Advances in Cannabinoid Research

Topic Information

Dear Colleagues,

The isolation of Δ9 tetrahydrocannabinol (THC) followed by the discovery of cannabinoid receptors as well as of endogenous cannabinoids led to the identification of the “endocannabinoid system”. Since then, this system has been recognized as a key modulator of a huge variety of physiological processes and neuroadaptive responses, including learning and memory, nociception, endocrine function, sex and feeding, and brain development. Furthermore, the endocannabinoid system is an important constituent of neuronal substrates involved in reinforcement and brain reward processes, modulating the addiction-producing actions of cannabinoids, as well as of other drugs of abuse. On the other hand, abnormalities in endocannabinoid signaling may be implicated in several diseases, including neurologic and psychiatric diseases, cancer, obesity, and neuropathic and inflammatory pain. As a consequence, cannabinoids have received growing attention for their possible therapeutic applications. Pharmacological strategies include cannabis preparations (raw cannabis, magistral preparations, and standardized cannabis preparations), synthetic analogs of THC, and inhibitors of endocannabinoid uptake or metabolism. Despite numerous advances in the field of cannabinoid research, further investigations are still needed in order to clarify many pending issues, relative to molecular mechanisms and actions of natural as well as synthetic cannabinoids and the precise assessment of the benefits and risks of using them for both therapeutic and recreational purposes. In this context, this Topic welcomes original research, meta-analyses, and review articles, ranging from preclinical research to human studies. Additionally, we also welcome the submission of research focusing on the therapeutical potential of new pharmaceutical preparations.

Dr. Maria Scherma
Prof. Dr. Paola Fadda
Dr. Fabrizio Sanna
Dr. Anna Lisa Muntoni
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600
Brain Sciences brainsci	2.7	4.8	2011	15.6 Days	CHF 2200
Antioxidants antioxidants	6.0	10.6	2012	16.9 Days	CHF 2900
Pharmaceuticals pharmaceuticals	4.3	6.1	2004	13.9 Days	CHF 2900

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Published Papers (10 papers)

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14 pages, 718 KiB  

Open AccessReview

Cannabinoids in Late Life Parkinson’s Disease and Dementia: Biological Pathways and Clinical Challenges

by Alana C. Costa, Helena P. G. Joaquim, João F. C. Pedrazzi, Andreia de O. Pain, Gustavo Duque and Ivan Aprahamian

Brain Sci. 2022, 12(12), 1596; https://doi.org/10.3390/brainsci12121596 - 22 Nov 2022

Cited by 11 | Viewed by 5855

Abstract

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and [...] Read more.

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of tremor, non-motor symptoms, anxiety, and sleep assistance in PD, and managing responsive behaviors of dementia such as agitation. However, strong evidence from clinical trials is scarce for most indications. Some clinicians consider cannabinoids an alternative for older adults bearing Parkinson’s disease and Alzheimer’s dementia with a poor response to first-line treatments. In our concept and experience, cannabinoids should never be considered a first-line treatment but could be regarded as an adjuvant therapy in specific situations commonly seen in clinical practice. To mitigate the risk of adverse events, the traditional dogma of geriatric medicine, starting with a low dose and proceeding with a slow titration regime, should also be employed with cannabinoids. In this review, we aimed to address preclinical evidence of cannabinoids in neurodegenerative disorders such as PD and AD and discuss potential off-label use of cannabinoids in clinical practice of these disorders. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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16 pages, 1462 KiB  

Open AccessReview

Recreational Drug Misuse and Its Potential Contribution to Male Fertility Levels’ Decline: A Narrative Review

by Nicolò Schifano, Stefania Chiappini, Alessio Mosca, Andrea Miuli, Maria Chiara Santovito, Mauro Pettorruso, Paolo Capogrosso, Federico Dehò, Giovanni Martinotti and Fabrizio Schifano

Brain Sci. 2022, 12(11), 1582; https://doi.org/10.3390/brainsci12111582 - 19 Nov 2022

Cited by 8 | Viewed by 5730

Abstract

Recreational drug intake may be associated with a range of medical untoward consequences, including male infertility. However, as the related evidence is still limited, the main outcome of this review is to provide a better understanding of the existence of any association between [...] Read more.

