SELECTION OF THE SCIENTIC ANALYSIS OF INDICATIONS FOR CBD OIL
ANXIETY DISORDERS AND POST TRAUMATIC STRESS DISORDER
DYSTONIA AND DYSKINESIA
DEPENDENCY AND WITHDRAWAL
NAUSEA AND VOMITING
OVINE SPONGIFORME ENCEPHALOPATHY (MAD COW DISEASE)
ANXIETY DISORDERS AND POST TRAUMATIC STRESS DISORDER
LIVER AND BRAIN DAMAGE
ALLERGIES AND ASTHMA
ANXIETY DISORDERS AND POST TRAUMATIC STRESS DISORDER
Animal models that have CBD have shown anxiolytic effects (Twardowschy et al. 2013, Do Monte et al. 2013, Campos et al. 2012, Stern et al. 2012, Elbatsh et al. 2012) and humans (Zuardi et al. 1993, Das et al. 2013, Bergamaschi et al. 2011, Crippa et al. 2010).
In a clinical study, a camera was placed in front of the subjects and they were asked to talk (Zuardi et al. 1993). In this method, the anxiolytic and anxiogenic compounds increase the subject nervousness and it is physiological related. Under a double-blind design CBD (300 mg, P.O.) was compared to ipsapirone (5-HT1A partial agonist, 5 mg), diazepam (anxiolytic benzodiazepine, 10 mg) or placebo. The test results showed that both CBD and the two other anxiolytic compounds reduced anxiety. When given at this dose CBD did not cause any major sedative effects. With these results, the claim that CBD has anxiolytic properties is strongly supported.
An experiment was conducted and the 48 healthy participants that were used underwent a fear-conditioning test CBD improved consolidation of later elimination learning and this might be useful in anxiety issues (Das et al. 2013). 32 mg of CBD were given to the participants either following before or after in a double blind, placebo-controlled design. The treatment groups showed successful conditioning and extinction. CBD gave post-extinction improved consolidation of extinction learning. No serious effects of CBD were found on extinction.
The effects of CBD on patients that had generalized social disorder were studied by Scientists at the University of Sao Paulo, Brazil (Bergamaschi et al. 2011). Three groups were analyzed, 12 healthy controls with no drugs, 12 patients with anxiety disorder, who got a single dose of CBD (600 mg) and a group of 12 patients, who got a placebo in a double-blind design. Pretreatment with CBD greatly reduced anxiety, cognitive impairment and inconvenience in the speech performance of patients with social anxiety disorder, and it greatly reduced alert in their anticipatory speech. The placebo group exhibited higher anxiety, cognitive impairment, distress, and alert levels when compared and the control group. No huge differences were seen between patients, who had gotten CBD, and healthy controls in anxiety cores or in cognitive impairment, discomfort, and alert factors. This study verifies past research of a similar group involving 10 patients with social anxiety disorder (Crippa et al. 2010).Research has shown that the anxiolytic effects of CBD in mice were caused by the presence of serotonin 5-TH1A receptor (Twardowschy et al. 2013). When this receptor is blocked the anti-panic effects of the natural cannabinoid is reduced. When microinjections of CBD are continually injected into the infralimbic cortex of mice it helped in fear extinction (Do Monte et al. 2013). The CB1 receptor helped reduced this effect. CBD reduced the fear in rats that were exposed to cats one hour after they were exposed to the predator (Campos et al. 2012). The 5-HT1A receptor to a certain extent reduced the effect. “Our results suggest that CBD has a beneficial potential for PTSD [posttraumatic stress disorder] treatment and that 5-HT1A receptors could be a therapeutic target in this disorder” this was the conclusion that was reached by the authors. Animal researchers at the University of Nottingham, UK, reached a different conclusion, that cannabidiol increased anxiety in rats (Elbatsh et al. 2012). CBD was administered to the rats for 14 days. The researchers concluded that when CBD is administered in excess it creates an anxiogenic-like impact in clear opposition to the acute anxiolytic profile previously reported.”
