Medical Cannabis in Hand Surgery: A Review of the Current Evidence

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The Journal of Hand Surgery

“Acute and chronic pain management remains an ongoing challenge for hand surgeons. This has been compounded by the ongoing opioid epidemic in the United States.

With the increasing legalization of medical and recreational cannabis throughout the United States and other countries, previous societal stigmas about this substance keep evolving, and recognition of medical cannabis as an opioid-sparing pain management alternative is growing. A review of the current literature demonstrates a strong interest from patients regarding the use of medical cannabis for pain control.

Current evidence demonstrates its efficacy and safety for chronic musculoskeletal and neuropathic pain. However, definitive conclusions regarding the efficacy of cannabis for pain control in hand and upper extremity conditions require continued investigation.

The purpose of this article is to provide a general review of the mechanism of medical cannabis and a scoping review of the current evidence for its efficacy, safety, and potential applicability in hand and upper extremity conditions.”

https://pubmed.ncbi.nlm.nih.gov/36609049/

https://www.jhandsurg.org/article/S0363-5023(22)00710-9/fulltext

Preoperative Preparation and Guidelines for Cannabis-Using Patients Undergoing Elective Surgery

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“Purpose: Appropriate preoperative screening techniques are needed to safely provide anesthesia to increasing numbers of cannabis using surgical patients.

Design: This was a quasi-experimental quality improvement project.

Methods: Preoperative identification of cannabis users by registered nurses (RNs) and certified registered nurse anesthetists (CRNAs) was compared to baseline identification rates. CRNAs’ compliance with evidenced base guidelines was recorded. Perioperative medication requirements were recorded and compared between cannabis-users and non-cannabis users.

Findings: Identification of cannabis users by CRNAs conducting preanesthetic assessments increased from 4.08% to 14.36% while RN identification improved from 11.22% to 13.81%. Compliance with identification guidelines was 69.2% among CRNAs.

There were no differences in anesthetic requirements, complications, or postanesthesia care unit (PACU) length of stay between cannabis users and non-users.

Conclusion: Preoperative identification of cannabis users allows for safer, more effective perioperative care by CRNAs, registered nurses, and surgical staff.”

https://pubmed.ncbi.nlm.nih.gov/36609136/

https://www.jopan.org/article/S1089-9472(22)00544-5/fulltext

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer

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International Journal of Pharmaceutics

“Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells.

Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers.

Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs.

In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.”

https://pubmed.ncbi.nlm.nih.gov/36608807/

https://www.sciencedirect.com/science/article/abs/pii/S0378517322011358?via%3Dihub

[A mini-review on anti-tumor effect of cannabidiol]

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“Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions.

In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol.

In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.”

https://pubmed.ncbi.nlm.nih.gov/36604902/

https://kns.cnki.net/kcms/detail/detail.aspx?doi=10.19540/j.cnki.cjcmm.20220906.601

Potential effects of cannabinoids on audiovestibular function: A narrative review

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Frontiers - Crunchbase Company Profile & Funding

“The growing interest in the development of drugs that target the endocannabinoid system has extended to conditions that affect the audiovestibular pathway. The expression of cannabinoid (CB) receptors in that pathway has been widely demonstrated, indicating a therapeutic potential for drug development at this level. These medications may be beneficial for conditions such as noise-induced hearing loss, ototoxicity, or various forms of vertigo of central or peripheral origin. The therapeutic targets of interest include natural or synthetic compounds that act as CB1/CB2 receptor agonists/antagonists, and inhibitors of the endocannabinoid-degrading enzymes FAAH and MAGL. Furthermore, genetic variations implicated in the response to treatment and the development of related disorders such as epilepsy or migraine have been identified. Direct methods of administering these medications should be examined beyond the systemic strategy.”

https://pubmed.ncbi.nlm.nih.gov/36605398/

https://www.frontiersin.org/articles/10.3389/fphar.2022.1010296/full

Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials

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“Background: Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain.

Objective: The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain.

Evidence review: Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients’ global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized.

Findings: Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to -0.61, 95% prediction interval (PI): -0.12 to 0.88, p-value=0.002, I2=55.26, τ2=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: -0.55, 95% CI:-0.69 to -0.19, 95% PI: -1.51 to 0.39, p=0.003, I2=82.49, τ2=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness.

