Category Archives: Pain

The role of Cannabis in treatment-resistant Fibromyalgia women

Posted on by
Reply

“Background: Fibromyalgia is a complex pain-focused syndrome. Previous studies showed that Cannabis is efficacious in promoting sleep, deepening and lengthening the sleep cycle, and good pain relief (compared to SSRIs and SNRIs).

Purpose: This study aimed to use the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref) to characterize the impact of Cannabis Treatment initiation on the quality of life in women suffering from treatment-resistant fibromyalgia.

Methods: a prospective cohort study involving 30 women aged 18-70 years old diagnosed with fibromyalgia, exhausted pharmacological fibromyalgia treatment, and started Cannabis treatment. Pregnant women were excluded. WhoQoL-bref was filled before Cannabis treatment initiation and one month following treatment.

Results: Women’s average age was 46 years(±5), with a poor general quality of life (1.47±0.63), poor general health (1.47±0.78), pain and discomfort, and dependence on medication (3.77±1.3 and 3.07±1.74 respectively) prior to Cannabis intervention. Cannabis treatment for 30 days showed a marked improvement in general quality of life (1.97 scores, p < 0.01), general health (1.83, p<0.01), physical health ( 1.5, p<0.01), and psychological domain (1.3, p<0.01). Financial resources and home environment were not influenced by cannabis treatment (p=0.07, p=0.31, respectively).

Conclusion: Results suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, physical and psychological domains. Further studies are still indicated to understand this potential and its long-term beneficial impact.”

https://pubmed.ncbi.nlm.nih.gov/36333278/

https://onlinelibrary.wiley.com/doi/10.1111/papr.13179

” Flower Power”: Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients

Posted on by
Reply
biomedicines-logo

“In November 2018, the UK’s Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration (“oils”) and dried flowers for inhalation (“flos”). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; p < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; p < 0.001) and interference (T = 7.19; p < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; p < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.”

https://pubmed.ncbi.nlm.nih.gov/36289837/

“Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos was associated with a robust improvement in patient-reported pain scores, general mood, anxiety, sleep, and overall HRQoL in a treatment-resistant clinical population.”

https://www.mdpi.com/2227-9059/10/10/2576/htm

Combinations of Cannabidiol and Δ9-Tetrahydrocannabinol in Reducing Chemotherapeutic Induced Neuropathic Pain

Posted on by
Reply
biomedicines-logo

“Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios.

We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data suggest that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant.

We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model.”

https://pubmed.ncbi.nlm.nih.gov/36289810/

https://www.mdpi.com/2227-9059/10/10/2548/htm

Cannabidiol as a modulator of α7 nicotinic receptors

Posted on by
Reply
SpringerLink

“Cannabidiol (CBD), an important terpenoid compound from marijuana with no psychoactive effects, has become of great pharmaceutical interest for several health conditions. As CBD is a multitarget drug, there is a need to establish the molecular mechanisms by which CBD may exert therapeutic as well as adverse effects. The α7 nicotinic acetylcholine receptor (α7 nAChR) is a cation-permeable ACh-gated channel present in the nervous system and in non-neuronal cells. It is involved in different pathological conditions, including neurological and neurodegenerative disorders, inflammation, and cancer. By high-resolution single-channel recordings and confocal microscopy, we here reveal how CBD modulates α7 nAChR ionotropic and metabotropic functions. CBD leads to a profound concentration-dependent decrease of α7 nAChR single-channel activity with an IC50 in the sub-micromolar range. The inhibition of α7 nAChR activity, which takes place through a membrane pathway, is neither mediated by receptor phosphorylation nor overcome by positive allosteric modulators and is compatible with CBD stabilization of resting or desensitized α7 nAChR conformational states. CBD modulation is complex as it also leads to the later appearance of atypical, low-frequency α7 nAChR channel openings. At the cellular level, CBD inhibits the increase in intracellular calcium triggered by α7 nAChR activation, thus decreasing cell calcium responses. The modulation of α7 nAChR is of pharmacological relevance and should be considered in the evaluation of CBD potential therapeutic uses. Thus, our study provides novel molecular information of CBD multiple actions and targets, which is required to set the basis for prospective applications in human health.”

https://pubmed.ncbi.nlm.nih.gov/36282426/

https://link.springer.com/article/10.1007/s00018-022-04600-y

“Targeting α7 nicotinic acetylcholine receptors for chronic pain”

https://pubmed.ncbi.nlm.nih.gov/36245927/

Efficacy and mechanism of the antinociceptive effects of cannabidiol on acute orofacial nociception induced by Complete Freund’s Adjuvant in male Mus musculus mice

Posted on by
Reply
Archives of Oral Biology

“Objectives: The objectives were to investigate the efficacy and mechanisms of cannabidiol on orofacial nociception induced by Complete Freund’s Adjuvant (CFA) in male Mus musculus mice.

