Clinical Trials on CBD

1. TITLE: Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial

PUBLISHED: May 21, 2019

SOURCE: The American Journal of Psychiatry

CONCLUSION: Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues. CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure. In addition, CBD reduced the drug cue-induced physiological measures of heart rate and salivary cortisol levels. There were no significant effects on cognition, and there were no serious adverse effects. CBD’s potential to reduce cue-induced craving and anxiety provides a strong basis for further investigation of this phytocannabinoid as a treatment option for opioid use disorder.

RESEARCH: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191

2. TITLE: Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle

PUBLISHED: March 22, 2018

SOURCE: Neuropsychopharmacology volume 43

CONCLUSION: The results document two unique “therapeutic” dimensions of CBD. First, CBD exerted beneficial effects relevant for several relapse-promoting conditions including sensitivity to drug-related contexts and stress, anxiety, and impaired impulse control. These observations are consistent with the hypothesis and provide proof of principle supporting the potential of CBD to concurrently ameliorate multiple vulnerability states that underlie relapse risk. Second, CBD produced unexpected long-lasting “therapeutic” effects following only brief treatment in the two reinstatement models of relapse. Further adding to the treatment promise of CBD, the efficacy of the cannabinoid to reduce reinstatement in rats with both alcohol and cocaine—and, as previously reported, heroin [11]—histories predicts therapeutic potential for addiction treatment across several classes of abused drugs.

RESEARCH: https://www.nature.com/articles/s41386-018-0050-8

1. TITLE: Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

PUBLISHED: June 2021

SOURCE: Biology (Basel)

CONCLUSION: This review was aimed at exploring the potentiality of drugging the endocannabinoid system as a therapeutic option for Alzheimer’s disease (AD). Recent discoveries have demonstrated how the modulation of cannabinoid receptor 1 (CB1) and receptor 2 (CB2) can exert neuroprotective effects without the recreational and pharmacological properties of Cannabis sativa. Thus, this review explores the potential of cannabinoids in AD, also highlighting their limitations in perspective to point out the need for further research on cannabinoids in AD therapy.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234911/

2. TITLE: Attitudes, beliefs, and changing trends of cannabidiol (CBD) oil use among caregivers of individuals with Alzheimer’s disease

PUBLISHED: March 2021

SOURCE: Complementary Therapies in Medicine

CONCLUSION: A high percentage of caregivers were satisfied with the effectiveness of CBD oil. Most caregivers believed that healthcare professionals should offer CBD oil as a part of treatment options for Alzheimer’s disease. Only 63 % reported consulting with their physician about using CBD oil. Caregivers of individuals with Alzheimer’s disease have certain misconceptions about CBD oil. Programs designed to increase individuals’ awareness regarding the difference between medical cannabis and CBD are needed.

RESEARCH: https://www.sciencedirect.com/science/article/pii/S0965229921000017

TITLE: Endocannabinoids, cannabinoids and the regulation of anxiety

PUBLISHED: September 2021

SOURCE: International Journal of Neuropharmacology

CONCLUSION: Evidence reviewed here has outlined a convincing argument for cannabinoids being powerful regulators of both the manifestation and amelioration of anxiety symptoms, and highlights the therapeutic potential of targeting the eCB system for the development of novel classes of anxiolytics.

RESEARCH: https://www.sciencedirect.com/science/article/abs/pii/S0028390821001805

TITLE: Caring for Behavioral Symptoms of Dementia (CBD): A New Investigation into Cannabidiol for the Treatment of Anxiety and Agitation in Alzheimer's Dementia

PUBLISHED: April 2021

SOURCE: The American Journal of Geriatric Psychiatry

CONCLUSION: We seek a safe and effective treatment for the neuropsychiatric symptoms of anxiety and agitation in older adults with AD. With no current FDA-approved treatments for these behavioral symptoms, patients with AD risk ineffective therapies or mortality-associated antipsychotic treatments to address their NPS. Treating anxiety and agitation in these patients not only alleviates their symptoms but could also reduce caregiver burden and lengthen the time to institutionalization. CBD is a promising anxiolytic treatment that could advance our available treatment options for anxiety and agitation in AD.

