Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils

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“The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state.

Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation.

While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress.

Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states.

Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.”

https://pubmed.ncbi.nlm.nih.gov/34067450

“Hemp oils derived from the cannabis plant (Cannabis sativa L.) are a rich source of lipid bioactive compounds, including cannabinoids, β-caryophyllene, and polyunsaturated fatty acids that potentially interact with the ECS.”

https://www.mdpi.com/1422-0067/22/11/5479

Cannabinoids Treatment for Agitation in Alzheimer’s Disease: A Systematic Review and Meta-Analysis With Bayesian and Sequential Trial Analyses

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“Objective: Agitation and related neuropsychiatric symptoms are common in Alzheimer’s disease (AD) and contribute to caregiver burden, functional decline, and institutionalization. Cannabinoid-based therapies have been investigated as potential symptomatic interventions, but evidence remains limited by small trials, heterogeneous formulations, and variable outcome reporting. We aimed to evaluate the efficacy, cognitive outcomes, and safety of cannabinoid-based therapies in AD.

Methods: This systematic review and meta-analysis were prospectively registered in PROSPERO and conducted following PRISMA 2020 guidelines. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched through April 2025 for randomized placebo-controlled trials evaluating cannabinoid-based therapies for agitation or neuropsychiatric symptoms in AD. One nonrandomized open-label study was retained as supplementary evidence for sensitivity analyses. Primary efficacy analyses were restricted to randomized between-group contrasts. Outcomes included Neuropsychiatric Inventory (NPI) total score, Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF), NPI agitation/aggression, Mini-Mental State Examination (MMSE), and safety outcomes. Random-effects meta-analyses were complemented by Bayesian models and Trial Sequential Analysis.

Results: Seven studies met the inclusion criteria, including six randomized trials and one open-label prospective cohort, with 221 participants enrolled. Cannabinoid-based therapies showed lower neuropsychiatric symptom and agitation scores than placebo in randomized between-group analyses: NPI total score (standardized mean difference [SMD], -0.31; 95% confidence intervals [CI], -0.47 to -0.15; k = 4), CMAI-SF (SMD, -0.40; 95% CI, -0.69 to -0.10; k = 3), and NPI agitation/aggression (SMD, -0.47; 95% CI, -0.69 to -0.25; k = 3). Bayesian posterior probabilities for lower symptom scores exceeded 95%. MMSE findings did not support a consistent cognitive benefit. Somnolence was the principal safety signal (risk ratios, 2.25; 95% CI, 1.43-3.54), with Trial Sequential Analysis suggesting sufficient accrued information for this outcome. Falls and fatigue were imprecisely estimated.

Conclusions: Cannabinoid-based therapies showed lower agitation and neuropsychiatric symptom scores than placebo in AD, with somnolence as the main safety concern. Interpretation remains limited by few trials, heterogeneous formulations and outcome instruments, short follow-up, and concentrated statistical weight. Larger randomized trials with formulation-specific protocols, longer follow-up, active comparators, and systematic safety monitoring are needed.”

https://pubmed.ncbi.nlm.nih.gov/42315374

https://www.ajgponline.org/article/S1064-7481(26)00400-8/abstract

Harnessing the advances of genetic engineering in microalgae for the production of cannabinoids

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“Cannabis is widely recognized as a medicinal plant owing to bioactive cannabinoids. However, it is still considered a narcotic plant, making it hard to be accessed.

Since the biosynthetic pathway of cannabinoids is disclosed, biotechnological methods can be employed to produce cannabinoids in heterologous systems. This would pave the way toward biosynthesizing any cannabinoid compound of interest, especially minor substances that are less produced by a plant but have a high medicinal value.

In this context, microalgae have attracted increasing scientific interest given their unique potential for biopharmaceutical production. In the present review, the current knowledge on cannabinoid production in different hosts is summarized and the biotechnological potential of microalgae as an emerging platform for synthetic production is put in perspective. A critical survey of genetic requirements and various transformation approaches are also discussed.”

https://pubmed.ncbi.nlm.nih.gov/35762029

https://www.tandfonline.com/doi/full/10.1080/07388551.2022.2071672

“The process of metabolic engineering extracts the genes responsible for cannabinoid production from cannabis plants and inserts them into algae, creating a type of cannabis surrogacy in algae.”