The first study was carried out on the likely antipsychotic effects in humans and the test was carried out on a schizophrenic patient who had serious hormonal side effects during treatment with a common antipsychotic (Zuardi et al. 1995). The patient used was a 19-year-old lady who was admitted to the inpatient unit of the Clinical Hospital of Ribeirão Preto in the light of her aggressive behavior, self injury, incoherent thoughts and auditory hallucinations. She was administered CBD in relatively high amounts, up to 1500 mg/day (in two separate doses) within four weeks. The administration of CBD was stopped and it was replaced by a placebo for 4days. From that point onward, haloperidol was administered. The dosage was changed depending on clinical assessment. Diazepam was administered when the patient was very agitated. After the beginning of the CBD treatment the average daily dose of diazepam was reduced from 16.3 to 5.7 mg/day. Two therapists and two medical attendant assistants assessed the patient and the meetings were recorded. The patient was videoed and analyzed by two psychiatrists and two auxiliary nurses. After the study the video tapes were analyzed blindly in a random order by another psychiatrist. The symptoms reduced after the CBD treatment and there was a pattern that emerged that showed that the symptoms got worse after the drug withdrawal. The change obtained with CBD was not increased by haloperidol. This change was found in all items of the rating scale used, including all things that can be associated with psychotic symptoms, making it impossible that an anxiolytic activity was the sole effect of the antipsychotic effect.
The University of Sao Paulo conducted an open pilot study and CBD was found to be effective in the treatment of psychotic symptoms in patients with Parkinson’s disease (Zuardi et al. 2008). The study was conducted by six consecutive patients (four men and two ladies) who had been diagnosed with the Parkinson’s disease and who had psychosis for no less than 3 months were chosen for the study. All patients were administered CBD in flexible doses (starting with an oral dose of 150 mg/day) for 4 weeks, along with their usual therapy. With CBD the psychotic symptoms were drastically reduced. While under the treatment of CBD their motor function was not worsened. During the treatments no adverse effects were observed. The conclusion that was reached by the Authors was that “the preliminary data indicates that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.”
The University of Cologne conducted the first controlled clinical study with 42 patients experiencing acute schizophrenia. The study showed that CBD drastically reduced the psychopathological symptoms, when compared to the initial status (Leweke et al. 2012). 800mg of oral CBD was administered to half of them daily for four weeks and the other half were given a standard medicinal drug Amisulpride, a potent antipsychotic, in a double-blinded way. Both treatments were safe and it led to significant clinical changes, but CBD’s effects were significantly lower. In addition, the increase in blood anandamide levels was caused by the cannabidiol treatment. The Authors concluded that “The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.”
Experiments have shown that several cell and animals have demonstrated that THC as well as CBD has anticancer effects (Ligresti et al. 2006, McKallip et al. 2006, McAllister et al. 2007, Marcu et al. 2010, Solinas et al. 2013, Scott et al. 2013, Solinas et al. 2012, De Petrocellis et al. 2013, Ramer et al. 2012, Shrivastava et al. 2011, Torres et al. 2011). Up until now, no clinical examinations have been carried out and no conclusion can be drawn on it impacts in humans.
The anti-tumor effects have been examined by Italian researchers of five natural cannabinoids of the cannabis plant (cannabidiol, cannabigerol, cannabichromene, cannabidiol-corrosive and THC-corrosive) in breast cancer (Ligresti et al. 2006). Cannabidiol was found to be the most potent cannabinoid and it stopped the growth of human breast cancer cells that had been infused under the skin of mice. CBD was also found to reduce the lung metastases of human breast cancer cells that had been infused into the paws of the animals. Researchers also discovered that the anti-tumour impacts of CBD were caused by the induction of apoptosis. They reached a conclusion with the data that supports further testing of cannabidiol and cannabidiol-rich concentrates for the potential treatment of cancer.
