CBD Clinical Trials

CBD Clinical Trials
CBD Clinical Trials

Whilst CBD seems to be the new craze, many people still don’t fully
understand the true benefits that CBD has to offer. The widespread
notoriety of CBD has garnered a variety of clinical trials to be
undertaken with the purpose of bringing awareness to how CBD
affects the body. We believe our consumers should be fully
educated on cannabidiol and have easy access to the various trials
for themselves. As a result we are on the mission to create a full
database with the newest and most reliable research conducted on
CBD worldwide.
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1. Pain and Inflammation
2. Anxiety, Stress, PTSD
3. Addiction (opioid epidemic)
4. Arthritis
5. Cancer
6. Covid-19
7. Weight loss and Metabolism
8. Insomnia
9. Neurodegenerative Disorders
10. Skin
Pain and Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid
Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment
of Neuropathic Pain Including Neuropathic Orofacial Pain
Inflammation 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/
Pharmacokinetics, Safety, and Clinical Efficacy

of Cannabidiol Treatment in Osteoarthritic Dogs
PUBLISHED: July 23, 2018
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.
Cannabinoids and Pain: New Insights From Old Molecules
Pain and
PUBLISHED: November 13, 2018
CONCLUSION: Cannabinoids (plant-derived, synthetic) themselves or endocannabinoid-directed therapeutic
Inflammation 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.
Cannabinoids in intestinal inflammation and cancer

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: 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]
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
Cannabidiol as a Potential Treatment for Anxiety Disorders
PUBLISHED: September 4, 2015
Anxiety, Stress,
CONCLUSION: Preclinical evidence conclusively demonstrates CBD’s efficacy in reducing anxiety
behaviours relevant to multiple disorders, including PTSD, GAD, PD, OCD, and SAD, with a notable
PTSD
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.
Overall, existing preclinical evidence strongly supports the
RESEARCH: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/ potential of CBD as a treatment for anxiety disorders. CBD
exhibits a broad range of actions, relevant to multiple symptom
An experimental randomized study on the analgesic effects of domains, including anxiolytic, panicolytic, and anticompulsive
actions, as well as a decrease in autonomic arousal, a
pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia decrease in conditioned fear expression, enhancement of fear
extinction, reconsolidation blockade, and prevention of the
PUBLISHED: April 2019
long-term anxiogenic effects of stress.
SOURCE: US National Library of Medicine: National Institutes of Health (NCBI) Evidence from human studies strongly supports the potential
CONCLUSION: The most important observation is that when simultaneously inhaled, THC and CBD for CBD as a treatment for anxiety disorders: at oral doses
ranging from 300 to 600 mg, CBD reduces experimentally
interact in complex fashions with synergistic pharmacokinetic but antagonistic pharmacodynamic
induced anxiety in healthy controls, without affecting baseline
interactions. The analgesic efficacy of active treatment was limited to varieties that contained THC anxiety levels, and reduces anxiety in patients with SAD.
and was observed exclusively in the evoked pressure pain model.
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
Addiction PUBLISHED: May 21, 2019
SOURCE: The American Journal of Psychiatry
(opioid epidemic) 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
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 —histories predicts therapeutic potential for addiction
treatment across several classes of abused drugs.
RESEARCH: https://www.nature.com/articles/s41386-018-0050-8
Cannabidiol (CBD): a killer for inflammatory rheumatoid
Arthritis
arthritis synovial fibroblasts
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.
Transdermal cannabidiol reduces inflammation and pain-related

behaviours in a rat model of arthritis
PUBLISHED: October 30, 2015
CONCLUSION: These data indicate that topical CBD application has therapeutic potential for relief
of arthritis pain-related behaviours and inflammation without evident side-effects.
Cannabidiol directly targets mitochondria and disturbs calcium
homeostasis in acute lymphoblastic leukemia
PUBLISHED: October 14, 2019
Cancer
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 plausible candidate to
be included into chemotherapeutic protocols.
Cannabinoids as therapeutic agents in cancer: current status