The effects of oral cannabidiol supplementation on blood pressure in adults: a systematic review of randomised controlled trials

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Background: Hypertension is a leading risk factor for cardiovascular disease, particularly in ageing populations. While pharmacological interventions are common, issues with long-term adherence and side effects have prompted interest in alternative treatments. Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been proposed as a potential agent for blood pressure regulation due to its anxiolytic, anti-inflammatory, and vasodilatory properties. This systematic review aimed to evaluate the effects of oral CBD supplementation on blood pressure in adults with normotension and hypertension.

Methods: A systematic search of PubMed, Web of Science, Scopus, and Medline was conducted in September 2024. Eligible studies were randomised controlled trials (RCTs) involving oral CBD administration in normotensive or hypertensive adults, with blood pressure as an outcome. Studies involving animals, inhaled CBD, or non-English texts were excluded. Risk of bias was assessed using the Cochrane Risk of Bias tool. Clinical heterogeneity was assessed by comparing study populations, CBD dosing regimens, outcome measures, and assessment conditions. Substantial variability in dosing and blood pressure outcome reporting precluded quantitative pooling; therefore, results were synthesised narratively due to clinical heterogeneity.

Results: Four RCTs involving 120 participants met the inclusion criteria. Studies varied in CBD dose (225-600 mg/day), duration (two hours to 5 weeks), and participant health status. An association was observed between CBD dosage (mg/day) and reductions in blood pressure indicators, with greater reductions occurring at higher doses. All four studies reported statistically significant reductions in systolic blood pressure compared to placebo, particularly under stress or during sleep. Two studies reported lower diastolic pressure. The strongest effects were observed with acute administration of the highest-dose studies of 600 mg/day. Side effect severity was generally mild to moderate, including nausea, diarrhoea, and fatigue. No serious cardiovascular events were reported.

Conclusion: Oral CBD may reduce blood pressure amongst healthy and hypertensive individuals, particularly under stressful conditions and during sleep. Limitations included small sample sizes, short trial durations, variability in CBD matrices and dosages, lack of pharmacokinetic data, and uncertainty surrounding hepatic safety. Larger, longer-term trials with homogeneous supplementation strategies and bioavailability measures are needed to determine CBD’s therapeutic role in blood pressure management.”

https://pubmed.ncbi.nlm.nih.gov/42321899

https://link.springer.com/article/10.1186/s42238-026-00463-3

Inflammasome formation and interleukin-1β secretion are reduced in peripheral blood monocytes from HIV+ cannabis users

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“Chronic systemic inflammation remains a defining feature of human immunodeficiency virus (HIV) infection, partly driven by the translocation of microbial-derived products, including toll-like receptor 4 agonist lipopolysaccharide, from the gut, which is a well established HIV reservoir. These products activate peripheral blood monocytes, leading to the secretion of proinflammatory cytokines, particularly interleukin-1β (IL-1β), which exacerbates systemic inflammation.

Cannabis and its bioactive constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol, exhibit immune-modulating properties, yet their effects on innate immune pathways in HIV remain poorly defined. Here, we investigated the impact of cannabis use and individual cannabinoids, THC and cannabidiol, on toll-like receptor 4-induced ASC-incorporating inflammasome activation, IL-1β secretion, and caspase-1 activity in monocytes derived from HIV-negative and HIV-positive individuals. We hypothesized that cannabis use and cannabinoid treatment impair inflammasome-mediated inflammation in HIV+ individuals, potentially mitigating IL-1β-driven immune activation.

Our results show that inflammasome formation was reduced in both HIV+ marijuana (cannabis use status, MJ)- and HIV+MJ+ (MJ: cannabis use) derived monocytes compared with HIV- derived monocytes. Despite this, HIV+MJ- monocytes secreted more IL-1β than HIV- monocytes, whereas HIV+MJ+ monocytes secreted IL-1β at levels comparable to those of HIV- cells.

