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16 pages, 3948 KiB

Open AccessArticle

Licofelone, a Dual COX/LOX Inhibitor, Ameliorates Paclitaxel-Induced Mechanical Allodynia in Rats in a Cannabinoid Receptor-Dependent Manner

by Willias Masocha, Esraa Aly, Aisha Albaloushi and Altaf Al-Romaiyan

Biomedicines 2024, 12(7), 1545; https://doi.org/10.3390/biomedicines12071545 - 11 Jul 2024

Viewed by 1094

Abstract

The use of paclitaxel as a chemotherapeutic drug is limited by the development of dose-dependent paclitaxel-induced neuropathic pain (PINP). Recently, we observed that the combination of indomethacin plus minocycline (IPM) attenuates PINP in a mouse model in a cannabinoid (CB) receptor-dependent manner. Indomethacin [...] Read more.

The use of paclitaxel as a chemotherapeutic drug is limited by the development of dose-dependent paclitaxel-induced neuropathic pain (PINP). Recently, we observed that the combination of indomethacin plus minocycline (IPM) attenuates PINP in a mouse model in a cannabinoid (CB) receptor-dependent manner. Indomethacin inhibits cyclooxygenase (COX) activity, and minocycline inhibits 5-lipoxygenase (5-LOX) activity. Male Sprague Dawley rats with paclitaxel-induced mechanical allodynia were treated with indomethacin, minocycline, IPM combination, licofelone (a dual COX/LOX inhibitor), or their vehicles. AM251, a CB1 receptor antagonist, and AM630, a CB2 receptor antagonist, were administered before the IPM combination or licofelone. Mechanical allodynia was measured using a dynamic plantar aesthesiometer. Molecular docking was performed using CB-Dock2. Licofelone and IPM combination had antiallodynic effects, which were significantly higher than either indomethacin or minocycline alone. AM251 and AM630 blocked the antiallodynic effects of IPM combination and licofelone. Molecular docking showed that licofelone binds to both CB1 and CB2 receptors with a high affinity similar to the phytocannabinoid 1-trans-delta-9-tetrahydrocannabinol and the synthetic cannabinoid WIN 55,212-2. Licofelone inhibits COX and LOX and/or directly interacts with CB receptors to produce antiallodynic effects in a rat model of PINP. The findings further suggest that licofelone could be a therapeutic agent for managing PINP. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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26 pages, 5983 KiB

Open AccessArticle

Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis

by Islauddin Khan, Sukhmandeep Kaur, Arun K. Rishi, Breana Boire, Mounika Aare and Mandip Singh

Biomedicines 2024, 12(7), 1442; https://doi.org/10.3390/biomedicines12071442 - 28 Jun 2024

Cited by 1 | Viewed by 1391

Abstract

Background: In this study, we investigated in detail the role of cannabidiol (CBD), beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods: Briefly, streptozotocin (STZ) (55 mg/kg) [...] Read more.

Background: In this study, we investigated in detail the role of cannabidiol (CBD), beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods: Briefly, streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague–Dawley rats, and we performed procedures involving Randall Sellito calipers, a Von Frey aesthesiometer, a hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed using a laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, and JC1 and Mitosox staining were performed to determine mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides in vitro. The rats were administered BC (30 mg/kg), CBD (15 mg/kg), or combination via i.p. injections, while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results: Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides. Furthermore, the BC and CBD combination treatment in vivo could prevent the deterioration of the mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted using Western blotting. Conclusions: the present study demonstrated that STZ and HG-induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that a CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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22 pages, 3974 KiB

Open AccessArticle

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

by Alessandra Trainito, Agnese Gugliandolo, Luigi Chiricosta, Stefano Salamone, Federica Pollastro, Emanuela Mazzon and Maria Lui

Biomedicines 2024, 12(6), 1340; https://doi.org/10.3390/biomedicines12061340 - 17 Jun 2024

Viewed by 896

Abstract

Cannabinoids are reported to have neuroprotective properties and play a role in neurogenesis and neuroplasticity in in vitro and in vivo models. Cannabinol (CBN) is a minor cannabinoid produced by the degradation of Δ⁹-tetrahydrocannabinol in Cannabis sativa L. and exhibits anti-oxidant, [...] Read more.

