Category Archives: Pain

Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia

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“Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain.

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potentcy in addressing this particular issue remains to be determined.

Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity.

CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.”

https://pubmed.ncbi.nlm.nih.gov/38428482/

“CBD could be a candidate for treating sleep deprivation induced hyperalgesia.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390824000601?via%3Dihub

Cannabinoids for Cancer-related Pain Management: An Update on Therapeutic Applications and Future Perspectives

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“Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management.

Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids.

Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials.

In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief.”

https://pubmed.ncbi.nlm.nih.gov/38423660/

https://ar.iiarjournals.org/content/44/3/895

Targeting the endocannabinoid system for the management of low back pain

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“Low back pain (LBP) is a major unmet clinical need. The endocannabinoid system (ECS) has emerged as a promising therapeutic target for pain, including LBP. This review examines the evidence for the ECS as a therapeutic target for LBP. While preclinical studies demonstrate the potential of the ECS as a viable therapeutic target, clinical trials have presented conflicting findings. This review underscores the need for innovative LBP treatments and biomarkers and proposes the ECS as a promising avenue for their exploration. A deeper mechanistic understanding of the ECS in LBP could inform the development of new pain management strategies.”

https://pubmed.ncbi.nlm.nih.gov/38401317/

https://www.sciencedirect.com/science/article/pii/S1471489224000080?via%3Dihub

Tetrahydrocannabinol and Cannabidiol for Pain Treatment-An Update on the Evidence

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“In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available.

Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression.

On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain.

Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly.

The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.”

https://pubmed.ncbi.nlm.nih.gov/38397910/

https://www.mdpi.com/2227-9059/12/2/307

Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial

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“Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine.

In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was 1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization.

Results Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events.

Conclusions Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.”

https://pubmed.ncbi.nlm.nih.gov/38405890/

https://www.medrxiv.org/content/10.1101/2024.02.16.24302843v1

Cannabidiol for Postoperative Pain Control After Arthroscopic Rotator Cuff Repair Demonstrates No Deficits in Patient-Reported Outcomes Versus Placebo: 1-Year Follow-up of a Randomized Controlled Trial

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“Background: Cannabidiol (CBD) has been shown recently to positively affect patient pain and satisfaction immediately after arthroscopic rotator cuff repair (ARCR). However, it is unclear whether the addition of CBD to a perioperative regimen could affect postoperative outcomes.

Purpose: To evaluate patient-reported outcomes among patients who underwent ARCR and received buccally absorbed CBD or an identical placebo for early postoperative pain management at 1-year follow-up.

Study design: Randomized controlled trial; Level of evidence, 2.

Methods: Eligible patients had previously participated in a multicenter, placebo-controlled, randomized, double-blinded trial that evaluated the analgesic effects of CBD in the immediate postoperative period after ARCR. The experimental group received 25 mg of CBD 3 times/day if <80 kg and 50 mg of CBD 3 times/day if >80 kg for 14 days, with the control group receiving an identical placebo. The following outcomes were assessed at minimum 1-year follow-up: visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and patient satisfaction. The rates of achievement of the Patient Acceptable Symptom State (PASS) were compared based on ASES at latest follow-up. Continuous and categorical variables were compared with the Mann-Whitney U test and Fisher exact test, respectively.

Results: Follow-up was obtained from 83 of 99 patients (83.8%) who completed the original trial. There were no significant differences between the CBD and control groups with respect to age, sex, body mass index, rate of concomitant procedures, or number of anchors used intraoperatively. At 1-year follow-up, there were no significant differences between the CBD and control groups in VAS pain (0.8 vs 1.2, P = .38), ASES (93.0 vs 91.1, P = .71), SANE (87.6 vs 90.1, P = .24), or satisfaction (97.4 vs 95.4, P = .41). A majority of patients achieved the PASS (81.0% [CBD] vs 77.5% [control]; P = .79).

Conclusion: Perioperative use of CBD for pain control among patients undergoing ARCR did not result in any significant deficits in pain, satisfaction, or patient-reported outcomes at 1-year postoperatively compared with a placebo control group. These findings suggest that CBD can be considered in a postoperative multimodal pain management regimen without detrimental effects on outcome.”

https://pubmed.ncbi.nlm.nih.gov/38322981/

“The Cannabis sativa plant is a promising alternative for augmented pain control”

https://journals.sagepub.com/doi/10.1177/23259671231222265

Perceptions of Orthopaedic Sports Medicine Surgeons About Medical Cannabidiol Use: A Survey Study

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“Introduction: Multiple studies exist identifying cannabidiol (CBD) as an effective part of an orthopaedic patient’s pain regimen; however, there is a paucity of studies elucidating orthopaedic surgeons’ perception of the use and prescription of CBD in the medical setting. This study surveys orthopaedic sports medicine surgeons about their previous education on and current perceptions and usage of CBD in their medical practice.