RESEARCH: https://www.sciencedirect.com/science/article/abs/pii/S1064748121001330

Abstract

Overall, existing preclinical evidence strongly supports the potential of CBD as a treatment for anxiety disorders. CBD exhibits a broad range of actions, relevant to multiple symptom domains, including anxiolytic, panicolytic, and anticompulsive actions, as well as a decrease in autonomic arousal, a decrease in conditioned fear expression, enhancement of fear extinction, reconsolidation blockade, and prevention of the long-term anxiogenic effects of stress.

Evidence from human studies strongly supports the potential for CBD as a treatment for anxiety disorders: at oral doses ranging from 300 to 600 mg, CBD reduces experimentally induced anxiety in healthy controls, without affecting baseline anxiety levels, and reduces anxiety in patients with SAD.

1. TITLE: Cannabidiol as a Potential Treatment for Anxiety Disorders

PUBLISHED: September 4, 2015

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Preclinical evidence conclusively demonstrates CBD’s efficacy in reducing anxiety behaviors relevant to multiple disorders, including PTSD, GAD, PD, OCD, and SAD, with a notable lack of anxiogenic effects. CBD’s anxiolytic actions appear to depend upon CB1Rs and 5-HT1ARs in several brain regions; however, investigation of additional receptor actions may reveal further mechanisms. Human experimental findings support preclinical findings, and also suggest a lack of anxiogenic effects, minimal sedative effects, and an excellent safety profile. Current preclinical and human findings mostly involve acute CBD dosing in healthy subjects, so further studies are required to establish whether chronic dosing of CBD has similar effects in relevant clinical populations.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

2. TITLE: An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia

PUBLISHED: April 2019

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: The most important observation is that when simultaneously inhaled, THC and CBD interact in complex fashions with synergistic pharmacokinetic but antagonistic pharmacodynamic interactions. The analgesic efficacy of active treatment was limited to varieties that contained THC and were observed exclusively in the evoked pressure pain model.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430597/

1. TITLE: Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts

PUBLISHED: September 1, 2020

SOURCE: Cell Death Dis 11

CONCLUSION: In this study, we demonstrated that CBD decreases cell viability, proliferation, and cytokine production but increases intracellular calcium and PoPo3 levels of RASF and all effects were enhanced by TNF pre-stimulation. These effects were mediated by TRPA1 and by the assembly of the mPTP under pro-inflammatory conditions, whereas under unstimulated conditions, TRPA1 was not involved. In conclusion, CBD might be beneficial as an adjuvant treatment in rheumatoid arthritis that might support the action of currently used disease-modifying anti-rheumatic drugs.

RESEARCH: https://www.nature.com/articles/s41419-020-02892-1

2. TITLE: Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis

PUBLISHED: October 30, 2015

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side effects.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/

1. TITLE: Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

PUBLISHED: September 2021

SOURCE: Pharmaceutics journal

CONCLUSION: Using chitosan to wrap CBD-loaded PLGA nanoparticles may significantly enhance the adhesion of CBD in the bladder wall, which may not only avoid damage caused by repeated perfusion of organic solvents but also achieve the purpose of long-term treatment. These results can be developed as a promising strategy for a safer and more efficient anticancer therapy.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471856/

2.TITLE: The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer

PUBLISHED: August 2021

SOURCE: Cancers journal

CONCLUSION: There is enough evidence in the literature stating the ability of cannabinoids to induce cell death by various pathways in prostate cancer, but there is still more research needed to be undertaken to understand their mechanism [104,105]. Although cannabinoids may well be able to help with the management of prostate cancer, there is still an urgent need to identify the best and the most effective combination for these and other cancers. Furthermore, it is potentially desirable for cannabinoids to work on several hallmarks of cancer at one point in time. Many pre-clinical studies report the anti-tumor activity of cannabinoids [31,72,106]. An important aspect of cannabinoid pharmacology is their selectivity towards cancer cells and not to the normal cells in the body. Another aspect that needs more research is the identification of the mechanism of action by which cannabinoids show synergistic activity/entourage effect with other secondary plant metabolites.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392233/