US researchers supported their findings and also discovered that exposure of leukemia cells to CBD drastically reduced cell viability and induction of apoptosis (McKallip et al. 2006). CBD has been found to reduce the number of leukemia cells in living animals. In a mouse model of metastatic breast cancer CBD greatly diminished the aggressive behavior of breast cancer cells (McAllister et al. 2007). CBD stopped the growth of a protein called Id-1. Id proteins that is vital in the growth of tumor cells. Researchers at the California Pacific Medical Center Research Institute came to a conclusion that, CBD is the first nontoxic exogenous agent that can greatly reduce Id-1 expression in metastatic breast cancer cells which reduces the tumor aggressiveness.
Cannabidiol (CBD) has also been discovered to stop the formation of new blood vessels, called angiogenesis, in tumors by various ways (Solinas et al. 2012). Scientists reached a conclusion that “It’s double impact on both tumor and endothelial cells gives strength to the theory that CBD could help in the treatment of cancer.”
Researchers at the California Pacific Medical Center Research Institute in San Francisco discovered that CBD increased the inhibitory impacts of dronabinol (THC) on human brain cancer cell multiplication and survival (Marcu et al. 2010). The two natural cannabinoids were tested on two glioblastoma cells lines. THC and CBD acted synergistically to stop cell multiplication. When the glioblastoma cells were treated with both compounds it led to significant adjustments of the cell cycle, induction of reactive oxygen species (free radicals) and apoptosis (programmed cell). There were detailed changes that were not seen with either compound separately, showing that the signal transduction pathways influenced by the combination treatment were unique. Scientists concluded that these results propose that the addition of cannabidiol to delta-9-THC may improve the general viability of delta-9-THC in the treatment of glioblastoma in disease patients.”
Different groups ascertained the anti-cancer effects of CBD in glioma (Solinas et al. 2013) and leukemia cells (Scott et al. 2013). Different Cannabinoids in the study of leukemia increased the effect of cancer. The lead scientist stated that “These agents are able to hinder the development of cancerous cells, thereby stopping and preventing them from growing. In some cases, when specific dosage patterns are used they can destroy cancer cells on their own. When used in combination with existing treatment, it could be highly effective in the treatment of cancer.”
CBD and a few cannabis extracts can reduce the potency of prostate cancer cells (De Petrocellis et al. 2013). With the cell findings at the University of Rostock, Germany, CBD represses lung cancer metastasis by increasing the concentration of a specific protein (ICAM-1) (Ramer et al. 2012).
Researchers at the Complutense University in Madrid, Spain, researched the effects of a blend of cannabinoids and temozolomide (TMZ) in the treatment of glioblastoma multiforme in animals (Torres et al. 2011). When submaximal dosages of THC and CBD were administered it greatly reduced the growth of gliomas. In addition, treatment with TMZ and submaximal doses of THC and CBD delivered a powerful anti-tumoural activity in both TMZ-sensitive and TMZ-resistant tumors. The Authors proposed that the combined administration of TMZ and cannabinoids could be therapeutically exploited for the management of glioblastoma multiforme (glioma).
4 DYSTONIA AND DYSKINESIA
A couple of clinical examinations propose a therapeutic potential of CBD in movement disorders (Consroe et al. 1986, Snider et al. 1984).
A case of Meige disorder in a patient was reported in 1984 and the news was published (Snider et al. 1984). The patient benefitted from the treatment with 200 mg CBD. Meige syndrome is a type of dystonia affecting the eyelid and muscles of the face.
Five patients with dystonic movement disorder were given CBD in the beginning of the open pilot study (Consroe et al. 1986). Oral doses of CBD were given to them and it rose from 100 to 600 mg/day over 6 weeks and it was administered alongside the standard medication. Dosage related changes in dystonia were seen in all patients and it ranged from 20 to 50%. The side effects of CBD were gentle and included hypotension, dry mouth, psychomotor slowing, lightheadedness, and sedation. Two patients with coexisting Parkinsonian symptoms, CBD at doses more than 300 mg/day worsen the hypokinesia and resting tremor.
