Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: randomized, double-blind and controlled placebo clinical trial

“Introduction: Autism Spectrum Disorder is characterized by persistent deficits in social communication, social interaction, and restricted and repetitive patterns of behavior. Some studies have shown that substances derived from Cannabis sativa improve the quality of life of autistic children without causing serious adverse effects, thus providing a therapeutic alternative.

Method: This was a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of a cannabis extract rich in cannabidiol (CBD) in autistic children. Sixty children, aged between 5 and 11 years, were selected and divided into two groups: the treatment group, which received the CBD-rich cannabis extract, and the control group, which received the placebo, both used the product for a period of 12 weeks. Statistical analysis was done by two-factor mixed analysis of variance (ANOVA two way).

Results: Significant results were found for social interaction [F(1,116)=14.13, p=0.0002)], anxiety [F(1,116)=5.99, p=0.016], psychomotor agitation [F(1,116)=9.22, p=0.003)], number of meals a day [F(1,116)=4.11, p=0.04)] and concentration [F (1,48)=6.75, p=0.01], the latter being significant only in mild autism spectrum disorder. Regarding safety, it was found that only three children in the treatment group (9.7%) had adverse effects, namely dizziness, insomnia, colic and weight gain.

Conclusion: CBD-rich cannabis extract was found to improve one of the diagnostic criteria for ASD (social interaction), as well as often co-existing features, and to have few serious adverse effects.”



Efficacy of cannabis and its constituents in disease management: Insights from clinical studies

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“There is a long history of informal use of Cannabis sativa (commonly called cannabis) for many purposes, including treating various ailments worldwide. However, the legalization of cannabis in multiple countries, specifically for medical purposes, has grabbed the researchers’ attention to discover the scientific evidence of cannabis’s beneficial effects. Among over 500 identified compounds (cannabinoids), Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two major active cannabinoids derived from cannabis. Cannabinoids exert their effects through cannabinoid receptors (CB1R and CB2R). In the recent past, clinical trials have shown the efficacy of cannabis and cannabinoids for various human ailments such as cancer, neurological disorders, inflammatory bowel disease, chronic pain, and metabolic disorders. The commonly used constituents and derivatives of cannabis include CBD, THC, THCV, dronabinol, nabilone, and nabiximol. The cannabis constituents have also been used in combination with other agents such as megestrol acetate in some clinical trials. The common routes for the administration of cannabis are oral, sublingual, or topical. Cannabis has also been consumed through smoking, inhalation, or with food and tea. As high as 572 patients and as low as nine patients have participated in a single clinical trial. Cannabis is legalized in some countries with restrictions, such as Belize, Canada, Colombia, Costa Rica, The Czech Republic, Jamaica, Netherlands, South Africa, Spain, and Uruguay. This article provides a compilation of published studies focusing on clinal trials on the therapeutic effects of cannabis. The adverse effects of cannabis and its constituents are also discussed.”



Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol: An in vitro study

Archives of Oral Biology

“Objective: To evaluate the anti-inflammatory and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol (CBD).

Design: The cellular bioactivities of hemp extract and CBD were determined the inhibition of TNF-α and IL-1β in LPS-induced murine macrophage (RAW 264.7) cells by using ELISA while wound healing activity in human gingival fibroblast (HGF-1) cells was performed by a scratch test assay. The cytotoxicity was also concerned and evaluated by MTT assay.

Results: The hemp extract and CBD significantly decreased TNF-α release by up to 91.05 ± 2.91% and 50.78 ± 7.21% of LPS activity, respectively, in a dose-dependent manner, compared to 10 µg/mL hydrocortisone (61.67 ± 3.79%). The hemp extract and CBD also significantly decreased IL-1β release, also in dose-dependent response, up to 78.03 ± 3.34% and 85.87 ± 1.11% of LPS activity, respectively, compared to 5 µg/mL hydrocortisone (80.81 ± 3.55%). The mean percentage of closure of the wound area was 27.92 ± 1.21% when exposed to 5 µg/mL hemp extract and 33.49 ± 1.67% when exposed to 0.5 µg/mL CBD, compared to 24.34 ± 2.29% for non-treated control.