3. TITLE: Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia

PUBLISHED: October 14, 2019

SOURCE: Cell Death Dis 10

CONCLUSION: In conclusion, CBD directly targets mitochondria in T-ALL and changes their capacity to handle Ca2+, which in turn affects multiple cellular functions, including ROS production and Ca2+ signaling, metabolic switch, and the induction of autophagy and cell death. The latter is directly proved for our experimental model as the inhibitor of mitochondrial Ca2+ uptake Ru360 protected T-ALL cells from the CBD-induced cell death. Considering the pivotal role of mitochondria in oncogenic re-programming, CBD may be a plausible candidate to be included into chemotherapeutic protocols.

RESEARCH: https://www.nature.com/articles/s41419-019-2024-0

4. TITLE: Cannabinoids as therapeutic agents in cancer: current status and future implications

PUBLISHED: July 17, 2014

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Cannabinoids exert a direct anti-proliferative effect on tumors of different origins. They have been shown to be anti-migratory and anti-invasive and inhibit MMPs which in turn degrade the extra-cellular matrix (ECM), thus affecting metastasis of cancer to the distant organs. Also, cannabinoids modulate other major processes in our body like energy metabolism, inflammation, etc. These data are derived not only from cell culture systems but also from more complex and clinically relevant animal models. The administration of single cannabinoids might produce limited relief compared to the administration of crude extract of plants containing multiple cannabinoids, terpenes, and flavanoids. Thus, a combination of cannabinoids with other chemotherapeutic drugs might provide a potent clinical outcome, reduce toxicity, increase specificity and overcome drug resistance complications.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171598/

5. TITLE: Cannabinoids Induce Cancer Cell Proliferation via Tumor Necrosis Factor α-Converting Enzyme (TACE/ADAM17)-Mediated Transactivation of the Epidermal Growth Factor Receptor

PUBLISHED: March 2004

SOURCE: American Association for Cancer Research

CONCLUSION: Cannabinoids were suggested as useful drugs to support cancer therapy. Here we show that various cannabinoids potently induce mitogenic kinase signaling in different cancer cell lines. Moreover, it’s demonstrated, in contrast to other studies that used cannabinoids such as THC at micromolar concentrations, that nanomolar concentrations of THC induce proliferation of cancer cells.

RESEARCH: Hart S., Fischer O.M., Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res. 2004;64:1943–1950. doi: 10.1158/0008-5472.CAN-03-3720. [PubMed][CrossRef][Google Scholar]

6. TITLE: Cannabinoids for Cancer Treatment: Progress and Promise

PUBLISHED: January 2008

SOURCE: American Association for Cancer Research

CONCLUSION: Cannabinoids are proving to be unique based on their targeted action on cancer cells and their ability to spare normal cells. Variation in the effects of cannabinoids in different cell lines and tumor models could be due to the differential expression of CB1 and CB2receptors. Thus, overexpression of cannabinoid receptors may be effective in killing tumors, whereas low or no expression of these receptors could lead to cell proliferation and metastasis because of the suppression of the antitumor immune response. It is also reported that low doses of cannabinoid administration accelerate the proliferation of cancer cells instead of inducing apoptosis and, thereby, contribute to cancer progression.

RESEARCH: https://cancerres.aacrjournals.org/content/68/2/339#sec-11

TITLE: Neuroprotective Effects of Cannabidiol but Not Δ9-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with Cannabis Extracts and Selected Cannabinoids

PUBLISHED: September 2021

SOURCE: International Journal of Molecular Sciences

CONCLUSION: Appropriate concentrations of CBD or CBD/THC ratios can be considered as a promising therapeutic strategy in the treatment of post-ischemic neuronal death.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468213/

TITLE: Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA

PUBLISHED: September 2, 2020

SOURCE: Cannabis and Cannabinoid Research Vol. 5, No. 3

CONCLUSION: Results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.