Cannabinoids are reported to have neuroprotective properties and play a role in neurogenesis and neuroplasticity in in vitro and in vivo models. Cannabinol (CBN) is a minor cannabinoid produced by the degradation of Δ⁹-tetrahydrocannabinol in Cannabis sativa L. and exhibits anti-oxidant, analgesic, anti-bacterial, and anti-inflammatory effects. In this study, we explored the biological effects of 20 µM CBN (6.20 µg/mL) on differentiated NSC-34 cells by MTT assay and next-generation sequencing analysis on the transcriptome. KEGG and Gene Ontology enrichment analyses have been performed to evaluate potential CBN-associated processes. Our results highlighted the absence of any cytotoxic effect of CBN. The comparative transcriptomic analysis pointed out the downregulation of Cdkn2a, Cdkn2c and Cdkn2d genes, which are known to suppress the cell cycle. Ccne2, Cdk2, Cdk7, Anapc11, Anapc10, Cdc23, Cdc16, Anapc4, Cdc27, Stag1, Smc3, Smc1a, Nipbl, Pds5a, Pds5b, and Wapl genes, renowned for their role as cell cycle progression activators, were instead upregulated. Our work suggests that CBN regulates the expression of many genes related to the cell cycle, which are required for axonal maturation, migration, and synaptic plasticity, while not affecting the expression of genes involved in cell death or tumorigenesis. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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14 pages, 2409 KiB

Open AccessArticle

Single and Combined Effects of Cannabigerol (CBG) and Cannabidiol (CBD) in Mouse Models of Oxaliplatin-Associated Mechanical Sensitivity, Opioid Antinociception, and Naloxone-Precipitated Opioid Withdrawal

by Sean A. Hayduk, Amanda C. Hughes, Rachel L. Winter, Mia D. Milton and Sara Jane Ward

Biomedicines 2024, 12(6), 1145; https://doi.org/10.3390/biomedicines12061145 - 22 May 2024

Cited by 3 | Viewed by 1573

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients, with estimates of at least 30% of patients experiencing persistent neuropathy for months or years after treatment cessation. An emerging potential intervention for the treatment of CIPN is cannabinoid-based pharmacotherapies. We have previously demonstrated that treatment with the psychoactive CB1/CB2 cannabinoid receptor agonist Δ⁹-tetrahydrocannabinol (Δ⁹-THC) or the non-psychoactive, minor phytocannabinoid cannabidiol (CBD) can attenuate paclitaxel-induced mechanical sensitivity in a mouse model of CIPN. We then showed that the two compounds acted synergically when co-administered in the model, giving credence to the so-called entourage effect. We and others have also demonstrated that CBD can attenuate several opioid-associated behaviors. Most recently, it was reported that another minor cannabinoid, cannabigerol (CBG), attenuated cisplatin-associated mechanical sensitivity in mice. Therefore, the goals of the present set of experiments were to determine the single and combined effects of cannabigerol (CBG) and cannabidiol (CBD) in oxaliplatin-associated mechanical sensitivity, naloxone-precipitated morphine withdrawal, and acute morphine antinociception in male C57BL/6 mice. Results demonstrated that CBG reversed oxaliplatin-associated mechanical sensitivity only under select dosing conditions, and interactive effects with CBD were sub-additive or synergistic depending upon dosing conditions too. Pretreatment with a selective α2-adrenergic, CB1, or CB2 receptor selective antagonist significantly attenuated the effect of CBG. CBG and CBD decreased naloxone-precipitated jumping behavior alone and acted synergistically in combination, while CBG attenuated the acute antinociceptive effects of morphine and CBD. Taken together, CBG may have therapeutic effects like CBD as demonstrated in rodent models, and its interactive effects with opioids or other phytocannabinoids should continue to be characterized. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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15 pages, 2675 KiB