Both THC and cannabidiol suppressed inflammasome formation and IL-1β secretion in a concentration-dependent manner, with THC producing a greater magnitude of reduction in caspase-1 activity in HIV- monocytes. Cannabis use by HIV+ individuals lowered IL-1β secretion by peripheral blood monocytes compared with that of non-cannabis-using HIV+ donors, implicating an inhibitory role in immune activation.

These findings support the therapeutic potential of cannabinoids in reducing HIV-associated systemic inflammation.

SIGNIFICANCE STATEMENT: Cannabis use reduced inflammasome activation and interleukin-1β (IL-1β) release in human immunodeficiency virus (HIV)+ monocytes. HIV+ cannabis users showed IL-1β levels comparable to HIV- individuals, whereas HIV+ cannabis nonusers displayed elevated levels of IL-1β secretion. The combination of reduced ASC-incorporating inflammasome formation but elevated IL-1β in HIV+ nonusers suggests involvement of noncanonical IL-1β maturation pathways.”

https://pubmed.ncbi.nlm.nih.gov/42320431

“Collectively, these findings highlight a complex role for cannabinoids in modulating innate immune responses. The suppression of IL-1β via reduced inflammasome formation and caspase-1 activity, without direct enzymatic inhibition, suggests that cannabinoids may have therapeutic utility for regulating inflammation, particularly in chronic and systemic inflammation incurred by HIV.”

https://jpet.aspetjournals.org/article/S0022-3565(26)01151-1/fulltext


Case Report: Oral and topical chronic administration of THC-rich and CBD-rich cannabis oil as palliative care in a rescued horse with open wound, sarcoid and chronic pain

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“Cannabinoid-based therapies have shown analgesic, anti-inflammatory, and wound-healing potential across veterinary species; however, clinical data on long-term use of THC-rich formulations in horses remain scarce.

This case report describes the use of combined oral and topical THC-rich and CBD-rich full-spectrum cannabis oils as part of a palliative care strategy in a rescued horse with severe chronic disease.

A senior mixed-breed gelding was rescued with a large, chronic ulcerative lesion of the left hind limb, severe malnutrition, non-weight-bearing lameness (AAEP grade 5/5), and refractory pain. Diagnostic workup identified a fibroblastic equine sarcoid complicated by complete suspensory tendon rupture, early osteomyelitis, and chronic joint disease. Conventional medical and surgical options were limited due to poor response, disease severity, and resource constraints.

A long-term palliative protocol was initiated using oral THC-rich and CBD-rich full-spectrum cannabis oils (1:1 ratio; 100 mg/mL each) with gradual dose escalation to a target of 0.5 mg/kg of each compound every 12 hours. The same formulation was applied topically to the wound once to twice daily. Treatment duration was 10 months, with concurrent multimodal analgesia as needed.

Cannabinoid therapy was associated with sustained improvements in appetite, body condition, pain, and mobility. Marked wound improvement was observed, including reduced granulation tissue, improved epithelialization, and resolution of self-mutilation.

No clinically relevant adverse effects or laboratory abnormalities occurred during routine dosing. Transient ataxia and sedation were noted only at high rescue doses near end of life. Despite eventual disease progression and euthanasia due to refractory pain, quality of life was substantially improved for most of the treatment period.

This case supports the potential role of combined THC-rich and CBD-rich cannabis oils as a safe and effective adjunct in multimodal palliative care for horses with chronic, refractory conditions. Controlled studies are warranted to define optimal dosing and indications.”

https://pubmed.ncbi.nlm.nih.gov/42311392

“Across veterinary species, cannabinoids have shown therapeutic potential with favorable safety and tolerability profiles.”

“The aim of this case report is to describe a long-term multimodal clinical approach using cannabinoids (THC and CBD) in a rescued horse affected by a wound/sarcoid and joint disease, as part of a palliative care strategy for pain management, inflammation control, and wound-healing enhancement.”

“This case suggests that long-term administration of THC-rich and CBD-rich cannabis oils may be a useful adjunct for palliative management in horses with chronic, refractory conditions.”

