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

Analgesic Potential of Terpenes Derived from Cannabis sativa

Pharmacological Reviews“Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics.

Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief.

Cannabis sativa contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ9-THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes β-myrcene, α-pinene, limonene, and linalool, as well as the sesquiterpenes β-caryophyllene and α-humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects.

The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management.

SIGNIFICANCE STATEMENT: Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.”

https://pubmed.ncbi.nlm.nih.gov/34663685/

“Cannabis sativa has been used for medical, recreational, and spiritual purposes for thousands of years. Modern scientific studies have provided increasing amounts of preclinical and clinical evidence about its beneficial pharmacological effects, including pain relief. Recent changes in the legislation of cannabis usage and possession have resulted in cannabis-based products becoming widely used alternatives in fighting against many different illnesses. Medical marijuana has been applied to treat a host of indications, but the most frequent, and evidence-backed indication, is pain. Overall, cannabis terpenes have a high potential for pain management, alone or as adjunctive therapeutics, and are attractive compounds for the development of terpene-based analgesics given their generally-recognized-as-safe status with low side effect and toxicity profiles.”

Green Hope: Perspectives on Cannabis from People who Use Opioids

Sociological Inquiry“While states are implementing policies to legalize cannabis for medical or recreational purposes, it remains a Schedule 1 controlled substance with no medical uses according to US federal law. The perception of cannabis depends on social and cultural norms that impact political institutions involved in implementing policy. Because of negative social constructions, such as the “gateway hypothesis,” legalization of cannabis has been slow and contentious.

Recent studies suggest that cannabis can help combat the opioid epidemic.

This paper fills a gap in our understanding of how cannabis is viewed by people who are actively misusing opioids and not in treatment. Using ethnographic methods to recruit participants living in a state that legalized cannabis and a state where cannabis was illegal, survey and interview data were analyzed informed by a social constructionist lens.

Findings from their “insider perspective” suggest that for some people struggling with problematic opioid use, cannabis can be beneficial.”

https://pubmed.ncbi.nlm.nih.gov/34538961/

https://onlinelibrary.wiley.com/doi/10.1111/soin.12359

The Effect of Medical Cannabis on Pain Level and Quality of Sleep among Rheumatology Clinic Outpatients

logo“Introduction: Medical cannabis (MC) is becoming increasingly popular for the treatment of chronic pain conditions.

In this study, we evaluated the effect of MC treatment on pain level and quality of sleep of patients with different medical conditions at the rheumatology clinic.

Conclusions: MC had a favorable effect on pain level and quality of sleep among all spectrums of problems at the rheumatology clinic.”

https://pubmed.ncbi.nlm.nih.gov/34531934/

“MC has a favorable effect on pain level and sleep quality among nearly the entire spectrum of resistant “chronic pain syndromes” seen or referred to rheumatology clinics, including inflammatory diseases resistant to biological treatment, although the effect of MC on synovitis was relatively mild.

Cannabis should be seriously considered in every “chronic pain condition” whenever the accepted modalities of treatment are insufficient for alleviating patient’s pain and sleep problems.”

https://www.hindawi.com/journals/prm/2021/1756588/

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

Risk and benefit of cannabis prescription for chronic non-cancer pain

Taylor and Francis Online“Objectives: We investigated whether cannabis usage was associated with reduced opioid usage, and the rates of opioid and cannabis use disorders among chronic pain patients who had been prescribed medical cannabis.

Results: Of the 100 participants aged 18-70 years (compliance 67% (aged >40) and 33% (aged ≤ 40y)), 76 ever used opioids. Of them, 93% decreased or stopped opioids following cannabis initiation. Ten patients (10%), 17.4% of the ≤40 y age group, met the criteria for cannabis use disorder. Compared to those who did not meet the criteria, their lifetime depression was higher (80% vs. 43.2%, respectively, P=.042), and they were less educated (12.2 ± 0.6y vs. 13.5 ± 2.1y, p = 0.05).

Conclusions: Cannabis usage was associated with reduced opioid usage. The prevalence of cannabis use disorder was high among the younger participants who also had a lower study compliance rate, suggesting the higher actual prevalence of cannabis use disorder. While medical cannabis may help reduce opioid use in chronic non-cancer pain patients, younger age, depression, and other risk factors should be carefully evaluated before cannabis is prescribed.”

https://pubmed.ncbi.nlm.nih.gov/34338621/

“Cannabis usage was associated with reduced opioid usage.”

https://www.tandfonline.com/doi/abs/10.1080/10550887.2021.1956673?journalCode=wjad20

Prolonged Medical Cannabis Treatment is Associated With Quality of Life Improvement and Reduction of Analgesic Medication Consumption in Chronic Pain Patients

Frontiers in Pharmacology (@FrontPharmacol) | Twitter“Introduction: Chronic non-cancer pain (CNCP) is one of the most prevalent indications for medical cannabis (MC) treatment globally. In this study, we investigated CNCP parameters in patients during prolonged MC treatment, and assessed the interrelation between CNCP parameters and the chemical composition of MC chemovar used. 