Open AccessArticle

The Sobering Sting: Oleoyl Serotonin Is a Novel Stephanoconus Snail Venom-Derived Antagonist of Cannabinoid Receptors That Counteracts Learning and Memory Deficits

by Dongchen An, Guilherme Salgado Carrazoni, Ben-Hur Souto das Neves, Rudi D’Hooge, Steve Peigneur and Jan Tytgat

Biomedicines 2024, 12(2), 454; https://doi.org/10.3390/biomedicines12020454 - 18 Feb 2024

Viewed by 1219

Abstract

Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds. Here, we describe an [...] Read more.

Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds. Here, we describe an endocannabinoid-like molecule, oleoyl serotonin (OS), present in the venom of Stephanoconus snails. Using electrophysiological assays, it was shown that OS inhibits CB1 and CB2. Structure–activity relationship studies using a chimeric CB1/2 revealed that the domain encompassing the transmembrane helix V (TMHV)– intracellular loop 3 (ICL3)–TMHVI of the CB2 is critical for the binding and function of OS. We concluded that OS binds to sites of the CB2 that are different from the binding sites of the non-selective CB agonist WIN55,212-2. Behavioral assays in mice showed that OS counteracted learning and memory deficits caused by WIN55,212-2. Furthermore, a selectivity screening of OS showed high selectivity for CB over various ion channels and receptors. Overall, OS may represent a new approach to the prevention and treatment of learning and memory cognition impairment in neurological diseases. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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15 pages, 2288 KiB

Open AccessArticle

Therapeutic Potential of Cannabinoid Profiles Identified in Cannabis L. Crops in Peru

by Pedro Wong-Salgado, Fabiano Soares, Jeel Moya-Salazar, José F. Ramírez-Méndez, Marcia M. Moya-Salazar, Alfonso Apesteguía and Americo Castro

Biomedicines 2024, 12(2), 306; https://doi.org/10.3390/biomedicines12020306 - 29 Jan 2024

Cited by 1 | Viewed by 2997

Abstract

Cannabis is a plant that is cultivated worldwide, and its use is internationally regulated, but some countries have been regulating its medicinal, social, and industrial uses. This plant must have arrived in Peru during the Spanish conquest and remains widely cultivated illicitly or [...] Read more.

Cannabis is a plant that is cultivated worldwide, and its use is internationally regulated, but some countries have been regulating its medicinal, social, and industrial uses. This plant must have arrived in Peru during the Spanish conquest and remains widely cultivated illicitly or informally to this day. However, new regulations are currently being proposed to allow its legal commercialization for medicinal purposes. Cannabis contains specific metabolites known as cannabinoids, some of which have clinically demonstrated therapeutic effects. It is now possible to quantitatively measure the presence of these cannabinoids in dried inflorescences, thus allowing for description of the chemical profile or “chemotype” of cannabinoids in each sample. This study analyzed the chemotypes of eight samples of dried inflorescences from cannabis cultivars in four different regions of Peru, and based on the significant variation in the cannabinoid profiles, we suggest their therapeutic potential. The most important medical areas in which they could be used include the following: they can help manage chronic pain, they have antiemetic, anti-inflammatory, and antipruritic properties, are beneficial in treating duodenal ulcers, can be used in bronchodilators, in muscle relaxants, and in treating refractory epilepsy, have anxiolytic properties, reduce sebum, are effective on Methicillin-resistant Staphylococcus aureus, are proapoptotic in breast cancer, can be used to treat addiction and psychosis, and are effective on MRSA, in controlling psoriasis, and in treating glioblastoma, according to the properties of their concentrations of cannabidiol, cannabigerol, and Δ9-tetrahydrocannabinol, as reviewed in the literature. On the other hand, having obtained concentrations of THC, we were able to suggest the psychotropic capacity of said samples, one of which even fits within the legal category of “non-psychoactive cannabis” according to Peruvian regulations. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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17 pages, 2621 KiB