Studies that have been carried out on mice indicate that natural cannabinoid CBD weakened catalepsy, characterized by rigidity and fixture of posture (Gomes et al. 2013). Catalepsy was caused by the antipsychotic drug haloperidol, by L-nitro-N-arginine (L-NOARG) or by the engineered cannabinoid WIN55,212-2, which acts like THC. Scientists discovered that “these results show that CBD can weaken catalepsy caused by various mechanisms (…) by means of 5-HT1A receptors activation, proposing that it could be valuable in the treatment of striatal disorders.” Parkinson’s disease and dyskinesia are amongst the disorders.
Animal research (Shirazizand et al. 2013, Jones et al. 2012, Jones et al. 2011), anecdotal evidence and one clinical study (Cunha et al. 1980) demonstrates that CBD has anti-epileptic properties. In the first phase of the only clinical study up to now, 3 mg/kg day by day of CBD was given for 30 days to 8 healthy human volunteers (Cunha et al. 1980). In a double-blind setting another 8 volunteers got a similar number of identical capsules containing glucose as placebo. Neurological and physical examinations, blood and urine analysis, ECG and EEG were carried out at weekly intervals.
In the second stage of the study, 15 patients suffering from secondary generalize epilepsy with temporal focus were divided into two random groups. Every patient got, a double-blinded procedure, 200-300 mg daily of CBD or placebo. The drugs were administered to the patients for 4½ months. All through the experiment the patients kept on taking the antiepileptic drugs recommended before the experiment, despite the fact that these drugs never controlled the signs of the disease. During the experiment all the patients and volunteers tolerated CBD exceptionally well and no indications of toxicity or side effects. Out of all the patients 4 of the 8 CBD subjects remained free of convulsive crisis all through the experiment and 3 different patients exhibited improvements in their clinical condition. One patient did not respond to CBD. Seven of the placebo patients’ clinical conditions stayed unchanged while the condition of 1 patient greatly improved.
CBD reduced seizures in mice, in which seizures were caused by pentylenetetrazol (PTZ) and electroshocks (Shirazizand et al. 2013). In two other animal models of seizures, CBD showed antiepileptic effects (Jones et al. 2012). CBD greatly reduced the percentage of animals experiencing the most serious seizures in the pilocarpine model. In the penicillin model, CBD greatly reduced the rate of mortality because of seizures; CBD likewise reduced the rate of animals experiencing the most severe tonic-clonic seizures. Researchers at the University of Reading, UK, concluded that CBD exerted anti-convulsant effects in animal models of temporal lobe or partial seizures (Jones et al. 2011).
6 DEPENDENCY AND WITHDRAWAL
Basic research (Justinova et al. 2013, Mahgoub et al. 2013, Katsidoni et al. 2013) and one case report (Crippa et al. 2013) suggest that CBD has a therapeutic potential in dependency and withdrawal.
Two basic research groups in the United Arab Emirates and the USA point to a possible mechanism, in which CBD can be used to treat cannabis dependence. Researchers of the National Institute on Drug Abuse in Baltimore, USA, showed that kynurenic acid, which stops the alpha-7-nicotinic acetylcholine receptors (alpha7-nACh receptor), lessened the rewarding effects of THC in rats and monkeys, who were reliant on THC (Justinova et al. 2013). Kynurenic acid is a result of the normal digestion of the amino acid L-tryptophan. Researchers wrote that the modulation of kynurenic acid “offers a pharmacological strategy for accomplishing abstinence from marijuana and preventing relapse.”
A group from the College of Medicine and Health Sciences of the University of Abu Dhabi in AL Ain, United Arab Emirates, demonstrated that CBD stops acetylcholine-induced currents at the alpha-7-nicotinic acetylcholine receptors (Mahgoub et al. 2013). The conclusion reached was that their results “demonstrate that CBD stops the role of the alpha7-nACh receptor.” Other components might be involved in these effects of CBD.
When rats with CBD were studied it showed that it stopped the reward-facilitating effects of morphine (Katsidoni et al. 2013). The effects were mediated by activation of 5-HT1A receptors in a central brain region (dorsal raphe). Researchers reached a conclusion that “cannabidiol might be clinically helpful in weakening the rewarding effects of opioids.”