Methods: Between April 2023 and July 2023, orthopaedic sports medicine surgeons from across the country were surveyed. This survey was designed in hopes of identifying physician perceptions and current use of CBD as well as their previous education and training on its use.

Results: Overall, 75 orthopaedic surgeons responded. More than three-fourths of responders had not received formal education on medical CBD use, nor did they have partners or colleagues who used CBD in their practice. More than half of all surgeons believed that there is a stigma associated with CBD use. A higher proportion of surgeons from CBD legal states recommended CBD to help patients control their pain (53.7% vs. 37.5%). Less than 15% of responders believed that CBD can adversely affect surgical outcomes. Finally, four-fifths of all responders believed that CBD is easy to legally access and affordable to buy by patients who desire it.

Discussion: The relative novelty of CBD inclusion in medicine has led to a lack of early education and overall experience with its use among orthopaedic sports medicine surgeons. Still, surgeons believe that CBD is a safe and effective option to control pain. As surgeons continue to gain more familiarity and trust with CBD’s medical uses over time, it has the potential to be a mainstay in orthopaedic multimodal pain regimens.”

https://pubmed.ncbi.nlm.nih.gov/38318555/

https://www.cureus.com/articles/205336-perceptions-of-orthopaedic-sports-medicine-surgeons-about-medical-cannabidiol-use-a-survey-study#!/

Cannabinoids in anesthesia and chronic pain: Where do we stand?

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“Cannabis derivatives have been conventionally employed globally for their curative and restorative properties for various ailments. However, its recreational use and consequent legal restrictions have substantially cramped its scientific research.

An emerging interest regarding the profound therapeutic potential of cannabinoids has been observed among clinicians. Despite a rich cultural background, high-quality research on cannabinoids is lacking in the Indian scenario. This review readdresses the challenges on this front and brings an insight into the current status of cannabinoids and their utility in scientific exploration.

Cannabinoids have a significant medicinal value in various clinical disorders. Its use so far has been based on scarce resources and corroborations, as evidence-based substantiation is limited.

Through this review article, we emphasize the remarkable role enacted by cannabinoids in the treatment of various clinical disorders and an utterly significant need to formulate stringent research methodologies to promote its systematic investigation.”

https://pubmed.ncbi.nlm.nih.gov/38313715/

https://journals.lww.com/sjan/fulltext/2024/18010/cannabinoids_in_anesthesia_and_chronic_pain__where.16.aspx

Pain management for post-treatment survivors of complex cancers: a qualitative study of opioids and cannabis

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“Aim: We aimed to understand experiences with opioids and cannabis for post-treatment cancer survivors. 

Patients & methods: We conducted seven focus groups among head and neck and lung cancer survivors, using standard qualitative methodology to explore themes around 1) post-treatment pain and 2) utilization, perceived benefits and perceived harms of cannabis and opioids. 

Results & conclusion: Survivors (N = 25) experienced addiction fears, stigma and access challenges for both products. Opioids were often perceived as critical for severe pain. Cannabis reduced pain and anxiety for many survivors, suggesting that anxiety screening, as recommended in guidelines, would improve traditional pain assessment. Opioids and cannabis present complex harms and benefits for post-treatment survivors who must balance pain management and minimizing side effects.”

https://pubmed.ncbi.nlm.nih.gov/38318666/

https://www.futuremedicine.com/doi/10.2217/pmt-2023-0067

Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine)

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“Background: Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis.

Methods: This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use.

Results: 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2-6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3-58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6-52.8%) of their current analgesics. Age (β = – 0.3, CI – 0.6-0.0), higher pain severity (β = 0.4, CI 0.1-0.6) and previous cannabis use (β = 14.7, CI 5.1-24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier.

Conclusions: Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.”

https://pubmed.ncbi.nlm.nih.gov/38291451/

https://josr-online.biomedcentral.com/articles/10.1186/s13018-024-04558-6