Open AccessArticle

Cannabinerol (CBNR) Influences Synaptic Genes Associated with Cytoskeleton and Ion Channels in NSC-34 Cell Line: A Transcriptomic Study

by Osvaldo Artimagnella, Emanuela Mazzon, Stefano Salamone, Federica Pollastro, Agnese Gugliandolo and Luigi Chiricosta

Biomedicines 2024, 12(1), 189; https://doi.org/10.3390/biomedicines12010189 - 15 Jan 2024

Cited by 2 | Viewed by 1868

Abstract

Cannabinoids are receiving great attention as a novel approach in the treatment of cognitive and motor disabilities, which characterize neurological disorders. To date, over 100 phytocannabinoids have been extracted from Cannabis sativa, and some of them have shown neuroprotective properties and the [...] Read more.

Cannabinoids are receiving great attention as a novel approach in the treatment of cognitive and motor disabilities, which characterize neurological disorders. To date, over 100 phytocannabinoids have been extracted from Cannabis sativa, and some of them have shown neuroprotective properties and the capacity to influence synaptic transmission. In this study, we investigated the effects of a less-known phytocannabinoid, cannabinerol (CBNR), on neuronal physiology. Using the NSC-34 motor-neuron-like cell line and next-generation sequencing analysis, we discovered that CBNR influences synaptic genes associated with synapse organization and specialization, including genes related to the cytoskeleton and ion channels. Specifically, the calcium, sodium, and potassium channel subunits (Cacna1b, Cacna1c, Cacnb1, Grin1, Scn8a, Kcnc1, Kcnj9) were upregulated, along with genes related to NMDAR (Agap3, Syngap1) and calcium (Cabp1, Camkv) signaling. Moreover, cytoskeletal and cytoskeleton-associated genes (Actn2, Ina, Trio, Marcks, Bsn, Rtn4, Dgkz, Htt) were also regulated by CBNR. These findings highlight the important role played by CBNR in the regulation of synaptogenesis and synaptic transmission, suggesting the need for further studies to evaluate the neuroprotective role of CBNR in the treatment of synaptic dysfunctions that characterize motor disabilities in many neurological disorders. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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15 pages, 3069 KiB

Open AccessArticle

Antinociceptive Effects of Cannabichromene (CBC) in Mice: Insights from von Frey, Tail-Flick, Formalin, and Acetone Tests

by Wesley M. Raup-Konsavage, Diana E. Sepulveda, Jian Wang, Nikolay V. Dokholyan, Kent E. Vrana and Nicholas M. Graziane

Biomedicines 2024, 12(1), 83; https://doi.org/10.3390/biomedicines12010083 - 29 Dec 2023

Cited by 6 | Viewed by 2423

Abstract

Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound–protein interaction estimates with cannabichromene (CBC) [...] Read more.

Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound–protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling. Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0–20 mg/kg, i.p.) and time (0–6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing. The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1–2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test. In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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18 pages, 1675 KiB

Open AccessArticle

Cannabidiol Modifies the Glutamate Over-Release in Brain Tissue of Patients and Rats with Epilepsy: A Pilot Study

by Christopher Martínez-Aguirre, Luis Alfredo Márquez, Cindy Lizbeth Santiago-Castañeda, Francia Carmona-Cruz, Maria de los Angeles Nuñez-Lumbreras, Vladimir A. Martínez-Rojas, Mario Alonso-Vanegas, Gustavo Aguado-Carrillo, Norma L. Gómez-Víquez, Emilio J. Galván, Manola Cuéllar-Herrera and Luisa Rocha

Biomedicines 2023, 11(12), 3237; https://doi.org/10.3390/biomedicines11123237 - 7 Dec 2023

Cited by 4 | Viewed by 1968

Abstract

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as [...] Read more.