In an examination at the Ribeirão Preto Medical School of the University of São Paulo, Brazil, a 19-year-old lady with withdrawal symptoms after she stopped the use of cannabis benefitted from a treatment with CBD (Crippa et al. 2013). The daily symptom assessments showed the absence of significant withdrawal, anxiety and other symptoms during the treatment. Scientists reached the conclusion that “CBD can be powerful for the treatment of cannabis withdrawal symptoms.”
Basic research hints that CBD might be valuable in the treatment of diabetes and it may prevent complications of the disease, for example, damage to the blood vessels (Weiss et al. 2006, Stanley et al. 2013, Liou et al. 2009, Ohki et al. 2010).
Scientists at the Hadassah University Hospital of Jerusalem examined the impacts of CBD in mice that were affected by diabetes, which developed by genetic factors (Weiss et al. 2006). So-called NOD mice developed insulitis inside 4 to 5 weeks of age followed by diabetes inside an average of 14 weeks. Insulitis is an inflammation of the cells in the pancreas that produce insulin, and diabetes is a consequence of a destruction of these cells. NOD mice that were 6 to 12 weeks were treated with 10 to 20 injections of CBD (5 mg for each kilogram of body weight) this resulted in a great reduction in the incidence of diabetes of 30% compared to 86% in untreated control mice. Also, in the mice that had diabetes in the treated group, the disease symptoms were drastically delayed. Blood levels of two cytokines that enhance inflammation, IFN-gamma and TFN-alpha, are normally increased in NOD mice. A treatment with CBD caused a huge decrease (more than 70%) in levels of the two cytokines. In another analysis CBD-treated mice were observed for 26 weeks. While the 5 control mice developed diabetes, 3 of 5 of the CBD-treated mice remained without diabetes at 26 weeks. Researchers reached a conclusion that confirmation of the observed immunomodulatory effects of CBD “may led the clinical use of this agent in the prevention of 1 diabetes” and plausibly other autoimmune diseases. They noted that a lot of patients with type 1 diabetes have adequate residual cells that produce insulin during the period of diagnosis, and might be a contender for immunomodulation therapy.
Studies suggest that increased circulating endocannabinoids may adjust the function of blood vessels both positively and adversely in type 2 diabetes, and “that part of the positive effect of cannabidiol in diabetes might be because of improved endothelium-subordinate vasorelaxation” (Stanley et al. 2013). Researchers at the Medical College of Georgia in Augusta, USA, proposed that CBD might be a helpful novel treatment choice for the damage of the retina in diabetes (diabetic retinopathy) (Liou et al. 2009). As indicated by the research that was conducted by the National Institutes of Health in Bethesda, USA, CBD lessens cardiac dysfunction, oxidative stress, fibrosis, inflammation, and cell death in animal models of diabetic cardiomyopathy (Ohki et al. 2010). The authors concluded that “the results coupled with the excellent safety and tolerability profile of CBD in people, give strong reason that it might have great therapeutic potential in the treatment of diabetic complications and maybe other cardiovascular disorders.”
8 NAUSEA AND VOMITING
Anecdotal evidence and basic research suggest the possibility of CBD acid (CBDA) to decrease nausea and vomiting as a result of various causes (Rock et al. 2013, Rock et al. 2013b, Rock et al. 2012, Parker et al. 2011).
In rats, the impacts of metoclopramide, a medicinal drug used as a part of the treatment of nausea and vomiting, were increased by cannabidiolic acid (CBDA) (Rock et al. 2013). Researchers reached a conclusion that “CBDA could be a strong adjunct treatment to anti-emetic regimens for chemotherapy-incited nausea.” CBDA likewise acted synergistically in the mix with low doses of the highly effective anti-nausea drug ondansetron (Rock et al. 2013b). A study involving rats and shrews cannabidiolic acid (CBDA) reduced nausea and vomiting by enhancing 5-HT1A receptor activation (Rock et al. 2012).