and future implications
CONCLUSION: Cannabinoids exert a direct anti-proliferative effect on tumors of different origin. 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 plant
containing multiple cannabinoids, terpenes and flavanoids. Thus, combination of cannabinoids with other
chemotherapeutic drugs might provide a potent clinical outcome, reduce toxicity, increase specificity and
overcome drug resistance complications.
Cannabinoids Induce Cancer Cell Proliferation via Tumor
Necrosis Factor α-Converting Enzyme (TACE/ADAM17)-Mediated
Transactivation of the Epidermal Growth Factor Receptor
Cancer 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]
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 model
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 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
Covid-19
Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress
Syndrome Induced by Simulated Viral Infection Using Synthetic RNA
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
Role of Cannabinoids in Obesity
Weight loss PUBLISHED: September 10, 2018

CONCLUSION: CB1 receptor antagonists may help reduce appetite and control obesity. This is because CB1
and Metabolism 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.
Cannabinol and cannabidiol exert opposing effects on rat feeding patterns

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/
Cannabidiol promotes browning in 3T3-L1 adipocytes

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
Weight loss 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
and Metabolism PUBLISHED: April 20, 2018
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.
An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical

Data and Relevant Animal Studies
PUBLISHED: June 1, 2017
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.
Cannabidiol in Anxiety and Sleep: A Large Case Series
PUBLISHED: January 7, 2019
Insomnia
CONCLUSION: Cannabidiol may hold benefit 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.
Cannabinoids and Pain: New Insights From Old Molecules

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

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
Potential Effects of Cannabidiol as a Wake-Promoting Agent

PUBLISHED: May 2014
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.
Neurodegenerative
Disorders Cannabinoid Actions on Neural Stem Cells: Implications
for Pathophysiology
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 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
potential to be impactful in clinics and society.
Cannabinoid Signaling in the Skin: Therapeutic Potential of the
“C(ut)annabinoid” System
Skin
CONCLUSION: Research efforts of the past two decades have undoubtedly proven that cannabinoid
signaling profoundly influences several aspects of the cutaneous biology, and its dysregulation is
likely to contribute to the pathogenesis of several skin diseases.
The endocannabinoid system of the skin in health and disease: novel

perspectives and therapeutic opportunities
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.
Cannabidiol exerts sebostatic and antiinflammatory effects
Skin
on human sebocytes
PUBLISHED: September 2014
CONCLUSION: In this study, we provide the first evidence that the nonpsychotropic 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.
Efficacy and tolerance of the cream containing structured physiological lipids

with endocannabinoids in the treatment of uremic pruritus: a preliminary study
PUBLISHED: 2005
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.
Potential Effects of Cannabidiol as a Wake-Promoting Agent
PUBLISHED: May 2014
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
Skin
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.
A therapeutic effect of CBD-enriched ointment in inflammatory skin

diseases and cutaneous scars
PUBLISHED: April 2019
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 treatment. The topical administration of CBD ointment, without any THC,
is a safe and effective non-invasive alternative for improve the quality of life in patients with some skin
disorders, especially on inflammatory background.

CBD Clinical Trials - Reakiro (02.08)

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CBD Clinical Trials

Inflammation PUBLISHED: February 20, 2020

Pharmacokinetics, Safety, and Clinical Efficacy

Cannabinoids in intestinal inflammation and cancer

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

Unique treatment potential of cannabidiol for the prevention of relapse

Transdermal cannabidiol reduces inflammation and pain-related

Cannabinoids as therapeutic agents in cancer: current status

Cancer PUBLISHED: March 2004

Cannabinoids for Cancer Treatment: Progress and Promise

Weight loss PUBLISHED: September 10, 2018

Cannabinol and cannabidiol exert opposing effects on rat feeding patterns

Cannabidiol promotes browning in 3T3-L1 adipocytes

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical

Cannabinoids and Pain: New Insights From Old Molecules

Cannabis, Cannabinoids, and Sleep: a Review of the Literature

Potential Effects of Cannabidiol as a Wake-Promoting Agent

The endocannabinoid system of the skin in health and disease: novel

Efficacy and tolerance of the cream containing structured physiological lipids

A therapeutic effect of CBD-enriched ointment in inflammatory skin

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