Recreational drug intake may be associated with a range of medical untoward consequences, including male infertility. However, as the related evidence is still limited, the main outcome of this review is to provide a better understanding of the existence of any association between recreational drug misuse and male fertility levels’ decline. Whilst searching the MEDLINE/PubMed, a comprehensive overview of the literature regarding male infertility and substances of abuse (e.g., phytocannabinoids, opiates/opioids, stimulants, ‘herbal highs’, psychedelics, and ‘novel psychoactive substances) was here undertaken. Due to the paucity of robust, high-quality, empirical, human studies, a narrative strategy was here preferred over a systematic approach. Relevant data are qualitatively analyzed and presented in a table. Although most available evidence is in support of a detrimental role of cannabis on human spermatogenesis, a few remaining studies failed to document any effect of this drug on seminal quality, and it is not clear to which extent this drug impacts fertility rates/time to pregnancy. The current understanding of the impact of opiate-, cocaine- and amphetamine/stimulant-misuse on human reproduction is widely unknown, and most studies dealing with this matter represent only an extrapolation of data derived from specific clinical circumstances. Although the message of ‘no smoking, no alcohol and no street drugs’ should always be offered as good health advice to all patients seeking medical help for fertility issues, robust scientific clinical evidence in support of a direct detrimental impact of recreational drugs on spermatogenesis is scant to date. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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40 pages, 6526 KiB  

Open AccessReview

Recent Advances in Endocannabinoid System Targeting for Improved Specificity: Strategic Approaches to Targeted Drug Delivery

by Mendhi Henna Dasram, Roderick B. Walker and Sandile M. Khamanga

Int. J. Mol. Sci. 2022, 23(21), 13223; https://doi.org/10.3390/ijms232113223 - 30 Oct 2022

Cited by 16 | Viewed by 6194

Abstract

Opportunities for developing innovative and intelligent drug delivery technologies by targeting the endocannabinoid system are becoming more apparent. This review provides an overview of strategies to develop targeted drug delivery using the endocannabinoid system (ECS). Recent advances in endocannabinoid system targeting showcase enhanced [...] Read more.

Opportunities for developing innovative and intelligent drug delivery technologies by targeting the endocannabinoid system are becoming more apparent. This review provides an overview of strategies to develop targeted drug delivery using the endocannabinoid system (ECS). Recent advances in endocannabinoid system targeting showcase enhanced pharmaceutical therapy specificity while minimizing undesirable side effects and overcoming formulation challenges associated with cannabinoids. This review identifies advances in targeted drug delivery technologies that may permit access to the full pharmacotherapeutic potential of the ECS. The design of optimized nanocarriers that target specific tissues can be improved by understanding the nature of the signaling pathways, distribution in the mammalian body, receptor structure, and enzymatic degradation of the ECS. A closer look at ligand-receptor complexes, endocannabinoid tone, tissue distribution, and G-protein activity leads to a better understanding of the potential of the ECS toolkit for therapeutics. The signal transduction pathways examine the modulation of downstream effector proteins, desensitization, signaling cascades, and biased signaling. An in-depth and overall view of the targeted system is achieved through homology modeling where mutagenesis and ligand binding examine the binding site and allow sequence analysis and the formation of libraries for molecular docking and molecular dynamic simulations. Internalization routes exploring receptor-mediated endocytosis and lipid rafts are also considered for explicit signaling. Furthermore, the review highlights nanotechnology and surface modification aspects as a possible future approach for specific targeting. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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8 pages, 1542 KiB  

Open AccessArticle

The Antioxidant Role of Hemp Phytocomplex in Cannabis Oil-Based Extracts

by Camillo Morano, Michele Dei Cas, Gabriella Roda, Adalberto Fabbriconi, Eleonora Casagni, Marco Pallavicini, Cristiano Bolchi, Gloria Pallotti, Francesco Romaniello and Pierangela Rovellini

Pharmaceuticals 2022, 15(9), 1102; https://doi.org/10.3390/ph15091102 - 4 Sep 2022

Cited by 1 | Viewed by 2174

Abstract

The therapeutic use of Cannabis oil extracts is constantly increasing. However, in Italy, they are allowed to be prepared with only a few methods and matrices. With this work, we aimed to assess how the different processes might affect the chemical composition of [...] Read more.