CBD might be useful in obesity (Farrimond et al. 2012, Ignatowska-Jankowska et al. 2010, Scopinho et al. 2011). Please see above paragraph on “Antagonism of THC effects.”
GW Pharmaceuticals state that four small clinical studies are being conducted to investigate the effects of two natural cannabinoids in obesity related diseases (UPI of 8 July 2012). These cannabinoids are CBD and tetrahydrocannabivarin (THCV), which have shown to reduce appetite in animal studies. The compounds had an effect on the level of fat in the body and its reaction to insulin.
CBD greatly reduced food consumption in animals (Farrimond et al. 2012). According to the University of Gdansk, Poland, CBD reduced body weight gain in rats in a dosage dependent manner (Ignatowska-Jankowska et al. 2010). CB2 receptor had an effect. Specialists at the University of Sao Paulo, Brazil, showed that CBD stopped the increased appetite caused by CB1 receptor agonists (Scopinho et al. 2011). The study suggests that “its role as a possible food intake regulator should be studied further.”
In young rats the results of mechanical damage to the sciatic nerve was lessened by CBD (Perez et al. 2013). The authors concluded that “the present outcomes demonstrate that CBD has neuroprotective properties that may, in turn, be promising for future clinical use.”
11 BOVINE SPONGIFORME ENCEPHALOPATHY (MAD COW DISEASE)
Scientists conducted some basic research at the National Center for Scientific Research in Valbonne, France, that CBD may prevent the development of prion disease, the most known being BSE (bovine spongiforme encephalopathy), which is frequently called distraught dairy animals ailment (Dirikoc et al. 2007). There is an assumption that BSE maybe transmitted to human beings. In humans, it is known as Creutzfeldt-Jakob disease.
The infectious agent in prion diseases is believed to be a specific type of misfolded protein called prion. Misfolded prion proteins carry the infection amongst people and causes deterioration of the brain. The researchers reported that CBD stopped the aggregation of prion proteins in both mouse and sheep prion-infected cells, while different cannabinoids were either powerless or not successful. In addition, after infection with mouse scrapie, a prion disease, CBD constrained the amassing of the prion protein in the brain and significantly increased the survival time of infected mice. CBD stopped the nerve damaging effects of prions in a concentration-dependent manner. Scientists noted that CBD might be a promising operator for the treatment of prion disease.
12 ALZHEIMER’S DISEASE
According to research at the Sapienza University of Rome, Italy, CBD has shown to reduce the effects of inflammation in the brain caused by amyloid-beta in a rat model of Alzheimer’s disease (Esposito et al. 2011). CBD has also shown to stimulate the formation of new nerve cells in the hippocampus, a brain region important for memory. A research conducted at the Cajal Institute in Madrid, Spain, CBD was shown to able to modulate the function of microglia, immune cells in the brain, in a mouse model of Alzheimer‘s disease (Martín-Moreno et al. 2011). Scientists reached a conclusion that, “since CBD lacks psychoactivity it may represent a novel therapeutic approach for this neurologic disease.”
When CBD was given intravenously for one hour before and 12 hours after reducing blood supply to the kidneys for 30 minutes in rats reduced damage to the organs. Researchers reached a conclusion that “Cannabidiol, through its antioxidant and anti- inflammatory properties, may represent a potential therapeutic option to protect” against damage to kidneys caused by temporarily reduced blood supply.
According to research at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, USA, CBD reduced the concerns of reduced blood supply to the liver in a mouse model of hepatic ischemia injury (Mukhopadhyay et al. 2011). Blood supply to the liver was stopped for this reason and later restored. CBD greatly reduced the extent of liver inflammation and cell death. This effect was not facilitated by cannabinoid receptors.
CBD is a potent anti-inflammatory agent (Kozela et al. 2013, Mecha et al. 2013, Li et al. 2013, Ribeiro et al. 2012, Kozela et al. 2011, Buccellato et al. 2010).