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release (p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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11 pages, 889 KiB

Open AccessArticle

Medical Cannabis Is Not Associated with a Decrease in Activities of Daily Living in Older Adults

by Ran Abuhasira, Lihi Schwartz and Victor Novack

Biomedicines 2023, 11(10), 2697; https://doi.org/10.3390/biomedicines11102697 - 3 Oct 2023

Cited by 1 | Viewed by 6511

Abstract

The proportion of older adults using medical cannabis is rising. Therefore, we aimed to assess the effects of herbal medical cannabis on the functional status of older adults. We conducted a prospective observational study of patients aged 65 years or older that initiated [...] Read more.

The proportion of older adults using medical cannabis is rising. Therefore, we aimed to assess the effects of herbal medical cannabis on the functional status of older adults. We conducted a prospective observational study of patients aged 65 years or older that initiated cannabis treatment for different indications, mostly chronic non-cancer pain, during 2018–2020 in a specialized geriatric clinic. The outcomes assessed were activities of daily living (ADL), instrumental activities of daily living (IADL), pain intensity, geriatric depression scale, chronic medication use, and adverse events at six months. A cohort of 119 patients began cannabis treatment: the mean age was 79.3 ± 8.5 and 74 (62.2%) were female. Of the cohort, 43 (36.1%) experienced adverse effects due to cannabis use and 2 (1.7%) required medical attention. The mean ADL scores before and after treatment were 4.4 ± 1.8 and 4.5 ± 1.8, respectively (p = 0.27), and the mean IADL scores before and after treatment were 4.1 ± 2.6 and 4.7 ± 3, respectively (p = 0.02). We concluded that medical cannabis in older adults has a number of serious adverse events, but was not associated with a decrease in functional status, as illustrated by ADL and IADL scores after six months of continuous treatment. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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Review

Jump to: Research

15 pages, 317 KiB

Open AccessReview

Tetrahydrocannabinol and Cannabidiol for Pain Treatment—An Update on the Evidence

by Kawthar Safi, Jan Sobieraj, Michał Błaszkiewicz, Joanna Żyła, Bartłomiej Salata and Tomasz Dzierżanowski

Biomedicines 2024, 12(2), 307; https://doi.org/10.3390/biomedicines12020307 - 29 Jan 2024

Cited by 3 | Viewed by 4785

Abstract

In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are [...] Read more.

In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression. On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly. The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

23 pages, 2976 KiB

Open AccessReview

Neuroinflammation in the Central Nervous System: Exploring the Evolving Influence of Endocannabinoid System

by Sumit S. Rathod, Yogeeta O. Agrawal, Kartik T. Nakhate, M. F. Nagoor Meeran, Shreesh Ojha and Sameer N. Goyal

Biomedicines 2023, 11(10), 2642; https://doi.org/10.3390/biomedicines11102642 - 26 Sep 2023

Cited by 3 | Viewed by 2704

Abstract

Neuroinflammation is a complex biological process that typically originates as a protective response in the brain. This inflammatory process is triggered by the release of pro-inflammatory substances like cytokines, prostaglandins, and reactive oxygen and nitrogen species from stimulated endothelial and glial cells, including [...] Read more.

Neuroinflammation is a complex biological process that typically originates as a protective response in the brain. This inflammatory process is triggered by the release of pro-inflammatory substances like cytokines, prostaglandins, and reactive oxygen and nitrogen species from stimulated endothelial and glial cells, including those with pro-inflammatory functions, in the outer regions. While neuronal inflammation is common in various central nervous system disorders, the specific inflammatory pathways linked with different immune-mediated cell types and the various factors influencing the blood-brain barrier significantly contribute to disease-specific characteristics. The endocannabinoid system consists of cannabinoid receptors, endogenous cannabinoids, and enzymes responsible for synthesizing and metabolizing endocannabinoids. The primary cannabinoid receptor is CB1, predominantly found in specific brain regions such as the brainstem, cerebellum, hippocampus, and cortex. The presence of CB2 receptors in certain brain components, like cultured cerebellar granular cells, Purkinje fibers, and microglia, as well as in the areas like the cerebral cortex, hippocampus, and cerebellum is also evidenced by immunoblotting assays, radioligand binding, and autoradiography studies. Both CB1 and CB2 cannabinoid receptors exhibit noteworthy physiological responses and possess diverse neuromodulatory capabilities. This review primarily aims to outline the distribution of CB1 and CB2 receptors across different brain regions and explore their potential roles in regulating neuroinflammatory processes. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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19 pages, 1578 KiB