Conclusions: Our study demonstrates that both hemp extract and CBD can inhibit TNF-α and IL-1β production in LPS-induced RAW 264.7 cells and promote wound healing in HGF-1 cells. This is the first to show that short-term exposure to hemp extract and CBD promoted gingival fibroblast wound healing, demonstrating that hemp extract and CBD have potential benefits in the treatment of oral inflammation and ulcers.”




Medical Cannabis Activity Against Inflammation: Active Compounds and Modes of Action

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“Inflammation often develops from acute, chronic, or auto-inflammatory disorders that can lead to compromised organ function. Cannabis (Cannabis sativa) has been used to treat inflammation for millennia, but its use in modern medicine is hampered by a lack of scientific knowledge. Previous studies report that cannabis extracts and inflorescence inhibit inflammatory responses in vitro and in pre-clinical and clinical trials. The endocannabinoid system (ECS) is a modulator of immune system activity, and dysregulation of this system is involved in various chronic inflammations. This system includes cannabinoid receptor types 1 and 2 (CB1 and CB2), arachidonic acid-derived endocannabinoids, and enzymes involved in endocannabinoid metabolism. Cannabis produces a large number of phytocannabinoids and numerous other biomolecules such as terpenes and flavonoids. In multiple experimental models, both in vitro and in vivo, several phytocannabinoids, including Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabigerol (CBG), exhibit activity against inflammation. These phytocannabinoids may bind to ECS and/or other receptors and ameliorate various inflammatory-related diseases by activating several signaling pathways. Synergy between phytocannabinoids, as well as between phytocannabinoids and terpenes, has been demonstrated. Cannabis activity can be improved by selecting the most active plant ingredients (API) while eliminating parts of the whole extract. Moreover, in the future cannabis components might be combined with pharmaceutical drugs to reduce inflammation.”


“Cannabis compounds, in some cases via the endocannabinoids system, were shown to affect some of the cornerstones of chronic inflammation. However, in light of the large number of active molecules produced by cannabis and their sometimes-synergistic interactions, there is a need to better specify cannabis-based treatments and the active compounds, while utilizing the synergy identified between cannabis phytomolecules. Thus, even if CBD or THC are considered potentially leading molecules, additional cannabis-derived compounds may be selected for improved activity.

Future approaches for improved usage of cannabis demand the development, transformation and formulation of full-spectrum cannabis extracts into active plant ingredients (APIs) to achieve higher effectivity.

Importantly, once the mode of action of phytocannabinoids and that of their combination is known, APIs might be targeted towards specific mechanisms involved with inflammation.

Moreover, it might be that cannabis components can be combined with other pharmaceutical drugs to reduce inflammation. “


Medical cannabis use in Canada and its impact on anxiety and depression: A retrospective study

Psychiatry Research

“This was a retrospective study of patients utilizing medical cannabis who received their medical cannabis documentation and allotment from a Harvest Medicine clinic in Canada to determine the impact of medical cannabis on anxiety and depression outcomes. Patients included in the study were at least 18 years of age with completed validated questionnaires for anxiety (GAD-7) and depression (PHQ-9) at their initial evaluation and at least one follow-up visit. There were 7,362 patients included in the sample, of which the average age was 49.8 years, and 53.1% were female.

There were statistically significant improvements between baseline and follow-up scores for both the GAD-7 and PHQ-9, with larger improvements seen for patients who were actively seeking medical cannabis to treat anxiety or depression. From 12 months on, those reporting anxiety had an average decrease in GAD-7 scores that was greater than the minimum clinically important difference of 4, and the same was seen for patients reporting depression from 18 months on, with the average decrease in PHQ-9 scores more than the MCID minimum clinically important difference of 5. This study provides some evidence to support the effectiveness of medical cannabis as a treatment for anxiety and depression.”



Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells

International Immunopharmacology

“Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood.

In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4.

We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.”


“CBD represses viability of human colorectal cancer cells.•

CBD induces cell cycle arrest and increases apoptosis and ER stress in human colorectal cancer cells.•

CBD represses cell viability and induces apoptotic cell death via a CB2-dependent mechanism.”


