A Case Report of Treatment-Resistant Agitation in Dementia with Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics

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“Palliative care teams are often consulted to assist in treating persistent dementia-related behavioral issues. Delta-9-tetrahydrocannabinol (THC) offers an alternative to traditional antipsychotic drugs in the long-term management of dementia with behavioral change. We present the case of an 85-year-old man with dementia with Lewy bodies with worsening aggression refractory to antipsychotic management. Multiple regimens of antipsychotics failed both in the outpatient and inpatient settings. After exhausting other options and in the setting of worsening agitation, a tincture of THC was prescribed. After starting THC tincture, the patient’s behavior rapidly improved, and he was discharged home to the care of his spouse. The challenges of prescribing and obtaining THC are discussed.”

https://pubmed.ncbi.nlm.nih.gov/36576970/

https://www.liebertpub.com/doi/10.1089/jpm.2022.0343

Cannabis Use Among Lower-Extremity Arthroplasty Patients Does Not Lead to Worse Postoperative Outcomes

“Introduction: Smoking and general categorizations of substance use are linked with increased postoperative complications following total knee arthroplasty (TKA) and total hip arthroplasty (THA). There is a lack of similar evidence on how cannabis use may affect outcomes after arthroplasty. The present study aims to compare postoperative outcomes in cannabis users versus non-cannabis users who underwent THA/TKA. We hypothesize that cannabis users will have no difference in primarily the complication rate, revision rate, and secondarily post-operative Patient-Reported Outcomes Information System (PROMIS) scores, hospital stay, or pain compared to matched controls.

Methods: Billing codes were used to generate lists of hip/knee arthroplasty patients from 2013 to 2019 at our institution. In the case group, cannabis use was confirmed via chart review. Cannabis-using patients were matched appropriately with non-users by (1) the same arthroplasty procedure; (2) BMI ± 3.5; (3) age ± 3 years; (4) sex. Data on postoperative outcomes were collected from charts and compared between groups using either a Chi-square test for qualitative variables or a paired t-test for quantitative variables.

Results: A total of 24 patients with an average age of 57.1 and a BMI of 30.6 were confirmed to have isolated cannabis use. They were matched to 24 patients with an average age of 57.6 and a BMI of 31.4. There were no significant differences in the complication rate (4.2% vs 4.2%, p=1.00), the revision rate (0% vs 4.2%, p=0.31), days of hospital stay (2.7 vs 3.3, p=0.22), or postoperative pain (4.7 vs 4.9, p=0.86). Similarly, there were no significant differences in all PROMIS score measures.

Discussion/conclusions: Current research shows that cannabis use may lead to increased revision arthroplasty and decreased mortality, with mixed findings regarding post-surgical complications. The present study suggests that cannabis-using patients have no difference in postoperative complication rate, revision rate, PROMIS scores, hospital stay, or pain compared to matched controls.”

https://pubmed.ncbi.nlm.nih.gov/36582568/

https://www.cureus.com/articles/126590-cannabis-use-among-lower-extremity-arthroplasty-patients-does-not-lead-to-worse-postoperative-outcomes


Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report

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“Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products.

Case summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2.

Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma.

Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis’s effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day.

Conclusion and relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.”

https://pubmed.ncbi.nlm.nih.gov/35898257/

https://journals.sagepub.com/doi/10.1177/00185787211061374

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis

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“Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. 

Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. 

Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. 

Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. 

Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. 

Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. 

Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. 

Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.”

https://pubmed.ncbi.nlm.nih.gov/36579921/

https://www.liebertpub.com/doi/10.1089/can.2022.0041

Assessment of clinical outcomes of medicinal cannabis therapy for depression: Analysis from the UK Medical Cannabis Registry

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“Background: Although pre-clinical experiments associate cannabinoids with reduced depressive symptoms, there is a paucity of clinical evidence. This study aimed to analyze the health-related quality of life changes and safety outcomes in patients prescribed cannabis-based medicinal products (CBMPs) for depression.

Methods: An uncontrolled case series of the UK Medical Cannabis Registry was analyzed. Primary outcomes were changes from baseline in the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L at 1, 3, and 6 months. Secondary outcomes included adverse events incidence.

Results: 129 patients were identified for inclusion. Median PHQ-9 at baseline was 16.0 (IQR: 9.0-21.0). There were reductions in PHQ-9 at 1-month (median: 8.0; IQR: 4.0-14.0; p<0.001), 3-months (7.0; 2.3-12.8; p<0.001), and 6-months (7.0; 2.0-9.5; p<0.001). Improvements were also observed in GAD-7, SQS, and EQ-5D-5L Index Value at 1, 3, and 6 months (p<0.050). 153 (118.6%) adverse events were recorded by 14.0% (n=18) of participants, 87% (n=133) of which were mild or moderate.