Methods: A cross-sectional questionnaire-based study was performed in one-month intervals for the duration of six months. Subjects were adult patients licensed for MC treatment who also reported a diagnosis of CNCP by a physician. Data included self-reported questionnaires. MC treatment features included administration route, cultivator, cultivar name and monthly dose. Comparison statistics were used to evaluate differences between the abovementioned parameters and the monthly MC chemovar doses at each time point. 

Results: 429, 150, 98, 71, 77 and 82 patients reported fully on their MC treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% (p < 0.005) and good Quality of Life (QoL) rates increased from 49 to 62% (p < 0.05). These changes overlapped with increase in rates of (-)-Δ9trans-tetrahydrocannabinol (THC) and α-pinene high dose consumption. 

Conclusion: Even though we observed that pain intensities did not improve during the study, QoL did improve and the rate of analgesic medication consumption decreased alongside with increasing rates of high dose THC and α-pinene consumption. Understanding MC treatment composition may shed light on its long-term effects.”

https://pubmed.ncbi.nlm.nih.gov/34093173/

“In this study, although pain intensities did not change under long-term MC treatment, analgesic medication consumption rates decreased and ‘better’ QoL rates increased. These changes coincided with the increased rates of patients’ consumption of high dose THC and α pinene. These results may shed light on the long-term beneficial effects of MC on CNCP.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.613805/full

Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study

Pain Medicine“Objectives: This article presents findings from a large prospective examination of Canadian medical cannabis patients, with a focus on the impacts of cannabis on prescription opioid use and quality of life over a 6-month period.

Results: Participants were 57.6% female, with a median age of 52 years. Baseline opioid use was reported by 28% of participants, dropping to 11% at 6 months. Daily opioid use went from 152 mg morphine milligram equivalent (MME) at baseline to 32.2 mg MME at 6 months, a 78% reduction in mean opioid dosage. Similar reductions were also seen in the other four primary prescription drug classes identified by participants, and statistically significant improvements were reported in all four domains of the WHOQOL-BREF.

Conclusions: This study provides an individual-level perspective of cannabis substitution for opioids and other prescription drugs, as well as associated improvement in quality of life over 6 months. The high rate of cannabis use for chronic pain and the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis, potentially improving the quality of life of patients and overall public health.”

https://pubmed.ncbi.nlm.nih.gov/33367882/

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnaa396/6053211?redirectedFrom=fulltext

Antinociception mechanisms of action of cannabinoid-based medicine: an overview for anesthesiologists and pain physicians

 Pain Rounds“Cannabinoid-based medications possess unique multimodal analgesic mechanisms of action, modulating diverse pain targets.

Cannabinoids are classified based on their origin into three categories: endocannabinoids (present endogenously in human tissues), phytocannabinoids (plant derived) and synthetic cannabinoids (pharmaceutical). Cannabinoids exert an analgesic effect, peculiarly in hyperalgesia, neuropathic pain and inflammatory states.

Endocannabinoids are released on demand from postsynaptic terminals and travels retrograde to stimulate cannabinoids receptors on presynaptic terminals, inhibiting the release of excitatory neurotransmitters. Cannabinoids (endogenous and phytocannabinoids) produce analgesia by interacting with cannabinoids receptors type 1 and 2 (CB1 and CB2), as well as putative non-CB1/CB2 receptors; G protein-coupled receptor 55, and transient receptor potential vanilloid type-1. Moreover, they modulate multiple peripheral, spinal and supraspinal nociception pathways.

Cannabinoids-opioids cross-modulation and synergy contribute significantly to tolerance and antinociceptive effects of cannabinoids. This narrative review evaluates cannabinoids’ diverse mechanisms of action as it pertains to nociception modulation relevant to the practice of anesthesiologists and pain medicine physicians.”

https://pubmed.ncbi.nlm.nih.gov/33239391/

https://rapm.bmj.com/content/early/2020/11/24/rapm-2020-102114

Medical Cannabis Treatment for Chronic Pain: Outcomes and Prediction of Response

Although studied in a few randomized controlled trials (RCTs), the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicenter, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various etiologies and to identify predictors for MC treatment success.

Results: 1045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12 month follow-up. At one year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI= -2.13 to -1.81; p<0.001)]. All other parameters improved by 10-30% (p<0.001). A significant decrease of 42% [reduction of 27mg; (95%CI= -34.89 to -18.56, p<0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index (BMI) and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite.

Conclusions: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild to modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

Significance: This “real world” paper shows that MC mildly to modestly attenuates chronic pain and related symptoms. MC treatment can also cause frequent, but mostly non-serious adverse effects, although central nervous system (CNS)-related AEs that can impair the ability to drive vehicles are not uncommon. This study is novel in identifying possible predictors for treatment success, including normal to long sleep duration, lower BMI and lower depression scores. In contrast to current beliefs the diagnosis of neuropathic pain predicts a less favorable outcome. These findings provide physicians with new data to support decision making on recommendations for MC treatment.”

https://pubmed.ncbi.nlm.nih.gov/33065768/

https://onlinelibrary.wiley.com/doi/10.1002/ejp.1675