Special Issue "Cannabinoids for Medical Use"

A special issue of Medicines (ISSN 2305-6320).

Deadline for manuscript submissions: closed (30 June 2018) | Viewed by 46836

Special Issue Editor

Prof. Dr. Raffaele Capasso
E-Mail Website
Guest Editor
Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Interests: pharmacology; natural products; neurotransmission; behavioral pharmacology; experimental pharmacology; preclinical pharmacology; CB1 receptor; PPARs; cannabinoids; endocannabinoids; CB2 receptor
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Special Issue Information

Dear Colleagues,

There is a growing interest in the use of cannabinoids in medicine since the multiple advancements in basic science and clinical accomplishments using cannabis or cannabinoids. Cannabinoids is the generic term used to indicate: (a) Cannabis-derived compounds (namely phytocannabinoids), mainly isolated by two Cannabis species (i.e., sativa and/or indica); (b) endocannabinoids—neurotransmitters produced endogenously, acting on cannabinoid receptors and/or other actors of the endocannabinoid system; (c) synthetic cannabinoids, structurally analogous to phytocannabinoids and/or endocannabinoids and having comparable biological mechanisms.

Cannabinoids exert many pharmacological actions with numerous therapeutic beneficial effects. They have antispastic, analgesic, antiemetic, neuroprotective, anti-inflammatory, and antitumoral actions, and are effective against certain psychiatric diseases. 

The purpose of this Special Issue is to publish original research papers and/or relevant updates of literature data on the beneficial effects of cannabinoids in many pathologic conditions, thus sustaining the use of cannabinoids for medical purposes. The papers should contribute significantly and originally to further scientific knowledge in the cannabinoid field.

Dr. Raffaele Capasso
Guest Editor

Manuscript Submission Information

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Keywords

  • cannabinoids
  • Cannabis sativa
  • phytocannabinoids
  • endocannabinoids
  • cannabinoid receptors
  • medical cannabis
  • marijuana

Published Papers (8 papers)

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Research

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Article
Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions
Medicines 2018, 5(3), 75; https://doi.org/10.3390/medicines5030075 - 11 Jul 2018
Cited by 15 | Viewed by 17043
Abstract
Background: We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a [...] Read more.
Background: We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf AppTM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level. Results: Releaf AppTM users showed an average symptom severity reduction of −4.5 points on a 0–10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes. Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
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Article
Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials
Medicines 2018, 5(3), 59; https://doi.org/10.3390/medicines5030059 - 21 Jun 2018
Cited by 18 | Viewed by 4318
Abstract
Background. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established. MS patients generally [...] Read more.
Background. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established. MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration. Methods. 19 MS patients underwent clinical examination, numerical rating scale (NRS), quantitative sensory testing (QST), and laser-evoked potentials (LEPs) before and after 1 month of therapy. Psychophysiological and neurophysiological data were compared to sex- and age-matched controls. Results. Patients reported a significant reduction in pain. We found statistically significant differences in LEP parameters between patients and controls but no significant change in LEP measures after THC/CBD therapy. Cold and heat detection thresholds were altered in patients but did not change after THC/CBD therapy. There was a significant increase in cold pain threshold by hand stimulation and a significant reduction in abnormal cold perception thresholds. Conclusions. Our results indicate that Sativex® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
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Review

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Review
New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders
Medicines 2018, 5(4), 107; https://doi.org/10.3390/medicines5040107 - 02 Oct 2018
Cited by 18 | Viewed by 5908
Abstract
Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant [...] Read more.
Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
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Review
Traditional Uses of Cannabinoids and New Perspectives in the Treatment of Multiple Sclerosis
Medicines 2018, 5(3), 91; https://doi.org/10.3390/medicines5030091 - 15 Aug 2018
Cited by 10 | Viewed by 2665
Abstract
Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported [...] Read more.
Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported in the literature that cannabinoids might be used to control MS symptoms and that they also might exert neuroprotective effects and slow down disease progression. This review aims to give an overview of the principal cannabinoids (synthetic and endogenous) used for the symptomatic amelioration of MS and their beneficial outcomes, providing new potentially possible perspectives for the treatment of this disease. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
Review
Plant-Based Cannabinoids for the Treatment of Chronic Neuropathic Pain
Medicines 2018, 5(3), 67; https://doi.org/10.3390/medicines5030067 - 01 Jul 2018
Cited by 6 | Viewed by 5785
Abstract
Chronic neuropathic pain is a prevalent condition that places a heavy burden on individuals and the healthcare system. Current medications have limitations and new approaches are needed, particularly given the current opioid crisis. There is some clinical evidence that the plant Cannabis sativa [...] Read more.
Chronic neuropathic pain is a prevalent condition that places a heavy burden on individuals and the healthcare system. Current medications have limitations and new approaches are needed, particularly given the current opioid crisis. There is some clinical evidence that the plant Cannabis sativa produces relief from neuropathic pain. However, current meta-analyses suggest that this efficacy is limited and there are problems with side effects. Most of this clinical research has examined whole cannabis, the psychoactive phytocannabinoid 9-tetrahydrocannabinol (THC), and nabiximols, which are a mixture of THC and the non-psychoactive phytocannabinoid cannabidiol. In the past, there has been little evidence based, preclinical animal research to guide clinical studies on phytocannabinoids. Recent animal studies indicate that while THC and high dose nabiximols are effective in animal neuropathic pain models, significant pain relief is only achieved at doses that produce substantial side effects. By contrast, cannabidiol and low dose nabiximols have moderate pain relieving efficacy, but are devoid of cannabinoid-like side effects. This animal data suggests that cannabidiol and low dose nabiximols warrant consideration for clinical studies, at least as adjuvants to current drugs. Preclinical research is also required to identify other phytocannabinoids that have therapeutic potential. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
Review
The Role of Cannabinoids in the Setting of Cirrhosis
Medicines 2018, 5(2), 52; https://doi.org/10.3390/medicines5020052 - 09 Jun 2018
Cited by 14 | Viewed by 3309
Abstract
Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis [...] Read more.
Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
Review
Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease
Medicines 2018, 5(2), 47; https://doi.org/10.3390/medicines5020047 - 28 May 2018
Cited by 13 | Viewed by 2125
Abstract
Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)

Other

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Perspective
The Role of Cannabis within an Emerging Perspective on Schizophrenia
Medicines 2018, 5(3), 86; https://doi.org/10.3390/medicines5030086 - 08 Aug 2018
Cited by 3 | Viewed by 5112
Abstract
Background: Approximately 0.5% of the population is diagnosed with some form of schizophrenia, under the prevailing view that the pathology is best treated using pharmaceutical medications that act on monoamine receptors. Methods: We briefly review evidence on the impact of environmental forces, particularly [...] Read more.
Background: Approximately 0.5% of the population is diagnosed with some form of schizophrenia, under the prevailing view that the pathology is best treated using pharmaceutical medications that act on monoamine receptors. Methods: We briefly review evidence on the impact of environmental forces, particularly the effect of autoimmune activity, in the expression of schizophrenic profiles and the role of Cannabis therapy for regulating immunological functioning. Results: A review of the literature shows that phytocannabinoid consumption may be a safe and effective treatment option for schizophrenia as a primary or adjunctive therapy. Conclusions: Emerging research suggests that Cannabis can be used as a treatment for schizophrenia within a broader etiological perspective that focuses on environmental, autoimmune, and neuroinflammatory causes of the disorder, offering a fresh start and newfound hope for those suffering from this debilitating and poorly understood disease. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
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