The therapeutic use of Cannabis oil extracts is constantly increasing. However, in Italy, they are allowed to be prepared with only a few methods and matrices. With this work, we aimed to assess how the different processes might affect the chemical composition of two different matrices (olive oils and medium chain triglycerides oils - MCT), accounting as variables for both the presence of Cannabis dried apices of the female flower and the adding of tocopherol acetate as an antioxidant. The macerated oils were prepared with four of the methods allowed according to the Italian legislation (Romano-Hazekamp, Cannazza-Citti, SIFAP and Calvi) and analyzed for normal and oxidized tocopherols, oxidized and conjugated fatty acids and volatile carbonyl compounds (VCCs), all using liquid chromatography coupled to UV or PDA detectors. According to our results, neither normal nor oxidized tocopherols are affected by the addition of antioxidants or Cannabis, while the oxidation state (according to the levels of oxidized and conjugated fatty acids) is often altered in either case. The VCCs concentrations, on the other hand, are never notably altered. These results suggest a worthless use of antioxidants in Cannabis macerated oils preparations, while the dried apices of female flowers might have a protective role in maintaining the oil oxidation state. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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15 pages, 930 KiB  

Open AccessArticle

Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)—A Pilot Study

by Thorsten Rudroff, Craig D. Workman, Phillip E. Gander, Justin R. Deters and Laura L. Boles Ponto

Brain Sci. 2022, 12(7), 819; https://doi.org/10.3390/brainsci12070819 - 23 Jun 2022

Cited by 1 | Viewed by 3008

Abstract

Δ9-Tetrahydrocannabinol is the main psychoactive component of cannabis and cannabidiol is purportedly responsible for many of the medicinal benefits. The effects of Δ9-tetrahydrocannabinol and cannabidiol in younger populations have been well studied; however, motor function, cognitive function, and cerebral glucose metabolism in older [...] Read more.

Δ9-Tetrahydrocannabinol is the main psychoactive component of cannabis and cannabidiol is purportedly responsible for many of the medicinal benefits. The effects of Δ9-tetrahydrocannabinol and cannabidiol in younger populations have been well studied; however, motor function, cognitive function, and cerebral glucose metabolism in older adults have not been extensively researched. The purpose of this study was to assess differences in cognitive function, motor function, and cerebral glucose metabolism (assessed via [¹⁸F]-fluorodeoxyglucose positron emission tomography) in older adults chronically using Δ9-tetrahydrocannabinol, cannabidiol, and non-using controls. Eight Δ9-tetrahydrocannabinol users (59.3 ± 5.7 years), five cannabidiol users (54.6 ± 2.1 years), and 16 non-users (58.2 ± 16.9 years) participated. Subjects underwent resting scans and performed cognitive testing (reaction time, Flanker Inhibitory Control and Attention Test), motor testing (hand/arm function, gait), and balance testing. Δ9-tetrahydrocannabinol users performed worse than both cannabidiol users and non-users on the Flanker Test but were similar on all other cognitive and motor tasks. Δ9-tetrahydrocannabinol users also had lower global metabolism and relative hypermetabolism in the bilateral amygdala, cerebellum, and brainstem. Chronic use of Δ9-tetrahydrocannabinol in older adults might negatively influence inhibitory control and alter brain activity. Future longitudinal studies with larger sample sizes investigating multiple Δ9-tetrahydrocannabinol:cannabidiol ratios on functional outcomes and cerebral glucose metabolism in older adults are necessary. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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22 pages, 5335 KiB  

Open AccessArticle

Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats

by Marek Zubrzycki, Maria Zubrzycka, Grzegorz Wysiadecki, Janusz Szemraj, Hanna Jerczynska and Mariusz Stasiolek

Int. J. Mol. Sci. 2022, 23(9), 4665; https://doi.org/10.3390/ijms23094665 - 23 Apr 2022

Cited by 5 | Viewed by 2757

Abstract

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal [...] Read more.