RESEARCH: https://www.liebertpub.com/doi/full/10.1089/can.2020.0043

1. TITLE: Cannabidiol (CBD) and cognition in epilepsy

PUBLISHED: November 2021

SOURCE: Epilepsy & Behaviour

CONCLUSION: In multiple animal models of epilepsy, CBD was shown to improve cognition. Studies in humans demonstrate neutral or positive effects of CBD on cognition in epilepsy. Cannabidiol can induce functional brain changes important in cognition in epilepsy.

RESEARCH: https://www.sciencedirect.com/science/article/abs/pii/S1525505021005771

2. TITLE: Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy

PUBLISHED: September 2021

SOURCE: Epilepsy & Behaviour

CONCLUSION: An observational cohort study of patients with epilepsy. Cannabidiol Users had higher quality of life and lower psychiatric symptom severity. Cannabidiol Users also had better epilepsy medication tolerability.

RESEARCH: https://www.sciencedirect.com/science/article/pii/S1525505021004662

3. TITLE: UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations

PUBLISHED: June 2021

SOURCE: Pharmaceuticals Journal

CONCLUSION: The method was applied to clinical samples derived from nine patients under treatment with different formulations of CBD for the treatment of drug-resistant epilepsy. Significantly higher and more stable serum levels of either CBD or its metabolites were detected in those patients taking the purified formulation of CBD as compared to those treated with galenic preparations. From a clinical perspective, these findings may suggest patients treated with GW pharma CBD formula have more drug “coverage” between the daily dose intakes, translating into better seizure control.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308640/

TITLE: The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation

PUBLISHED: August 2021

SOURCE: Molecules Journal

CONCLUSION: Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347461/

1. TITLE: Cannabidiol in Anxiety and Sleep: A Large Case Series

PUBLISHED: January 7, 2019

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Cannabidiol may hold benefits for anxiety-related disorders. The study involved 72 subjects, with 47 experiencing anxiety and 25 experiencing poor sleep. The subjects were each given 25 milligrams (mg) of CBD in capsule form each day. In the first month, 79.2 percent of the patients reported lower anxiety levels and 66.7 percent reported better sleep.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/

2. TITLE: Cannabinoids and Pain: New Insights From Old Molecules

PUBLISHED: November 13, 2018

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Cannabinoids (plant-derived, synthetic) themselves or endocannabinoid-directed therapeutic strategies have been shown to be effective in different animal models of pain (acute nociceptive, neuropathic, inflammatory). The authors note that by reducing chronic pain, CBD can improve sleep.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277878/

3. TITLE: Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series

PUBLISHED: May 21, 2014

SOURCE: National Library of Medicine

CONCLUSION: Four patients treated with CBD had a prompt and substantial reduction in the frequency of RBD-related events without side effects. This case series indicates that CBD is able to control the symptoms of RBD.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/24845114/

4. TITLE: Cannabis, Cannabinoids, and Sleep: a Review of the Literature

PUBLISHED: March 27, 2017

SOURCE: Curr Psychiatry Rep 19

CONCLUSION: CBD may be helpful in treating RBD, and that it shows potential for treating excessive daytime sleepiness.

RESEARCH: https://link.springer.com/article/10.1007%2Fs11920-017-0775-9#citeas

5. TITLE: Potential Effects of Cannabidiol as a Wake-Promoting Agent

PUBLISHED: May 2014

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: CBD could have the potential to promote wakefulness, based on both human and animal research. The authors noted they weren’t sure exactly how or why CBD promoted wakefulness in some instances.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023456/

TITLE: Cannabinoid Actions on Neural Stem Cells: Implications for Pathophysiology

PUBLISHED: April 5, 2019

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Cannabinoid-based treatment is a very promising avenue of therapy due to the wide distribution of the ECS throughout the CNS and its complex interactions with other neuromodulatory systems, although these represent challenging factors per se when it comes to designing neural repair approaches. Moreover, the multiplicity of cannabinoid actions on NSCs, particularly in a disease context, opens avenues of research to uncover the exact mechanisms behind cannabinoid effects, therefore, providing knowledge that should be invested in developing refined targeting strategies to alleviate/arrest disease burden. Combining both cannabinoid and NSC therapy may yield translational power with the potential to be impactful in clinics and society.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480122/

1. TITLE: Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms

PUBLISHED: October 2021

SOURCE: Plos Global Public Health

CONCLUSION: Cannabis appears to be effective for pelvic pain, gastrointestinal issues, and mood, with effectiveness differing based on the method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547625/

2. TITLE: Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

PUBLISHED: September 2021

SOURCE: Drugs. The definitive journal of drugs and therapeutics.

