Labour and premature delivery differentially affect the expression of the endocannabinoid system in the human placenta

/by

Plasma concentrations of N-arachidonyletholamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) increase at term and can predict when a woman is likely to go into labour. We hypothesised that increased plasma AEA concentrations in women in preterm and term labour might also be increased and have a function in the placenta at the end of pregnancy. Here we examined the expression of the N-acylethanolamine-modulating enzymes fatty acid amide hydrolase (FAAH) and N-acyl-phosphatidylethanolamine-specific phospholipase-D (NAPE-PLD) and of the cannabinoid receptors (CB1 and CB2) in the placenta and their activation in an in vitro model of the third-trimester placenta to determine if those expressions change with labour and have functional significance. Expression of CB1, CB2, FAAH and NAPE-PLD was examined by immunohistochemistry (IHC) and RT-qPCR in placental samples obtained from four patient groups: preterm not in labour (PTNL), term not in labour (TNL), preterm in labour (PTL) and term in labour (TL). Additionally, the effects of AEA on a third-trimester human cell line (TCL-1) were evaluated. All ECS components were present in the third-trimester placenta, with NAPE-PLD and CB2 being the key modulated proteins in terms of expression. Functionally, AEA reduced TCL-1 cell numbers through the actions of the CB2 receptor whilst CB1 maintained placental integrity through the expression of the transcription regulators histone deacetylase 3, thyroid hormone receptor β 1 and the modulation of 5α reductase type 1. The placenta in the third trimester and at term is different from the placenta in the first trimester with respect to the expression of CB1, CB2, FAAH and NAPE-PLD, and the expression of these proteins is affected by labour. These data suggest that early perturbation of some ECS components in the placenta may cause AEA-induced PTL and thus PTB.

Read more

Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence

/by

Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined can- nabinoids which contain the psychoactive constituent delta-9-tetrahydrocannabinol (THC). While there have been some positive findings, meta-analyses of this clinical work indicates that this effectiveness is limited and hampered by side-effects. This review focuses on how recent preclinical studies have predicted the clinical limita- tions of THC-containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and recep- tors other than cannabinoid CB1 receptors which mediate many of the side-effects of cannabis.

Read more

Delta-8-Tetrahydrocannabinol: A Phytocannabinoid on the Rise

/by

Delta-8-tetrahydrocannabinol (THC) is a minor psychoactive phytocannabinoid, similar to delta-9-tetrahydrocannabinol. Recent statements released by the FDA and CDC reported around 660 delta-8-THC exposure cases. With the rise in commercially available products, it is crucial to understand the pharmacological and toxicological properties of this compound. The objective of this review is to summarize current literature regarding the pharmacokinetic, and pharmacologic properties of delta-8- THC.

Read more

Cannabinoids in Spine Surgery: A Comprehensive Review

/by

Cannabinoids have gained attention for their potential therapeutic effects in various fields, including pain control, augmenting fusion, neuroprotection, wound healing, inflammation, mental health, and clinical outcomes/complications. We explore the history and mechanism of action of cannabinoids, as well as their role in each of these areas. By examining existing research, the potential benefits and limitations of incorporating cannabinoids into spine non-operative and operative protocols are highlighted. Ultimately, this review aims to contribute to the understanding of cannabinoids as a viable option for optimizing patient outcomes in the context of spine surgery.

Read more

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males

/by

Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products.

Read more

Cannabinoids for the Treatment of Hair, Scalp, and Skin Disorders: A Systematic Review

/by

Cannabinoid products have been studied in the treatment of various dermatologic conditions. We searched PubMed/MEDLINE for articles published before 1 February 2023 that described the use of cannabinoids in the management of hair, scalp, and skin conditions, identifying 18 original articles that encompassed 1090 patients who used various forms of cannabinoid products. Where specified, topical cannabidiol (CBD) was the most commonly utilized treatment (64.3%, 173/269), followed by oral dronabinol (14.4%, 39/269), oral lenabasum (14.1%, 38/269), and oral hempseed oil (5.9%, 16/269). Using the GRADE approach, we found moderate-quality evidence supporting the efficacy of cannabinoid products in managing atopic dermatitis, dermatomyositis, psoriasis, and systemic sclerosis and moderate-quality evidence supporting a lack of efficacy in treating trichotillomania. There was low to very low quality evidence supporting the efficacy of cannabinoid products in managing alopecia areata, epidermolysis bullosa, hyperhidrosis, seborrheic dermatitis, and pruritus. Our findings suggest that cannabinoids may have efficacy in managing symptoms of certain inflammatory dermatologic conditions. However, the evidence is still limited, and there is no standardized dosage or route of administration for these products. Large randomized controlled trials and further studies with standardized treatment regimens are necessary to better understand the safety and efficacy of cannabinoids.