Design: For the study of efficacy, mice were divided into seven groups: sham; inflammation; and cannabidiol 0.5, 1, 3, 5, and 10 mg. For the study of mechanisms of cannabidiol, mice were divided into six groups: sham, inflammation, calcitonin gene-related peptide (CGRP) antagonist with and without cannabidiol, and vanilloid receptor 1 antagonist with and without cannabidiol. Spontaneous pain-like behaviors, trigeminal nociception, and trigeminal modulating activity were investigated.

Results: CFA injected in the right masseter muscle significantly induced spontaneous pain-like behaviors and the trigeminal nociceptive pathway. This effect was inhibited by injection of 1, 3, 5, and 10 mg of cannabidiol. The 50 % inhibitory concentration of cannabidiol on antinociception was found to be 3 mg/kg. In addition, there was no difference in spontaneous pain-like behaviors with vanilloid receptor 1 antagonist injected before treatment with cannabidiol compared to saline control. Reduced c-fos expression was observed in the trigeminal nucleus caudalis and periaqueductal gray in the group injected with CGRP antagonist before treatment with cannabidiol.

Conclusion: The antinociceptive effects of cannabidiol induced by acute orofacial nociception is mediated by vanilloid receptor 1 but not by CGRP. Cannabidiol can act with peripheral nonpeptidergic neurons and can be used as an alternative drug or as a synergistic medication in pain treatment.”

https://pubmed.ncbi.nlm.nih.gov/36265395/

“Our results may imply that cannabidiol can be used as an alternative drug or as synergistic medication in orofacial pain treatment.”

https://www.sciencedirect.com/science/article/abs/pii/S0003996922002278?via%3Dihub

Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain

Posted on by
Reply
Lopiccolo & Chang in PLoS ONE – BU Linguistics

“This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.”

https://pubmed.ncbi.nlm.nih.gov/36240167/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270543

Changes in the expression of endocannabinoid system components in an experimental model of chemotherapy-induced peripheral neuropathic pain: Evaluation of sex-related differences

Posted on by
Reply
Experimental Neurology

“Chemotherapy-induced neuropathic pain is a serious clinical problem and one of the major side effects in cancer treatment. The endocannabinoid system (ECS) plays a crucial role in regulating pain neurotransmission, and changes in the expression of different components of the ECS have been reported in experimental models of persistent pain. In addition, sex differences have been observed in ECS regulation and function. The aim of our study was to evaluate whether administration of oxaliplatin, a neurotoxic antineoplastic agent, induced changes in the expression of ECS components in peripheral and central stations of the pain pathway, and if those changes exhibited sexual dimorphism. Adult male and female rats were injected with oxaliplatin or saline, and mechanical and cold hypersensitivity and allodynia were evaluated using Von Frey and Choi Tests. The mRNA levels corresponding to cannabinoid receptors (CB1, CB2), cannabinoid-related receptors (GPR55, 5HT1A, TRPV1) and to the main enzymes involved in the synthesis (DAGL, DAGL, NAPE-PLD) and degradation (MGL, FAAH) of endocannabinoids were assessed in lumbar dorsal root ganglia (DRGs) and spinal cord by using real time RT-PCR. In addition, the levels of the main endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), were evaluated using commercial ELISA kits. Oxaliplatin administration induced the development of mechanical and cold hypersensitivity and allodynia in male and female animals. Oxaliplatin also induced early and robust changes in the expression of several components of the ECS in DRGs. A marked upregulation of CB1, CB2, 5HT1A and TRPV1 was detected in both sexes. Interestingly, while DAGL mRNA levels remained unchanged, DAGL was downregulated in male and upregulated in female rats. Finally, MGL and NAPE-PLD showed increased levels only in male animals, while FAAH resulted upregulated in both sexes. In parallel, reduced 2-AG and AEA levels were detected in DRGs from male or female rats, respectively. In the lumbar spinal cord, only TRPV1 mRNA levels were found to be upregulated in both sexes. Our results reveal previously unreported changes in the expression of cannabinoid receptors, ligands and enzymes occurring mainly in the peripheral nervous system and displaying certain sexual dimorphism. These changes may contribute to the physiopathology of oxaliplatin-induced neuropathic pain in male and female rats. A better understanding of these dynamic changes will facilitate the development of mechanism- and sex-specific approaches to optimize the use of cannabinoid-based medicines for the treatment of chemotherapy-induced pain.”

https://pubmed.ncbi.nlm.nih.gov/36179876/

https://www.sciencedirect.com/science/article/abs/pii/S0014488622002576?via%3Dihub

Medical Cannabis Patients Report Improvements in Health Functioning and Reductions in Opiate Use

Posted on by
Reply
Publication Cover

“Purpose: Opioid use rates have dropped as North American patients gain access to medical cannabis, indicating a harm reduction role, yet health outcomes remain mostly unexplored. This study presents self-reported medical cannabis use, perceptions of health functioning, and changes in opioid pain medication use in Florida medical cannabis patients.

Methods: Patients (n = 2,183) recruited from medical dispensaries across Florida completed a 66-item cross-sectional survey that included demographic, health, and medication usage items, along with items from the Medical Outcomes Survey (SF-36) to assess health functioning before and after cannabis initiation.