CONCLUSION: The examples reported in the present review indicate that many remarkable formulations involving cannabinoids are now evolving and are being validated in several clinical trials. Nevertheless, there is an urgent need for further research to investigate the optimal route and composition of cannabinoids in pain treatment, in large, high-quality randomized clinical trials that can shed light on the risks and benefits of cannabinoids in a controlled patient population.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417625/

3. TITLE: Prevalence of Cannabidiol Use in Patients With Spine Complaints: Results of an Anonymous Survey

PUBLISHED: August 2021

SOURCE: International Journal of Spine Surgery

CONCLUSION: Out of 300 surveys, 214 (71%) were completed. CBD use for spine-related pain was reported by 54 (25.2%) patients. CBD was initially used for potential relief of back pain (66.7%), neck pain (37.0%), leg pain (35.2%), and/or arm pain (9.3%). Users also sought improvements in insomnia (25.9%) and mood (18.5%). Oil was the most popular formulation (64.8%). CBD was most often consumed 2–5 times (40.7%) or 6–10 times (31.5%) per week. The most common source of initial recommendation for CBD was friends or family (75.9%). Reported benefits were pain relief (46.3%), improved sleep (33.3%), and reduced anxiety (20.4%); however, 24.1% of patients reported no benefit from CBD use. The most reported side effect was fatigue (7.4%). Most users (63.0%) would recommend CBD to a friend for pain relief.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375682/

1. TITLE: Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

PUBLISHED: February 20, 2020

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: A large number of preclinical studies have provided evidence that targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoid degrading enzymes is a potentially effective strategy to attenuate neuropathic pain symptoms with limited side effects. In particular, enhancing the action of endocannabinoids at the sites of the pain pathway using endocannabinoid degradative enzyme inhibitors is an attractive strategy for the treatment of neuropathic pain.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073137/

2. TITLE: Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

PUBLISHED: July 23, 2018

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: CBD was shown to be bioavailable across the small number of dogs examined in the PK portion of the study, and dogs with OA receiving this industrial hemp extract high in CBD (2 mg/kg of CBD) were perceived to be more comfortable and active. There appear to be no observed side effects of the treatment in either the dogs utilized in the PK study at 2 and 8 mg/kg or dogs undergoing OA treatment for a month duration. There were some dogs with incidental rises in alkaline phosphatase that could be related to the treatment.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065210/

3. TITLE: Cannabinoids and Pain: New Insights From Old Molecules

PUBLISHED: November 13, 2018

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Cannabinoids (plant-derived, synthetic) themselves or endocannabinoid-directed therapeutic strategies have been shown to be effective in different animal models of pain (acute nociceptive, neuropathic, inflammatory). However, medical cannabis is not equally effective against all types of pain in humans.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277878/

4. TITLE: Cannabinoids in intestinal inflammation and cancer

PUBLISHED: March 8, 2009

SOURCE: Science Direct

CONCLUSION: Studies on epithelial cells have shown that cannabinoids exert antiproliferative, antimetastatic, and apoptotic effects as well as reducing cytokine release and promoting wound healing. In vivo, cannabinoids – via direct or indirect activation of CB1 and/or CB2 receptors – exert protective effects in well-established models of intestinal inflammation and colon cancer. Pharmacological elevation of endocannabinoid levels may be a promising strategy to counteract intestinal inflammation and colon cancer.