Conclusion: CBMP treatment was associated with reductions in depression severity at 1, 3, and 6 months. Limitations of the study design mean that a causal relationship cannot be proven. This analysis provides insights for further study within clinical trial settings.”

https://pubmed.ncbi.nlm.nih.gov/36573268/

“This study reports that treatment with CBMPs was associated with improvements in PHQ-9 (p<0.050) after 1, 3, and 6 months in a case series of patients with a primary diagnosis of depression on the UKMCR. This suggests that CBMPs could have antidepressant effects, although the limitations of the study design mean that a causal relationship cannot be proven. CBMP use was also associated with improvements in anxiety, sleep quality, and overall HRQoL (p<0.050).”

https://www.tandfonline.com/doi/full/10.1080/14737175.2022.2161894

Therapeutic Molecular Insights into the Active Engagement of Cannabinoids in the Therapy of Parkinson’s Disease: A Novel and Futuristic Approach

SpringerLink

“Parkinson’s disease is a neurodegenerative disorder which is characterised mostly by loss of dopaminergic nerve cells throughout the nigral area mainly as a consequence of oxidative stress. Muscle stiffness, disorganised bodily responses, disturbed sleep, weariness, amnesia, and voice impairment are all symptoms of dopaminergic neuron degeneration and existing symptomatic treatments are important to arrest additional neuronal death.

Some cannabinoids have recently been demonstrated as robust antioxidants that might protect the nerve cells from degeneration even when cannabinoid receptors are not triggered. Cannabinoids are likely to have property to slow or presumably cease the steady deterioration of the brain’s dopaminergic systems, a condition for which there is now no treatment.

The use of cannabinoids in combination with currently available drugs has the potential to introduce a radically new paradigm for treatment of Parkinson’s disease, making it immensely useful in the treatment of such a debilitating illness.”

https://pubmed.ncbi.nlm.nih.gov/36567416/

https://link.springer.com/article/10.1007/s12640-022-00619-y

Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?

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“Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties.

This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea.

Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant.

This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth.

In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.”

https://pubmed.ncbi.nlm.nih.gov/36555842/

“Dysmenorrhoea is a medical term used to describe painful menstruation. Cannabis-based products are entering both healthcare and commercial markets with a surge in availability. With further research, cannabis-based medicines may become the norm in the management of severe or treatment-resistant dysmenorrhoea.”

https://www.mdpi.com/1422-0067/23/24/16201

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases

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“The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin’s immune response.

In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.”

https://pubmed.ncbi.nlm.nih.gov/36552866/

“Based on the current publications, it can be summarised that cannabinoid compounds have great potential in the treatment of skin diseases, both as topical applications and as systemic medications.”

https://www.mdpi.com/2073-4409/11/24/4102

Sustained cannabis use does not predispose clinical hypertension: Findings from a national survey

“Cannabis is among the most used recreational and medicinal drugs in the United States. The effects of chronic use on hypertension remain poorly understood.

Our study retrospectively evaluated data collected by the National Health and Nutrition Examination Survey from 2017 to 2018. Cannabis use was measured with five metrics: (1) sustained use at any point in the past, (2) sustained use within the past year, (3) frequency of use, (4) age of first cannabis use, and (5) current use. Hypertension status was determined by individuals reporting having been diagnosed in the past. Multivariable logistic regressions were performed, controlling for age, race, and gender. A total of 4565 respondents were identified, of which 867 (19.0%) reported sustained cannabis use in the past.

Participants who reported past sustained cannabis use did not have statistically different odds of having hypertension (OR: 1.12; 95% CI: .66-1.91; p = .6). Moderate (OR: 1.08; 95% CI: .36-3.25; p = .8) and highly-frequent users (OR: 1.30; 95% CI: .56-3.03; p = .4) did not have different odds of having hypertension than infrequent users. No relationship between the age of first cannabis use and hypertension was observed. The recency of sustained cannabis use was not associated with hypertension status. Current cannabis users had similar odds of hypertension as past users (OR: 1.03; 95% CI: .59-1.79; p = .9).

The findings of this study indicate that neither past nor current cannabis use is associated with clinical hypertension.”

https://pubmed.ncbi.nlm.nih.gov/36545898/

“The findings of this study indicate that neither past nor current cannabis use are associated with the likelihood of having clinical hypertension. Among cannabis users, frequency of use was not associated with hypertension. Similarly, the age of first cannabis use was not associated with hypertension status.”

https://onlinelibrary.wiley.com/doi/10.1111/jch.14623

Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study

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“Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target.

The objective of this study was to test Cannabis sativa‘s phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes.

Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of -6.02 and -6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively.

Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.”

https://pubmed.ncbi.nlm.nih.gov/36548655/

“Since CL is still a public health problem in low-income and developing countries, the discovery of an efficient, less toxic, and accessible therapy is a necessity. The present in silico study was the first to investigate C. sativa’s selected constituents as selective inhibitory agents for parasitic as well as host arginases, which play an important role in this parasitic infection pathology. Interestingly, THC showed a great inhibitory potential for both species’ enzymes and will allow a better control of leishmaniasis.”

https://www.mdpi.com/2414-6366/7/12/400