Read more

Pharmacological blockade of 2-AG degradation ameliorates clinical, neuroinflammatory and synaptic alterations in experimental autoimmune encephalomyelitis

/by

The endocannabinoid system (ECS) is critically involved in the pathophysiology of Multiple Sclerosis (MS), a neuroinflammatory and neurodegenerative disease of the central nervous system (CNS). Over the past decade, the neuroprotective and anti-inflammatory effects of the ECS have been studied, and inhibiting the degradation of the endocannabinoid 2-arachydonoylglycerol (2-AG) is emerging as a promising strategy to counteract brain damage in MS. In this study, a systemic and preventive in vivo treatment with MAGLi 432, the reversible inhibitor of monoacylglycerol lipase (MAGLi), was performed in experimental autoimmune encephalomyelitis (EAE) mice. Clinical, biochemical, electrophysiological and immunofluorescence analyses were carried out to evaluate the impact of the drug on motor disability, neuroinflammation and synaptic damage. MAGLi 432 induced a less severe EAE disease, accompanied by an increase of 2-AG and a reduction of acid arachidonic (AA) and prostaglandins (PGs) brain levels.

Read more

Toxicity of Cannabigerol: Examination of Long-Term Toxicity and Lifespan in Caenorhabditis elegans and 14-Day Study in Sprague Dawley Rats

/by

Cannabigerol (CBG) is becoming widely available despite little being known about its potential toxicity or long-term effects. The present investigation involved two distinct studies. The first study explored acute and long-term effects of CBG on toxicity, lifespan, and aging in adult Caenorhabditis elegans (C. elegans). Animals were treated with CBG (0.075 lM–3.75 mM) to determine acute toxicity, mortality, and motility. Acute heat- induced stress survival (thermotolerance; 37°C for 4 h) following CBG administration (0.075–3.75 mM) was measured. Long-term toxicity of lifelong CBG administration (7.5, 75, or 375 lM CBG) was determined through changes in motility and lifespan duration. In the second study, healthy, adult, Sprague Dawley rats received 0, 35, 70, or 140 mg/kg-bw/day CBG (n = 5 per sex per group) daily for 14 days via oral gavage. Signs of gross toxicity and changes in behavior, body weight, food consumption, and serum chemistry were monitored. Liver, kidney, and adrenal gland weights were recorded, and histopathology of select tissues was examined.

Read more

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral D8-Tetrahydrocannabivarin in Healthy Participants

/by

Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses. This was a two-phase, dose-ranging, placebo-controlled trial of the D8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n = 3). Phase 2 used a double-blind, random- ized, within-participant crossover design (n = 18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose.

Read more

The Use of Dispensary-Obtained Tetrahydrocannabinol as a Treatment for Neuropsychiatric Symptoms of Dementia

/by

Neuropsychiatric symptoms (NPS) of dementia represent a large driver of health care costs, caregiver burden, and institutionalization of people with dementia. Management options are limited, and antipsychotics are often used, although they carry a significant side effect profile. One novel option is tetrahydrocannabinol (THC); however, in the US, to obtain THC for patients with dementia, caregivers have to go to a commercial dispensary. We evaluated the effectiveness of dispensary-obtained THC for patients with dementia and NPS. Two independent reviewers reviewed charts of patients with diagnosed dementia (N = 50) seen in geriatric psychiatry between 2017 and 2021 for whom dispensary-obtained THC was recommended. The primary outcome was effectiveness in treating NPS; secondary outcomes were the proportion of caregivers who obtained and administered THC (uptake), post-THC antipsychotic use, and adverse reactions leading to treatment discontinuation.

Read more

Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases

/by

Medical cannabis may provide a treatment option for chronic neuropathic pain. However, empirical disease-specific data are scarce. This is a retrospective observational study including 99 patients with chronic neuropathic pain. These patients received medical cannabis by means of inhaling dried flowers with tetrahydrocannabinol content of <12–22% at a maximal daily dose of 0.15–1 g. Up to six follow-ups were carried out at intervals of 4–6 weeks. Pain severity, sleep disturbance, general improvement, side effects, and therapy tolerance at the follow-up consultations were assessed in interviews and compared with the baseline data using non-parametric Wilcoxon signed-rank test.

Read more

Targeting Trauma-Induced Endocannabinoid System Dysfunction: A Novel Neuroprotective Approach For Traumatic Brain Injury

/by

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The primary injury results in neuronal damage and initiates secondary injuries like neuroinflammation, excitotoxicity, oxidative stress and blood-brain barrier disruption. This results in long-term cognitive, behavioral and motor deficits. Existing therapeutic options for TBI focus on symptomatic management rather than directly addressing the cellular processes that drive secondary damage. Novel neuroprotective therapies are urgently needed. The endocannabinoid system (ECS) is a promising therapeutic target for TBI. The ECS comprises the endocannabinoids anandamide and 2-AG, cannabinoid receptors CB1 and CB2, and metabolic enzymes like fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). It is involved in synaptic function, neuroinflammation, excitotoxicity, blood-brain barrier disruption, oxidative stress and neuronal loss. Modulation the ECS through receptor agonists/antagonists, inhibitors of endocannabinoid catabolism, or combination approaches represents a novel neuroprotective strategy in TBI.

Read more