Conclusions: Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy.”

https://pubmed.ncbi.nlm.nih.gov/36598058/

https://rapm.bmj.com/content/early/2022/12/04/rapm-2021-103431

The function of the endocannabinoid system in the pancreatic islet and its implications on metabolic syndrome and diabetes

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“The following review focuses on the scientific studies related to the role of endocannabinoid system (ECS) in pancreatic islet physiology and dysfunction. Different natural or synthetic agonists and antagonists have been suggested as an alternative treatment for diabetes, obesity and metabolic syndrome. Therapeutic use of Cannabis led to the discovery and characterization of the ECS, a signaling complex involved in regulation of various physiological processes, including food intake and metabolism. After the development of different agonists and antagonists, evidence have demonstrated the presence and activity of cannabinoid receptors in several organs and tissues, including pancreatic islets. Insulin and glucagon expression, stimulated secretion, and the development of diabetes and other metabolic disorders have been associated with the activity and modulation of ECS in pancreatic islets. However, according to the animal model and experimental design, either endogenous or pharmacological ligands of cannabinoid receptors have guided to contradictory and paradoxical results that suggest a complex physiological interaction. In consensus, ECS activity modulates insulin and glucagon secretions according to glucose in media; over-stimulation of cannabinoid receptors affects islets negatively, leading to glucose intolerance, meanwhile the treatment with antagonists in diabetic models and humans suggests an improvement in islets function.”

https://pubmed.ncbi.nlm.nih.gov/36598083/

https://www.tandfonline.com/doi/full/10.1080/19382014.2022.2163826

Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes

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Psychological Medicine

“Background: The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.

Methods: We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24-49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).

Results: In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (βw = 0.11, p = 1.3 × 10-3), and had fewer AUD symptoms (βw = -0.11, p = 6.7 × 10-3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.

Conclusions: Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.”

https://pubmed.ncbi.nlm.nih.gov/36601811/

https://www.cambridge.org/core/journals/psychological-medicine/article/abs/recreational-cannabis-legalization-has-had-limited-effects-on-a-wide-range-of-adult-psychiatric-and-psychosocial-outcomes/D4AB5EB78D588473A054877E05D45F16

Delta-9 tetrahydrocannabinol (THC) effects on the cortisol stress response in bovine granulosa cells

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Toxicology in Vitro

“Maternal stress can result in changes in the hypothalamic-pituitary-adrenal (HPA) axis and lead to stress-related behaviours in offspring. Under physiological conditions, delta-9 tetrahydrocannabinol (THC) appears to be detrimental for fertility. However, cannabis is also commonly used for stress-relief. THC acts on the endocannabinoid receptors in granulosa cells (GCs), which affects oocyte competency. The objective of this study was to evaluate the effects of THC on in vitro bovine granulosa cell viability, apoptosis, and stress response pathway. GCs were cultured in vitro in the presence of clinically relevant therapeutic and recreational plasma doses of THC. Cortisol doses reflecting normal and elevated plasma levels were used to evaluate the effects of THC under induced stress in vitro. No effect of THC was observed on cell viability or apoptosis. High and low cortisol concentrations caused significant increases in 11β-HSD1 mRNA expression (n = 6, p < 0.0001). Interestingly, when combined with high [THC], there was a significant decrease in 11β-HSD1 expression compared to high and low cortisol treatments alone (p < 0.001, p < 0.05). GR expression was unaffected by cortisol treatments, and low [THC] treatment maintained increased expression in the presence of high and low cortisol treatments (n = 6, p < 0.01, p < 0.0001). Our findings represent a foundation to obtain useful data for evaluating THC potential therapeutic benefit.”

https://pubmed.ncbi.nlm.nih.gov/36596389/

“THC treatment does not affect granulosa cell viability or apoptosis.•

Cortisol treatments increase 11β-HSD1 gene expression.•

11β-HSD1 gene expression is reduced by THC treatment in combination with cortisol.•

Glucocorticoid receptor gene expression is increased in response to THC.”

https://www.sciencedirect.com/science/article/abs/pii/S0887233322002478?via%3Dihub


Cannabidiol Suppresses Cytokine Storm and Protects Against Cardiac and Renal Injury Associated with Sepsis

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“Background: Cytokine release syndrome, also termed “cytokine storm,” is the leading cause of morbidity and mortality among patients with various conditions such as sepsis. While cytokine storm is associated with multiple organ damage, acute cardiac and renal injury represents a hallmark of cytokine storm. Since recent reports have suggested that cannabidiol (CBD) may assist in the treatment of inflammatory diseases, our objective was to examine the effect of CBD on cytokine storm-induced cardiac and renal injury using the lipopolysaccharide (LPS)-induced sepsis mouse model. 

Materials and Methods: At 8 weeks of age, mice were randomly assigned to receive CBD (15 mg/kg) or vehicle one hour before a single injection of either phosphate-buffered saline or LPS (10 mg/kg) for an additional 24 h. 

Results: Our results show that CBD improves cardiac function and reduces renal injury in a mouse model of cytokine storm. Moreover, our data indicate that CBD significantly reduces systemic and renal inflammation to contribute to the improvements observed in a cytokine storm-model of cardiac and renal injury. 

Conclusions: Overall, the findings of this study suggest that CBD could be repurposed to reduce morbidity in patients with cytokine storm particularly in severe infections such as sepsis.”

https://pubmed.ncbi.nlm.nih.gov/36594988/

https://www.liebertpub.com/doi/10.1089/can.2022.0170