Results: Most participants were between the ages of 20 and 70 years of age (95%), over 54% were female, 47% were employed, and most (85%) were white. Commonly reported ailment groups were Pain and Mental Health combined (47.92%), Mental Health (28.86%) or Pain (9.07%). Health domains of bodily pain, physical functioning, and social functioning improved while limitations due to physical and emotional problems were unchanged. Most patients rated medical cannabis as being important to their quality of life. Many (60.98%) reported using pain medications prior to medical cannabis, 93.36% of these reported a change in pain medication after medical cannabis. The majority of participants (79%) reported either cessation or reduction in pain medication use following initiation of medical cannabis and 11.47% described improved functioning.

Conclusions: The findings suggest that some medical cannabis patients decreased opioid use without harming quality of life or health functioning, soon after the legalization of medical cannabis. The public health implications of medical cannabis as an alternative pain medication are discussed.”

https://pubmed.ncbi.nlm.nih.gov/36168127/

“In conclusion, some patients may reduce or even cease use of OBPM upon access to medical cannabis, potentially without harming quality of life or health functioning. This is suggestive of the harm reduction role and opioid-sparing effects of medical cannabis in a quality-controlled and regulated medical-use only state. Given the great individual and societal costs associated with the opioid crisis (Florence et al., 2021; National Institute on Drug Abuse, n.d.), the public health implications of these findings are important to consider.”

https://www.tandfonline.com/doi/full/10.1080/10826084.2022.2107673

Self-Reported Cannabis Use Is Associated With a Lower Rate of Persistent Opioid Use After Total Joint Arthroplasty

Posted on by
Reply
Arthroplasty Today (@ArthroToday) / Twitter

“Background: Legalization of cannabis, along with concern over prescription opiate use, has garnered interest in cannabis for adjuvant pain control. This study examines the relationship between cannabis and opioid consumption after total hip (THA) or knee (TKA) arthroplasty.

Methods: Patients undergoing primary THA or TKA with minimum 6-month follow-up who self-reported cannabis use were retrospectively reviewed. A total of 210 patients (128 TKAs and 82 THAs) were matched by age; gender; type of arthroplasty; Charlson Comorbidity Index; and use of nicotine, antidepressants, or benzodiazepines to patients who did not self-report cannabis use. Patients receiving an opioid prescription after 90 days postoperatively were classified as persistent opioid users (POUs). Duration of opioid use (DOU) was calculated for non-POU patients as the time between surgery and their last opioid prescription. Differences in inpatient morphine milligram equivalents (MMEs), outpatient MMEs, POU, and DOU were analyzed.

Results: Cannabis users required equivalent inpatient and outpatient MMEs. There was no difference in DOU. There was a significant difference in POU between cannabis users and matched controls (1.4% [n = 3] vs 9.5% [n = 20], P < .001, respectively). Grouping patients by TKA or THA, there remained a difference in POU for TKA (1.5% [n = 2] vs 10.9% [n = 14], P = .002) and THA (1.2% [n = 1] vs 7.3% [n = 6], P = .04). There was no difference in inpatient or outpatient MMEs or DOU for THA and TKA patients.

Conclusions: There is a reduced rate of POU in patients who self-report perioperative cannabis use. Prospective studies are needed to clarify the role of cannabis as an adjunct to perioperative pain control.”

https://pubmed.ncbi.nlm.nih.gov/36158462/

“This study helps to shed light on what role if any cannabis should play as a part of an opioid-sparing multimodal pain protocol after TJA. Self-reported perioperative cannabis use appeared to significantly reduce the number of patients that persistently used opioids greater than 90 days after TJA from 9.5% to 1.4%.”

https://www.arthroplastytoday.org/article/S2352-3441(22)00164-9/fulltext

Preoperative cannabis use does not increase opioid utilization following primary total hip arthroplasty in a propensity matched analysis

Posted on by
Reply
SpringerLink

“Purpose: The recreational and medical use of cannabis is being legalized worldwide. Its use has been linked to an increased risk of developing opioid use disorders. As opioids continue to be prescribed after total hip arthroplasty (THA), the influence that preoperative cannabis use may have on postoperative opioid consumption remains unknown. The purpose of this study was to assess the relationship between preoperative cannabis use and opioid utilization following primary THA.

Methods: We identified all patients over the age of 18 who underwent unilateral, primary THA for a diagnosis of osteoarthritis at a single institution from February 2019 to April 2021. Our cohort was grouped into current cannabis users (within 6 months of surgery) and those who reported never using cannabis. One hundred and fifty-six current users were propensity score matched 1:6 with 936 never users based on age, sex, BMI, history of chronic pain, smoking status, history of anxiety/depression, ASA classification and type of anesthesia. Outcomes included inpatient and postdischarge opioid use in morphine milligram equivalents.

Results: Total inpatient opioid utilization, opioids refilled, and total opioids used within 90 postoperative days were similar between the groups.

Conclusion: In propensity score matched analyses, preoperative cannabis use was not independently associated with an increase in inpatient or outpatient, 90-days opioid consumption following elective THA.”

https://pubmed.ncbi.nlm.nih.gov/36129515/

https://link.springer.com/article/10.1007/s00402-022-04619-7