RESEARCH: Izzo A.A., Camilleri M. Cannabinoids in intestinal inflammation and cancer. Pharmacol. Res. 2009;60:117–125. doi: 10.1016/j.phrs.2009.03.008. [PubMed] [CrossRef] [Google Scholar]

5. TITLE: Cannabidiol (CBD) and its analogs: a review of their effects on inflammation

PUBLISHED: April 1, 2015

SOURCE: Science Direct

CONCLUSION: In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed. Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD, and combined THC plus CBD treatment.

RESEARCH: https://www.sciencedirect.com/science/article/abs/pii/S0968089615000838

TITLE: Cannabidiol and the corticoraphe circuit in post-traumatic stress disorder

PUBLISHED: December 2021

SOURCE: IBRO Neuroscience Reports

CONCLUSION: CBD reduces PTSD symptoms via the DRN and corticoraphe circuit. Acute effects of CBD reduce DRN-amygdala excitatory signaling to lessen the activity disparity between the amygdala and mPFC Chronic CBD officially resolves mPFC hypoactivity by facilitating 5-HT release from DRN to mPFC. CBD-facilitated endocannabinoid signaling stabilizes DRN activity and restores mPFC inhibitory control. Chronically administered CBD acts via the corticoraphe circuit to favor fear extinction over fear memory reconsolidation.

RESEARCH: https://www.sciencedirect.com/science/article/pii/S2667242121000324/

1. TITLE: Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

PUBLISHED: March 6, 2019

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Research efforts of the past two decades have undoubtedly proven that cannabinoid signaling profoundly influences several aspects of cutaneous biology, and its dysregulation is likely to contribute to the pathogenesis of several skin diseases.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429381/

2. TITLE: The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities

PUBLISHED: July 14, 2009

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: The main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation, and survival, as well as immune competence and/or tolerance, of skin cells. Pathological alterations in the activity of the fine-tuned cutaneous ECS might promote or lead to the development of certain skin diseases. Therefore, it is envisaged (this is also strongly supported by pilot studies) that the targeted manipulation of the ECS (aiming to normalize the unwanted skin cell growth, sebum production, and skin inflammation) might be beneficial in a multitude of human skin diseases.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/

3. TITLE: Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

PUBLISHED: September 2014

SOURCE: National Library of Medicine

CONCLUSION: In this study, we provide the first evidence that the non-psychotropic phytocannabinoid CBD, which is already applied in clinical practice (16), exerted a unique “trinity of cellular anti-acne actions.” Namely, CBD, without compromising viability (Figure 2, B and C), (a) normalized the pathologically elevated lipogenesis induced by “pro-acne” agents, both in a quantitative and qualitative manner; (b) suppressed cell proliferation (antiproliferative effect); and (c) prevented the actions of TLR activation or “pro-acne” agents to elevate proinflammatory cytokine levels.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/25061872/

4. TITLE: Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study

PUBLISHED: 2005

SOURCE: National Library of Medicine

CONCLUSION: The test product was very well tolerated by all patients. The test product appeared to be effective in reducing both pruritus and xerosis in hemodialysis patients. It is very probable that the observed decrease of pruritus with the test product therapy was not only the result of dry skin improvement but that the addition of endocannabinoids may have also played a role.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/16324422/

5. TITLE: Potential Effects of Cannabidiol as a Wake-Promoting Agent

PUBLISHED: May 2014

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: Several pieces of evidence have shown that CBD acts as a positive compound in different treatments to manage several health conditions, such as psychiatric and neurodegenerative disorders. Thus, it could be plausible to consider the use of CBD to explore its medical properties in somnolence. The current review highlights the pharmacological evidence on the effects of CBD on sleep modulation and provides a putative mechanism of action.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023456/

6. TITLE: A therapeutic effect of CBD-enriched ointment in inflammatory skin diseases and cutaneous scars

PUBLISHED: April 2019

SOURCE: National Library of Medicine

CONCLUSION: Based on skin evaluations (hydration, TEWL, elasticity), clinical questionnaires (SCORAD, ADI, PASI), and supported by photographic data and investigators' clinical assessment, the results showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI index score. No irritant or allergic reactions were documented during the period of treatment. The topical administration of CBD ointment, without any THC, is a safe and effective non-invasive alternative for improving the quality of life in patients with some skin disorders, especially on the inflammatory background.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/30993303/