“Cannabinoid therapy was associated with improved comfort, mobility, and quality of life, supporting its potential role within multimodal palliative care.”

https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2026.1794084/full


Benefits of Medical Cannabis in Patients With Pain Registered in the Minnesota Medical Cannabis Program

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“Purpose: Medical cannabis is commonly used to treat chronic pain. Clinical trials typically use only one type and dosage of medical cannabis product, which is not reflective of real-world use. The use of a state-run medical cannabis program can bridge the gap between clinical research and real-world use of medical cannabis to estimate the benefits of cannabis use on patient symptoms. This study aimed to describe medical cannabis use among patients with intractable and chronic pain in the Minnesota Medical Cannabis Program and estimate pain reduction benefits received from medical cannabis.

Methods: Patients who enrolled in the Minnesota Medical Cannabis Program between March 2022 and February 2023 for chronic pain and purchased medical cannabis for at least 8 months were included in this study. Patients were required to complete the Patient Self-Evaluation before each medical cannabis purchase, which included the PEG (Pain, Enjoyment of Life, and General Activity) scale. The main outcome of this analysis was a ≥30% change in PEG component score within 4 months of first medical cannabis purchase. The proportion of patients who maintained that reduction for an additional 4 months was also calculated. Medical cannabis product purchases were queried from the first 4 months in the program and categorized by route of administration and tetrahydrocannabinol:cannabidiol ratio. Medical cannabis purchasing profiles were created using k-means clustering to group patients who purchased similar proportions of product types. Adjusted logistic regression models were run to investigate the association between medical cannabis purchasing profile and reporting ≥30% reduction in PEG score.

Findings: Among patients reporting moderate-to-severe scores at program enrollment, 54.9% reported a ≥30% score improvement for life enjoyment, 54.7% reported improvement in general activity interference, and 40.8% reported improvement in pain score within 4 months of their first purchase. Cannabis flower products were most commonly purchased by patients. High tetrahydrocannabinol:cannabidiol products were the most commonly purchased in all medical cannabis product categories. K-means clustering created 5 product purchasing profiles, which were not associated with PEG score improvement outcomes after adjustment for number of purchasing transactions.

Implications: Medical cannabis patients report reduction in PEG scores within 4 months of first medical cannabis purchase using a variety of medical cannabis products. Future research on medical cannabis should determine the frequency of use of different products and administration methods to further investigate how cannabis can be used for effective pain management in patients with chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/42303550

“Medical cannabis patients report improvement in pain symptoms after four months.”

https://www.clinicaltherapeutics.com/article/S0149-2918(26)00187-6/fulltext

Exploratory Prospective Study of Self-Titrated Medical Cannabis for Nonmotor Symptoms in Parkinson’s Disease

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“Background: Medical cannabis (MC) has emerged as a potential therapy for Parkinson’s disease (PD), targeting motor and nonmotor symptoms (NMS), such as pain, sleep disturbance, and urinary dysfunction. Cannabinoid receptors in central and peripheral systems, including the bladder, provide a mechanistic basis for symptom modulation. This study evaluated the feasibility, safety, and preliminary clinical effects of MC on NMS in PD within a real-world, regulated framework.

Methods: In this single-center, open-label, prospective cohort, 68 patients with PD initiating MC were assessed at baseline and at 3 months using validated scales: the Non-Motor Symptoms Scale (NMSS), King’s Parkinson’s Disease Pain Scale (KPPS), PD Sleep Scale-2 (PDSS-2), PD Quality-of-Life Questionnaire-8 (PDQ-8), and International Prostate Symptom Score (IPSS), along with 2-day urinary diaries. Participants used either cannabis oil extract or inflorescence products with varying THC/CBD (Δ9-tetrahydrocannabinol/cannabidiol) ratios. Adverse events and withdrawals were recorded. Cannabinoid composition was analyzed via ultra-high-performance liquid chromatography and correlated with clinical outcomes.