Antioxidant Activity of Hemp ( Cannabis sativa L.) Seed Oil in Drosophila melanogaster Larvae under Non-Stress and H 2 O 2-Induced Oxidative Stress Conditions


“The oil extracted from hemp seeds has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. The potential of this oil for the prevention of oxidative stress and for the treatment of oxidative-stress-induced ailments is of increasing interest. Most studies of hemp seed oil were conducted in-vitro, meaning we lack information about effects and activity in vivo. In the present study, we evaluated the hypothesis that hemp seed oil at different concentrations improves the oxidative state of D. melanogaster, under non-stress as well as hydrogen-peroxide-induced stress. We analyzed the effects of hemp seed oil on oxidative stress markers and on the life cycle of D.melanogaster under non-stress and hydrogen-peroxide-induced stress conditions. D.melanogaster larvae were exposed to hemp seed oil concentrations ranging from 12.5 to 125 μL/mL. The results revealed that under non-stress conditions, oil concentrations up to 62.5 µL/mL did not induce negative effects on the life cycle of D. melanogaster and maintained the redox status of the larval cells at similar levels to the control level. Under oxidative stress conditions, biochemical parameters were significantly affected and only two oil concentrations, 18.7 and 31.2 µL/mL, provided protection against hydrogen peroxide stress effects. A higher oil concentration (125 μL/mL) exerted negative effects on the oxidative status and increased larval mortality. The tested oil was characterized chemically by NMR, transesterification, and silylation, followed by GC-MS analyses, and was shown to contain polyunsaturated fatty acid triglycerides and low levels of tocopherols. The high levels of linoleic and linolenic acids in the oil are suggested to be responsible for the observed in vivo antioxidant effects. Taken together, the results show that hemp seed oil is effective for reducing oxidative stress at the cellular level, thus supporting the hypothesis. The obtained results point to the potential of hemp seed oil for the prevention and treatment of conditions caused by the action of reactive oxygen species.”



A review on the techno-functional, biological, and health-promoting properties of hempseed-derived proteins and peptides

Journal of Food Biochemistry

“Protein-energy malnutrition is a global challenge that demands urgent attention, especially with the increasing population growth and unmatched food security plans. One strategy is to expand the list of protein sources, such as neglected and underutilized crops, with high protein content. A good number of plant proteins, in addition to their nutritional benefits, exert therapeutic properties as seen in seeds derived from legumes and emerging sources such as hemp. In this review, the transepithelial transport, functional, and biological properties of hempseed proteins (HSPs) and peptides were discussed. The review also described the potential safety issues of incorporating hempseeds in food products. Due to the multitargeted effects of hempseed-derived proteins and their peptides against many chronic diseases, and their functional properties, current knowledge shows that hempseed has tremendous potential for functional food and nutraceutical applications.

PRACTICAL APPLICATIONS: The alarming rate of malnutrition and the attendant health consequences demand that underexploited nutrient-rich crops should be incorporated as part of our common dietary sources. Among these crops, hempseed is gaining attention as an emerging source of proteins and peptides with promising potential in prevention and management of chronic diseases such as diabetes, hypertension, cancer, hypercholesterolemia, obesity, and diseases whose etiology involves oxidative stress and inflammation. Fortunately, a growing body of research evidence is demonstrating that hempseed is a reservoir of proteins and peptides with nutraceutical potentials for curbing life-threatening diseases.”



Tobacco, but Neither Cannabis Smoking Nor Co-Drug Use, Is Associated With Hearing Loss in the National Health and Nutrition Examination Survey, 2011 to 2012 and 2015 to 2016

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A relationship between tobacco smoking and hearing loss has been reported; associations with cannabis smoking are unknown. In this cross-sectional population-based study, we examined relationships between hearing loss and smoking (tobacco, cannabis, or co-drug use).