Studies with mice, both THC and CBD dose-dependently repressed the production and secretion of the cytokine interleukin 17 (IL-17) (Kozela et al. 2013). This pro-inflammatory substance is increased in inflammatory diseases such as multiple sclerosis. Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10.
In a viral model of several sclerosis with mice, CBD reduced inflammation and this effect was long-lasting, ameliorating motor deficits in the chronic phase of the disease in conjunction with the reduced production of substances, which gave rise to inflammation (pro-inflammatory cytokines) (Mecha et al. 2013).
CBD also reduced inflammation in acute pancreatitis of mice (Li et al. 2013). It reduced the concentration of pro-inflammatory substances (interleukin-6, tumour necrosis factor alpha). Research at the University of São Paulo, Brazil, confirmed that CBD reduced inflammation in a mouse model of acute lung injury (Ribeiro et al. 2012). This effect may be mediated through the adenosine A2A receptor.
Scientists at the University of South Carolina in Columbia, USA, investigated the effects of CBD on acute hepatitis induced by concanavalin A (ConA) in mice (Hegde et al. 2011). CBD reduced inflammation by growing the number of myeloid-derived suppressor cells through activation of TRPV1 vanilloid receptors.
16 LIVER AND BRAIN DAMAGE
According to scientists from Greece and Israel CBD improves brain and liver function in an animal model for brain damage (encephalopathy) caused by liver failure (Avraham et al. 2010).
According to Spanish scientists, CBD prevented from negative concerns of sepsis in a mouse model (Ruiz-Valdepeñas et al. 2011). It prevented dilation of small arteries and veins.
18 SKIN DISEASES
The proliferation of human skin cells was influenced by the cannabinoids CBD and cannabigerol (CBG) (Pucci et al. 2013). Researchers concluded that, “(especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”
Endocannabinoid signaling has shown to have a part in the control of epidermal physiology, whereby anandamide is able to control the appearance of skin variation genes through DNA methylation. In this study CBD and CBG significantly reduced the expression of all the genes tested (keratins 1 and 10, involucrin and transglutaminase 5) in differentiated HaCaT cells, by increasing DNA methylation of keratin 10 gene, but cannabidivarin was ineffective. Remarkably, cannabidiol reduced keratin 10 mRNA through a CB1 receptor-dependent mechanism, whereas cannabigerol did not affect either CB1 or CB2 receptors of HaCaT cells. In addition, CBD, but not CBG, increased global DNA methylation levels by selectively enhancing DNMT1 expression, without affecting DNMT 3a, 3b or 3L.
19 ALLERGIES AND ASTHMA
Study with Guinea-pigs the inhalation of ovalbumin caused constriction of the airways and this was reduced by CBD (Dudášová et al. 2013). Scientists concluded that CBD “may have beneficial effects in the treatment of obstructive airway disorders.”
According to research at the Taipei Medical University, Taiwan, the administration of CBD reduced delayed-type hypersensitivity reactions in mice to the protein ovalbumin (Liu et al. 2010). Scientists found out that CBD curbs delayed type hypersensitivity reactions by suppressing the infiltration and functional activity of certain immune cells (T cells and macrophages) in the inflammatory site, „suggesting a therapeutic potential for CBD for the treatment of type IV hypersensitivity“, a certain type of allergic reaction.
The effects of CBD on sleep may depend on dose, with lower doses having telling properties and high doses being calming. In a clinical study, eight volunteers received four treatments before sleep (at 10 p.m.): placebo, 15 mg THC, 5 mg THC combined with 5 mg CBD, and 15 mg THC combined with 15 mg CBD (Nicholson et al. 2004). Fifteen milligrams THC would appear to increase sleepiness, while 15 mg CBD appears to have alerting properties.
CBD increased total sleep time and increased sleep latency, the time needed to fall asleep, in the light period of the day in rats (Chagas et al. 2013). In the animals that received the highest dose, the phase of deepest sleep (so-called slow-wave sleep) was increased. Sedation was noted as a side effect in some clinical studies (e.g. Consroe et al. 1986).