Results: Fifty participants (mean age 65.6 ± 11.0 years; 68% male) completed follow-up. MC use was associated with improvements in NMSS total (Δ 14.5, p = 0.001), PDSS-2 (Δ 5.9, p < 0.001), KPPS (Δ 8.1, p = 0.004), PDQ-8 (Δ 1.5, p = 0.040), and the NMSS urinary domain (Δ 2.1, p = 0.050). Nighttime urinary frequency decreased (median Δ 0.5, p = 0.016), while daytime parameters were unchanged. No correlations were found between cannabinoid composition or THC/CBD enrichment type and clinical response. The dropout rate was 26.5%, mainly due to loss to follow-up.

Conclusions: Short-term, self-titrated MC was feasible and appeared generally well tolerated in this open-label setting, suggesting potential benefits for pain, sleep, and nocturnal urinary frequency in PD. These exploratory findings warrant randomized controlled trials focused on these domains and incorporating standardized dosing, pharmacokinetic monitoring, and predefined cognitive safety assessments to determine efficacy, safety, and optimal dosing.”

https://pubmed.ncbi.nlm.nih.gov/42304702

https://journals.sagepub.com/doi/10.1177/25785125261458680

Unexpected improvement of hyperhidrosis with cannabidiol

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“Hyperhidrosis is characterized by excessive sweating and it affects almost 5% of the population. The affected age group is wide, and it can affect from children to elderlies. There are two types of hyperhidrosis: generalized and focal. Treatment depends on the symptoms presented. In more severe cases, radiofrequency sympatholysis and bilateral thoracic sympathectomy are the options. However, recurrence is possible or the postoperative appearance of conditions called compensatory hyperhidrosis or reflex hyperhidrosis.

We describe two cases of patients treated with Cannabidiol who had significant and unexpected improvement of hyperhidrosis.

The first patient received Cannabidiol specific for public presentations at work, and the second patient had a diagnosis of autism spectrum disorder.

The hyperhidrosis improved in both patients immediately after using Cannabidiol.”

https://pubmed.ncbi.nlm.nih.gov/35170710

Don’t Sweat It: Cannabinoid CB1 Receptors Reduce Sweating in a Mouse Model

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“Numerous exocrine glands play key physiological roles in the body that include tearing, salivation, and lactation, as well as the control of body temperature via sweating. Malfunction of sweat glands can be deeply problematic or-in the case of anhidrosis-life-threatening. The prevalence of sweating disorders is high, affecting millions. The few available therapies are generally of limited effectiveness.

Several lines of evidence point to regulation of sweating by the cannabinoid signaling system, an arrangement that would mirror cannabinoid regulation of tearing and salivation.

Mice sweat in their paws via glands that closely resemble human eccrine sweat glands, including regulation by muscarinic signaling and by temperature. We applied a galvanic skin response-based assay to investigate cannabinoid regulation of sweating in awake, unanesthetized mice. The muscarinic agonist pilocarpine increased conductance while the antagonist glycopyrrolate reduced conductance, validating the model as a measure of sweating. The cannabinoid receptor agonist CP55940 substantially reduced conductance in wild-type and CB2 but not CB1 receptor knockout mice.

The phytocannabinoid tetrahydrocannabinol (THC) also reduced conductance, while the non-psychoactive cannabidiol (CBD) did not. Using immunohistochemistry, we detected CB1 receptors in periglandular cholinergic axons, the anandamide-synthesizing enzyme NAPE-PLD in myoepithelial cells, and the anandamide metabolizing enzyme FAAH in acinar cells. This indicates that a local CB1/anandamide-based circuit is present in mouse walking pads.

In summary, we employed a novel galvanic skin response-based assay to determine that cannabinoid CB1 receptors reduce sweating in a mouse model. This may point to a previously unappreciated effect on sweating in cannabis users.”

https://pubmed.ncbi.nlm.nih.gov/42287607

“In summary, we have made use of a galvanic skin response-based assay to measure the conductivity in the hind paws of awake, unanesthetized mice as a measure of sweating. We find the galvanic skin responses to be stable and consistent over time and, importantly, to be responsive to stimuli that increase or decrease basal sweating. Using this model, we determined that cannabinoid CB1 receptor activation reduces the galvanic skin response.

We propose that cannabinoid CB1 receptor activation reduces basal sweating in mice.

This effect may point the way to a new class of therapeutics for hyperhidrosis.”

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202601143R