Methods: We explored the relationship between hearing loss and smoking among 2705 participants [mean age = 39.41 (SE: 0.36) years] in the National Health and Nutrition Examination Survey (2011 to 12; 2015 to 16). Smoking status was obtained via questionnaire; four mutually exclusive groups were defined: nonsmokers, current regular cannabis smokers, current regular tobacco smokers, and co-drug users. Hearing sensitivity (0.5 to 8 kHz) was assessed, and two puretone averages (PTAs) computed: low- (PTA0.5,1,2) and high-frequency (PTA3,4,6,8). We defined hearing loss as threshold >15 dB HL. Multivariable logistic regression was used to examine sex-specific associations between smoking and hearing loss in the poorer ear (selected based on PTA0.5,1,2) adjusting for age, sex, race/ethnicity, hypertension, diabetes, education, and noise exposure with sample weights applied.

Results: In the age-sex adjusted model, tobacco smokers had increased odds of low- and high-frequency hearing loss compared with non-smokers [odds ratio (OR) = 1.58, 95% confidence ratio (CI): 1.05 to 2.37 and OR = 1.97, 95% CI: 1.58 to 2.45, respectively]. Co-drug users also had greater odds of low- and high-frequency hearing loss [OR = 2.07, 95% CI: 1.10 to 3.91 and OR = 2.24, 95% CI: 1.27 to 3.96, respectively]. In the fully adjusted multivariable model, compared with non-smokers, tobacco smokers had greater odds of high-frequency hearing loss [multivariable adjusted odds ratio = 1.64, 95% CI: 1.28-2.09]. However, in the fully adjusted model, there were no statistically significant relationships between hearing loss (PTA0.5,1,2 or PTA3,4,6,8) and cannabis smoking or co-drug use.

Discussion: Cannabis smoking without concomitant tobacco consumption is not associated with hearing loss. However, sole use of cannabis was relatively rare and the prevalence of hearing loss in this population was low, limiting generalizability of the results. This study suggests that tobacco smoking may be a risk factor for hearing loss but does not support an association between hearing loss and cannabis smoking. More definitive evidence could be derived using physiological measures of auditory function in smokers and from longitudinal studies.”



Management of chronic pain with Jalaprakshalana (water-wash) Shodhita (processed) Bhanga ( Cannabis sativa L.) in cancer patients with deprived quality of life: An open-label single arm clinical trial

“Introduction: Pain is a common and complex symptom of cancer having physical, social, spiritual and psychological aspects. Approximately 70%-80% of cancer patients experiences pain, as reported in India. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis) for the management of pain but no research yet carried out on its clinical effectiveness.

Objective: To assess the analgesic potential of Jala-Prakshalana (Water-wash) processed Cannabis sativa L. leaves powder in cancer patients with deprived quality of life (QOL) through openlabel single arm clinical trial.

Materials and methods: Waterwash processed Cannabis leaves powder filled in capsule, was administered in 24 cancer patients with deprived QOL presenting complaints of pain, anxiety or depression; for a period of 4 weeks; in a dose of 250 mg thrice a day; along with 50 ml of cow’s milk and 4 g of crystal sugar. Primary outcome i.e. pain was measured by Wong-Bakers FACES Pain Scale (FACES), Objective Pain Assessment (OPA) scale and Neuropathic Pain Scale (NPS). Secondary outcome namely anxiety was quantified by Hospital Anxiety and Depression Scale (HADS), QOL by FACT-G scale, performance score by Eastern Cooperative Oncology Group (ECOG) and Karnofsky score.

Results: Significant reduction in pain was found on FACES Pain Scale (P < 0.05), OPA (P < 0.05), NPS (P < 0.001), HADS (P < 0.001), FACT-G scale (P < 0.001), performance status score like ECOG (P < 0.05) and Karnofsky score (P < 0.01).

Conclusion: Jalaprakshalana Shodhita Bhanga powder in a dose of 250 mg thrice per day; relieves cancerinduced pain, anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period.”


“Administration of Jalaprakshalana Shodhita Bhanga (water-wash processed Cannabis) leaves powder in dose of 250 mg thrice a day with 50 ml of cow’s milk and 4 g sugar as an adjuvant, for a period of 1 month; significantly relieves pain, anxiety and depression of cancer patients without creating any major side effects, dependency and withdrawal symptoms. Processed Cannabis is significantly effective for improvement in QOL of a cancer patient.”