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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23 pages, 3680 KiB  

Open AccessArticle

Portable Neuroimaging-Guided Noninvasive Brain Stimulation of the Cortico-Cerebello-Thalamo-Cortical Loop—Hypothesis and Theory in Cannabis Use Disorder

by Pushpinder Walia, Abhishek Ghosh, Shubhmohan Singh and Anirban Dutta

Brain Sci. 2022, 12(4), 445; https://doi.org/10.3390/brainsci12040445 - 26 Mar 2022

Cited by 4 | Viewed by 6066

Abstract

Background: Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in [...] Read more.

Background: Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on a competing neurobehavioral decision systems model. The next objective was to develop the theory by conducting a computational simulation of NIBS of the cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD)-related dysfunctional “cue-reactivity”—a construct closely related to “craving”—that is a core symptom. Our third objective was to test the feasibility of a neuroimaging-guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) metrics of sensorimotor gating. Therefore, we conducted a computational simulation of NIBS, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) of the cerebellar cortex and deep cerebellar nuclei (DCN) of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging-guided NIBS approach for the cerebellar lobule (VII) and prefrontal cortex based on a healthy human study. Results: Simulation of cerebellar tDCS induced gamma oscillations in the cerebral cortex, while transcranial temporal interference stimulation induced a gamma-to-beta frequency shift. A preliminary healthy human study (N = 10) found that 2 mA cerebellar tDCS evoked similar oxyhemoglobin (HbO) response in the range of 5 × 10⁻⁶ M across the cerebellum and PFC brain regions (α = 0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO-driven phase–amplitude-coupled (PAC; 4 Hz, ±2 mA (max)) cerebellar tACS evoked HbO levels in the range of 10⁻⁷ M that were statistically different (α = 0.01) across these brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC and closed-loop fNIRS-driven ctACS at 4 Hz, which may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging for closed-loop NIBS during operant conditioning. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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17 pages, 2036 KiB  

Open AccessArticle

Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity

by Tomasz Charytoniuk, Klaudia Sztolsztener, Patrycja Bielawiec, Adrian Chabowski, Karolina Konstantynowicz-Nowicka and Ewa Harasim-Symbor

Int. J. Mol. Sci. 2022, 23(4), 2232; https://doi.org/10.3390/ijms23042232 - 17 Feb 2022

Cited by 8 | Viewed by 3039

Abstract

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, [...] Read more.

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol—CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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15 pages, 1829 KiB  

Open AccessSystematic Review

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials

by Ákos Bajtel, Tivadar Kiss, Barbara Tóth, Szabolcs Kiss, Péter Hegyi, Nóra Vörhendi, Boglárka Csupor-Löffler, Noémi Gede, Judit Hohmann and Dezső Csupor

Pharmaceuticals 2022, 15(1), 100; https://doi.org/10.3390/ph15010100 - 14 Jan 2022

Cited by 28 | Viewed by 5526

Abstract

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched [...] Read more.

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64–31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92–152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33–68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19–9.78), dizziness (OR: 4.60 95% CI: 2.39–8.83) and headache (OR: 2.90; 95% CI: 1.07–7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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18 pages, 2475 KiB  

Open AccessEditor’s ChoiceArticle

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells

by Hussein Hamad and Birgitte Brinkmann Olsen

Pharmaceuticals 2021, 14(11), 1169; https://doi.org/10.3390/ph14111169 - 17 Nov 2021

Cited by 30 | Viewed by 10301

Abstract

Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer [...] Read more.

Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells. Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells. We found that CBD decreased viability and induced cell death in both cell populations. Furthermore, we found that CBD activated the effector caspases 3/7, increased the expression of pro-apoptotic proteins, increased the levels of reactive oxygen species, as well as a leading to a loss of mitochondrial membrane potential in both populations. We also found that CBD decreased self-renewal, a hallmark of cancer stem cells. Overall, our results suggest that CBD is effective against the otherwise treatment-resistant cancer stem cells and joins a growing list of compounds effective against cancer stem cells. The effects and mechanisms of CBD in cancer stem cells should be further explored to find their Achilles heel. Full article

(This article belongs to the Topic Advances in Cannabinoid Research)

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