Open AccessReview

Therapeutic Potential of Cannabis: A Comprehensive Review of Current and Future Applications

by Zach J. Leinen, Rahul Mohan, Lakmini S. Premadasa, Arpan Acharya, Mahesh Mohan and Siddappa N. Byrareddy

Biomedicines 2023, 11(10), 2630; https://doi.org/10.3390/biomedicines11102630 - 25 Sep 2023

Cited by 15 | Viewed by 13026

Abstract

Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, and Chinese medicines recognized their therapeutic potential. The discovery of the endocannabinoid system, which interacts with cannabis phytoconstituents, has scientifically explained how cannabis affects the [...] Read more.

Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, and Chinese medicines recognized their therapeutic potential. The discovery of the endocannabinoid system, which interacts with cannabis phytoconstituents, has scientifically explained how cannabis affects the human immune system, including the central nervous system (CNS). This review explores the evolving world of cannabis-based treatments, spotlighting its diverse applications. By researching current research and clinical studies, we probe into how cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) help to manage conditions ranging from chronic pain, persistent inflammation, cancer, inflammatory bowel disease, and neurological disorders to even viral diseases such as Human Immunodeficiency virus (HIV), SARS-CoV-2. and the emerging monkeypox. The long-term recreational use of cannabis can develop into cannabis use disorder (CUD), and therefore, understanding the factors contributing to the development and maintenance of cannabis addiction, including genetic predisposition, neurobiological mechanisms, and environmental influences, will be timely. Shedding light on the adverse impacts of CUD underscores the importance of early intervention, effective treatment approaches, and public health initiatives to address this complex issue in an evolving landscape of cannabis policies and perceptions. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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25 pages, 476 KiB

Open AccessReview

Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn’t

by Catalina Christensen, Martin Rose, Claus Cornett and Morten Allesø

Biomedicines 2023, 11(8), 2323; https://doi.org/10.3390/biomedicines11082323 - 21 Aug 2023

Cited by 12 | Viewed by 5413

Abstract

The ‘entourage effect’ term was originally coined in a pre-clinical study observing endogenous bio-inactive metabolites potentiating the activity of a bioactive endocannabinoid. As a hypothetical afterthought, this was proposed to hold general relevance to the usage of products based on Cannabis sativa L. [...] Read more.

The ‘entourage effect’ term was originally coined in a pre-clinical study observing endogenous bio-inactive metabolites potentiating the activity of a bioactive endocannabinoid. As a hypothetical afterthought, this was proposed to hold general relevance to the usage of products based on Cannabis sativa L. The term was later juxtaposed to polypharmacy pertaining to full-spectrum medicinal Cannabis products exerting an overall higher effect than the single compounds. Since the emergence of the term, a discussion of its pharmacological foundation and relevance has been ongoing. Advocates suggest that the ‘entourage effect’ is the reason many patients experience an overall better effect from full-spectrum products. Critics state that the term is unfounded and used primarily for marketing purposes in the Cannabis industry. This scoping review aims to segregate the primary research claiming as well as disputing the existence of the ‘entourage effect’ from a pharmacological perspective. The literature on this topic is in its infancy. Existing pre-clinical and clinical studies are in general based on simplistic methodologies and show contradictory findings, with the clinical data mostly relying on anecdotal and real-world evidence. We propose that the ‘entourage effect’ is explained by traditional pharmacological terms pertaining to other plant-based medicinal products and polypharmacy in general (e.g., synergistic interactions and bioenhancement). Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

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