TITLE: Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study

PUBLISHED: September 2021

SOURCE: Orphanet Journal of Rare Diseases

CONCLUSION: Cannabinoid-based medicines (CBMs) improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduce concomitant medication use. Nevertheless, a direct relation between the use of CBMs and the reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardized CBM preparations in EB are warranted to delineate the risks and benefits of CBMs.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419930/

1. TITLE: Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study

PUBLISHED: October 2021

SOURCE: CNS Drugs

CONCLUSION: Our results strongly suggest the utility of cannabidiol in reducing interictal epileptiform discharges (IEDs) and improving sleep microstructure in children with drug-resistant epilepsy. Larger controlled studies are needed to evaluate the clinical relevance of this effect in different epilepsy types.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551105/

2. TITLE: Cannabis use and sleep: Expectations, outcomes, and the role of age

PUBLISHED: January 2021

SOURCE: Addictive Behaviors

CONCLUSION: Cannabis users have increased expectations of cannabis being a sleep aid, but few associations existed between cannabis use and sleep outcomes. The two exceptions were endorsing any cannabis use and frequency of edible use. Additionally, age may be an important moderator of the potential positive influence CBD concentration can have on sleep.

RESEARCH: https://www.sciencedirect.com/science/article/abs/pii/S0306460320307723

3. TITLE: The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial

PUBLISHED: January 2024

SOURCE: Journal of the American Nutrition Association

CONCLUSION: These findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/37162192/

1. TITLE: Role of Cannabinoids in Obesity

PUBLISHED: September 10, 2018

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: CB1 receptor antagonists may help reduce appetite and control obesity. This is because CB1 receptor agonists block off or “deactivate” the receptor. CBD does not deactivate CB1 receptors but may influence other molecules to block them off. Shutting off these receptors may help reduce the appetite and prevent overeating in some people.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163475/

2. TITLE: Cannabinol and cannabidiol exert opposing effects on rat feeding patterns

PUBLISHED: April 28, 2012

SOURCE: National Library of Medicine

CONCLUSION: Exposure to CBD reduced appetite in rats. While there is plenty of anecdotal evidence to suggest that CBD is helpful for appetite suppression, there have been no direct studies that show CBD reduces appetite in humans.

RESEARCH: https://pubmed.ncbi.nlm.nih.gov/22543671/

3. TITLE: Cannabidiol promotes browning in 3T3-L1 adipocytes

PUBLISHED: April 11, 2016

SOURCE: Molecular and Cellular Biochemistry volume 416

CONCLUSION: The researchers found that CBD plays multiple roles in how the body interacts with fat. Not only did CBD help convert white fat cells into brown fat cells, it also stimulated the body to break down fats more efficiently. The researchers note that CBD may be a promising therapy for preventing obesity, but more studies in humans are necessary.

RESEARCH: https://link.springer.com/article/10.1007/s11010-016-2702-5

4. TITLE: LH-21, A Peripheral Cannabinoid Receptor 1 Antagonist, Exerts Favorable Metabolic Modulation Including Antihypertensive Effect in KKAy Mice by Regulating Inflammatory Cytokines and Adipokines on Adipose Tissue

PUBLISHED: April 20, 2018

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: There is a close link between obesity and several metabolic disorders, such as type 2 diabetes, high blood pressure, and high cholesterol. The overactivation of the CB receptors in the body may be partly responsible for this. Overactivation of the CB1 receptors in the fat tissue throughout the body could contribute to obesity and metabolic risks. CBD helps block off the CB1 receptors, meaning that it might reduce the risk of obesity.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920035/

5. TITLE: An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

PUBLISHED: June 1, 2017

SOURCE: US National Library of Medicine: National Institutes of Health (NCBI)

CONCLUSION: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking. A treatment using CBD reduced total cholesterol by 25 percent in obese rats. The anti-inflammatory and antioxidant effects of CBD also appeared to decrease blood sugar levels and increase markers for liver health.

RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/