were younger than 65 years, 24 were 65-80 years and 10 were older than 80 years. Indications for CAM were chronic pain and the limitations for opioids because of side effects and worsening of quality of life. To total of 1001 CAM were prescribed, 557 (55.6%) dronabinol as liquid, 328 (32.7%) as full spectrum extracts and 66 (6.6%) as oro-mucosal nabiximols spray. 50 prescriptions (5%) contained more than one CAM simultaneously. The daily consumption of dronabinol liquor and extracts were 9.6 mg/day (median), and of spray 13.6 mg. The dosage over time did not change in patients older than 64; in younger patients, there was a non-significant increasing trend. Women requested lower THC dosages compared to men (8.1 mg vs. 14.8 mg). Furthermore, 10 patients (5.6%) stopped CAM because of failing effectivity, 7 (3.9%) because of failing cost coverage and only 5 because of adverse side effects. 115 patients (65%) with CAM also received opioids a median 65 mg/day morphine equivalents. This opioid dosage was significantly reduced in course of time by 24 mg/day morphine equivalents or 50%. This reduction was independent on CAM dosage, age and gender.

Discussion: Patients with chronic pain profit from long-term CAM which safely and significantly lower the consumption of comedicated opioids, even at low dosages (< 7.5 mg/day). For women, low-dose THC may be sufficient. Older patients benefit from CAM, and adverse effects do not limit the (chronic) use and prescription of CAM in the elderly.”

https://pubmed.ncbi.nlm.nih.gov/35384481/

Analyzing the Impact of Cannabinoids on the Treatment of Spinal Disorders

“Purpose of review: Cannabis is among the most used illicit substances globally, with medical applications, increased legalization, and shifting social attitudes leading to increased use in recent years. Cannabinoids are a group of psychoactive substances found within the cannabis plant, with the most common being Δ9-tetrahydrocannabinol and cannabidiol. Due to the high prevalence of use, it is increasingly important to evaluate the effects of cannabis and cannabinoids on spine patients, in both operative and nonoperative settings.

Recent findings: Cannabis and cannabinoids may be effective in treating patients with chronic conditions such as back pain and spinal cord injuries. Longitudinal effects and implications on surgical outcomes and complications are poorly understood. High-quality, outcomes-focused research can inform approaches for clinicians to approach cannabis and cannabinoid use. Studies to elucidate the standardization of cannabis regimens can help develop guidelines for potential therapeutic applications. Cannabis and cannabinoids may be useful alternatives or additions for many spine patients, but future research is needed for recommendations to be determined. Our manuscript reviews the available literature regarding cannabis use and various spinal conditions, organizing our findings into the following narrative themes: (1) the management of chronic lower back pain, (2) perioperative outcomes, (3) cannabis use in general orthopaedic procedures, and (4) spinal cord injuries.”

https://pubmed.ncbi.nlm.nih.gov/35132567/

Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms

Ostovari, Yu research published in PLOS ONE - Healthcare Ergonomics  Analytics Lab - Purdue University“Background: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain.

Results: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion.

Conclusions: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.”

“Recent studies have suggested that a dysfunction in the endocannabinoid system (ECS) is present in endometriosis patients, and that aspects of endometriosis-associated pain may be targeted by modulating the ECS .Previous research on the use of illicit cannabis in women with endometriosis has shown promise in the treatment of endometriosis pain and co-morbid symptoms such as poor sleep, gastrointestinal upset and mood disorders.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258940

Health Outcomes among Adults Initiating Medical Cannabis for Chronic Pain: A 3-month Prospective Study Incorporating Ecological Momentary Assessment (EMA)

“In response to the need of more rigorous data on medical cannabis and chronic pain, we conducted a 3-month prospective study incorporating ecological momentary assessment (EMA) to examine the effects of medical cannabis on pain, anxiety/depression, sleep, and quality of life.

Data were collected from 46 adults (Mean age=55.7±11.9, 52.2% male) newly initiating medical cannabis treatment for chronic pain. Participants completed a baseline survey, EMA for approximately 1 week pre- and up to 3 weeks post- medical cannabis treatment, and a 3-month follow-up survey.

The self-reported EMA data (2535 random and 705 daily assessments) indicated significant reductions in momentary pain intensity (b = -16.5, p < .001, 16.5 points reduction on 0-100 visual analog) and anxiety (b = -0.89, p < .05), and significant increase in daily sleep duration (b = 0.34, p < .01) and sleep quality (b = 0.32, p <.001) after participants initiated medical cannabis for a few weeks.

At 3 months, self-reported survey data showed significantly lower levels of worst pain (t = -2.38, p < .05), pain interference (t = -3.82, p < .05), and depression (t = -3.43, p < .01), as well as increased sleep duration (t = 3.95, p < .001), sleep quality (t = -3.04, p < .01), and quality of life (t = 4.48, p < .001) compared to baseline.

In our sample of primarily middle-aged and older adults with chronic pain, medical cannabis was associated with reduced pain intensity/inference, lower anxiety/depression, and improved sleep and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/34671723/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/97